FitSugar

When Is a Fever Too High?

FitSugar — Mon, 03 Mar 2008 02:30:00 -0800

With the nasty flu bug making its rounds, there's only so much eating healthy, getting enough rest, washing your hands, getting a flu shot, and avoiding germs one can do. If you're unlucky enough to get the flu, your body will hike up your body temperature to boil away all those germs. So, is there a point when your temperature can get too high?

When you get the flu, a sudden high fever is totally normal, and it can get as high as 104° F, and last for three to four days. The best thing you can do is to rest and drink plenty of fluids, since a fever can cause you to become dehydrated. Don't attempt to cool off your skin with cold packs since they'll just make you shiver, which will end up raising your body temperature. Instead you should alternate between taking Tylenol and ibuprofen every four hours to help reduce your fever. Alternating these meds will help to prevent accidental overdose, and sometimes the combination of the two will be more effective in bringing down your fever.

Fit's Tips: If your fever persists for more than five days, or it goes over 104° F, call your doctor and get some medical advice immediately.

Source

Immunizations

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Diphtheria, Tetanus, and Pe...
Measles, Mumps, and Rubella...
Varicella-Zoster Virus (Chi...
Varicella-Zoster Virus (Shi...
Hepatitis A
Hepatitis B
Pneumococcal Pneumonia
Poliomyelitis
Viral Influenza
Haemophilus Influenzae Type...
Human Papillomavirus (HPV)...
Rotavirus
Smallpox
Other Vaccinations
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Vaccines

The Centers for Disease Control and Prevention now recommends that children receive 2 doses of the varicella-zoster (Chickenpox) vaccine: the initial vaccine between ages 12 - 15 months, and a booster between 4 - 6 years. Children aged 12 and older and adults who have not had the vaccine should receive 2 doses. Immunization guidelines were changed following research that indicated the effectiveness of the vaccine declines over time. A 2007 study indicated that children who were vaccinated 5 or more years earlier were 2.6 times more likely to have a moderate-to-severe breakthrough case of chickenpox than those who had been vaccinated more recently.
A study finds that the conjugate pneumococcal vaccine, which was introduced for children in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has also caused hospital admissions to drop 26% among adults aged 18 - 39. Another study found that recurrent ear infections have fallen by 28% since the introduction of the vaccine.
In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus. The avian flu vaccine is designed for people ages 18 - 64 who are at risk for exposure to the virus. The vaccine is given in 2 shots, spaced about 1 month apart. The U.S. government is stockpiling the vaccination in case of an avian influenza outbreak, but the vaccine is not available to the general public.
Research finds that the human papillomavirus (HPV) vaccine (Gardisil) is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18).

Introduction

Immunizations against childhood diseases have saved millions of lives. American vaccination rates are now at an all-time high. Disease and death from diphtheria, pertussis, tetanus, measles, mumps, rubella, and Haemophilus influenzae (H. influenzae) type b are at or near record lows. In adults, immunizations against influenza (the flu), pneumococcal pneumonia, hepatitis, and other ailments have likewise saved many lives and prevented many more cases of serious illness. A new vaccine has been shown to be highly effective for preventing the virus that leads to cervical cancer.

More than 70 bacteria, viruses, parasites, and other infectious microbes cause major human disease. Fortunately, vaccines are either available or being developed against many of them. With the advent of new or newly feared biological threats, emerging infections, and bacterial resistance to common antibiotics, immunizations are assuming an increasingly important role in maintaining the health of billions of people worldwide.

Immunizations (vaccinations) are given to initiate or augment resistance to an infectious disease. Immunizations provide a specialized form of immunity that provides long-lasting protection against specific antigens, which cause disease.

Routine Childhood Vaccines. Experts recommend that all children be routinely vaccinated against the following diseases:

Measles
Mumps
Rubella (German measles)
Diphtheria
Tetanus
Pertussis (whooping cough)
Poliomyelitis (polio)
Varicella (chickenpox)
Hepatitis B
Hepatitis A
H. influenzae type B (a cause of meningitis)
Influenza (children aged 6 - 59 months)
Pneumococcal disease
Meningococcal disease (for selected populations)
Rotavirus (children aged 6 - 32 weeks)

Many vaccinations are first given during infancy. Even premature infants can, in most cases, be given vaccinations on a normal schedule. There is even some evidence that doing so may offer some slight protection against sudden infant death syndrome. Note: These facts pertain to children in the United States. Children from other countries have not been well studied. Parents who adopt internationally may want to have their children's immunity assessed by a physician. Some evidence suggests that their medical records may not correctly reflect immunization status and that many adopted children, such as those from China, have not had many important vaccinations.

Click the icon to see an animation about vaccines.

Common Adult Vaccines. Vaccinations against the following disorders are also recommended routinely for certain adults:

Influenza (flu). Every year in high-risk adults under 49 and everyone over 50. When supplies are limited, as with the 2004 - 2005 flu season, the vaccine should be administered preferentially to adults only over age 65 and to individuals with heart disease, lung disease, and other significant chronic illnesses. Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.
Pneumococcal pneumonia. One dose in high-risk adults under 64 and a first dose or a revaccination in everyone over 65.
Hepatitis A and B and Meningococcal vaccine. Given to high-risk individuals.
Tetanus. Adults need a booster shot every 10 years.
Measles, mumps, rubella. Typically given to adults under 56 who are unsure of their vaccination history. High-risk individuals may receive two doses.
Diphtheria and pertussis are now recommended with tetanus (Tdap vaccine) booster every 10 years until age 65.
Herpes zoster (shingles) vaccine. One dose for adults 60 and older.
Human papillomavirus (HPV). Three doses in young women aged 11 - 26.

Vaccines are currently taken by mouth (orally) or given by a shot (injection). Vaccines are usually made of one of two agents that cause the body to produce antibodies that attack a specific disease. A vaccine may contain:

A live but weakened virus. Live-virus vaccines provide longer immunity than inactivated ones, but they can cause serious infection in people with weakened immune systems and have also been associated with severe medical disorders in rare instances.
Inactivated bacteria, viruses, or toxoids. Inactivated vaccines are safe even in people with impaired immune systems.

Click the icon to see an image of antibodies.

The weakened or inactivated agent in the vaccine teaches the immune system to recognize the real, harmful substance and attack it when the person becomes exposed to the infection. The antibodies remain in the body, preventing future illness from the disease. This is called immunity.

Combination Vaccines. The American Academy of Pediatrics and American Academy of Family Physicians recommend that health care providers use, whenever possible, combination vaccines instead of individual components. Combination shots containing vaccines for diphtheria, tetanus, and pertussis (DTaP), and for measles, mumps, and rubella (MMR), have been available for years. New combinations that cover up to 5 vaccinations are being developed and are proving to be safe and well tolerated in infants as young as 2 months. For example, one that combines DTaP, hepatitis B, and the polio vaccine (Pediarix) has been approved and should simplify the immunization process.

There is some concern that increasing use of combinations may reduce the potency of some of the vaccines. Some parents are also worried about increased side effects. Studies to date, however, are reporting that combinations are effective and safe.

Passive Immunity. Another form of protection against disease is called passive immunity. This approach uses immune globulin, which are blood products containing antibodies. Immune globulin is generally used for people who cannot be vaccinated, when immediate protection is required, or to prevent severe complications of the disease. In some circumstances, passive immunity can interfere with active vaccinations, particularly live-virus vaccines, so, if possible, they should not be administered within weeks or even months of each other.

General Information on Side Effects. Vaccines can have side effects, such as swelling at the injection site or fever, which are nearly always mild. There have been a number of reports in the popular press about alarming side effects in many vaccines. Anti-vaccine groups vocally oppose immunizations in children. Although it is true that no vaccine is 100% safe, childhood infections have not been wiped out. Without immunization, children risk diseases that have in the past killed millions of young children.

Thimerosal is a preservative used in many vaccines. It has been in use since the 1930s. The preservative contains small amounts of mercury. Some people are concerned about possible neurologic consequences from cumulative doses of mercury contained in vaccines given to infants. A 2003 study did report an association between thimerosal in DTaP vaccines and a higher risk for problems in neurologic development, including autism and speech problems.

In 2004, the Institute of Medicine (IOM) Safety Review Committee reported the results of studies in the U.S. and several European countries evaluating a possible association between thimerosal and autism. They concluded that scientific studies did not find that thimerosal caused autism.

In any case, manufacturers have been removing this preservative from vaccines. At the time of this report, all vaccines recommended for children age 6 or younger contain either no thimerosal or only trace amounts, with the exception of the inactivated influenza vaccine (although a limited supply of a version of the vaccine containing only trace amounts of thimerosal is available for use in infants, children, and pregnant women). A trace amount means that a given dose of vaccine contains less than 1 part per million.

Inactivated-virus and toxoid vaccines are usually safe in pregnant women, although any vaccination should be delayed, if possible, until the second or third trimester. Because of a possible risk to the fetus, live-virus vaccines should not be given to pregnant women or those likely to become pregnant within 28 days unless such women need immediate protection against life-threatening diseases, such as yellow fever, that are only prevented using live-virus vaccines. The live-virus MMR combination, which vaccinates against measles, mumps, and rubella, is not given to pregnant women because of the theoretical risk of the live-rubella vaccine on the fetus.

Click the icon to see an image of rubella syndrome.

Live-virus vaccines are not usually given to people whose immune system has been compromised by illness or the use of medication such as long-term corticosteroids. They include:

Click the icon to see an image of HIV.

Persons who have immune deficiency diseases (such as HIV or AIDS).
Patients with active leukemia or lymphoma.
Patients who are taking treatments that suppress the immune system, such as corticosteroids, alkylating drugs, antimetabolites, or radiation. (There are important exceptions, however, which are noted in the discussion of individual vaccinations below.) Short-term corticosteroids (given for less than 2 weeks) do not suppress the immune system and so should not affect any live-virus vaccination. It should be noted that some topical corticosteroids are suppressive. Patients who need vaccinations and who take long-term or high-dose topical steroids should check with their physicians.

In general, vaccines are not completely effective for patients whose immune systems are compromised by disease or medications. Often, such patients are given immune globulin if they are exposed to infection. It may take 3 months to 1 year before a person who has stopped taking immunosuppressant drugs regains the full ability to be successfully immunized against disease.

People who are traveling to developing countries should check with the US Centers for Disease Control (www.cdc.gov/travel) for up-to-date information on immunization requirements for their destination.

Below are some general guidelines for vaccinations, immunizations, and other preventive steps for travel:

Everyone should be up-to-date on any recommended vaccinations for childhood diseases, regardless of their age. Booster shots may be required for travelers to developing countries even if they have completed the initial series. Vaccinations may include polio, H. influenzae, the series for diphtheria, pertussis, and tetanus (DTaP), hepatitis B, rotavirus, measles, and varicella-zoster (chickenpox). If children have not completed their DTaP series, parents should consider having it completed while overseas.
Pregnant women should have vaccinations that are appropriate to their trimester. Not all vaccinations are safe during pregnancy.
Older adults may not respond to a vaccination as quickly as younger people or they may have a higher risk for side effects. They should check with their physicians.
Upper respiratory infections are very common after foreign travel. The flu vaccine may be recommended when traveling to any country during flu season, particularly for the elderly and people at risk for serious illness. This group may also need the pneumococcal vaccine.
Travelers to areas where there are tuberculosis (TB) outbreaks should have skin tests before traveling; those with negative tests should have a repeat test 2 - 4 months after they return.
Vaccination against hepatitis A is recommended for all travelers to developing countries. Some expert groups believe that such travelers should have hepatitis B vaccinations as well, but the CDC does not generally recommend them at this time except under certain circumstances.
Travelers to countries with malaria should take preventive agents.
Some countries may require vaccinations against yellow fever, meningitis, typhoid, cholera, Japanese encephalitis, and rabies under certain circumstances. Some of these vaccinations are covered in this report.
Studies indicate that multiple vaccines may be given at the same time to most adults without significantly increasing adverse effects.

[For more information, see In-Depth Report #1: Travel to developing countries.]

Childhood Immunization Schedule**
Age	Chickenpox (Varicella Zoster)	Diphtheria, Tetanus, Pertussis (DTaP)*	Haemophilus influenzae type (Hib)	Hepatitis A	Rotavirus
Birth
2 months		DTaP*	Hib		Rotavirus
4 months		DTaP*	Hib		Rotavirus
6 months		DTaP*	Hib (Depending on brand. For example, no third dose is required for PedvaxHIB or ComVax.)		Rotavirus
12 to 15 months	Varicella	DTaP* (Typically between 15 and 18 months. May be given as early as 12 months in high-risk children as long as 6 months have passed since the third dose.)	Hib (Sometime between 12 and 15 months.)	HepA (In 2 does, between 12 and 23 months)
2 years old				In children who have not been fully vaccinated.
4 to 6 years	Varicella	DTaP
11 to 12 years	Varies. (If previously missed, two doses should be given at least four weeks apart.)			In adolescents through age 18 in selected areas.

Age	Hepatitis B (Hep-B)*	Measles, Mumps, Rubella (MMR)	Pneumococcal Vaccine (PCV7)	Polio (Inactive virus) (IPV)*	Human Papillomavirus (HPV)
Birth	Hep-B immediately after birth. (This is very important when mothers are infected.) No later than 2 months in children of noninfected mothers. *
2 months	Hep-B some time between 1 and 4 months depending on risk. *		PCV7	IPV*
4 months			PCV7	IPV*
6 months	Hep-B some time between 6 and 18 months. *		PCV7	IPV* (Advised at some point between 6 and 18 months.) *
12 to 15 months	Varies.	MMR (Some time between 12 and 15 months.)
2 years old			PCV7 -- 1 dose for children not previously vaccinated.
4 to 6 years		MMR	PCV7 -- 1 dose in high-risk children.	IPV*
11 to 12 years	Hep-B (If vaccinations were previously missed). Two or 3 doses a few months apart.	MMR (If vaccinations were previously missed).			HPV (Females)
* A one-shot combination vaccine (Pediarix) has been approved that covers polio, hepatitis B, diphtheria, pertussis, and tetanus (DTaP) and should simplify the immunization process. It would be given as a single injection at 2, 4, and 6 months with booster shots given at 12 to 15 months and 4 to 6 years. **All children aged 6 - 59 months should receive an annual flu shot. Children older than 5 years of age who have chronic medical conditions should also receive the influenza vaccination. The flu shot is not approved for children younger than 6 months of age.

Of great concern are anti-immunization organizations and websites, which were formed mostly because of unsubstantiated reports linking small numbers of serious problems to some vaccines. The following watchdog systems are now in effect to monitor side effects from vaccination:

VAERS (Vaccine Adverse Event Reporting System) is a government service that registers all adverse events reported after vaccination, including those not related to the vaccine. It is useful for surveillance but has limitations. For example, the service may record the same case more than once. In addition, more serious events that occur after a vaccination are more likely to be reported than later and milder events, and such events are not necessarily linked to the vaccine.
VSD (Vaccine Safety Datalink) is a linked database that analyzes the records of more than 5 million patients each year. It is more accurate than VAERS, although the information it contains is not as timely.
The CDC has established the national network of Clinical Immunization Safety Assessment (CISA) Centers. It will provide services to physicians to help them evaluate and manage patients who may have had a side effect.

Studies using these systems are ongoing and none to date have confirmed reports of any significant association between most vaccines and severe side effects that would outweigh the benefits of these important and lifesaving agents.

No vaccine is 100% safe. Allergic and serious reactions are possible. In 2 cases, the early polio vaccine and the rotavirus vaccine, problems did occur, and some were serious. It is important to note, however, that even in these cases, the vaccines were withdrawn and the severe events still were far fewer than the number of lives saved.

The focus on vaccination side effects is ironic due to the fact that reports of such adverse effects outnumber the number of actual infections. Because vaccinations have been in existence for so long, today's parents have no direct knowledge of the consequences of these dreaded infections, which killed or severely sickened millions of children in the past.

It should be noted that studies are reporting that the risk for infection increases significantly in children who are not vaccinated. There is also a rise in infections among immunized children, suggesting resistance to the vaccines.

Infants often accept the first injection easily, since they are not expecting it. It gets more difficult, however, with each additional shot. Simply providing love and warmth can help children of all ages tolerate immunizations.

Additional tips:

Do not lie and tell an older child that a shot will be painless. Some health care providers suggest telling them that it stings a little and to count to 5 while it is being administered.
Ask the doctor if it is OK to give the child a dose of acetaminophen (Tylenol) before or after a shot. Ibuprofen (Motrin, Advil) or other non-aspirin pain relievers may be acceptable alternatives. (Children should NEVER take aspirin after vaccinations.)
Ask the doctor about EMLA cream, a topical anesthetic containing lidocaine and prilocaine. This product can be applied about an hour before the injection. (Note: EMLA may interact with acetaminophen and certain vaccinations, so be sure to check with the doctor first.)
A cooling spray may work as well as EMLA and have fewer side effects.
Longer needles, rather than shorter ones, may help reduce pain. One study reported that using longer needles decreased redness at the injection site by about two-thirds. Parents may want to ask their doctor about this study.
Have your child take a deep breath right before the shot and blow out very hard while it is being given. One study reported very good results with this breathing technique.
Give a sweet fluid before the shot and a little reward, such as a lollipop, immediately after the shot. Sugar actually has mild pain relieving properties for infants.

Diphtheria, Tetanus, and Pertussis

Diphtheria. Diphtheria is caused by the bacterium Corynebacterium diphtheriae, which can occur as either a toxic or nontoxic strain. When only the skin is involved, it is known as cutaneous diphtheria, and is likely to be a nontoxic strain. If the toxic strain affects the mucus linings in the body, such as the throat, diphtheria becomes life threatening. Between 1900 and 1925, diphtheria infected 200,000 people every year and killed between 5 - 10% of them, mostly the very young and very old. Because of immunizations, only one case was reported in 2000.

Tetanus. Tetanus is a disease that causes severe muscular contractions and convulsions. It is caused by a powerful toxin secreted by the bacterium Clostridium tetani. The bacterium is anaerobic, which means it lives without oxygen. People become infected by this dangerous bacterium through wounds in the skin. It is fatal in 15 - 40% of cases. Only 35 cases were reported in the U.S. in 2000, mostly in adults. One case, however, occurred in a 12-year-old boy whose parents refused to vaccinate him.

Pertussis. Pertussis (whooping cough) was a very common childhood illness throughout the first half of the 1900s. The disease is very easily spread from one person to another, and it is most severe in babies. Because of immunizations, which began in the 1940s, cases of whooping cough reached an all-time low of 1,010 in 1976 in the U.S. The incidence has risen recently, with almost 25,837 cases reported in 2004. Many more cases are reported worldwide. Nearly half of pertussis cases now occur in people 10 years of age or older, perhaps due to waning immunity in adolescents and adults. Such cases may be greatly underreported. One study suggested that as many as 25% of adults who see a doctor for persistent cough may actually have pertussis, but it may go undiagnosed because symptoms are usually mild and adults are unlikely to have the classic whooping cough. This is of some concern, because such adults may unknowingly infect unvaccinated children. The younger the patient, the higher the risk for severe complications, including pneumonia, seizures, and even death. Children younger than 6 months are at particular risk because even with vaccination, protection is incomplete.

The Initial Vaccination. Diphtheria, tetanus, and pertussis (DTaP) are very different disorders, but a combination injection has been routinely given to children since the 1940s. Since the early 1990s, the standard vaccine is DTaP, which uses a form of the pertussis component known as acellular pertussis that consists of a single weakened toxoid. (The older vaccine, DTP, includes a pertussis vaccine that contains multiple toxins against different variants of the disease. DTaP is just as effective but has fewer side effects than DTP.)

Pertussis is increasing among adults; the Centers for Disease Control data indicate that there were more than 25,000 cases of pertussis in 2004.

The Booster. Protection against diphtheria and tetanus from the vaccine lasts about 10 years. At that point a booster may be given against tetanus and diphtheria (Td). The Td vaccine contains the standard dose against tetanus and a less potent one against diphtheria and does not contain the pertussis component. In April 2005, the FDA approved the first pertussis booster shot ("Boostrix") for kids aged 10 - 18. Boostrix is a lower dose of infant pertussis vaccine. The infant pertussis vaccine can start to wear off after about 5 years, and some previously immunized teens and adults can get a mild form of the disease. The booster shot may help reduce the number of pertussis cases in adolescents and adults. The FDA also approved in 2005 another novel booster vaccine called Adacel for protection against tetanus, diphtheria and pertussis from adolescence through adulthood.

DTaP Schedule in Childhood. All children younger than 7 years old should receive the DTaP vaccine. In general, the vaccinations are given as follows:

Infants receive a series of three vaccinations at 2, 4, and 6 months of age (doctors may delay a vaccination in infants with suspected neurologic problems until their neurologic situation is clarified, but no later than their first birthday). Children with neurologic problems that have been corrected can be vaccinated.
A fourth dose is given between 15 and 18 months. (Infants at higher risk, such as those exposed to an outbreak of pertussis, may be given this vaccination earlier.) Of note, children who receive their third shot late in the schedule are at higher risk for skipping the fourth dose than children who were on schedule. Parents should be sure to adhere to a schedule that includes the fourth shot, even if they were late on the third.
A fifth dose is given at 4 - 6 years. This fifth shot now usually includes a vaccine against H. influenzae as well.
Children between the ages of 11 and 15 years old should receive a tetanus and diphtheria (Td) booster shot.
Boostrix is a single-dose booster that can be given to children age 10 - 18 years.
Adacel is a single-dose booster Tdap for people age 11 - 64 years.

If a child has a moderate or severe current or recent fever-related illness, vaccinations should be postponed until after recovery. Colds or other mild respiratory infections are no cause for delay. Parents should not be unduly concerned if the interval between shots is longer than that recommended. The immunity from any previous vaccinations persists, and the doctor does not have to start a new series from scratch.

Recommendations for Adults. All vaccinated adults should have a Td booster at least every 10 years throughout their lifetimes. One study reported that fewer than half of adult Americans ages 20 and older were protected against both tetanus and diphtheria, and immunity rates were even lower in those over 70. The results indicate that many people are not getting routine boosters.

Other recommendations for adults are as follows:

Adults who did not receive the primary childhood vaccinations should have the tetanus, diphtheria, and pertussis (Tdap) vaccine, approved in 2005, every 10 years.
Unvaccinated pregnant women should receive two doses of Td, properly spaced, and previously vaccinated women should have a booster.

Preventing Tetanus in Individuals with Wounds. Wounds that put patients at highest risk for tetanus are puncture wounds or wounds contaminated with dirt, feces, or saliva. However, any patient who requires medical care for any wound is a candidate for tetanus immunity.

Some considerations for tetanus vaccinations in wounded people are as follows:

A booster is needed if the last shot was 5 or more years before the injury.
Children under 7 are usually given DTP if they are not fully vaccinated.
Most individuals are given the Td vaccination if they have been vaccinated.
Older patients who had experienced an allergic response to a previous tetanus booster may be given the tetanus immune globulin (TIG).

Allergic Reactions. In rare cases, people may be allergic to the older diphtheria, tetanus, and pertussis vaccine, DTP. Parents should tell their doctor if their children have any allergies. The newer vaccine, DTaP, may pose a slightly higher risk for an allergic reaction than the older vaccine, DTP. Children who have severe responses should not be given further vaccinations. A rash that occurs after a dose of DTP is of little consequence. In fact, it does not usually indicate an allergic response but only a temporary immune reaction and does not usually recur with subsequent shots. It should be noted that no deaths have been reported from allergic reactions, even severe (anaphylactic) ones, to the DTP vaccine.

Pain and Swelling at the Injection Site. Children may feel pain at the injection site. In some cases, a small lump may remain at the site for several weeks. Placing a clean, cool washcloth over any swollen, hot, or red area can help. Children should not be covered or wrapped tightly in clothes or blankets.

The risk for swelling, including of the whole arm or leg, increases with subsequent injections, particularly the fourth and fifth doses. If possible, parents should request that their children receive the same vaccine brand each time to help reduce the risk of side effects.

Feverand Other Symptoms. A child may develop a mild fever, irritability, drowsiness, and loss of appetite after a shot.

The following remedies may be helpful:

Acetaminophen (for example, Children's Tylenol) and a sponge bath in lukewarm -- NOT cold -- water may help relieve fever and pain.
The doctor may suggest that children who have had previous high fevers or other reactions to the shot be given acetaminophen at the time of the vaccination and every 4 hours afterward for 24 hours. (The doctor will determine the dosage according to the weight of the child.)
Children should NEVER be given aspirin.

Fevers that should cause concern include the following:

The older DTP vaccine posed some risk for fever-related seizures on the day of vaccination. The newer DTaP has significantly reduced this side effect. Any very high fever in children (over 105° F) that causes convulsions should be reported immediately to the doctor. Although frightening, such fever-related seizures are uncommon and rarely have any long-term effect, and a recurrence after a subsequent vaccination is very unlikely.
A new fever that develops 24 hours after the vaccination, a fever that persists for longer than 24 hours, or seizures without fever are most likely due to other causes.

Hypotonic-Hyporesponsive Episode (HHE). HHE is an uncommon response to the pertussis component and occurs within 48 hours of the injection in children under 2. The child usually starts out feverish and irritable and then becomes pale, limp, and unresponsive. Breathing is shallow, and the child's skin may turn bluish. The reaction lasts an average of 6 hours and, although it is frightening, virtually all children return to normal. This side effect is less common since the introduction of the DTaP vaccine, but it can still occur.

Neurologic Effects in Pertussis Component. Of concern have been a few reports of permanent neurologic abnormalities that have occurred after children have been vaccinated. Such reports include attention deficit disorder, learning disorders, autism, brain damage (encephalopathy), and even death.

It is well known that the diphtheria and tetanus components cause no adverse neurologic effects, so some people suspect the pertussis component. However, many major studies, including an important statistically sound analysis in 2002, found no causal relationship between neurologic problems and the pertussis vaccination. In fact, one study indicated that children who received pertussis vaccine had fewer problems in school than those who were not vaccinated, regardless of family income levels. Studies on the newer DTaP have reported no safety concerns to date.

There may be some exceptions. Studies now suggest that in cases where neurologic problems have been strongly linked to the vaccination, high fevers -- not immunization -- are responsible. Children with known neurologic abnormalities may also be at risk for an outbreak of symptoms 2 or 3 days after the vaccination. Such a temporary worsening of their disease rarely poses a danger to the child. (Some experts suggest that children who have new neurologic events following their shot may already have a preexisting impairment, such as epilepsy, which is revealed -- but not caused -- by the vaccine.) To date, there is no proof that the pertussis vaccine causes these neurologic events, which, in any case, are so infrequent as to be nearly statistically unmeasurable.

Important Note: Unwarranted fears of side effects from vaccinations can be dangerous. In England such fears have caused a significant decline in immunization rates since the 1970s. Outbreaks of whooping cough have occurred as a result, causing a number of deaths and brain damage in many children. Small babies are particularly endangered if they become infected from older unvaccinated children (who usually have a mild disease).

Call the doctor immediately if a child has any of the following symptoms.

Extremely High Fever. A rectal temperature of 105° F or higher. (Temperatures taken under the arm or by mouth often register lower than actual temperatures.)
Inconsolable Crying. The child has been crying for over 3 hours without stopping or has a cry that isn't normal, such as being high-pitched.
Convulsions. The child's body starts shaking, twitching, or jerking. This is usually in response to a high fever. Place the child face down with the head to one side, protecting the head from hitting anything hard. Be sure the child can breathe freely. Seizures caused by fevers usually last less than 15 minutes.
Shock. The child collapses, turns pale, and becomes unresponsive.
Severe Allergic (Anaphylactic) Reaction. Swelling in the mouth and throat, wheezing and breathing difficulties, dizziness. The child collapses or is pale and limp.

Call the doctor if the following symptoms persist for more than 24 hours:

The injection site is still red and tender.
Fever does not go down.
The child is still fussy.

Measles, Mumps, and Rubella

Measles. Measles, one of the most contagious of all human infections, used to be a very common childhood disease. Most cases go away without serious complications. In severe cases, however, measles can cause pneumonia, and in about 1 out of 1,000 cases it can lead to encephalitis (inflammation in the brain) or death. The risk for these severe complications is highest in the very young and very old. In pregnant women, measles increases the rates for miscarriage, low birth weight, and birth defects.

Measles outbreaks still occur in the United States, usually among groups of people who do not believe in immunizations or in areas where immunization levels have fallen below the critical level. It is a fairly serious childhood infection that is recognized by the rash (as seen here), Koplik spots (small white spots on red background), red eyes, photophobia (sensitivity to light), and coughing.

Aggressive vaccination programs have reduced the incidence of measles in the U.S., to a low of 86 cases in 2000, most imported from other countries. Full-blown measles cases among unvaccinated children still remain a serious international problem, with 42 million cases and over 1 million deaths in small children each year.

Mumps. Mumps is at record lows in the US, with only 338 cases reported in 2000. In about 15% of cases, mumps affects the lining of the brain and spinal cord, although this is usually not ultimately harmful. Swelling of the testicles occurs in between 20 - 30% of males who have reached puberty, although sterility is rare. Deafness in one ear occurs in one patient out of 20,000 with mumps.

Click the icon to see an image of the meninges of the brain.

Rubella (German Measles). When rubella, commonly known as German measles, infects children or adults, it causes a mild illness that includes a rash, enlarged lymph nodes, and sometimes a fever. If a pregnant woman is infected during her first trimester, however, her baby has a 80% chance for developing birth defects, including heart abnormalities, cataracts, mental retardation, and deafness.

Click the icon to see an image of a cataract.

Before the vaccine became available, about 56,000 cases of rubella occurred annually in the U.S. Vaccination programs have dramatically reduced the number of cases to a low of 176 in 2000, but between 6 - 11% of adults are still susceptible, particularly unvaccinated Hispanic Americans who were born outside of the U.S.

Click the icon to see an image of rubella.

Safe and effective live-virus vaccines for measles, mumps, and rubella have been developed over recent decades. They are usually combined in children as the measles, mumps, and rubella (MMR) vaccine. Individual live-virus vaccines or the combined MMR may be given to adults, depending on their risk factors.

Measles-Mumps-Rubella (MMR) Vaccine in Early Childhood. The combined MMR vaccine should be given in two doses:

Between ages 12 and 15 months for the first dose. (Some doctors believe that the vaccine may be effective and safe in children younger than 9 months who are in areas of measles outbreaks. It should be noted that there were only 86 reported cases of measles in the U.S. in 1999.)
Between ages 4 and 6 years for the second dose. (Children who receive only one dose at 15 months or older have five times the risk of measles compared to those who had two doses.)

Measles-Mumps-Rubella (MMR) Vaccine in Adolescents and Adults. The general recommendations for adult MMR vaccinations are as follows:

Most people born before 1957 have experienced these once-common childhood diseases and do not require vaccination.
All unvaccinated people born after 1956 who did not already have measles and mumps should be given two doses of the live MMR vaccine administered at least 1 month apart.
Many people received an inactivated measles-virus vaccine in the early 1960s or an inactivated mumps-virus vaccine between 1950 and 1978; such people need revaccination with two doses of the live MMR vaccine. (This will cause no harm even if someone had a previous live-virus-mumps vaccination.)
The American Academy of Pediatrics now recommends the live-virus MMR vaccine for HIV-infected children, teenagers, and young adults, except for those who are severely immunocompromised. At this time, however, the vaccine appears to be safe in HIV-infected children, and it should be stressed that measles is very dangerous in this population.

Rubella Vaccinations During Pregnancy. It is particularly important for any unvaccinated nonpregnant woman who wants children to be vaccinated against rubella. It is recommended that women wait at least 28 days after vaccination to start trying to conceive. Except under very special circumstances, no live-virus vaccine, especially MMR, is given to an already pregnant woman, since there is a theoretical risk for birth defects from the rubella vaccine. Fortunately, the risk is low. In fact, studies have reported no increase in birth defects in women who were inadvertently vaccinated for rubella early in their pregnancy.

Common side effects from the MMR vaccination include fever, rash, and joint pain. Children are more likely to experience such side effects from the second dose (at 10 - 12 years) than from the first (at 4 - 6 years).

Fever. About 5 - 15% of people who are vaccinated with any live measles virus vaccine develop a fever of 103° F or greater, usually between 5 and 15 days after the vaccination. It usually lasts 1 or 2 days but can persist up to 5 days. In very young children, seizures can occur from high fever 8 - 14 days after vaccination, but they are rare and almost never have any long-term effects.

Swollen Glands. The live-mumps vaccine can cause mild swelling in the glands that are situated near the ears.

Joint Pain. Up to 25% of women have joint pain 1 - 3 weeks after a vaccination with a live-rubella virus; it lasts for 1 day to 3 weeks. Such pain does not usually interrupt daily activities. Rarely, it recurs or becomes persistent.

Allergic Reaction. People who have known anaphylactic allergies (very severe reactions) to eggs or neomycin are at high risk for a severe allergic response to the MMR vaccine. People with allergies that do not cause anaphylactic shock to these substances are not at higher risk for a serious allergic reaction to the vaccine. Mild allergic reactions may occur in some people, including rash and itching. A rash occurs in about 5% of people who are vaccinated with a live-measles vaccine. A live-mumps vaccination has caused rash and itching, but these symptoms are usually mild.

Interaction with Tuberculosis Test. The live-measles vaccine may interfere with a tuberculosis test, so the two should be administered at least 4 - 6 weeks apart. No evidence exists that the vaccine has an adverse effect on tuberculosis itself.

Mild Infection. One study suggests that a mild form of measles that has no symptoms may develop in previously immunized people who are exposed to the virus, although this mild infection may not be significant.

Idiopathic Thrombocytopenic Purpura (ITP). In about 1 in 22,300 doses, MMR can cause a rare bleeding disorder called idiopathic thrombocytopenic purpura (ITP). This can cause a purple, bruise-like discoloration that can spread across the body, nose bleeds, or tiny red spots. It is nearly always mild and temporary. (Of note, the risk for ITP is much higher with the actual infections, particularly rubella.)

Note: Unsubstantiated Reports of Neurologic Side Effects and Decline in Immunization. Much controversy has arisen over unsubstantiated reports of neurologic side effects attributable to MMR. This is of great concern since such reports have resulted in a decline in immunizations in certain areas, notably affluent areas in England where the vaccination rate has dropped from 92% in 1996 to 84% currently. Here, measles outbreaks are now climbing, and doctors fear that unless immunization rates increase rapidly, case numbers will significantly increase. In these and other regions, some parents mistakenly believe that the dangers of immunization outweigh a dangerous childhood illness that only older people remember. It should be strongly noted that measles still cause about 745,000 deaths in unvaccinated children who live in underdeveloped countries, primarily in Africa.

Most publicity has centered on a possible link between the MMR vaccine, which was introduced in 1988, and a variant of autism that includes inflammatory bowel disease (IBD) and impaired behavioral development. Such findings have been rigorously reviewed and refuted in a number of well-conducted studies. Of special note, a 2002 analysis of vaccination records of children born between 1979 and 1998 found no higher incidence in autism, with or without behavioral problems and gastrointestinal disorders. In the study, there was a link between impaired behavioral development and bowel problems, but they were not related to the vaccine.

Despite considerable publicity, there is no evidence linking MMR vaccination with the development of autism. The Centers for Disease Control & Prevention website provides extensive information on this matter. The popular media has incorrectly reported the possible link between autism and MMR as causing a split in the scientific community, but virtually all experts refute any association. In fact, reports of symptoms related to autism increased only after widespread publicity of this supposed side effect.

The potential benefits from receiving the MMR vaccine far outweigh the potential adverse effects. Measles, mumps, and rubella are all very serious illnesses and each may have complications resulting in lifetime disabilities or even death. The incidence of such complications, related to having the actual diseases, is far greater than the potential of developing serious, or even moderate, adverse effects due to the MMR vaccine.

Click the icon to see an image of inflammatory bowel disease.

Varicella-Zoster Virus (Chickenpox)

Chickenpox (caused by the varicella-zoster virus) is one of the most contagious childhood diseases. Nearly every unvaccinated child becomes infected with it. The affected child or adult may develop hundreds of itchy, fluid-filled blisters that burst and form crusts.

The infection rarely causes complications in healthy children, but it is not always harmless. Five out of every 1,000 children are hospitalized and, in rare cases, it can be fatal. Before the vaccination became widespread, chickenpox resulted in about 11,000 hospitalizations and 100 deaths a year.

This is a close-up picture of chickenpox. Early chickenpox lesions consist of small red papules that quickly fill with a yellowish or straw colored fluid to form small blisters (vesicles), as seen in this photograph. Later, these vesicles will rupture, forming shallow erosions that crust over and then ultimately heal.

Click the icon to see an x-ray of pneumonia following exposure to chickenpox.

Chickenpox can be especially severe in adults and very serious in anyone with a compromised immune system. In addition, the varicella virus (which persists after the childhood disease) erupts as a painful and distressing condition called herpes zoster (shingles) in about 20% of adults with a history of chickenpox. Chickenpox itself usually occurs only once, although a few cases of mild second infections, marked by the telltale rash, have been reported in older children years after their first infection.

Click the icon to see an image of the shingles.

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. Data show that the vaccine can prevent chickenpox or reduce the severity of the illness even if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

Recommendations for the Vaccine in Children. The vaccine against chickenpox is now recommended in the U.S. for all children between the ages of 18 months and adolescence who have not yet had chickenpox. Children are given one dose of the vaccine. Two doses 1 - 2 months apart are given to people over 13 years of age. To date, more than 75% of children have been vaccinated.

Doctors recommend that the chickenpox vaccine be given at the same time as the measles-mumps-rubella (MMR) vaccine or that there is a delay of at least 1 month between the two vaccinations. (If the chickenpox vaccination is given within that 30-day period -- but not at the same time -- there is a higher risk for a breakthrough infection later on.)

A chickenpox vaccine is part of the routine immunization schedule. It is about 100% effective against moderate or severe illness, and 85 - 90% effective against mild chickenpox. Parents often express concern that the immunity from the vaccine might not last. The chickenpox vaccine, though, is the only routine vaccine that does not require a booster.

Recommendations for the Vaccine in Adults.

Some doctors suggest that every healthy adult without a known history of chickenpox be vaccinated. In general, however, the following adults should consider vaccinations:

Older people without a history of chickenpox and who are at high risk of exposure or transmission (such as hospital or day care workers and parents of young children)
People who live or work in environments in which viral transmission is likely
Nonpregnant women of childbearing age
Adolescents and adults living in households with children
International travelers

As with other live-virus vaccines, the chickenpox vaccine is not recommended for the following:

Pregnant women (including the 3 months prior to pregnancy). Of note, an encouraging study suggested that pregnant women who were inadvertently vaccinated did not face a higher risk for birth defects in their offspring.
People whose immune systems are compromised by disease or drugs (such as after organ transplantation). The vaccine is being studied, however, for its safety in some of these patients, particularly children with cancer or other high-risk conditions. Experts report that it is safe in children with acute lymphoblastic leukemia (ALL), who should receive two doses. Certain children who are HIV positive may be candidates for the vaccine. An inactivated varicella vaccine may be safe and effective in patients undergoing bone marrow transplants, when given before and after the operation.
Most patients who cannot be vaccinated but are exposed to chickenpox are given immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected.

Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.

Mild Rash and Risk of Transmission. The vaccine may produce a mild rash within about a month of the vaccination, which has been known to transmit chickenpox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chickenpox until the risk for a rash has passed.

Severe Side Effects. Between 1995 and 2001, 759 serious adverse effects were reported. Such events included seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnson syndrome, neuropathy, herpes zoster, and blood abnormalities. Anecdotal reports have found a higher association of side effects when varicella vaccine is given at the same time as the measles, mumps, and rubella (MMR) vaccination. Because combined vaccinations are being developed, such effects should be closely studied.

There is intense debate over the long-term protection of the vaccine. The incidence of breakthrough infections after vaccination stimulates the controversy. It should be noted, however, that evidence is showing improvements in quality of life and better survival rates since the introduction of the vaccine. Any negative studies to date on long-term effectiveness simply raise the question of the need for booster or higher doses -- not the elimination of the vaccine altogether.

Long-Term Protection in Vaccinated Children. Most studies suggest that the vaccine is not wholly effective in up to 30% of vaccinated children. However, they also report if chickenpox occurs, more than 95% of the cases are mild. It is also usually less contagious. In such people, the infection appears to be caused by a wild virus, not a reactivation of the vaccine. (Of concern was a 2002 study of a day care center reporting a much higher rate -- 56% -- of break-through infection, with only 86% of cases being mild. The implications of this study are unclear.) The longer the interval since vaccination occurs, the higher the risk for a breakthrough infection.

This does not necessarily mean, however, that children who are vaccinated eventually lose total immunity. A breakthrough infection is often due to issues with the primary vaccine (improper storage, low potency, the duration between the chickenpox and measles, mumps, and rubella vaccines being less than a month) or the child's history (having asthma, being less than 14 months at the time of vaccination). Nevertheless, there is also some evidence that either having the vaccination or even having chickenpox itself is not as protective against a later infection as experts have thought.

Long-Term Protection in Vaccinated Adults. The protective effects for adults are even less clear. An encouraging 2002 study of adults vaccinated between 1979 and 1999 reported that 9% developed chickenpox months to years after their last vaccination. The length of time since the vaccination did not seem to affect whether the adults would catch chickenpox or not. (Nearly half of those had been exposed to the disease in their homes.) In all cases, infection was mild, with none of the serious complications of adult chickenpox.

Vaccine's Effect on Shingles. A primary concern is whether the vaccine protects against shingles later on, particularly in people who have breakthrough infections -- however mild. As more and more children get vaccinated, the actual protection of the vaccine and the implication of the breakthrough infection will become clearer.

[For more information, see In-Depth Report #82: Shingles and chickenpox (Varicella-zoster virus).]

In September, 2005, the Food and Drug Administration approved a combination vaccine to protect against measles, mumps, rubella, and chickenpox. Proquad, produced by Merck & Co., protects against all four infections with one shot, thus sparing young children from multiple painful injections. Proquad is approved for use in children from 12 months to 12 years of age. Proquad was studied in four randomized trials involving 5,446 healthy children aged 12 - 23 months received Proquad. Proquad’s immune response rates were 97.4% for measles, 95.8 - 98.8% for mumps, 98.5% for rubella, and 91.2% for chickenpox, similar to the rates induced by the concomitant administration of single doses of M-M-R II and Varviax at separate injection sites in 2,038 children.

Varicella-Zoster Virus (Shingles)

Shingles is a painful infection caused by the varicella zoster virus, the same virus responsible for chickenpox. Once a person has chickenpox, the virus lies dormant in the body. It can emerge years later as shingles.

Shingles causes a painful, red, and sometimes blistery rash to form on the body or face. The disease can cause intense pain, called post herpetic neuralgia. Other symptoms include fever, headache, and chills. In rare cases, complications, such as pneumonia, blindness, and brain inflammation (encephalitis), can occur. Shingles is most common in adults over age 50.

In May 2006, the U.S. Food and Drug Administration licensed the herpes zoster vaccine (Zostavax) for the prevention of shingles. The vaccine can reportedly cut the incidence of shingles in half for adults over age 60.

Recommendations for the Vaccine in Adults. All adults age 60 or older should get a single dose of the herpes zoster vaccine, regardless of whether they have previously had shingles.

The following people should not receive the herpes zoster vaccine:

Anyone who has a weakened immune system due to HIV/AIDS or cancer of the lymph, bone, or blood, or due to treatments such as radiation or corticosteroid drugs
Women who are pregnant, or anyone who is in close contact with a pregnant woman who has not had chickenpox
Children -- they should receive only the chickenpox vaccine

Redness, pain, and swelling. About 1 out of every 3 people who get the vaccine have mild redness, soreness, swelling, or itching at the injection site.

Headache. About 1 in 70 people experience headache after taking the vaccine.

There have been no serious side effects reported with the shingles vaccine.

Research has found that the herpes zoster vaccine reduces the incidence of shingles by about 50%. The benefit is as high as 64% in people ages 60 - 69. In people who are vaccinated but still develop shingles, the vaccine reduces the duration of the pain involved with the disease.

One 2007 study found that doing tai chi might boost the immune response to the vaccine. According to the study, people aged 59 - 86 who took part in a 16-week tai chi program had immunity similar to that of 30- and 40-year-old adults who had been vaccinated. Combining tai chi with the vaccine increased the effects of the vaccine by about 40%.

Hepatitis A

The hepatitis A virus infected an estimated 56,000 people in 2004. Hepatitis A, formerly called infectious hepatitis, is always acute and never becomes chronic. The virus is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. It can also be acquired by close contact with individuals infected with the virus. It is estimated that 11 - 16% of reported cases occur among children or employees in daycare centers or among their contacts. The hepatitis A virus does not directly kill liver cells, and experts do not yet know how the virus actually injures the liver.

A fly may act as a mechanical vector of diseases such as hepatitis A. The fly may carry the infective organism on its feet or mouth parts and contaminate food or water, which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

All children should get 2 doses of the hepatitis A vaccine starting at 1 year, according to CDC recommendations. The doses should be given at least 6 months apart. Others who should be vaccinated against hepatitis A include travelers to developing countries, people living in communities where outbreaks occur, people with blood-clotting disorders, sexually active homosexual men, and health care workers exposed to the virus. People with chronic liver disease, including those with hepatitis C, should also be vaccinated, particularly if they have not been exposed to hepatitis A, since the infection can cause liver failure in these patients.

The hepatitis A vaccine can be given along with immune globulin and other vaccines. Individuals should also receive immune globulin if they are exposed within 4 weeks of the vaccination. A combined vaccine against both hepatitis A and B is now available as well for those at high risk for both these infections. People should get 3 doses of this vaccine, and the last dose should be given 6 months after the first dose.

Side Effects. The vaccine is very safe and effective, although allergies can occur. The most common side effects reported are soreness at the injection site, headache, and general malaise.

Click the icon to see an image about hepatitis A immunization.

Hepatitis B

About 2 billion people have been infected with the hepatitis B virus (HBV) worldwide, and each year 1 million people die, mostly due to cirrhosis and liver cancers that develop in the chronic form of this disease. In the U.S., about 1.25 million people have chronic hepatitis B.

Hepatitis B is also known as serum hepatitis. It spreads through blood and sexual contact. The infection is seen with increased frequency among intravenous drug users who share needles and among the homosexual population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Courtesy of the CDC.)

Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitis B before age 5. Although hepatitis B infections have dropped 95% since routine immunization began in the early 1990s, there are still children who aren't immunized, and the disease persists. Universal vaccination against this disease during childhood is very important.

Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B. Twinrix is a vaccine against both hepatitis A and B. They are safe, even for infants and children. Vaccination programs are proving to reduce the risk for liver cancer.

Click the icon to see an image of hepatitis B.

Hepatitis B Vaccine for Early Childhood. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade. Typical schedules for hepatitis B vaccinations in childhood are as follows:

All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be delayed if the mother has no evidence of infection, but only with the doctor's permission.) The second dose should be given at 1 - 2 months; and the third between 6 and 18 months (at least 16 weeks after first dose and 8 weeks after second dose). (A fourth dose may also be given if any of the previous doses was a combination vaccine.) This is a safe vaccine, even in newborns, and parents should be sure their infants are immunized.
Infants of mothers infected with hepatitis B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. The second dose should be given at 1 - 2 months and the third at 6 months. Infants should be tested for antibody status at 9 - 18 months to see if they are chronic virus carriers or need to be revaccinated. Immunization rates are still too low in this group.
When it is not known if a mother is infected, the infant should receive the vaccine within 12 hours of birth. The mother's blood should then be tested right away. If she is infected, the infant should receive immune globulin within 1 week of birth.
Children who are 11 - 12 and who have not been immunized should receive 2 or 3 doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection may wane over time. According to a 2007 study, 40% of adolescents who had received a first dose of the vaccine as newborns had declining immunity to the disease by age 14. As of now, routine booster shots are not recommended because more research is needed on the subject. Booster shots may be recommended for those at risk, such as from sexual exposure.

Hepatitis B Vaccine for Adults. The following adults are at very high risk and should be vaccinated:

Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B that ranges from 15 - 30%.
People in the same household ashepatitis B-infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitis B may be protected with immune globulin, which is sometimes administered with the vaccine.)
Travelers to countries with a high incidence of hepatitis B infection.
Patients who require transfusions and have not been infected with hepatitis B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)
Sexually active individuals with multiple partners.
People with any sexually transmitted diseases.

Other people at risk who would benefit from vaccinations include:

Patients and workers in mental institutions
Morticians
Patients undergoing hemodialysis. (These people may need larger doses or boosters; they also may need to be revaccinated if blood tests indicate they are losing immunity.)
People who use injected drugs
Pregnant women at risk for the virus. (There is no evidence that the vaccine is dangerous to the fetus.)
People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

Click the icon to see an image of the immune system structures.

The regimen in adults is typically 3 doses given over 6 months. One study reported that older adults would benefit from a fourth dose without incurring serious side effects. People who abuse alcohol may need higher doses.

A small percentage of people do not develop immunity, even after a vaccine has been given repeatedly. A more potent vaccine is proving to be effective for these people; it loses its effect after 5 years in about one-third of those who receive it.

Soreness. Soreness at the injection site is the most common side effect.

Nerve Inflammation. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and some questions about multiple sclerosis. A review article published in 2006 found no evidence that hepatitis B vaccine is associated with multiple sclerosis, sudden infant death syndrome, or chronic fatigue syndrome. Earlier studies also found no evidence linking the vaccine to multiple sclerosis. A 2007 study found that the vaccine doesn't increase the risk for rheumatoid arthritis.

Because of even a small theoretical risk of nerve damage in infants, some groups oppose the vaccination in children who are not in high-risk groups. Worldwide, 65 million people with chronic hepatitis are expected to die from liver disease and vaccinations are saving lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer. [For more information see In-Depth Report #59: Hepatitis.]

Pneumococcal Pneumonia

The pneumococcal bacterium (also called Streptococcus pneumoniae or S. pneumoniae ) is responsible for many respiratory infections in the upper and lower airways. This bacterium is dangerous for people with serious underlying chronic medical conditions and illnesses and is the leading cause of ear infections and sinusitis in children. The most serious complication is pneumonia.

More than 200,000 people in the U.S. are hospitalized each year for pneumonia-related complications. Although the majority of pneumonias respond well to treatment, the infection can still be a very serious problem. It kills approximately 36,000 people each year. Together with influenza, pneumonia is the eighth leading cause of death in the U.S.

Of particular concern is the increasing prevalence of pneumococcal bacteria that are resistant to many standard antibiotics. This has created a great sense of urgency in the medical community to find effective measures for preventing infection.

This picture shows the organism pneumococci. These bacteria are usually paired (diplococci) or appear in chains. Pneumococci are typically associated with pneumonia, but may cause infection in other organs, such as the brain (pneumococcal meningitis) and bloodstream (pneumococcal septicemia). (Courtesy of the CDC.)

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are 2 effective vaccines available: The 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and the 7-valent conjugate vaccine Prevnar (PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

The 7-valent conjugate vaccine Prevnar (PCV7) is very effective in children. Research finds that the vaccine, which was introduced in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has even lowered hospital admissions 26% among adults aged 18 - 39 the study found, likely because they are parents of young children who might otherwise have developed the disease. Another study found that the vaccine also has benefited children who regularly get ear infections. Recurrent ear infections have fallen by 28% since the introduction of the vaccine.

Click the icon to see an image of pneumococcal pneumonia.

The pneumococcal vaccine is now recommended by many experts for the following groups:

Children up to age 2. The vaccine is very effective in children. In one study, a similar vaccine under investigation not only protected children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as children with sickle cell disease, those with immune deficiencies, a damaged spleen or no spleen, or children with chronic medical conditions. One study has found that the rate of pneumococcal disease among children with sickle cell disease has dropped 90% since the vaccine was introduced.
Other children ages 2 - 5 who are at higher risk for serious pneumococcal infections should be considered for vaccinations. They include African- or Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to be effective in reducing the rate of pneumonia in young adults, although not to the degree that it protects young children. The benefit for the elderly -- other than protection against bloodstream infection -- is unclear. Still, pneumonia is declining among adults, which may be due to fewer infections being transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over 65 years old. Some experts believe that all adults 50 - 64 should also be vaccinated. Unfortunately, although the vaccination is protective against pneumococcal bacteremia (invasive infection) in people over 65, evidence suggests that it does not appear to protect against community-acquired pneumonia.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease (such as congestive heart failure), chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies (such as HIV) or those undergoing treatments that suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies show the vaccine may not be as effective in these patients as in those with healthy immune systems. Nevertheless, they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics, especially those with cirrhosis.
People living in long-term care facilities.
Alaska Natives or American Indians, who may be at increased risk for pneumonia.

The safety of the pneumococcal vaccine hasn't been proven during the first trimester of pregnancy; however, there have been no adverse effects reported. When the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although the protective value may be lost at a faster rate in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

The recommended schedule of immunization for Prevnar (PCV7) is 4 doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have 3 doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Side effects include pain and redness at the injection site, fever, and joint aches. Children are more likely to have fever within 48 hours if they receive other vaccines at the same time, and also after the second dose. Fortunately, severe reactions are very rare, even if a person is mistakenly revaccinated before the effects of the first vaccination have worn off. Allergic reactions are also very rare.

Poliomyelitis

Poliomyelitis, more commonly known as polio, is a disorder caused by a virus and marked by potentially paralyzing nerve-related damage, which can be fatal. Fifty years ago it was a major killer of children, and it remains a threat in parts of Asia and Africa today. Vaccination programs eliminated the disease in the Americas in 1994, with the last case of wild poliovirus in the U.S. reported in 1979. As of 2004, polio has been eradicated in the Americas, the Western Pacific, and Europe.

Poliomyelitis is a communicable disease caused by viral infection and occurs through direct contact with infected secretions. Polio is found worldwide, but immunization has reduced the incidence. Clinical polio affects the central nervous system (brain and spinal cord). Disability is more common than death.

Two poliovirus vaccines have been available in the U.S.: oral poliovirus vaccine (OPV), a live-virus vaccine, and inactivated poliovirus vaccine (IPV), a killed vaccine that is administered by a shot. Both produce immunity in more than 95% of people. The live-virus used in the vaccine, however, has, in some cases, reverted to a form that can cause polio in unvaccinated people. This is a particular danger in developing countries where vaccination rates are low. The Centers for Disease Control and Prevention now recommends only the inactivated IPV vaccine for children. The schedule is 4 doses of IPV at ages 2 months, 4 months, 6 - 18 months, and 4 - 6 years.

Poliovirus Vaccine in Older Children and Adults. The poliovirus vaccine is not usually recommended for people over 18. Exceptions are unvaccinated health care workers, laboratory technicians, or others exposed to polioviruses. Travelers to developing countries where outbreaks of poliovirus have been reported should be vaccinated. Adults should also be given the inactivated poliovirus vaccine (IPV).

Allergic Reactions. The inactivated poliovirus vaccine (IPV) contains small amounts of streptomycin and neomycin, so people allergic to these antibiotics can also have an allergic response to this vaccine. Patients should report any allergies to their physician.

Paralysis. Rare cases of paralysis have occurred in people taking the oral live poliovirus vaccine or in those exposed to recipients of this vaccine. It should be stressed the risk is very small, with only 1 case occurring out of 2.4 million doses. Since the introduction of the current recommended series that uses only IPV, no cases have been reported.

Contamination by Simian Virus 40. The public was alarmed by reports of contamination of polio vaccines given between 1955 and 1963 by a virus known as SV40. The virus has been detected in certain rare cancers, including mesothelioma (a lung cancer normally associated with asbestos exposure), osteosarcoma, some brain tumors, and non-Hodgkin's lymphoma.

Click the icon to see an image of a brain tumor.

Still, about 98 million people may have been exposed, and most of these cancers are very rare (although some, including non-Hodgkin's lymphoma, are increasing). At least 40 years of observation have raised no red flags that indicate any serious problem. However, polio, once a major killer of children, has nearly been wiped out worldwide.

Viral Influenza

Influenza, commonly called the flu, is always caused by a virus.

Influenza, also known as the flu, is caused by a virus.

There are different strains of influenza:

Influenza A is the most widespread and most severe strain. It can affect both animals and humans. Influenza A is the cause of the worldwide epidemics (pandemics) of the flu that have occurred. More than 200,000 hospitalizations per year are due to this strain of the flu. Influenza A is usually further categorized by 2 subtypes based on 2 substances that occur on the surface of the viruses: hemagglutinin (H) and neuraminidase (N).
Avian Influenza A (called “bird flu”) was first detected in humans in 1997 in China and the region of Hong Kong. Bird flu is spread easily from bird to bird. Humans usually contract the flu from contact with infected domesticated birds, such as chickens, turkeys, and ducks. The World Health Organization confirms that there were, as of the publishing of this report, 331 cases of bird flu in humans and 203 deaths. The greatest number of cases have occurred in Indonesia, followed by Vietnam, Egypt, Thailand, and China. In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus.
Influenza B infects only humans. It is less common than type A, but is often associated with specific outbreaks, such as in nursing homes. Flu caused by this strain tends to be milder than that caused by Influenza A.

Based on a final analysis of the 2005 - 2006 flu season, nearly 80% were type A and about 20% were type B. Influenza A usually causes more severe disease than type B. However, because influenza B has been less common in the past few years, there is concern that some people -- particularly small children -- may have fewer antibodies to it and so may be at higher risk for severe infection. (See Flu Vaccines in this report.)

Complications of the Flu. In general, the flu is usually self-limited and not serious. It is responsible, however, for 15 - 30% of the excess number of hospitalizations that occur in winter. More than 200,000 people who contract the flu end up in the hospital, and an estimated 36,000 people currently die each year of flu-related complications. The highest risks for serious complications occur in people age 65 and older and in those who are already sick with another disease. There have also been reports of flu-related deaths in very young children.

Pneumonia is the major serious complication of the flu and can be very serious. It can develop about 5 days after viral influenza. It is an uncommon event, however. It nearly always occurs in high-risk individuals, such as the very young or very old, and hospitalized or immunocompromised patients.

Note on Pandemics. Every year, flu strikes millions of people worldwide. Influenza epidemics are most serious when they involve a new strain against which most people are not immune. Such so-called pandemics can infect more than one fourth of the world's population within a 3-month period. For example, the Spanish flu in 1918 and 1919 killed 20 million people in the U.S. and Europe, and 17 million people in India. Although pandemics are still of great concern, there have been major improvements in private and public health since then, including the discovery of antibiotics to treat bacterial complications, new antiviral agents and vaccines, and intensive worldwide surveillance of outbreaks.

Description of Vaccines. Vaccines against the flu use inactivated (not live) viruses. The influenza vaccine is commonly called a "flu shot." It is designed to provoke the immune system to attack antigens contained on the surface of the virus. (Antigens are foreign molecules that the immune system specifically recognizes as alien and so targets for attack.)

Click the icon to see an image of antigens.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift ) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines are redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they, too, vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children will not have developed any immunity to the virus and will experience severe flu if they are exposed to type B.

Until recently the vaccine has been administered only by injection. A vaccine (FluMist) that can be delivered in a nasal spray has now been approved for people aged 5 - 49. The vaccine contains live viruses that have been engineered to replicate in the cool temperatures of the nasal passages, but not in the warmer lungs and lower airways. Its presence in the nasal passages boosts the specific immune factors in the mucous membranes that fight off the epidemic viruses. Studies in 2003 reported protection against the flu that ranged from 66 - 92%, depending on whether the flu was type A or type B. (The lower rates were those observed for influenza B, particularly a new variant.) A 2007 study found that children aged 6 months - 5 years who had the nasal spray had 55% fewer cases of the flu than those given the injection. However, the vaccine is not approved for children in this age group. A preservative-free intramuscular injectable vaccine (Fluzone) is also now available.

The avian flu vaccine is designed for people aged 18 - 64 who are at risk for exposure to the avian H5N1 virus. The vaccine is given as 2 shots, spaced about 1 month apart. In studies, the vaccine appeared to be effective and well tolerated. Currently, the government is stockpiling the vaccination in case of an avian influenza outbreak. The vaccine is not available to the general public.

Ideally, appropriate candidates should be vaccinated every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the flu virus usually develop within 2 weeks of vaccination, and immunity peaks within 4 - 6 weeks, then gradually wanes.

Because children under age 9 do not develop strong immune responses to 1 dose, the CDC recommends 2 vaccinations given 1 month apart.
Early research also suggests that it may be equally effective to administer children’s vaccinations in the spring and fall, rather than 1 month apart; further study is ongoing.
It should be noted that if an individual develops flu symptoms and is accurately diagnosed in time, vaccination of the other members of the household within 36 - 48 hours affords effective protection to those individuals, according to a 2004 Canadian analysis of multiple studies.

In healthy adults, immunization typically reduces the chance of getting the flu by about 70 - 90%. The current flu vaccines may be slightly less effective in certain patients, such as the elderly and those with certain chronic diseases. Some evidence suggests, however, that even in people with a weaker response, the vaccine is usually protective against serious flu complications, particularly pneumonia. The major outstanding question is whether the vaccination prevents complications of serious illness. One 2003 study, for instance, reported no reduction in severity of chronic lung diseases among vaccinated patients with asthma, emphysema, or chronic bronchitis. Some evidence suggests, on the other hand, that among the elderly, a flu shot may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated. The following children over 6 months should be vaccinated against the flu:

The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children ages 6 - 23 months. In addition, any child over age 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell disease, or immune deficiencies).
Children who are receiving long-term aspirin therapy should also receive a flu shot. Children who get the flu are at higher risk for Reye syndrome, a life-threatening disease.
Some doctors now advocate flu shots for all school-age children. Research indicates that children are responsible for transmitting the vast majority of cases of the flu, and that routine vaccination of school-age children would considerably reduce transmission rates throughout communities.

There has been some question concerning flu shots because of some reports that vaccines may worsen asthma. Recent and major studies have been reporting, however, that the vaccination is safe for children with asthma. It is also very important for these patients to reduce their risk for respiratory diseases. Yet many children with asthma are not vaccinated. One study by the CDC found that fewer than one-third of children with asthma were vaccinated during the 2004-2005 flu season.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first 2 groups have the highest need for flu shots and are given top priority:

All adults 65 years and older. Older adults who get a flu shot have lower hospitalization rates than those who do not. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of people in this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from the flu. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. Those with any condition that may compromise respiratory function or the handling of respiratory secretions, including people with cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders, are included in this group. (There have been concerns about the safety of the vaccinations in certain high-risk patients, such as those with HIV or asthma. Studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from the flu outweighs any potential adverse effects from the vaccines.)
Adults aged 50 - 64 who have chronic medical conditions. The U.S. Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 should be vaccinated, although this is not a recommendation of the CDC.
All health care workers should be vaccinated, according to the ACIP’s 2005 recommendations.
Household members in contact with individuals who are at high risk for complications from the flu should be vaccinated.

Other adults who should consider flu shots include:

People at risk for complications of the flu who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for complications of the flu and who will be in their second or third trimester during flu season. Women who are pregnant should receive only the inactivated flu vaccine. (Vaccinations should usually be given after the first trimester. Exceptions may be women who are in their first trimester during flu season, because their risk from complications of the flu is higher than any theoretical risk to the baby from the vaccine.)
People such as firemen or policemen who are critical for public safety.

Possible side effects of the flu vaccine include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two-thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 or 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include conjunctivitis, cough, wheeze, tightness in the chest, sore throat, or a combination. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last for up to 2 days. It should be noted that these symptoms are not the flu itself but an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Isolated cases of a paralytic illness known as Guillain-Barre syndrome have occurred, but if there is any higher risk, it is very small (one additional case per 1 million people), and does not outweigh the benefits of the vaccine.

Haemophilus Influenzae Type B

Haemophilus influenzae (H. influenzae) type B is a bacterium, which, despite its name, is entirely different from the viruses that cause influenza (the flu). Before vaccination, H. influenzae type B (Hib) was the most common cause of childhood bacterial meningitis, killing 600 American children every year and leaving others deaf, mentally retarded, or epileptic. It is rarely troublesome for adults, although it can be dangerous for anyone with chronic lung disease and those susceptible to infections.

This is a Gram stain of spinal fluid from a person with meningitis. The rod-like organisms seen in the fluid are Haemophilus influenza, one of the most common causes of childhood meningitis (prior to the widespread use of the H. influenza vaccine). The large red-colored objects are cells in the spinal fluid. A vaccine to prevent infection by Haemophilus influenza type B is available as one of the routine childhood immunizations (Hib), typically given at 2, 4, and 12 months.

Three equally effective inactivated bacterial vaccines (commonly called Hib vaccines) are available for H. influenzaetype B. All children under 5 should be vaccinated against H. influenzae type B. The vaccine is administered as an injection at 2 and 4 months. Depending on the vaccination preparation, a third shot in the series is administered at 6 months. A booster is required at some time between 12 and 15 months of age.

Click the icon to see an image of Hib immunization.

In children older than 12 months, the Hib and DTaP vaccines are being combined in a single injection. This combined injection can be given as a booster, but not as the initial Hib immunization.

Evidence suggests that in infants, this combined vaccine using acellular pertussis (the current DTaP standard) is less effective in protecting against Hib than one that uses the older form with whole-cell pertussis. The booster at 1 year should help maintain protection, however.

The Hib vaccine may benefit older people who have had their spleen removed or illnesses that put them at risk for pneumonia, including sickle cell disease, leukemia, and HIV infection.

Click the icon to see an image of sickle cells.

Side effects of the Hib vaccine include redness and pain at the injection site, moderate fever, and, in rare cases, weakness, nausea, and dizziness.

Human Papillomavirus (HPV)

In 2006, the U.S. Advisory Committee on Immunization Practices( ACIP) voted to recommend the use of the first vaccine (Gardasil) to protect against human papillomavirus (HPV). This group of 100 viruses includes some 40 sexually transmitted viruses. Some HPV viruses can significantly increase the risks of cervical cancer, as well as cancers of the vulva, vagina, anus, and penis.

HPV is a very common virus; an estimated 20 million people in the U.S. have it. At least half of all sexually active men and women will eventually develop the virus.

A 2007 study indicated that the Gardasil vaccine is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18); however, it does not protect against the other types of the virus. It is less effective in women who were exposed to the virus before they were vaccinated. A 2007 study indicated that the vaccine is effective for 5 years after women receive the initial dose. The manufacturer has applied to the FDA for approval of the vaccine to also help prevent cancers of the vagina and vulva.

A new experimental vaccine, called Cervarix, has been shown in research to be effective for 5 1/2 years against the 2 most prevalent strains of HPV. Research is also indicating that the vaccine might be effective against more types of infections than the Gardasil vaccine. Researchers are studying the vaccine further, and they're looking at whether Cervarix is effective in women over age 25.

Girls ages 11 - 12 should get the vaccine, but they can get it as early as age 9. Adolescents and women ages 13 - 26 also should get the vaccine if they haven't already received it. Young women should ideally get the vaccine before they are sexually active, but it is still effective in sexually active women who haven't yet been infected with HPV. Currently there is no research to confirm the vaccine's effectiveness in women over 26, so there is no recommendation yet for this age group. Gardasil is not recommended for pregnant women.

Young women should get 3 doses of the vaccine. They should get the second dose 2 months after the first dose, and the third dose 6 months after the first dose.

Studies have shown no significant side effects from the HPV vaccine. The most common side effect was soreness at the injection site.

Rotavirus

Rotavirus is the most common cause of diarrhea, cramps, and vomiting in infants, and affects about 3.5 million children in the U.S. each year. As many as 80% of small children become infected with the virus. Although most cases in this country are mild, more than 50,000 American children are hospitalized and as many as 125 die from severe diarrhea every year. Worldwide the virus can be devastating, causing more than 600,000 infant deaths annually. There is also some strong evidence that the virus can lead to childhood diabetes.

An oral vaccine (Rotashield) has been withdrawn after reports of a severe and even life-threatening condition called intussusception following use of the vaccine. Intussusception occurs when the bowel slips inside itself like a telescope and obstructs the intestine. The risk was very small and occurred within a week or two of the vaccination. Any child who previously had the vaccination no longer incurs any increased risk. Preliminary reports suggest that newer rotavirus vaccines may be highly effective in preventing infection among infants, although more research is needed to confirm these findings and to determine their safety record in a large number of children. The association between diabetes and the virus itself raises some alarm that the vaccine might also increase the risk in children who are genetically susceptible to type 1 diabetes.

The U.S. Food and Drug Administration (FDA) approved a new oral rotavirus vaccine (Rotavirus, Live, Oral, Pentavalent vaccine -- trade name RotaTeq) early in 2006, and the Advisory Committee on Immunization Practices (ACIP) recommended that all infants should be immunized (3 liquid doses by mouth at 2, 4, and 6 months of age). In February 2007, the FDA announced there had been 28 reports of intussusception in infants who received the vaccine. After carefully monitoring cases of intussusception and other adverse effects associated with RotaTeq the FDA announced in March 2007 that the vaccine does not pose an increased risk of intussusception.

Because this is a deadly virus for many children worldwide, international groups believe that the few cases of intussusception do not warrant withdrawing its use, at least for countries where the infection is so common and deadly.

Click the icon to see an x-ray of intussusception.

Smallpox

Vaccination against smallpox used to be routine in the U.S. until 1972, and most older Americans bear the telltale small round smallpox vaccination scar on their upper arms. Immunity may last 10 years or longer. The last case of smallpox, a highly contagious and deadly disease caused by the variola virus, occurred in a laboratory worker in the U.K. in 1978.

However, the growing threat of bioterrorism has raised fears that smallpox could be used as a biological weapon, and in 2002 the US government issued plans for vaccinating every citizen against the disease in the event of an outbreak. The vaccination, however, carries some risks. Currently, then, vaccination continues to be recommended only for laboratory workers and scientists who work with the virus.

If an outbreak occurs, guidelines from the CDC call for a so-called "ring vaccination" approach. This involves identifying anyone who comes into contact with an infected person and vaccinating them and their contacts with a single dose of vaccine. This includes people of all ages and even those at risk for vaccine complications. The vaccine may work even if given within the first few days of infection.

Those at increased risk of vaccine complications but who should still be immunized if they are actually exposed to an outbreak include the following:

Children younger than a year. About 42 infants out of a million will develop brain swelling that may result in retardation or death. A severe, body-wide rash may also occur, especially if children touch the vaccination site.
Pregnant women. There is a small risk of miscarriage or premature delivery, although smallpox itself in pregnant mothers has more serious implications.
People with skin conditions, particularly eczema. They may develop a widespread blistering rash called eczema vaccinatum, which is fatal in 1 - 6% of cases, and they should not be vaccinated unless they've been exposed to the disease. They should also avoid others who have been vaccinated until those persons' vaccination scabs heal and fall off. People with non-chronic skin conditions, such as allergic rashes, severe burns, or chickenpox, may be vaccinated once their skin condition clears up.
People with suppressed immunity due to HIV, organ transplants, high-dose steroids, cancer chemotherapy, or other conditions.
Should a severe rash or other complication develop, patients should notify their doctors immediately. Two investigational medications, vaccine immune globulin (derived from the blood of people who have been vaccinated against smallpox) and an antiviral drug called cidofovir (Vistide), may be administered intravenously in the hospital should serious complications arise.
In the event of an outbreak, current plans specify that vaccination against smallpox will remain voluntary, although unvaccinated people who are exposed to the disease may be quarantined for 18 days to help contain the spread of disease.

Other Vaccinations

Many other types of vaccinations are available.

Rabies is a frequently fatal, acute viral infection that is transmitted to humans by infected animals (often dogs or bats) via a bite or exposing broken skin to an infected animal's saliva. In the past, human cases in the U.S. usually resulted from a dog bite, but more cases of human rabies have been linked to bats. Meanwhile, there have not been any rabies cases caused by dog bites for a number of years. Few cases occur in the U.S. because of extensive animal vaccination programs.

Anyone who is exposed to bats or to secretions of an animal suspected of having rabies should receive the rabies vaccine. Exposed individuals should also receive immune globulin unless they were previously vaccinated. Veterinarians and animal handlers should be vaccinated. This does not eliminate the need for treatment if they are exposed to rabies, but it reduces the intensity of the treatment.

Side effects include pain, redness, swelling at the injection site, headache, nausea, stomach pain, muscle aches, and dizziness. Allergic response can occur after the first shot and as many as 21 days after a booster shot. Rare cases of neurologic disorders that cause pain and paralysis in the legs and arms have also been reported. These neurologic disorders usually clear up in about 12 weeks.

Click the icon to see an image of rabies.

Plague is a severe, and potentially deadly, infection. It is caused by the organism Yersinia pestis. Wild rodents, like rats, spread the disease to humans. Plague is spread among rodents by a flea bite. Humans may get the plague when they touch or eat the infected animal, or when they come in contact with its feces. Certain forms of the plague can be spread from human to human. Plague is rare in the United States, but has been known to occur in parts of California, Utah, Arizona, Nevada, and New Mexico.

Veterinarians and assistants in the western U.S. or anyone who works with potentially plague-infected animals and travelers to developing countries where outbreaks have occurred should be vaccinated. The plague vaccine is not 100%y protective; it may only lessen severity of the disease. Preventive antibiotics are needed for anyone exposed. Side effects include headache, malaise, fever, swollen lymph nodes, and, occasionally, non-infected abscesses. Allergic reactions may occur, particularly in those sensitive to beef, soy, milk, and phenol.

Anthrax is an infectious disease caused by the spore-forming bacteria called Bacillus anthracis. Infection in humans most often involves the skin, the gastrointestinal tract, or the lungs.

Anthrax commonly affects hoofed animals such as sheep and goats, but humans who come in contact with the infected animals can get sick from anthrax, too. Historically, the populations most at risk for anthrax included farm workers, veterinarians, and tannery and wool workers. Anthrax is a potential agent for use as a biological weapon or for bioterrorism. In 2001, bioterrorist activities involving the U.S. Postal Service infected 22 people with anthrax; 7 survivors had confirmed cutaneous anthrax disease.

Military personnel and vaccine researchers, as well as people who work with imported animal hides, furs, bone meal, wool, animal hair (especially goat hair), and bristles, should receive an anthrax vaccine. The anthrax vaccine appears to be safe and effective, even after exposure, but requires 6 shots over 18 months. Up to half of recipients develop temporary soreness; some develop fever. Pregnant women should not get the anthrax vaccine.

Click the icon to see an image of cutaneous anthrax.

Click the icon to see an image of tuberculosis.


Disease	Who Should Get It?	Additional Information
Adenovirus	Military personnel.	Vaccine given orally for the prevention of respiratory illness.
Yellow Fever	Travelers to developing countries where outbreaks have occurred, currently parts of Africa and Central and South America. Residents of these areas, particularly children.	Vaccinations safe and effective for the prevention of jaundice and kidney and liver failure. Anaphylactic reactions in those allergic to eggs. Very rarely, may cause a potentially fatal illness resembling yellow fever, with fever and diarrhea, particularly in seniors. Lower immunity when given with cholera vaccine; the vaccines should be given three weeks apart.
Cholera	Travelers to developing countries where outbreaks have occurred.	Recently developed vaccines (Dukoral, Mutacol) are more effective than previous ones, which provided little protection. Not recommended or available, however, in the US.
Typhoid	Travelers to developing countries where outbreaks have occurred.	Oral vaccines include: (Ty21a, Vivotif). The oral vaccines are not effective against parathyroid fever. One-shot vaccine (Typhim Vi). Can be taken as early as two weeks before travel. Vi-rEPA is a newer injected vaccine that is safe in children and may be more effective-than other vaccines to date. No vaccine is 100% effective. The response to the typhoid vaccine tends to be lower in older people.
Tuberculosis	Individuals exposed to infected people.	Bacille Calmette-Guerin vaccine has been the standard vaccine, but its effectiveness has been questioned. No longer recommended in US except for certain high-risk children. A new recombinant BCG vaccine, shown in early trials to be more effective, is now licensed for use and is undergoing continued study.
Meningitis caused by meningococcal bacteria	U.S. Advisory Committee on Immunization Practices (ACIP) recommendations now call for routine vaccination of all young adolescents (aged 11 - 12) as well as those previously defined as at increased risk: People exposed to single cases or outbreaks; freshmen college students living in dorms; military recruits; travelers to developing countries where outbreaks have occurred; patients with problems in the spleen.	Vaccines are available against four subtypes of meningococcal bacteria but not for serogroup B, which causes up to 40% of meningococcal disease in the U.S. Among young people, fatalities have been higher in 15- to 24-year-olds than those younger than 15.

Resources

www.immunize.org -- Immunization Action Coalition
www.cdc.gov/vaccines/ -- The National Immunization Program
www.fda.gov/cber/vaers/vaers.htm -- Vaccine Adverse Event Reporting System
www.909shot.com/Issues/Injury_Compensation.htm -- National Vaccine Injury Compensation Program
www.immunizationinfo.org -- The National Network for Immunization Information
www.vaccine.chop.edu -- Vaccine Education Center, Children's Hospital of Philadelphia
www.vaccinesafety.edu -- Institute for Vaccine Safety, Johns Hopkins School of Public Health
www.whathealth.com -- National Partnership for Immunization
www.immunofacts.com -- Information on vaccinations
www.vaccines.org -- The Vaccine Page

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2005. Pediatrics. 2005 Jan;115(1):182.

Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mor Mortal Wkly Rep. June 2007;56:1-40.

Centers for Disease Control and Prevention. Recommended Immunization Schedule for Ages 0-6 Years, United States, 2007.

Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L. Loss of vaccine-induced immunity to varicella over time. NEJM. March 15, 2007;356:1121-1129.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. NEJM. May 10, 2007;356:1928-1943.

Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. April 7, 2007;369:1179-1186.

Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 Jul 29;54(RR-8):1-40.

Poehling KA, Szilagyi PG, Crijalva CG, Martin SW, LaFleur B, Mitchel E, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. April 4, 2007;119:707-715.

Prevention of influenza in the general population: Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2004;171:10.

American Academy of Pediatrics Committee on Infectious Diseases. Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients. Pediatrics. 2005 Aug;116(2):496-505.

Pneumococcal vaccine cuts severe bacterial disease in US. Mor Mortal Wkly Rep CDC Surveill Summ 2005;54:893-896.

Wise R, Iskander J, Pratt D, et al. Postlicensure Safety Surveillance for 7-Valent Pneumococcal Conjugate. JAMA. 2004; 292:1702-1710.

Krym VF, MacDonald RD. Global efforts to eradicate polio. CMAJ. 2004 Jan 20;170(2):189-90.

Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J Med Virol. 2006 Feb;78(2):169-77.

Review Date:
10/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Fever

admin — Thu, 04 Sep 2008 19:05:08 -0700

Overview

Definition
Alternative Names
Considerations
Common Causes
Home Care
Call your health care provider if
What to expect at your health care provider's office
References

Illustrations

Thermometer temperature

Temperature measurement

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Normal body temperature varies by person, age, activity, and time of day. The average normal body temperature is 98.6°F (37°C).

Alternative Names

Elevated temperature; Hyperthermia; Pyrexia

Considerations

Normal body temperature varies.

In children younger than 6 months of age, the daily variation is small.
In children 6 months to 2 years old, the daily variation is about 1 degree.
Daily variations gradually increase to 2 degrees per day by age 6.

Body temperature varies less in adults. However, a woman's menstrual cycle can elevate temperature by 1 degree or more.

Your body temperature is usually highest in the evening. It can be raised by physical activity, strong emotion, eating, heavy clothing, medications, high room temperature, and high humidity. This is especially true in children.

A rectal temperature up to 100.4°F (38°C) may be entirely normal. A rectal temperature of 100.5°F or above should always be considered a fever. Lower temperatures might also be a fever, depending on the person.

Fever is not an illness. Far from being an enemy, it is an important part of the body's defense against infection. Many infants and children develop high fevers with minor viral illnesses. While a fever signals to us that a battle might be going on in the body, the fever is fighting for the person, not against.

Most bacteria and viruses that cause infections in people thrive best at 98.6°F. Raising the temperature a few degrees can give your body the winning edge. In addition, a fever activates the body's immune system to make more white blood cells, antibodies, and other infection-fighting agents.

Many parents fear that fevers will cause brain damage. Brain damage from a fever generally will not occur unless the fever is over 107.6°F (42°C). Many parents also fear that untreated fevers will keep going higher and higher. Untreated fevers caused by infection will seldom go over 105°F unless the child is overdressed or trapped in a hot place.

Some parents fear that fevers will cause seizures. For the great majority of children, this is not the case. However, febrile seizures do occur in some children. Once a child is already known to have a high fever, a febrile seizure is unlikely with the current illness. In any event, simple febrile seizures are over in moments with no lasting consequences.

Although infections are the most common causes of higher-than-normal body temperature, fevers have a long list of other causes, including toxins, cancers, and autoimmune diseases.

Heatstroke is a particularly dangerous type of high temperature, because the body is not able to stop the temperature from continuing to rise. It can happen when a child is left in a hot car or when you exercise too strenuously without enough to drink.

Unexplained fevers that continue for days or weeks are called fevers of undetermined origin (FUO).

Common Causes

Acute bronchitis
AIDS and HIV infection
Cancer
Colds or flu-like illnesses
Collagen vascular disease, rheumatoid diseases, and autoimmune disorders
Ear infections
Fever can occur in infants who are overdressed in hot weather or a hot environment
Hodgkin's disease
Infectious mononucleosis
Inflammatory bowel disease
Juvenile rheumatoid arthritis
Leukemia
Medications (such as antibiotics, antihistamines, barbiturates, and drugs for high blood pressure)
Neuroblastoma
Non-Hodgkin's lymphoma
Occasionally, more serious problems like pneumonia, appendicitis, tuberculosis, and meningitis
Periarteritis nodosa
Regional enteritis
Sore throats and strep throat
Systemic lupus erythematosus
Ulcerative colitis
Upper respiratory infections (such as tonsillitis, pharyngitis or laryngitis)
Urinary tract infections
Viral and bacterial infections
Viral gastroenteritis or bacterial gastroenteritis

Home Care

If the fever is mild and no other problems are present, no medical treatment is required. Drink fluids and rest. If a child is playful and comfortable, drinking plenty of fluids, and able to sleep, fever treatment is not likely to help.

Take steps to lower a fever if you or your child is uncomfortable, vomiting, dehydrated, or having difficulty sleeping. The goal is to lower, not eliminate, the fever.

When trying to reduce a fever:

DO NOT bundle up someone who has the chills.
Remove excess clothing or blankets. The environment should be comfortably cool. For example, one layer of lightweight clothing, and one lightweight blanket to sleep. If the room is hot or stuffy, a fan may help.
A lukewarm bath or sponge bath may help cool someone with a fever. This is especially effective after medication is given -- otherwise the temperature might bounce right back up.
DO NOT use cold baths or alcohol rubs. These cool the skin, but often make the situation worse by causing shivering, which raises the core body temperature.
Drink cool liquids, as tolerated.

Here are some guidelines for taking medicine:

Acetaminophen and ibuprofen help reduce fever in children and adults.
Take acetaminophen every 4-6 hours. It works by turning down the brain's thermostat. Take ibuprofen every 6-8 hours. Like aspirin, it helps fight inflammation at the source of the fever. Sometimes doctors advise you to use both types of medicine. Ibuprofen is not approved for use in children less than 6 months old.
Aspirin is very effective for treating fever in adults. DO NOT give aspirin to children unless specifically directed by your doctor.
Fever medicines come in different concentrations, so always check the instructions on the package.
Don't use any medicine to reduce fever in children under 3 months of age without first contacting a health care provider.

If someone has heat exhaustion or heat stroke, remove the person from the warm area. Sponge the person with tepid water. Place ice packs in the armpits, behind the neck, and in the groin. Give fluids if the person is alert. Seek medical attention. If heat illness is causing the fever, medicines may not lower the body temperature and may even be harmful.

Call your health care provider if

Call a doctor right away if:

A baby less than 90 days old has a rectal temperature of 100.4°F (38°C) or higher.
A baby 3 to 12 months old has a fever of 102.2°F (39°C) or higher.
A child under age 2 years has a fever that lasts longer than 24 to 48 hours.
A fever lasts longer than 48 to 72 hours in older children and adults.
Anyone has a fever over 105°F (40.5°C), unless it comes down readily with treatment and the person is comfortable.
There are other worrisome symptoms. For example, irritability, confusion, difficulty breathing, stiff neck, inability to move an arm or leg, or first-time seizure.
There are other symptoms that suggest an illness may need to be treated, such as a sore throat, earache, or cough.
You think you may have incorrectly dosed acetaminophen or ibuprofen.

What to expect at your health care provider's office

Your doctor will perform a physical examination, which may include a detailed examination of the skin, eyes, ears, nose, throat, neck, chest, and abdomen to look for the cause of the fever. Your doctor may ask questions such as:

How long has the fever lasted?
Is it increasing? Is it increasing rapidly?
Has the fever gone away?
How many days did it take for the fever to go away?
Do you have alternating chills and fever?
How frequently does it alternate (days, hours)?
Did it occur within four to six hours after exposure to something that you might be allergic to?
Does the fever follow an up-and-down pattern (is it high, then lower, then high)?
Did it develop suddenly?
Does the temperature go up and down suddenly (spike) or does it change slowly?
Does it go away and then come back again daily?

Treatment depends on the duration and cause of the fever, and on other accompanying symptoms.

The following diagnostic tests may be performed:

Blood studies, such as a CBC or blood differential
Urinalysis
X-ray of the chest

References

American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever. Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med. 2003; 42(4): 530-545.

Roth J. Molecular aspects of fever and hyperthermia. Neurol Clin. 2006; 24(3): 421-39, v.

Goldman L, Ausiello D. Cecil Textbook of Medicine, 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007.

Behrman RE. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, Pa: WB Saunders; 2004: 839-841.

This article uses information by permission from Alan Greene, M.D., © Greene Ink, Inc.

Review Date: 2/27/2008

Reviewed By: Rachel A. Lewis, MD, FAAP, Columbia Pediatric Faculty Practice, New York, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003090

Colds and the flu

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Vaccine News:

On September 28, 2007, the U.S. Food and Drug Administration (FDA) approved a new brand of inactivated influenza ("flu") vaccine, Alfuria, for adults aged 18 years or older. This vaccine is given by injection.
On September 19, 2007, the FDA approved the use of the live flu vaccine (FluMist) in healthy children as young as 2 years of age. This vaccine, given in the form of a nose spray, was previously approved for healthy children and non-pregnant adults aged 5 - 49.

Drug Resistance:

The World Health Organization reports that resistance to the anti-viral drug oseltamivir (Tamiflu) can develop with extensive use. Oseltamivir is one of two drugs the CDC recommends for treating the flu. It is also the current recommended treatment for the H5N1 avian flu virus.

Drug Recalls:

In October 2007, drug manufacturers voluntarily withdrew from the market all oral cough and cold products, including decongestants, aimed at children under 2, due to potential harm from misuse. The U.S. Food and Drug Administration (FDA) recommends against using these products to treat children under age 2. The FDA is currently reviewing the safety of cough and cold medicines in children ages 2 - 11 years.

Emerging Virus:

A new, more virulent strain of adenovirus has reportedly emerged in the United States in 2006. The adenovirus family causes upper respiratory infections, pneumonia, and several other diseases. The new strain of adenovirus 14 causes severe respiratory illness that has resulted in several deaths.

Introduction

Upper respiratory tract infections affect the airways in the nose, ears, and throat.

Structures of the throat include the esophagus, trachea, epiglottis, and tonsils.

The infections can be caused by viruses, bacteria, or other microscopic organisms. In most cases, these infections lead to colds or mild influenza (flu) and are temporary and harmless. In rare cases, flu can be severe, or the infections may turn into pneumonia.

Organisms that cause these upper respiratory tract infections are generally spread by:

Direct contact (such as hand-to-mouth)
Coughing or sneezing

The common cold (medically known as infectious nasopharyngitis) is the most common upper respiratory tract infection. More than 200 viruses can cause colds. The most common cause is the rhinovirus, which is responsible for about half of all colds. Symptoms usually develop 1 - 3 days after being exposed to the virus.

A cold usually progresses in the following manner:

It nearly always starts rapidly with throat irritation and stuffiness in the nose.
Within hours, full-blown cold symptoms usually develop, which can include sneezing, mild sore throat, fever, minor headaches, muscle aches, and coughing.
Fever is low-grade or absent. In small children, however, fever may be as high as 103°F for 1 or 2 days. The fever should go down after that time, and be back to normal by the 5th day.
Nasal discharge is usually clear and runny the first 1 - 3 days. It then thickens and becomes yellow to greenish.
The sore throat is usually mild and lasts only about a day. A runny nose usually lasts 2 - 7 days, although coughing and nasal discharge can persist for more than 2 weeks.

A new, more virulent strain of adenovirus has reportedly emerged in the United States in 2006. The adenovirus family causes upper respiratory infections (it is one of the many viruses that cause the common cold). It also causes pneumonia, conjunctivitis, and several other diseases. The new strain of adenovirus 14 causes severe respiratory illness that has resulted in several deaths. Some patients who contracted this new viral disease had to be hospitalized, sometimes in intensive care units.

Every year, influenza strikes millions of people worldwide. Influenza epidemics are most serious when they involve a new strain, against which most people around the world are not immune. Such global epidemics (pandemics) can rapidly infect more than one fourth of the world's population. For example, the Spanish flu in 1918 and 1919 killed an estimated 20 million people in the U.S. and Europe and 17 million people in India. With modern society's dependence on air travel, an influenza pandemic could potentially inflict catastrophic damage on human lives, and disrupt the global economy.

The influenza virus mutates (changes) rapidly as it moves from species to species. Most Type A influenza strains (the most common strains) first develop in migratory waterfowl populations. While most avian influenza (bird flu) virus strains are relatively harmless, a few develop into "highly pathogenic avian influenza," which can be very deadly for domesticated poultry and livestock. As recent events have shown, these strains can also be deadly to humans. People can become infected by these bird flu strains through contact with contaminated chickens and pigs. The medical community is now greatly concerned about the H5N1 bird flu virus, which has infected and even killed people in several countries.

Symptoms of influenza. Patients usually feel sick 1 - 4 days after exposure to the influenza (flu) virus. The flu usually involves:

Abrupt onset of severe symptoms, which include headache, muscle aches, fatigue, and high fever (up to 104°F).
Cough (which is usually dry but can be severe) and sometimes a runny nose and sore throat.
Children may experience vomiting, diarrhea, and ear infections, as well as other flu symptoms.
The symptoms usually resolve in 4 - 5 days, although some people can experience coughing and feelings of illness for more than 2 weeks. In some cases, flu can become more severe or make other conditions worse.

Transmitting the Virus. The flu virus is spread primarily when a person with the flu coughs or sneezes near someone else. Adults with flu typically spread it to someone else from 1 day before symptoms start to about 5 days after symptoms develop. Children can spread the infection for more than 10 days after symptoms begin, and young children can transmit the virus 6 days or even earlier before the onset of symptoms. People with severely compromised immune systems can transmit the virus for weeks or months.

Flu Strains. A virus is a cluster of genes wrapped in a protein membrane, which is coated with a fatty substance that contains molecules called glycoproteins. Strains of the flu are identified according to the number of membranes and type of glycoproteins present.

Click the icon to see an image of a virus.

The two major flu strains are referred to as A and B:

Influenza A is the most widespread and can infect animals and humans. Influenza A is the cause of the major pandemics (worldwide epidemics) of influenza that have occurred so far. It is usually further categorized by two subtypes based on two substances that occur on the surface of the viruses: hemagglutinin (H) and neuraminidase (N).
Influenza B infects only humans. It is less common than type A, but is often associated with specific outbreaks, such as in nursing homes.

The vast majority of flu cases are type A. Influenza A usually causes more severe disease than type B. There is some concern, however, that since influenza B has been less common in the past few years, some people, particularly small children, may have fewer antibodies to it and so may be at higher risk for severe infection.

Although the risk of lethal viruses is generally low, scientists are greatly concerned about a particular virus called H5N1, which causes avian influenza. Since 1997, the H5N1 virus has triggered deadly outbreaks in poultry across Southeast Asia. As of Janaury 15, 2008, 350 people had been infected with the bird flu in 12 countries. Of these people, 217 have died, according to the World Health Organization. No cases have been seen in the United States.

So far, the virus has spread from birds to humans. The virus does not seem to be easily spread from person to person. However, scientists and public health officials are monitoring the spread of H5N1 and working to contain it. Efforts include slaughtering infected birds, developing new vaccines, and stockpiling antiviral drugs such as oseltamivir (Tamiflu). Many poor nations have limited resources and already contend with other serious health problems, including HIV-AIDS. If H5N1 does mutate and spread, the consequences could be especially severe for these countries.

In April 2007, the FDA approved a vaccine to protect humans from avian influenza. Currently this vaccine is not being used for routine immunization. However, if the avian flu develops the ability to spread fairly easily from human to human, this vaccine may be made available.

Diagnosis

Differentiating between a cold and flu may be difficult. Cold symptoms are nearly always less severe than those of the flu.


Symptoms	Cold	Flu
Fever	Rare	Common and high (102-104°F); lasts 3 - 4 days
Headache	Rare	Almost always present
General aches and pains	Mild, if they occur at all	Often severe
Fatigue, exhaustion, and weakness	Mild, it they occur at all	Extreme exhaustion is early and severe; can last 2 - 3 weeks
Stuffy nose	Nearly always	Sometimes
Sneezing	Very common	Sometimes
Sore throat	Common	Sometimes
Chest discomfort and cough	Mild-to-moderate, hacking cough	Common, can be severe
Source: National Institute of Allergy and Infectious Disease

Several available tests can isolate and identify the viruses responsible for some respiratory infections. They are generally not needed, since most cases of the flu are self-evident. However, such tests can be very helpful in confirming or ruling out the flu. If a doctor believes a diagnosis would help, samples using a swab should be taken from the nasal passages or throat within 4 days of the first symptoms.

A nasopharyngeal culture is a test used to identify disease-causing organisms in nasal secretions. Nasopharyngeal cultures are useful in identifying Bordetella pertussis and Neisseria meningitidis (types of bacteria). The culture may help determine appropriate antibiotic therapy.

Several rapid tests for the flu can produce results in less than 30 minutes, but vary on the specific strain or strains that they can detect. They are not as accurate as a viral culture, however, in which the virus is reproduced in the laboratory. Culture results can take 3 - 10 days. Blood tests can also document the infection several weeks after symptoms appear.

In February 2006, the U.S. Food and Drug Administration approved a new, faster test for diagnosing H5 strains of avian influenza in people suspected of having the virus. The test is called the Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe Set. The test gives preliminary results within 4 hours. Older tests required 2 - 3 days. It checks for the presence of the Influenza A H5 strain. If the presence of this strain is confirmed through the rapid test, further testing will be needed to determine the exact subtype of the virus. For example, the current strain of concern is H5, subtype N1, designated as H5N1 for short.

Ruling out Allergic Rhinitis. Symptoms of allergic rhinitis include nasal obstruction and congestion, which are similar to the symptoms of a cold. People with allergies, however, are likely to have the following:

Thin, clear, and runny nasal discharge
An itchy nose, eyes, or throat
Recurrent sneezing

There are two forms of allergic rhinitis:

Symptoms that appear only during allergy season are called allergic rhinitis, commonly known as hay or rose fever. [For more information, see In-Depth Report #77: Allergic rhinitis.]
Allergens in the house, such as house dust mites, molds, and pet dander, can cause year-long allergic rhinitis, referred to as perennial rhinitis.

Click the icon to see an image of common allergens.

Ruling out Sinusitis. The signs and symptoms suggestive of true acute sinusitis include the following:

A return of congestion and discomfort after initial improvement in a cold (called double sickening)
Purulent (pus-filled) nasal secretion
A lack of response to decongestant or antihistamine
Pain in the upper teeth or pain on one side of the head
Pain above or below both eyes when leaning over

Children with sinusitis are less likely to have facial pain and headache and may only develop a high fever or prolonged upper respiratory symptoms (such as a daytime cough that does not improve for 11 - 14 days). When the diagnosis is unclear or complications are suspected, further tests may be required. [For more information, see In-Depth Report #62: Sinusitis.]

Acute Bronchitis. Acute bronchitis is usually caused by a virus and in most cases is self-limiting. The cough it causes typically lasts for about 7 - 10 days, but in about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for over 1 month.

Atypical Pneumonia. Pneumonia caused by atypical organisms (for example, Mycoplasma pneumonia, chlamydia, Legionella) can cause symptoms similar to the flu. Only laboratory tests can diagnose the difference. [For more information, see In-Depth Report #64: Pneumonia.]

Ruling out More Serious Viral Infections. Respiratory syncytial virus (RSV) and, possibly human parainfluenza viruses (HPV), are proving to be important causes of serious respiratory infections in infants, the elderly, and people with damaged immune systems. (Both also cause mild conditions.) RSV may be a much more common cause of flu-like symptoms than previously thought.

Pertussis. Pertussis (whooping cough) was a very common childhood illness throughout the first half of the century. Although immunizations caused a decline in cases to only 1,700 in the U.S. in 1980, the incidence has risen recently, with almost 30,000 cases reported between 1997 and 2000 (17 infants died of the disease in 2000). Many more cases are reported worldwide.

Nearly half of pertussis cases now occur in people 10 years of age or older, perhaps due to waning immunity in adolescents and adults. Such cases may be greatly underreported. Up to 25% of adults who see a doctor for persistent cough may actually have pertussis. It may go undiagnosed, however, because symptoms are usually mild, and adults are unlikely to have the classic "whooping" cough. This is of some concern because such adults may unknowingly infect unvaccinated children. The younger the patient, the higher the risk for severe complications, including pneumonia, seizures, and even death. Children younger than 6 months are at particular risk because protection is incomplete, even with vaccination.

In addition to common cold viruses, other, less frequent causes of sore throat include the following:

Strep throat
Foodborne and waterborne infections (Streptococcus C and G)
An uncommon organism called Arcanobacterium haemolyticum (infection with this bacterium can mimic strep throat and may even cause a rash)
Infectious mononucleosis ("mono")
Herpesvirus 1

Group A Streptococcal bacteria is the most common bacterial cause of the severe sore throat known commonly as "strep throat." It occurs mostly in school age children, but people of all ages are susceptible. (Strep throat constitutes about 12% of all sore throat cases seen by doctors.)

The symptoms of strep throat include the following:

A sudden onset of severe sore throat
Difficulty in swallowing
Fever
Headache
Stomach pain
Vomiting

Only about half of patients with strep throat have such clear-cut symptoms. Furthermore, half of people who have these symptoms do not actually have strep throat.

How Is Strep Throat Diagnosed? Most cold-related sore throats are caused by viruses and require no treatment. They usually do not last more than a day. When the sore throat persists and is very painful the doctor will want to rule out or confirm the presence of the strep bacteria.

The doctor will look for redness and pus-filled patches on the tonsils and back of the throat. Enlarged tonsils are less likely to indicate a strep throat.
The doctor will feel the sides of the neck for swollen lymph nodes. If the lymph nodes are not swollen, it is less likely to be a strep throat.
A cotton swab is used to take a sample of pus in the throat for a throat culture.

A throat culture is the most effective and least expensive test for confirming the presence of strep throat. It takes 24 - 48 hours to obtain a result.

Rapid Antigen-Detection Test for Strep Throat. A faster test, called the rapid strep antigen test, uses chemicals to detect the presence of bacteria in a few minutes. A positive result nearly always means that streptococcal bacteria is the cause of the infection. The test, however, fails to detect 10 - 20% of cases, so a culture may still be necessary to catch any missed infections, particularly in children.

How Serious is Strep Throat? The use of antibiotics has removed the threat of most complications from streptococcus infection in the throat (strep throat). However, untreated strep throat could lead to the following complications:

Abscess in the tonsils
Scarlet fever
Rheumatic fever (rare in the U.S.)

How Is Strep Throat Treated? Strep throat infections require antibiotics. Antibiotics prevent a serious complication called rheumatic fever, which can result in permanent damage to the heart. Fortunately, this complication occurs rarely in United States anymore. If started on time, antibiotic treatment of strep throat will almost always prevent this complication. In addition, antibiotics shorten the recovery time from strep throat.

The following antibiotics are generally used to treat strep throat:

Penicillin is usually the antibiotic of choice unless the patient is allergic. A full 10 days may be necessary. Amoxicillin, a form of penicillin, is proving to be effective when taken in a single daily dose for 10 days.
Macrolide antibiotics. Erythromycin is known as a macrolide antibiotic and is the first choice for patients with penicillin allergies. A 10-day regimen is needed. Another macrolide, azithromycin, can be given as a single daily dose and may be effective in 5 days. It is expensive, however, and bacterial resistance to macrolides is growing, so it should not be given as a first choice.
Cephalosporins are very effective in eradicating the bacteria.

Antibiotics are very commonly inappropriately prescribed for non-strep sore throats. One study reported that an estimated 6.7 million American adults visited their doctors because of sore throat between 1989 and 1999, with 73% of them receiving antibiotics. Studies indicate, however, that fewer than half of adults and far fewer children with even strong signs and symptoms for strep throat actually have strep infections.

Parents should be comforted that a delay in antibiotic treatment while waiting for lab results does not increase the risk that the child will develop serious long-term complications, including acute rheumatic fever. If a patient is severely ill, however, it is reasonable to begin administering antibiotics before the results are back. If the culture is negative (there is no evidence of bacteria), the doctor should call the family to make certain the patient stops taking the antibiotics and any remaining pills are discarded.

Children who have a sore throat and who have had rheumatic fever in the past should receive antibiotics immediately, even before culture results are back. Children with a sore throat who have a family member with strep throat or rheumatic fever should also receive immediate antibiotic treatment.

Complications

Colds rarely cause serious complications. In about 1% of cases, a cold can lead to other complications, such as sinus or ear infections. It can also aggravate asthma and, in uncommon situations, increase the risk for lower respiratory tract infections.

Ear Infections. The rhinovirus infection, a major cause of colds, also commonly predisposes children to ear infections, possibly by obstructing the Eustachian tube, which leads to the middle ear. Viruses may even attack the ear directly.

Sinusitis. Between 0.5 - 5% of people with colds develop sinusitis, an infection in the sinus cavities (air-filled spaces in the skull). Sinusitis is usually mild, but if it becomes severe, antibiotics generally eliminate further problems. In rare cases, however, sinusitis can be serious.

Lower Respiratory Tract Infections. The common cold poses a risk for bronchitis and pneumonia in nursing home patients, and in other people who may be vulnerable to infection. Some experts believe that the rhinovirus may play a more significant role than the flu in causing lower respiratory infections in the vulnerable population.

Aggravation of Asthma. Rhinovirus infections can aggravate asthma in both children and adults. In fact, rhinovirus has been reported to be the most common infectious organism associated with asthma attacks. Colds may promote allergic inflammation of the airways, and increase the intensity their responsiveness for weeks.

The flu is usually self-limited and not serious. However, each year in the United States, more than 200,000 people are hospitalized due to complications of the flu. An estimated 36,000 people die each year of influenza-related complications. People at highest risk for serious complications are those over 65 years old and those with chronic medical conditions. Influenza A is the most severe strain. Influenza B tends to be milder.

Pneumonia. Pneumonia is the major serious complication of influenza and can be very serious. It can develop about 5 days after viral influenza. More than 90% of the deaths caused by influenza and pneumonia occur among older adults. Flu-related pneumonia nearly always occurs in high-risk individuals, such as the following:

People with weakened immune systems, such as AIDS patients
Elderly patients, particularly patients in nursing home
Very young children -- [it may be difficult to tell whether pneumonia is related to influenza or caused by respiratory syncytial virus (RSV)]
Hospitalized patients and anyone with serious medical conditions, such as diabetes, heart, circulation, or lung disorders, particularly chronic lung disease
Drug abusers who use needles

Combinations of these factors further increase the risk. It should be noted that pneumonia is an uncommon outcome of influenza in healthy adults.

Complications in the Central Nervous System in Children. Influenza increases the risk for complications in the central nervous system of small children. Febrile seizures are the most common neurologic complication in children The risks decline after a child turns 1 year old, but are still high in children aged 3 - 5 years old.

Risk Factors

The very young and the very old are at higher risk for upper respiratory tract infections and their associated complications.

Children. Young children are prone to colds and may have 8 to 12 of them every year. Millions of cases of influenza develop in American children and adolescents each year.

Before the immune system matures, all infants are susceptible to uppper respiratory infections, with a possible frequency of one cold every 1 - 2 months. Smaller nasal and sinus passages also make younger children more vulnerable to colds than older children and adults. Upper respiratory infections gradually diminish as children grow, until at school age their rate of such infections is about the same as an adult's. There is almost never cause for concern when a child has frequent colds, unless the colds become unusually severe or more frequent than usual.

The Elderly. The elderly have diminished cough and gag reflexes, and their immune systems are often weaker. They are therefore at greater risk for serious respiratory infections than the young and middle-aged adults.

The risk of respiratory infections is increased by exposure to cigarette smoke, which can injure airways and damage the cilia (tiny hair-like structures that help keep the airways clear). Toxic fumes, industrial smoke, and other air pollutants are also risk factors. Parental smoking increases the risk of respiratory infections in their children.

People with AIDS and other medical conditions that damage the immune system are extremely susceptible to serious infections.

Cancers, especially leukemia and Hodgkin's disease, put patients at risk. Patients who are on corticosteroid (steroid) treatments, chemotherapy, or other medications that suppress the immune system are also prone to infection.

People with diabetes are at a higher risk for the flu.

Certain genetic disorders predispose people to respiratory infections. They include sickle-cell disease, cystic fibrosis, and Kartagener syndrome (which results in malfunctioning cilia).

Much evidence suggests that stress increases one's susceptibility to a cold. In one study, people with high stress levels averaged 2.7 upper respiratory infections during a 6-month period and those reporting low stress averaged 1.5 infections. Another study found the duration of colds in children with chronic, year-round colds decreased with help of a stress management program. Stress appears to increase the risk for a cold regardless of lifestyle or other health habits. And once a person catches a cold or flu, stress can make symptoms worse.

It is not clear why these events occur. Some experts believe that stress alters specific immune factors, which cause inflammation in the airways. One study reported that the only people who got sick after experiencing short stress were those whose body responded to stress with high levels of cortisol, a stress hormone, coupled with a low immune response.

In people who already have colds, exercise has no effect on the illness' severity or duration of the infection. High-intensity or endurance exercises, however, appear to suppress the immune system while they are being performed. Some highly trained athletes, for instance, report being susceptible to colds after strenuous events. People should avoid strenuous physical activity when they have high fevers or widespread viral illnesses. Note: Very low fat diets appear to worsen this dampening effect on the immune system. A higher fat-diet may help correct this imbalance (omega-3 fatty acids, found in fish and canola oil, are preferred). Whether carbohydrate loading provides much additional value is not clear.

Colds and flus occur predominantly in the winter. Flu season typically starts in October and lasts into mid March.

The reasons for this seasonal bias are not due to the cold itself, but to other factors. Certainly, flus and colds are more likely to be transmitted in winter because people spend more time indoors and are exposed to higher concentrations of airborne viruses. Dry winter weather also dries up nasal passages, making them more susceptible to viruses. Some experts theorize that the high rates of viral infections in winter may be due to certain immune factors, which react to light and dark and affect a person's susceptibility to viruses.

Traveling in close contact with people, whether on trains, planes, or buses, can increase the risk for respiratory infections.

Children who attend day care may have an increased risk of colds. However, one study suggested that although children in day care centers incur higher rates of the common cold in the preschool years, they have lower cold rates in their first years of regular school. The colds they catch in day care, then, may bestow some immunity to future colds for a few years. By age 13, such protection has worn off. There is also some evidence that frequent colds in young children may help protect against future allergies and asthma.

Prevention

Because colds and flus are easily spread, everyone should always wash their hands before eating and after going outside. Ordinary soap is sufficient. Waterless hand cleaners that contain an alcohol-based gel are also effective for every day use and may even kill cold viruses. (They are less effective, however, if extreme hygiene is required. In such cases, alcohol-based rinses are needed.)

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia. Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Colds are not caused by insufficiently warm clothes or by going outside with wet hair.

Foods Containing Lactobacilli (Good Bacteria). Researchers are also studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. Some of these strains, particularly acidophilus, are used to make yogurt. According to one Finnish study, children attending day care who ate milk containing the strain lactobacilli GG 10 - 20% fewer respiratory infections. (The strain used was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

Treatment

The following are some food and fluid recommendations. Most will not cure a cold, but they may help a person deal better with the symptoms:

Drinking plenty of fluids and getting lots of rest when needed is still the best bit of advice to ease the discomforts of the common cold. Water is the best fluid and helps lubricate the mucous membranes. (There is no evidence that drinking milk will increase or worsen mucus, although milk is a food and should not serve as fluid replacement.)
Chicken soup does indeed help congestion and body aches. The hot steam from the soup may be its chief advantage, although laboratory studies have actually reported that ingredients in the soup may have anti-inflammatory effects. In fact, any hot beverage may have similar soothing effects from steam. Ginger tea, fruit juice, and hot tea with honey and lemon may all be helpful.
Spicy foods that contain hot peppers or horseradish may help clear sinuses.
Foods rich in vitamins A and C are always recommended and may be helpful during a respiratory infection. They include oranges, kiwi, and tomatoes for vitamin C, and sweet potatoes, spinach, and broccoli for vitamin A.

Different studies have found that large doses of vitamin C may reduce the duration of a cold. Some precautions against taking high doses of vitamin C include the following:

High doses of vitamin C may cause headaches, intestinal and urinary problems, and even kidney stones.
Because vitamin C increases iron absorption, people with certain blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses of this vitamin.
Large doses of vitamin C can also interfere with anticoagulant medications ("blood thinners"), blood tests used in diabetes, and stool tests.
Vitamin E or multivitamin supplements do not appear to be helpful in reducing symptoms of the cold.

Zinc appears to have certain important effects on the immune system and it may have a direct effect on viruses. How it works is not entirely clear, however. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. Studies are very mixed on the effects of zinc on colds. The variance may be due to different zinc preparations. A review of available studies comparing zinc treatment to placebo ("sugar pill") found only one high-quality study, which showed that zinc nasal gels might provide a benefit. The overall benefit of zinc in the prevention of colds remains unproven. In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods, for the purpose of preventing colds.

Side Effects. Side effects, particularly of the lozenges form, include the following:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Severe vomiting, dehydration, and restlessness (signs of overdose, seek medical help)
Allergic response (rare)

Food and Drug Interactions. Zinc may also interact with drugs or other elements:

It may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
In high doses and for long periods of time, zinc can cause copper deficiencies.

Many people take medications to reduce mild pain and fever. Adults most often choose aspirin, ibuprofen (Advil), or acetaminophen (Tylenol).

The following are recommendations for children:

Acetaminophen (Tylenol) or ibuprofen (usually Advil or Motrin) are the typical pain-relievers parents give their children. Most pediatricians advise such medications for children who run fevers over 101°F. Some suggest alternating the two agents, although there is no evidence that this regimen offers any benefits, and it might be harmful.
Aspirin and aspirin-containing products are virtually never recommended for children or adolescents. Reye syndrome, a very serious condition, has been associated with aspirin use in children who have flu symptoms or chicken pox.

Nasal strips (such as Breathe Right) are placed across the lower part of the nose and pull the nostrils open. These strips may open the nasal passages and ease congestion due to a cold, sinusitis, or hay fever. As of yet, there is no scientific evidence that they offer such benefits.

A nasal wash can be helpful for removing mucus from the nose. A saline solution can be purchased at a drug store or made at home. One study reported that neither a homemade solution (using one teaspoon of salt and one pinch of baking soda in a pint of warm water) nor a commercial hypertonic saline nasal wash had any effect on symptoms. Further, one preliminary study found that over-the-counter saline nasal sprays that contain benzalkonium chloride as a preservative may actually worsen symptoms and infection.

Some physicians, however, advocate a traditional nasal wash that has been used for centuries and is different from that used in most studies. It contains no baking soda and uses more fluid for each dose and less salt. The nasal wash should be performed several times a day.

A simple method for administering a nasal wash:

Lean over the sink head down.
Pour some solution into the palm of the hand and inhale it through the nose, one nostril at a time.
Spit the remaining solution out.
Gently blow the nose.

The solution may also be inserted into the nose using a large rubber ear syringe, available at a pharmacy. In this case, the process is the following:

Lean over the sink head down.
Insert only the tip of the syringe into one nostril.
Gently squeeze the bulb several times to wash the nasal passage.
Then press the bulb firmly enough so that the solution passes into the mouth.
The process should be repeated in the other nostril.

Nasal-delivery decongestants are applied directly into the nasal passages with a spray, gel, drops, or vapors. Nasal forms work faster than oral decongestants and have fewer side effects. They often require frequent administration, although long-acting forms are now available. Ingredients and brands of nasal decongestants include the following:

Long Acting Nasal-Delivery Decongestants. They are effective in a few minutes and remain so for 6 - 12 hours. The primary ingredient in long-acting decongestant is:

Oxymetazoline: Brands include Vicks Sinex (12-hour brands), Afrin (12-hour brands), Dristan 12-Hour, Good Sense, Nostrilla, Neo-Synephrine 12-Hour
Xylometazoline: Inspire, Otrivin, Natru-vent

Short-Acting Nasal-Delivery Decongestants. The effects usually last about 4 hours. The primary ingredients in short-acing decongestants are:

Phenylephrine: Neo-Synephrine (mild, regular, high-potency), 4-Way, Dristan Mist Spray, Vicks Sinex
Naphazoline (Naphcon Forte, Privine)

Dependency and Rebound. The major hazard with nasal-delivery decongestants, particularly long-acting forms, is a cycle of dependency and rebound effects. The 12-hour brands pose a particular risk for this effect. This effect works in the following way:

With prolonged use (more than 3 - 5 days), nasal decongestants lose effectiveness and even cause swelling in the nasal passages.
The patient then increases the frequency of their dose. The congestion worsens, and the patient responds with even more frequent doses, in some cases as often as every hour.
Individuals then become dependent on them.

Tips for Use. The following precautions are important for people taking nasal decongestants:

When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
Keep the nasal passages moist. All forms of nasal decongestants can cause irritation and stinging. They also may dry out the affected areas and damage tissues.
Do not share droppers and inhalators with other people.
Use decongestants only for conditions requiring short-term use, such as before air travel or for a single-allergy attack. Do not take them more than 3 days in a row. With prolonged use, nasal decongestants become ineffective and result in the so-called rebound effect and dependence.
Discard sprayers, inhalators, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
Discard the medicine if it becomes cloudy or unclear.

Oral decongestants also come in many brands, which mainly differ in their ingredients. The most common active ingredient is pseudoephedrine (Sudafed, Actifed, Drixoral).

Side Effects of Decongestants. Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants and include the following:

Agitation and nervousness
Drowsiness (particularly with oral decongestants and in combination with alcohol)
Changes in heart rate and blood pressure

Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives

Individuals at Risk for Complications from Decongestants. People who may be at higher risk for complications are those with certain medical conditions, including disorders that make blood vessels highly susceptible to contraction. Such conditions include the following:

Heart disease
High blood pressure
Thyroid disease
Diabetes
Prostate problems that cause urinary difficulties
Migraines
Raynaud's phenomenon
High sensitivity to cold
Emphysema or chronic bronchitis

Anyone with the above conditions should not use either oral or nasal decongestants without a doctor's guidance. In addition, people taking medications that increase serotonin levels, such as certain antidepressants, anti-migraine agents, diet pills, St. John's wort, and methamphetamine, should avoid decongestants. The combinations can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

Others who should use these drugs with caution are the following (consult your health care provider):

Anyone who is pregnant.
Children: Children appear to metabolize decongestants differently than adults. Decongestants should not be used at all in infants and small children under the age of 2, according to a new recommendation from an advisory panel of the Food and Drug Administration. These children are at particular risk for side effects that depress the central nervous system. Such symptoms cause changes in blood pressure, drowsiness, deep sleep, and, rarely, coma. Studies have also shown that these cough and cold products generally are not effective in the treatment of children under 6 years of age.

In October 2007, drug manufacturers voluntarily withdrew from the market all oral cough and cold products, including decongestants, aimed at children under 2, due to potential harm from misuse.

Major studies have indicated that over-the-counter cough medicines are not very effective, but they are also not harmful.

For thick phlegm, patients may try cough medications that contain guaifenesin (Robitussin, Scot-Tussin Expectorant), which loosens mucus. Patients should not suppress coughs that produce mucus and phlegm. It is important to expel this substance. To loosen phlegm, patients should drink plenty of fluids and use a humidifier or steamer.
For patients with a dry cough, a suppressant may be useful, such as one that contains dextromethorphan (Drixoral Cough, Robitussin Maximum Strength Cough Suppressant).

Medications that contain both a cough suppressant and an expectorant are not useful and should be avoided. Medicated cough drops that contain dextromethorphan are not very useful. A patient is just as likely to find relief from hard candy or lozenges.

Prescription cough medications with small doses of narcotics are available. They are usually reserved for lower respiratory infections with significant coughs.

Sore throats that are associated with colds are generally mild. The following may be helpful:

Cough drops, throat sprays, or gargling warm salt water may help relieve sore throat and reduce coughing.
Throat sprays that contain phenol (for example, Vicks Chloraseptic) may be particularly helpful. Phenol has antibacterial properties. In one study, patients with sore throat who used the spray experienced faster resolution of the cold itself, including fever, headache, and other symptoms compared to a placebo. The patients were not taking antibiotics.
Cough drops that contain menthol and mild anesthetics, such as benzocaine, hexylrescorincol, phenol, and dyclonine (the most potent), may soothe a mild sore throat.
People with sore throats from postnasal drip might try taking a teaspoon of liquid antacid. They shouldn't drink anything afterward, since the intention is to coat the throat and help neutralize the acid in the mucus that might be causing pain.

If soreness in the throat is very severe and does not respond to mild treatments, the patient or parent should check with the physician to see if a strep throat is present, which would require antibiotics. [See What is Strep Throat? in the Diagnosis section.]

Dozens of remedies are available that combine ingredients aimed at more than one cold or flu symptom. In general, they do no harm, but they have the following problems:

Some ingredients may produce side effects without even helping a cold.
In some cases, the ingredients conflict (such as a cough expectorant and a cough suppressant).
In other cases, a patient may wish to increase the dosage to improve one symptom, which serves to increase other ingredients that do no good and, in higher doses, may cause side effects.

Note on Antihistamines. Many combination remedies contain antihistamines. Antihistamines are used for allergies and are not generally recommended to relieve the symptoms of the common cold. Some evidence suggests, however, that they may have some value.

First-generation antihistamines may reduce cold symptoms. Their benefits for the cold are likely to be due to the drowsiness they cause. Such antihistamines include Benadryl, Tavist, and Chlor-Trimeton. The newer, second-generation antihistamines (Claritin, Allegra, Zyrtec) do not have these effects and also appear to have no benefits against colds.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for colds or influenza:

Echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. A rigorous study, published in 2005 in the New England Journal of Medicine, determined that this herb does not help to prevent or treat colds. In addition, some people are allergic to echinacea. People who have autoimmune diseases or plant allergies should avoid it. There have been a few reports of people experiencing a skin reaction called erythema nodosum, which is characterized by tender, red nodules under the skin.
Chinese herbal cold and allergy products can contain trace amounts of aristolochic acid, a chemical that causes kidney damage and cancer. Many herbal remedies imported from Asia may contain potent pharmaceuticals, such as phenacetin and steroids, as well as toxic metals.

Medications

Vaccines are available to prevent influenza (See section on Viral Influenza Vaccines).

For mild influenza, symptom relief is similar to that for colds.

Two classes of antiviral agents have been developed to treat influenza: neuraminidase inhibitors and M2 inhibitors.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme, neuraminidase, which is involved with viral replication. According to a major review of over 50 studies published in 2006, these drugs are effective against the flu in about 60% of cases.

Important points about the use of these drugs:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. (M2 inhibitors are effective only against type A.) However, their main benefit has been to reduce the length of symptoms by about one day, and only when started within 48 hours after symptoms become evident.
They may help reduce transmission of the virus.
They have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. However, The World Health Organization reports that viral resistance to oseltamivir (Tamiflu) can develop with extensive use. The level of resistance averaged 0.3% over 3 flu seasons surveyed in Japan (2003 - 2006). During that time, 35 million Japanese patients used the drug.
They have fewer serious side effects than the M2 inhibitors.
Both show some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over 13.
They may reduce complications of influenza, although this needs to be confirmed. It is not yet known if they have any effect on overall survival rates.
Oseltamivir is the only drug studied in avian flu cases. Although it is active in lab experiments, it has not been successful clinically. Experience is very limited, however, and it is not clear whether people infected with avian flu received the drug in time for it to be useful.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, neuraminidase inhibitors are much more expensive. They also need to be taken within 2 days of the start of symptoms to be effective. Neither neuraminidase inhibitor is effective against influenza-like illness (one that is not caused by an influenza virus). There are also some differences between the two drugs that could be significant for some individuals:

Zanamivir is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are generally minor in most patients. It is important to make sure that elderly patients are able to properly use the zanamivir inhaler device.
Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

The current use of neuraminidase inhibitors in different age and patient groups is as follows:

Adults: Both drugs are approved for treatment in adult patients.
Children: Oseltamivir is approved for use in children age one and older. Studies report significant reduction in symptoms and in the incidence of ear infections in this population. However, studies from Japan point to the possibility of psychiatric side effects in children under 16 using oseltamivir. Zanamivir is approved for children over age 7, and studies are currently underway to determine its safety in younger children.
High-Risk Patients. Recent studies indicate neuraminidase inhibitors are safe and effective in patients with serious medical problems or other conditions that put them at risk for complications of flu.

Brands and Benefits. Amantadine (Symmetrel) and rimantadine (Flumadine) are M2 inhibitors. The following benefits may apply to the minority of strains of influenza A that remain sensitive to the drugs:

Both offer protection against influenza A and prevent severe illness if a person contracts the infection. (To be effective it must be administered within 2 days of onset.)
They may shorten the duration and lessen the severity of the flu if given within 48 hours of onset of symptoms.

Limitations. Drawbacks of M2 inhibitors include:

Viral resistance to these agents is rapidly emerging. For this reason, the Centers for Disease Control and Prevention Does not recommends M2 inhibitors for use during the 2007 - 2008 flu season in the United States.
M2 inhibitors are not effective against influenza B.
Neither drug has proven to reduce the risk for complications of the flu, including pneumonia and bronchitis.

Side Effects. Both M2 inhibitors occasionally cause nausea, vomiting, indigestion, insomnia, and hallucinations. Amantadine affects the nervous system and about 10% of people experience nervousness, depression, anxiety, difficulty concentrating, and lightheadedness. Rimantadine is less likely to do so. Rarely, amantadine can cause seizures, usually in elderly people already at risk for psychiatric symptoms.

Note: Amantadine is a standard treatment for Parkinson's disease and should be continued for that condition.

Flu Shots. These vaccines use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. (Antigens are foreign molecules that the immune system specifically recognizes as alien and targets for attack.)

Unfortunately, the antigens in these influenza viruses undergo genetic changes (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines are then redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem, because it can infect other species, such as pigs or chicken, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children will not have developed any immunity to the virus, and will experience severe flu if they are exposed to type B viruses.

Intranasal (inside the nose) vaccine. A live but weakened intranasal vaccine (FluMist) is proving to be effective and safe in healthy, non-pregnant people aged 2 - 49 years and has been approved by the FDA. It is known as a live, attenuated, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is given using a nasal spray.

Timing and Effectiveness of the Vaccine. Ideally, people should be vaccinated every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within 2 weeks of vaccination, and immunity peaks within 4 - 6 weeks, then gradually wanes.

Because children under age 8 do not develop strong immune responses to one dose, the CDC recommends two vaccinations given 1 month apart on the first year they receive the vaccine. If children under 8 received only 1 dose of the vaccine on their first immunization year, they should receive 2 doses the following year. Children under 8 who have received single doses for 3 or more years should continue to receive single doses.
It should be noted that if an individual develops influenza symptoms and is accurately diagnosed in time, vaccination of the other members of the household within 36 - 48 hours affords effective protection to those individuals.

In healthy adults, immunization typically reduces the chance of illness by about 70 - 90%. The current flu vaccines may be slightly less effective in certain patients, such as the elderly and those with certain chronic diseases. Even in people with a weaker response, however, the vaccine is usually protective against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated. The following children over 6 months should be vaccinated against influenza:

The American Academy of Pediatrics (AAP) and the CDC recommend influenza vaccination in all healthy children between 6 and 59 months old.
In addition, any child over the age of 2 years with a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle-cell, or immune deficiencies). If parents are concerned about vaccines that contain the mercury preservative thimerosal, they can ask their doctor about reduced-thimerosal flu vaccine.
Children who come in direct contact with a person vulnerable to complications from influenza should also be vaccinated.
Children who are receiving long-term aspirin therapy should also be immunized against the flu because they are at higher risk for Reye syndrome, a life-threatening disease, if they get the flu.
Some experts now advocate flu shots for all school-age children. Emerging research indicates that children are responsible for transmitting the vast majority of cases of seasonal flu, and that routine vaccination of school-age children would considerably reduce transmission rates throughout communities.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first two groups have the highest need for influenza vaccinations and are given top priority:

All adults 50 years and older. Vaccinated older adults have lower hospitalization rates than unvaccinated peers. Evidence now suggests that vaccination may help protect against adverse heart events (including those after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two thirds of the people in this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. Those with any condition that may compromise respiratory function or the handling of respiratory secretions, including people with cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders, are included in this group. (There have been concerns about the safety of the vaccinations in certain high-risk patients such as those with HIV or asthma. Studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.)
All health care workers should be vaccinated, according to the ACIP's recommendations.
Household members in contact with individuals who are at high-risk for complications from influenza should be vaccinated.

Other adults who should consider influenza vaccinations include:

People at risk for complications for influenza and who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for complications of influenza, and who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester. Exceptions may be women who are in their first trimester during flu season and their risk from complications of the flu is higher than any theoretical risk to the baby from the vaccine.)
Police officers, firefighters, and other public safety officials.

Negative Effects. Possible negative responses to the vaccines include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 - 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, sore throat, or a combination. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not influenza itself but an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Although iIsolated cases of a paralytic illness known as Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, it has not been a problem with subsequent vaccines.
There has been some question concerning influenza vaccinations because of some reports that vaccines may worsen asthma. Recent and major studies have been reporting, however, that the vaccination is safe for children with asthma. It is also very important for these patients to reduce their risk for respiratory diseases.

The FDA approved the first vaccine for humans against H5NI influenza virus in April 2007. The vaccine, which is made from a human strain of the virus, could be used in people ages 18 - 64 to prevent the spread of the virus from human to human. The vaccine requires two shots, given about a month apart. It will not be sold commercially, but instead is being purchased by the U.S. government to be stockpiled and distributed to public health officials in the event of an outbreak of avian flu.

In a study, 103 healthy adults received two g shots of the virus, 28 days apart. An additional group of 300 adults received the vaccine at a lower dose, while 48 people received placebo injections. The study showed that 45% of those who received the higher dose developed antibodies that may reduce their risk of getting the avian flu. The most common side effects reported were pain at the injection site, headache, and muscle pain. Research on the vaccine is continuing.

The intense and widespread use of antibiotics is leading to a serious global problem of antibiotic resistance. The inappropriate use of powerful newer antibiotics for conditions such as colds or sore throats poses a particular risk for resistant strains of bacteria. For example, the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in people who have no known risk factors. (MRSA causes sometimes-fatal skin infections.) In 2006, rates of Neisseria gonorrhoeae resistance to the fluoroquinolone antibiotics family exceeded 10%. The CDC no longer recommends treating gonorrhea infections with fluoroquinolone first.

When Antibiotics Are Needed for Upper Respiratory Infections.

Antibiotics do not affect viruses and, in healthy individuals, these drugs are almost never necessary or helpful for influenza or colds, even with persistent cough and thick, green mucus. In one disturbing study, antibiotics were prescribed for nearly half of children who went to the doctor for a common cold.

Antibiotics may be required for upper respiratory tract infections only under certain situations, such as the following:

Patients, particularly small children or elderly people, who have medical conditions that put them at high risk for complications from any respiratory tract infections, should usually be given antibiotics.
Patients with severe sinusitis that does not clear up within 7 days (some experts say 10 days) and whose symptoms include one or more of the following: green and thick nasal discharge, facial pain, or tooth pain or tenderness.
Some children with middle ear infections, although experts differ on who will benefit. Some experts recommend that only children under the age of 2 years should be treated with antibiotics, and children over 2 should be treated on a case-by-case basis.
Patients with strep throat or severe sore throat that involves fever, swollen lymph nodes, and absence of cough. (Strep throat makes up only 10 - 15% of all sore throat cases.)
Patients who have an acute cough that is caused by pneumonia (but in few other cases, regardless of the duration of the cough). Experts estimate that, outside the hospital setting, less than 20% of prescriptions for persistent coughing are necessary.

Patients at Highest Risk for Infection with Resistant Bacteria Strains. Some patients are at greater risk for developing an infection resistant to common antibiotics. At this time, the average person is not endangered by this problem. Risk factors include:

Very old or very young age
Exposure to patients with drug-resistant infection
Hospitalization in intensive care
History of an invasive surgical procedure
Staying in the hospital
Prolonged course of antibiotics, particularly within the past 4 - 6 weeks
Serious wounds
Tubes down the throat, catheters, or intravenous (I.V.) lines
Immunosuppression

Children at higher risk for antibiotic resistance are those who attend day care, who are exposed to cigarette smoke, who were bottle-fed, and who had siblings with recurrent ear infections.

What the Health Care Community Is Doing. Prescribing antibiotics only when necessary is the most important step in restoring bacterial strains that are susceptible to antibiotics. Encouraging studies are reporting that inappropriate antibiotic prescriptions are on the decline. Prescriptions for other common respiratory infections, such as otitis media, sore throat, acute bronchitis, and colds and flus have been decreasing.

What Patients and Parents Can Do. Patients and parents can also help with the following tips:

Use home or over-the-counter remedies to relieve symptoms of mild upper respiratory tract infections.
Realize that antibiotics will not shorten the course of a viral infection. It is important for patients and parents to understand that although antibiotics may bring a sense of security, they provide no significant benefit for a person with viral infection, and overuse can contribute to the growing problem of resistant bacteria.
Don't pressure a doctor into prescribing an antibiotic if it is clearly inappropriate. The doctor very often will give in.
If a child needs an antibiotic, ask the doctor whether it is appropriate to use high-dose short-term antibiotics, which may lower the risk for developing resistant strains.
If an antibiotic is prescribed, take the full course, even if you feel better before finishing it.

Resources

www.cdc.gov/flu -- U.S. Centers for Disease Control and Prevention
www.niaid.nih.gov -- National Institute for Allergy and Infectious Diseases
www.who.int/csr/disease/influenza/en -- World Health Organization
www.cdc.gov/vaccines -- National Immunization Program
www.immunize.org -- Immunization Action Coalition
www.entnet.org -- American Academy of Otolaryngology -- Head and Neck Surgery
www.cdc.gov/flu/avian -- Avian Influenza Information

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2005. Pediatrics. 2005 Jan;115(1):182.

Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis. 2007;45(5):569-74.

Centers for Disease Control and Prevention. Key Facts About Seasonal Influenza (Flu). Available online.

Centers for Disease Control and Prevention. 2007-08 Influenza Prevention & Control Recommendations: Vaccination of Specific Populations. Available online.

Centers for Disease Control and Prevention. Acute Respiratory Disease Associated with Adenovirus Serotype 14 -- Four States, 2006-2007. MMWR. 2007;56(45):1181-84.

Centers for Disease Control and Prevention. FDA Approves New Laboratory Test To Detect Human Infections With Avian Influenza A/H5 Viruses. February 3, 2006.

Hayden GF, Turner RB. Acute Pharyngitis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Behrman: Nelson Textbook of Pediatrics, 17th ed. Philadelphia, Pa: Saunders; 2004.

Interagency Task Force on Antimicrobial Resistance. Executive Summary: 2006 Annual Report on Progress on "A Public Health Action Plan to Combat Antimicrobial Resistance." Draft release, June 2007. Available online.

Jefferson T, Demichelli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006 Jan 28;367(9507):303-13.

Morantz CA. ACIP Updates Guidelines on Prevention and Control of Influenza. Am Fam Physician. 2005; 72(6); 1119-1127.

Reveiz L, Cardona AF, Ospina EG. Antibiotics for acute laryngitis in adults. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004783.

Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr. 2006;60(1):9 - 17.

Shah SA, Sander S, White CM, Rinaldi M, Coleman CI. Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis. 2007;7(7):473-80.

Simasek M, Blandino DA. Treatment of the common cold. Am Fam Physician. 2007;75(4):515-20.

Taverner D, Latte J. Nasal decongestants for the common cold. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001953.

U.S. Food and Drug Administration: Nonprescription Drugs and Pediatric Advisory Committee Meeting. Joint Meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee October 18-19, 2007. Available online.

World Health Organization: Neuraminidase Inhibitor Susceptibility Network. Monitoring of neuraminidase inhibitor resistance among clinical influenza virus isolates in Japan during the 2003-2006 influenza seasons. Weekly epidemiological record. 2007;82(17):149-50.

World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. January 15, 2008. Available online.

Review Date:
1/18/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Sinusitis

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Prevention
Treatment for Acute Sinusit...
Treatment for Chronic Sinus...
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Restriction

In February 2007, the FDA announced that the antibiotic telithromycin (Ketek) should no longer be used for treatment of acute bacterial sinusitis. In June 2006, the FDA reported that several people had died of liver damage after taking this drug. Telithromycin is now only approved for treatment of community-acquired pneumonia.

Acute Sinusitis Treatment

Antibiotics are widely over-prescribed for acute sinusitis, according to a 2007 study. Researchers also reported that inhaled corticosteroids are frequently prescribed for acute sinusitis, despite little evidence for their efficacy. Most cases of acute sinusitis resolve on their own and do not require antibiotic treatment.

Allergic Fungal Sinusitis

Allergic fungal sinusitis should be considered a distinct form of chronic sinusitis, according to research presented at the 2007 annual meeting of the American Academy of Allergy, Asthma, & Immunolology. Researchers found that patients with allergic fungal sinusitis have an increased allergic and inflammatory response to fungi compared to patients with other types of chronic sinusitis.

Anti-Fungal Drugs

Allergic fungal sinusitis is currently treated with oral corticosteroids such as prednisone, but researchers are investigating whether anti-fungal drugs may help. The anti-fungal drug Amphotericin B (SinuNase) is currently in Phase III trials for patients with chronic sinusitis who have had sinus surgery but are still experiencing sinusitis symptoms. However, several 2006 studies indicated disappointing results.

Balloon Sinuplasty

Balloon sinuplasty is a relatively new procedure that uses a catheter-inserted balloon to gently open and drain nasal passages. In a study of 115 patients with chronic sinusitis, balloon sinuplasty achieved promising results, according to research presented at the 2007 meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation. However, some experts believe that it is still too early to recommend this procedure for wide-scale use, especially until further large-scale clinical trials are conducted.

Introduction

The skull contains a number of air-filled spaces called sinuses. They perform the following functions:

Reduce the weight of the skull
Provide insulation for the skull
Provide resonance for the voice

Four pairs of sinuses, known as the paranasal air sinuses, connect to the nasal passages (the two airways running through the nose) and are those that are involved in sinusitis. These sinuses are the following:

Frontal sinuses (behind the forehead)
Maxillary sinuses (behind the cheekbones)
Ethmoid sinuses (between the eyes)
Sphenoid sinuses (behind the eyes)

Healthy sinuses are sterile and contain no bacteria. (The nasal passage, on the other hand, normally contains many bacteria that enter through the nostrils.) Maintaining sinus health depends on a cycle that involves a number of important factors and processes:

The sinuses are lined with a membrane that secretes mucus. Mucus drains down into the nasal passage from a small channel in each sinus. The mucous membranes must be intact and free of injury.
The mucus must be fluid in order to flow freely while being sticky enough to absorb pollutants and entrap bacteria.
The mucus must also contain sufficient amounts of bacteria-fighting substances, including immune factors called antibodies.
Small, hair-like projections called cilia must beat in unison to propel mucus outward, expelling bacteria and other particles.
The sinus passages must be open to allow mucus drainage and the circulation of air through the nasal passage.

Click the icon to see an image of an antibody.

The Disease Process. Sinusitis is an infection that occurs if one or more of the defense processes or factors are amiss, causing obstruction, and bacterial growth occurs in the paranasal sinuses. Among the many causes of such obstruction or congestion are the common cold, allergies, certain medical conditions, abnormalities in the nasal passage, and change in atmosphere. In any of these cases, sinusitis can develop as follows:

Mucus drainage and airflow are blocked.
Secretions build up, encouraging the growth of certain bacteria.
The resulting infection, swelling, and inflammation create further blockage, which may cause the sinuses to close up completely.

Forms of Sinusitis. Sinusitis is classified as acute, subacute, or chronic, or recurrent. The classification is based on how long symptoms last:

Acute: Less than 4 weeks
Subacute: 4 - 8 weeks
Chronic: 8 weeks or longer
Recurrent: 3 or more acute episodes in 1 year

Causes

Bacteria are the most common direct cause of acute sinusitis. (Other organisms might be the infecting cause in less common cases.) The ability of bacteria or other organisms to infect the sinuses, however, must first be set up by conditions that create a favorable environment in the sinus cavities. Sinusitis is most often an acute condition, which is self-limiting and treatable. In some cases, however, the inflammation in the sinuses persists or is chronic do begin with. The causes for such chronic sinusitis cases are sometimes unclear.

The typical process leading to acute sinusitis starts with a flu or cold virus. Viruses themselves do not usually cause sinusitis directly and are implicated in only about 10% of sinusitis cases. Instead, they set the stage by causing inflammation and congestion in the nasal passages (called rhinitis) that leads to obstruction in the sinuses. This creates a hospitable environment for bacterial growth, which is the direct cause of sinus infection. In fact, rhinitis is the precursor to sinusitis in so many cases that expert groups now refer to most cases of sinusitis as rhinosinusitis.

Rhinosinusitis tends to involve the following sinuses:

The maxillary sinuses (behind the cheekbones) are the most common sites.
The ethmoid sinuses (between the eyes) are the second most common sites affected by colds.
The frontal (behind the forehead) and sphenoid (behind the eyes) sinuses are involved in about a third of cold-related cases.

Nearly everyone with colds has inflamed sinuses. These inflammations are typically brief and mild, however, and most people with colds do not develop true sinusitis.

Chronic or recurrent acute sinusitis typically results from one of the following conditions:

Untreated acute sinusitis that results in damage to the mucous membranes
Chronic medical disorders that cause inflammation in the airways or persistent thickened stagnant mucus (such as diabetes, AIDS or other disorders of the immune system, hypothyroidism, cystic fibrosis, Kartagener's syndrome, and Wegener's granulomatosis)
Structural abnormalities
Allergic reaction to fungi

Chronic or recurrent acute sinusitis can be a lifelong condition.

The Role of Bacteria. The role of bacteria or other infectious organisms is complicated in chronic sinusitis. They may play a direct, an indirect, or, in some patients, no role at all. For example, one study reported the following for patients with chronic sinusitis who had not responded to antibiotics:

30% had no evidence of bacteria in their passageways.
20% had bacteria unrelated to infection.

Inflammatory Response, Allergies, and Asthma. The absence of bacterial organisms as a causal factor in many cases suggests that some instances of chronic sinusitis may be due to a continuing inflammatory condition. Such on-going inflammation may have been triggered immune factors that were produced in response to injuries from acute sinusitis. Many of the immune factors observed in people with chronic sinusitis resemble those that appear in allergic rhinitis, suggesting that sinusitis in some individuals is due to an allergic response.

Allergies, asthma, and sinusitis often overlap. Those with allergic rhinitis (so-called hay fever and rose fever) often have symptoms of sinusitis, and true sinusitis can develop as a result of the mucus blockage it causes. A causal association, however, has not been proved, and many experts believe allergies themselves rarely predispose to sinusitis. People with chronic sinusitis may also have an allergic reaction to fungal organisms.

Severe asthma (which is often associated with allergies) and chronic sinusitis often overlap, although the relationship is unclear. Between 53 - 75% of children with asthma caused by allergies have sinus abnormalities, and various studies have shown that between 17 - 30% of asthmatic patients develop true sinusitis. In fact, chronic sinusitis may actually be the cause of asthma in some cases.

Abnormalities of the Nasal Passage. Abnormalities in the nasal passage can cause blockage and thereby increase the risk for chronic sinusitis. Some abnormalities include:

Polyps (small benign growths) in the nasal passage block mucus drainage and restrict airflow. Polyps themselves may be consequences of previous sinus infections that caused overgrowth of the nasal membrane.
Enlarged adenoids can lead to sinusitis.

Adenoids are masses of tissue located high on the posterior wall of the pharynx. They are made up of lymphatic tissue, which trap and destroy pathogens in the air that enter the nasopharynx.

Cleft palate
Tumors
Deviated septum (a common structural abnormality in which the septum, the center section of the nose, is shifted to one side, usually the left)

Click the icon to see an image of a deviated septum.

The bacteria most commonly implicated in sinusitis include:

Streptococcus pneumoniae (also called pneumococcal pneumonia or pneumococci). This bacterium is found in between 20 - 43% of adults and children with sinusitis.
H. influenzae (a common bacterium associated with many upper respiratory infections). This bacterium colonizes nearly half of all children by age 2, and causes about 25% of sinusitis cases in this group. Studies have reported the presence of this bacterium in 22 - 35% of adult sinusitis patients.
Moraxella catarrhalis. Over 75% of all children harbor this bacterium, which causes about 25% of sinusitis cases.

Other possible bacterial culprits include:

Other streptococcal strains
Staphylococcus aureus

While fungi are an uncommon cause of sinusitis, the incidence of such infections is increasing. At least 5 - 10% of chronic rhinosinusitis patients may actually have allergic fungal sinusitis. At the 2007 meeting of the American Academy of Allergy, Asthma, & Immunology (AAAAI), experts presented evidence suggesting that allergic fungal sinusitis is a distinct form of chronic rhinosinusitis. Research indicates that allergic fungal sinusitis may provoke a distinct immune response. In the AAAAI study, patients with allergic fungal sinusitis showed increased antibody levels of immunoglobulin E (IgE) and immunoglobulin G (IgG) compared to patients with other types of chronic rhinosinusitis.

In earlier research from 2004, scientists from the U.S. National Institute of Allergy and Infectious Diseases exposed immune cells from patients with chronic sinusitis and healthy volunteers to four common types of fungi: Alternaria, Aspergillus, Penicillium, and Cladosporium. The study’s findings suggested that some people who suffer from chronic sinusitis have an extreme immune and inflammatory response to fungi and may benefit from anti-fungal treatment.

Fungi involved in sinusitis include:

Aspergillus is the most common cause of all forms of fungal sinusitis.
Other fungi include Curvularia, Bipolaris, Alternaria, Dreschslera, Cryptococcus, Candida, Sporothrix,Exserohilum, and Mucormycosis.
There have been a few reports of fungal sinusitis caused by Metarrhizium anisopliae, which is used in biological insect control.

There are four categories of fungal sinusitis:

Acute or invasive fungal sinusitis - This infection is most likely to affect people with diabetes and compromised immune systems.
Chronic or indolent fungal sinusitis - This form is generally found outside the U.S., most commonly in the Sudan and northern India.
Fungus ball (mycetoma) - This fungal sinusitis is noninvasive and occurs usually in one sinus, most often the maxillary sinus.
Allergic fungal sinusitis - This form typically occurs because of an allergy to the fungus Aspergillus (rather than being caused by the fungus itself). In such cases, a peanut butter-like fungal growth occurs in the sinus cavities that may cause nasal passage obstruction and the erosion of the bones.

Fungal infections can be very serious, and both chronic and acute fungal sinusitis require immediate treatment. Fungal ball is not invasive and is nearly always treatable.

Fungal infections should be suspected in people with sinusitis who also have diabetes, leukemia, AIDS, or other conditions that impair the immune system. Fungal infections can also occur in patients with healthy immune systems but they are far less common.

Risk Factors

Sinusitis is one of the most common diseases in the United States. According to the National Institute of Allergies and Infectious Diseases (NIAID), it affects an estimate 37 million Americans each year. However, a 2004 report in the Archives of Otolaryngology - Head and Neck Surgery suggests that sinusitis may not be as common as previously reported. The researchers found that accounts that rely solely on patient self-reporting may be exaggerated.

Everyone gets viral colds and flu, and most people develop symptoms in the upper respiratory tract (air passages in the head and neck) at some point. Over 85% of people with colds have inflamed sinuses. These inflammations are typically brief and mild, however, and only between 0.5 - 10% of people with colds develop true sinusitis. (One study suggested that nose blowing during a cold may transmit bacteria back into the sinuses and increase the risk for sinusitis.) Studies suggest that the following population groups have higher risks for sinusitis:

Young children and the elderly are at higher risk for more serious upper respiratory tract infections and for complications from them.
Women appear to be at higher risk than men.
People living in the Midwest and South have a higher incidence of sinusitis than those in the Northeast and West.
People in higher income and educational groups appear to have a greater risk than those in lower groups.
Caucasian and African Americans have a higher rate than Hispanic Americans.

Before the immune system matures, all infants are susceptible to respiratory infections, with a possible frequency of one cold every 1 - 2 months. Young children are prone to colds and may have 8 - 12 bouts every year. Smaller nasal and sinus passages also make children more vulnerable to upper respiratory tract infections than older children and adults. Ear infections such as otitis media are also associated with sinusitis. Nevertheless, true sinusitis is very rare in children under 9 years of age. Some experts believe it is greatly overdiagnosed in this population.

The elderly are at specific risk for sinusitis. Their nasal passages tend to dry out with age. In addition, the cartilage supporting the nasal passages weakens causing airflow changes. They also have diminished cough and gag reflexes and faltering immune systems and are at greater risk for serious respiratory infections than are young and middle-aged adults.

People with asthma, allergies or both are at higher risk for non-infectious inflammation in the sinuses. The risk for sinusitis is higher in patients with severe asthma. People with a combination of polyps in the nose, asthma, and sensitivity to aspirin (called Samter's or ASA triad) are specifically at very high risk for chronic or recurrent acute sinusitis.

Hospitalized patients are at higher risk for sinusitis, particularly those with:

Head injuries
Conditions requiring insertion of tubes through the nose
Antibiotics or steroids treatment
Breathing aided by mechanical ventilators. (Such patients may have a significantly higher risk for maxillary sinusitis. In fact, treating sinusitis in such patients may significantly reduce the risk for ventilator-associated pneumonia.)

A number of medical conditions put people at risk for chronic sinusitis. They include:

Diabetes
Gastroesophageal reflux disease
Nasal polyps or septal deviation
AIDS and other disorders of the immune system predispose the patient to sinusitis (fungal infections are especially risky)
Pregnancy -- may cause temporary congestion and symptoms of sinusitis
Hypothyroidism -- causes congestion that clears up when the condition is treated
Cystic fibrosis -- a genetic disorder in which the mucus is very thick and builds up
Kartagener's syndrome
Wegener's granulomatosis -- a serious but very rare illness that causes long-term swelling and tumor-like masses in air passages

Dental Problems. Anaerobic bacteria are associated with infections from dental problems or procedures, which precipitate about 10% of cases of sinusitis.

Changes in Atmospheric Pressure. People who experience changes in atmospheric pressure, such as while flying, climbing to high altitudes, or swimming, risk sinus blockage and therefore an increased chance of developing sinusitis. (Swimming increases the risk for sinusitis for other reasons, as well.)

Cigarette Smoke and Other Air Pollutants. Air pollution from industrial chemicals, cigarette smoke, or other pollutants can damage the cilia responsible for moving mucus through the sinuses. Whether air pollution is an important cause of sinusitis and, if so, which pollutants are critical factors is still not clear. Cigarette smoke, for example, poses a small but increased risk for sinusitis in adults. Second-hand smoke does not appear to have any significant effect on adult sinuses, although it does seem to pose a risk for sinusitis in children.

Symptoms

Symptoms Indicating a Bacterial Infection. Sinus symptoms are very common during a cold or the flu, but in most of these cases they are due to the effects of the infecting virus and resolve when the infection does. It is important to differentiate between inflamed sinuses associated with cold or flu virus and sinusitis caused by bacteria. With true acute bacterial sinusitis, the signs and symptoms typically have the following course:

Nasal congestion and discharge comes first and is typically thick with pus that is yellowish to yellow-green.
Pain in the teeth is increased by bending over. Symptoms may vary, however, depending on the sinuses involved.
Symptoms continue for 10 days or more after the start of a cold or flu.
They worsen after 5 - 7 days, or they return after initial improvement in a cold (called double sickening).

Other symptoms of acute sinusitis that usually occur in adults include:

Severe headache and pain or pressure in specific areas in the face -- eyes may be red, bulging or painful eyes if the sinus infection occurs around the eyes; in some cases, patients may also have double vision and even temporary vision loss.
A persistent cough (particularly during the day)
Fever
Fatigue (from lack of good rest)
Lack of response to decongestants or antihistamines

Sneezing, sore throat, and muscle aches may be present, but they are rarely caused by sinusitis itself. Muscle aches may be caused by fever, sore throat by post-nasal drip, and sneezing from cold or allergies.

Rare complications of sinusitis can produce additional symptoms, which may be severe or even life threatening.

Symptoms in Children. Children are most likely to develop infection in the ethmoid sinuses, located between the eyes. Children with sinusitis are also less likely to experience facial pain over the affected sinus and headache, which are the primary signs in adults. Symptoms of bacterial sinusitis may be less specific than in adults and include:

Persistent nasal discharge (of any type) and day time cough for more than 10 days, or
Severe symptoms last for at least 3 - 4 days in a row and include thick, greenish nasal discharge plus a fever of at least 102° F.

Other symptoms in children may include:

Irritability
Vomiting
Gagging on mucus
Cough

Recurrent acute and chronic sinusitis tend to take the following course:

Symptoms are more vague and generalized than acute sinusitis.
They last longer than 4 weeks. (Subacute sinusitis lasts longer than 4 weeks but less than 8 weeks. Chronic sinusitis lasts 8 weeks or longer.)
They occur throughout the year, even during nonallergy seasons.

Specifically symptoms may include:

Nasal congestion and obstruction
Chronic cough (day and night) -- research suggests that sinusitis is one of the main causes of chronic cough
Bad breath
Postnasal drip (which can cause repeated throat clearing)
Facial tenderness or pressure --patients do not usually experience facial pain unless the infection is in the frontal sinuses

Specific symptoms depend on the location of the infection:

Frontal sinusitis causes pain across the lower forehead.
The pain in maxillary sinusitis occurs over the cheeks and may travel to the teeth, and the hard palate in the mouth sometimes becomes swollen.
Ethmoid sinusitis causes pain behind the eyes and sometimes redness and tenderness in the area across the top of the nose.
Sphenoid sinusitis rarely occurs by itself; when it does, the pain may be experienced behind the eyes, across the forehead, or in the face.



ETHMOID SINUSITIS
Ethmoid sinuses are located between the eyes. They resemble a honeycomb and are vulnerable to obstruction. This is a common location for sinusitis in children.	Nasal congestion. Nasal discharge or postnasal drip. Pain or pressure around the inner corner of the eye or down one side of the nose. Headache in the temple or surrounding the eye. Symptoms worse when coughing, straining, or lying on the back and better when the head is upright. Fever. Symptoms of maxillary sinusitis often occur. Symptoms indicating medical emergency: Increasing severity of symptoms. Fever, swelling and drooping eyelid, loss of eye movement (possible orbital infection, which is in the eye socket). Fever, vision changes, pupil fixed or dilated. Symptoms spreading to both sides of face (may indicate blood clot).	Chronic nasal discharge, obstruction, and low-grade discomfort usually across the bridge of the nose. Symptoms worse in the late morning or when wearing glasses. Chronic sore throat and bad breath. Sinusitis also can recur in other sites.
ACUTE MAXILLARY SINUSITIS
Maxillary sinuses are located behind the cheek bones. They are present at birth and continue to develop as long as teeth erupt. Tooth roots, in some cases, can penetrate the floor of these sinuses.	Pain across the cheekbone, under or around the eye, or around the upper teeth; may occur on one or both sides of the face. Area over the cheekbone is tender and may be red or swollen. Possibly tooth pain. Symptoms are worse when the head is upright and improve when patient reclines. Nasal discharge or postnasal drip. Fever.	Discomfort or pressure below the eye. Chronic toothache. Symptoms become worse with colds, flu, or allergies. Discomfort increases during the day. Coughing increases at night.
FRONTAL SINUSITIS
Frontal sinuses are located on both sides of the forehead. These sinuses are late in developing, so infection here is uncommon in children.	Severe headache in the forehead. Fever (common but not always present). Symptoms are worse when lying on the back and when pressing against the area over the eye on the side closest to the nose. Symptoms are better when the head is upright. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain). Fever, vision changes, fixed or dilated pupil. Symptoms spreading to both sides of face (may indicate blood clot). Headache, fever, along with a soft swelling over the bone (may indicate bone infection).	Persistent, low-grade headache in the forehead. History of physical injury or other damage to the sinus area.
SPHENOID SINUSITIS
Sphenoid sinuses are located behind the eyes. They usually are present by age 3 and are fully developed by age 12.	Deep headache with pain in many places, including the back and top of the head, across the forehead, and behind the eye. Fever. Symptoms are worse when lying on the back or bending forward. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain).	Low grade, general headache (although not always present).

Complications

Bacterial sinusitis is nearly always harmless (although uncomfortable and sometimes even very painful). If an episode becomes severe, antibiotics generally eliminate further problems. In rare cases, however, sinusitis can be very serious.

Osteomyelitis. Adolescent males with acute frontal sinusitis are at particular risk for severe problems. One important complication is infection of the bones (osteomyelitis) of the forehead. In such cases, the patient usually experiences headache, fever, and a soft swelling over the bone known as Pott's puffy tumor.

Infection of the Eye Socket. Infection of the eye socket, or orbital infection, which causes swelling and subsequent drooping of the eyelid, is a rare but serious complication of ethmoid sinusitis. In these cases, the patient loses movement in the eye, and pressure on the optic nerve can lead to vision loss, which is sometimes permanent. Fever and severe illness are usually present.

Blood Clot. Another danger, although rare, from ethmoid or frontal sinusitis are blood clots. If a blood clot forms in the sinus area around the front and top of the face, symptoms are similar to orbital infection. In addition, the pupil may be fixed and dilated. Although symptoms usually begin on one side of the head, the process usually spreads to both sides.

Widespread Infection. The most dangerous complication of sinusitis, particularly frontal and sphenoid sinusitis, is the spread of infection by anaerobic bacteria to the brain, either through the bones or blood vessels. Abscesses, meningitis, and other life-threatening conditions may result. In such cases, the patient may experience mild personality changes, headache, altered consciousness, visual problems, and, finally, seizures, coma, and death.

Chronic and acute fungal sinusitis caused by the fungi Aspergillus and mucormycosis is difficult to treat and potentially lethal, particularly in people with diabetes and compromised immune systems. Mucormycosis is particularly dangerous if it is not treated quickly. Fungal ball (mycetoma) is not invasive and is nearly always treatable with surgery. Recurrence is rare.

The relationship between sinusitis and asthma is unclear. A number of theories have been proposed for a causal or shared association between sinusitis and asthma. Some include the following:

Stimulation of nerve pathways, inflammation, and overproduction of mucus in the nasal passages and sinus cavities may eventually affect the airways in the lung, causing them to hyperreact.
Breathing through the mouth when the sinuses are blocked allows in large particles that would other wise be filtered by the nasal defense system. Such particles could trigger allergic responses in the lungs that can trigger asthma in susceptible people.
Air breathed through the mouth is colder than air warmed in the nasal passages. Cold air is a known trigger of asthma.
Both may share similar immune abnormalities that cause inflammation in the airways in the lungs and sinuses.

Successful treatment of both allergic rhinitis and chronic sinusitis in children who also have asthma may reduce symptoms of asthma. It is particularly important to treat any coexisting bacterial sinusitis in people with asthma. They might not respond to asthma treatments unless the infection is cleared up first.

Pain and other symptoms of chronic sinusitis can have significant effects on the quality of life. This condition can cause emotional distress, impair normal activity, and reduce attendance at work or school. According to the American Academy of Allergy, Asthma, and Immunology, the average sinusitis patient misses about 4 work days a year. In fact, a 2003 study placed sinusitis in the top 10 medical conditions that most adversely affect American employers. In addition, some people may lose their sense of smell. Surgery or medical treatments can help restore this sense.

Diagnosis

Patients who have sinusitis symptoms that do not clear up within a few days, are severe, or are accompanied by high fever or acute illness should see a doctor. However, that only one-half to two-thirds of patients with such symptoms actually have sinusitis. Some experts complain that too many patients are diagnosed with true sinusitis and given unnecessary antibiotics when their symptoms would actually resolve easily in days with over-the-counter medications or no drugs at all. Others believe that true sinusitis is often mistakenly diagnosed as an allergy and not treated, which could lead to serious illness.

The first goal in diagnosing sinusitis is to rule out other possible causes of symptoms, and then determine:

The site where the infection has occurred
Whether the condition is acute or chronic
The organism causing the infection (if possible)

Ruling Out Sinus Symptoms Due to Cold or Flu Viruses. It is often difficult to tell when a viral infection converts to a bacterial infection. Studies have found that between 40 - 85% of patients with the common cold show signs of inflamed sinuses on x-rays or CT scans. A cold, however, unlike sinusitis, typically clears up without treatment within a week. (Only about 0.5 - 2% of adults with viral colds or flus actually develop bacterial infections.) In general, the doctor should suspect a bacterial infection under the following circumstances:

If sinus symptoms persist for 10 days or longer after a cold or flu, or
If symptoms become worse after 5 - 7 days

Ruling Out Allergies. Symptoms of both sinusitis and allergic rhinitis include nasal obstruction and congestion. The conditions often occur together. People with allergies and no sinus infection may have:

Thin, clear, and runny nasal discharge
Itchy nose, eyes, or throat (do not occur with bacterial sinusitis)
Recurrent sneezing
Symptoms of allergies appear only during exposure to allergens

Ruling Out Migraine and Other Headaches. Many primary headaches, particularly migraine or cluster, may closely resemble sinus headache. In fact, results presented at a 2004 meeting of the American Headache Society suggest that 90% of people who thought they had a sinus headache actually had migraines. Migraine and sinus headaches may even coexist in many cases. Sinus headaches are usually more generalized than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. The following symptoms suggest a migraine rather than a sinus headache:

The headache is recurrent
It has a significant impact on daily activities
The headache does not get worse over time

Ruling Out Neuralgia. In some cases, headache that persists after successful treatment of chronic sinusitis may be due to neuralgia (nerve-related pain) in the face. This condition requires specific drugs, such as tricyclic antidepressants or carbamazepine. Trials using such drugs may identify patients with neuralgia and help avoid unnecessary invasive treatments for chronic sinusitis.

Ruling Out Other Conditions. A number of other conditions can mimic sinusitis. They include:

Dental problems
A foreign object in the nasal passage
Temporal arteritis (headache caused by inflamed arteries in the head and neck)
Persistent upper respiratory tract infections
Chronic fatigue syndrome (CFS) or fibromyalgia. However, researchers reported in the Archives of Internal Medicine that there may be a link between CFS and sinusitis. In the study, patients with unexplained chronic fatigue were nine times more likely to suffer sinus problems than those without fatigue.
Temporomandibular disorders (problems in the joints and muscles of the jaw hinges)
Vasomotor rhinitis, a condition in which the nasal passages become congested in response to irritants or stress. It often occurs in pregnant women.

Medical History. The patient should describe all symptoms such as nasal discharge and specific pain in the face and head, including eye and tooth pain.

After assessing symptoms, the doctor should take a thorough medical history of the patient:

Any history of allergies or headaches
Recent upper respiratory infection (colds, flus, infection)
History of sinusitis episodes that is unresponsive to antibiotic treatment. (In such cases, the doctor will usually diagnose chronic or recurrent acute sinusitis and refer the patient to a specialist for more advanced testing.)
Exposure to cigarette smoke or other environmental pollutants
Recent travel
Recent dental procedures, particularly if there is pain toward the back of the mouth
Medications being taken (particularly decongestants)
Any known structural abnormalities in the nose and face
Injury to the head or face
History of medical conditions, such as chronic fatigue syndrome or fibromyalgia, which can produce tender areas in the face or sinus regions and nonspecific symptoms of ill health
Any family history of allergies, immune disorders, cystic fibrosis, or immotile cilia syndrome
In small children with sinusitis, whether they attend a day care center or nursery school

The doctor will press the forehead and cheekbones to check for tenderness and check for other signs of sinusitis, including yellow to yellow-green nasal discharge. The doctor will also check the inside of the nasal passages using a device with a bright light to check the mucus and look for any structural abnormalities.

In some cases, tests may be used to detect that presence of immune factors in sinus tissues that would suggest persistent inflammation. Such findings would strongly suggest a chronic or allergic condition. In 2005, a new laboratory test became available for diagnosing chronic sinusitis. The CRS Fungal Profile tests mucus samples for eosinophil major basic protein (a protein involved in allergic and inflammatory reactions) and a type of fungi.

Nasal endoscopy, or rhinoscopy, is now used for diagnosing chronic and recurrent acute sinusitis and for differentiating between allergies and true acute sinusitis. It involves the insertion of a flexible tube into the nasal passage and the use of a fiberoptic light that enables the doctor to see inside the sinuses. Endoscopy allows detection of even very small abnormalities in the sinuses. It can determine whether surgery is necessary and if medications are having any effect. Bacterial cultures can also be taken from samples removed using endoscopy. (Endoscopy is also used for treating sinusitis.)

Computer Tomography. Computed tomography (CT) scanning is the best method for viewing the paranasal sinuses. There is little relationship, however, between symptoms in most patients and findings of abnormalities on a CT scan. CT scans are recommended for acute sinusitis only if there is a severe infection, complications, or a high risk for complications. CT scans are useful for diagnosing chronic or recurrent acute sinusitis and for surgeons as a guide during surgery. They show inflammation and swelling and the extent of the infection, including that in deep hidden air chambers missed by x-rays and nasal endoscopy. Often, they can detect the presence of fungal infections.

X-Rays. Until the availability of endoscopy and CT scans, x-rays were commonly used. They are not as accurate, however as these procedure in identifying abnormalities in the sinuses. For example, more than one x-ray is needed for diagnosing frontal and sphenoid sinusitis. X-rays do not detect ethmoid sinusitis at all, which can be the primary site of an infection that has spread to the maxillary or frontal sinuses.

Magnetic Resonance Imaging. MRI is not as effective as CT in defining the paranasal anatomy and therefore is not typically used to image the sinuses for suspected sinusitis. MRI is also more expensive than CT. However, it can help rule out fungal sinusitis and may help differentiate between inflammatory disease, malignant tumors, and complications within the skull. It may also be useful for showing soft tissue involvement.

Transillumination is a procedure aimed at visualizing maxillary and frontal sinuses. First the doctor shines a bright light against the patient's cheek or forehead in a completely darkened room. If the sinuses are clear, the doctor will observe a glow on the hard palate of the open mouth or in the areas of the cheek where the sinus passages are located. It is fast, safe, and inexpensive, but it is useful only in adults and only to rule out any problems. It has largely been supplanted by more accurate diagnostic techniques.

Sinus puncture with bacterial culture is the gold standard for diagnosing a bacterial sinus infection. It is invasive, however, and is performed only when antibiotics have not worked. Sinus puncture involves using a needle to withdraw a small amount of fluid from the sinuses. It requires a local anesthetic and is performed by a specialist. The fluid is then cultured to determine what type of bacteria is causing sinusitis.

Prevention

The best way to prevent sinusitis is to avoid colds and influenza. If you are unable to avoid them, the next best way to prevent sinusitis is to effectively treat colds and influenza.

Colds and flu are spread primarily when an infected person coughs or sneezes near someone else. A very common method for transmitting a cold is by shaking hands. Everyone should always wash their hands before eating and after going outside. Ordinary soap is sufficient. Waterless hand cleaners that contain an alcohol-based gel are also effective for every day use and may even kill cold viruses. (They are less effective, however, if extreme hygiene is required. In such cases, alcohol-based rinses are needed.) Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia. Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Colds are not caused by insufficiently warm clothes or by going outside with wet hair. A 2002 study reported, however, that in older adults cold temperatures can thicken the blood and may increase the risk for respiratory infections and even circulatory and heart problems.

Foods Containing Lactobacilli (Good Bacteria). Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. Some of these strains, particularly acidophilus, are used to make yogurt. According to one study, milk containing the strain lactobacilli GG helped reduce respiratory infections in children attending day care by 10 - 20%.

Vitamins. Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

Studies on vitamin E specifically have been largely negative. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily.

Breastfeeding. Evidence suggests that women who breastfeed reduce the risk of respiratory infections in their children. The American Academy of Pediatrics recommends that babies be fed exclusively breastmilk for their first 6 months.

Low Stress and Active Social Life. More than one study has reported that people with low stress who also have an active social life have fewer colds than people who have high stress levels or those who have low stress and few social connections.

A nasal gel (Zicam), which contains zinc gluconate, has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, for example, the nasal gel shortened the duration and severity of the cold compared to placebo when it was started within 14 - 48 hours of the onset of symptoms. The supports earlier studies reporting that it shortened the duration of a cold by about 2 days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges may be more effective and have a better taste than other formulations, such as zinc gluconate. On the other hand, a 2002 study reported that zinc gluconate reduced cold duration significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds. Long-term use of zinc (100 mg or higher daily) has been associated with heart problems, anemia, and other conditions.

Side Effects. Side effects of zinc include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a doctor if any of these symptoms occur.
In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or food:

Zinc may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
In high doses, and for long periods of time, zinc can cause copper deficiencies.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for sinusitis:

Echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. However, a rigorous study published in 2005 in the New England Journal of Medicine determined that echinacea does not help to prevent or treat colds. In addition, allergic reactions have been reported. People with autoimmune diseases or plant allergies should particularly avoid this herbal remedy. Echinacea has also been associated with a reaction called erythema nodosum. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Some studies suggest that up to 30% of herbal patent remedies imported from China are laced with potent pharmaceuticals such as phenacetin and steroids. Chinese herbal remedies can also contain toxic metals such as lead.

Vaccines against influenza use inactivated (not live) viruses. Because influenza viruses change from year to year, influenza vaccines are redesigned annually to match the anticipated viral strains. Experts recommend that people receive annual influenza vaccinations in October or November. People who should definitely be vaccinated include: all adults 65 years or older; children age 6 months - 5 years; other adults or children who are at high risk for developing serious medical complications from influenza; health care workers and others who care for individuals who are at high risk for influenza complications. [See In-Depth Report #94: Colds and influenza.]

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are two effective vaccines available, one called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and a 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria. [See In-Depth Report #64: Pneumonia.]

Treatment for Acute Sinusitis

The primary objectives for treatment of sinusitis are reduction of swelling, eradication of infection, draining of the sinuses, and ensuring that the sinuses remain open. Less than half of patients reporting symptoms of sinusitis need aggressive treatment. Home remedies can be very useful.

Home remedies that open and hydrate sinuses may, indeed, be the only treatment necessary for mild sinusitis that is not accompanied by signs of acute infection.

Drinking plenty of fluids and getting lots of rest when needed is still the best bit of advice to ease the discomforts of the common cold. Water is the best fluid and helps lubricate the mucous membranes. (There is no evidence that drinking milk will increase or worsen mucus, although milk is a food and should not serve as fluid replacement.)
Chicken soup does indeed help congestion and aches. The hot steam from the soup may be its chief advantage, although laboratory studies have actually reported that ingredients in the soup may have anti-inflammatory effects. In fact, any hot beverage may have similar soothing effects from steam. Ginger tea, fruit juice, and hot tea with honey and lemon may all be helpful.
Spicy foods that contain hot peppers or horseradish may help clear sinuses.
Inhaling steam 2 - 4 times a day is extremely helpful, costs nothing, and requires no expensive equipment. The patient should sit comfortably and lean over a bowl of boiling hot water (no one should ever inhale steam from water as it boils) while covering the head and the bowl with a towel so the steam remains under the cloth. The steam should be inhaled continuously for 10 minutes. A mentholated or other aromatic preparation may be added to the water. Long, steamy showers, vaporizers, and facial saunas are alternatives.

Many people take medications to reduce mild pain and fever. Adults most often choose aspirin, ibuprofen (Advil), or acetaminophen (Tylenol).

The following are recommendations for children:

Acetaminophen (Tylenol) or ibuprofen (usually Advil or Motrin) is the pain-reliever of choice in children. Most pediatricians advise such medications for children who run fevers over 101°F.
Aspirin and aspirin-containing products are virtually never recommended for children or adolescents. Reye syndrome, a very serious condition, has been associated with aspirin use in children who have flu symptoms or chicken pox.

Some studies suggest that these anti-fever drugs may actually reduce the body's immune response against cold and flu viruses and prolong symptoms. A 2000 study, for example, reported a longer flu duration in people who took aspirin or acetaminophen (although people still felt better). Nevertheless, most doctors strongly recommend lowering fevers in children, since high fevers can sometimes cause seizures.

A nasal wash can be helpful for removing mucus from the nose. A saline solution can be purchased at a drug store or made at home. (Mix 1 teaspoon of table salt with a pinch of baking soda in 2 cups of warm water.) The nasal wash should be performed several times a day. Researchers have reported that daily irrigation of the nasal passages with a hypertonic saline solution relieves sinusitis symptoms and also reduces antibiotic use and the occurrence of acute exacerbations. Patients in the study had 72% fewer sinus infections, a 69% improvement in breathing, and they reduced medication usage by more than half.

A simple method for administering a nasal wash is:

Lean over the sink head down.
Pour some solution into the palm of the hand and inhale it through the nose, one nostril at a time.
Spit the remaining solution out.
Gently blow the nose.

The solution may also be inserted into the nose using a large rubber ear syringe, available at a pharmacy. In this case the process is:

Lean over the sink head down.
Insert only the tip of the syringe into one nostril.
Gently squeeze the bulb several times to wash the nasal passage.
Then press the bulb firmly enough so that the solution passes into the mouth.
The process should be repeated in the other nostril.

Decongestants are drugs that help reduce nasal congestion. They are available in a pill or nasal form. However, decongestants will not cure sinusitis. Nasal decongestants can actually worsen sinusitis by increasing sinus inflammation. Due to the lack of evidence for nasal decongestants’ benefits for sinusitis, the FDA has ruled that manufacturers of over-the-counter (OTC) nasal decongestant products remove from their labeling all references to sinusitis.

Your doctor may still recommend that you take either an OTC or prescription nasal decongestant to help relieve blockage symptoms associated with sinusitis. If you think you have sinusitis, it is important that you check with your doctor before taking a decongestant. Do not try to treat sinusitis by yourself.

Nasal Decongestants. Nasal decongestants come in long-acting or short-acting forms. The effects of short-acting decongestants last about 4 hours; long-acting decongestants last 6 - 12 hours. The active ingredients in nasal decongestants include oxymetazoline, xylometazoline, and phenylephrine.

Tips for Use. The following precautions are important for people taking nasal decongestants:

When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
Do not share droppers and inhalators with other people.
Discard sprayers, inhalators, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
Discard the medicine if it becomes cloudy or unclear.

Decongestants Taken by Mouth. Pseudoephedrine is the only decongestant taken by mouth that is currently available over-the-counter (OTC) in the United States. It decreases the volume of mucous in the nose, as well as within the Eustachian tubes. Many brands of OTC oral decongestants are available. A common brand is Sudafed. Oral decongestants such as Sudafed can also be helpful for relieving cough associated with postnasal drip.

Warning: Anyone with old forms of any decongestant should check the labels and discard them if they contain phenylpropanolamine. In November 2000, the FDA banned products, including decongestants, which contained phenylpropanolamine (PPA). This action was in response to a few reports of an increased risk of stroke. (Stroke tended to occur in people who took diet suppressants containing PPA rather than decongestants. In any case, serious events were still very rare.) All major brands that previously contained PPA have now substituted other active ingredients (usually pseudoephedrine) and are safe to use.

Side Effects of Decongestants. Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants and include:

Agitation and nervousness
Drowsiness (particularly with decongestants taken by mouth and in combination with alcohol)
Changes in heart rate and blood pressure
Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives

Heart disease
High blood pressure
Thyroid disease
Diabetes
Prostate problems that cause urinary difficulties
Migraines
Raynaud's phenomenon
High sensitivity to cold
Emphysema or chronic bronchitis. (Such individuals should particularly avoid high-potency short-acting nasal decongestant.)
People taking medications that increase serotonin levels, such as certain antidepressants, anti-migraine drugs, diet pills, St. John's wort, and methamphetamine. The combinations can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

Anyone with these conditions should not use either oral or nasal decongestants without a doctor's guidance. Other groups who should not use these drugs without first consulting a doctor include:

Pregnant women
Children. The American College of Chest Physicians advises against the use of over-the-counter decongestants and other cold medications in children ages 14 years or younger. Children are at particular risk for side effects that depress the central nervous system. Such symptoms cause changes in blood pressure, drowsiness, deep sleep, and, rarely, coma. In 2007, the FDA began reviewing the safety and effectiveness of cough and cold remedies for children.

Older antihistamines such as diphenhydramine (Benadryl) are helpful in relieving cough when used alone or in combination with a decongestant.

Expectorants are drugs that cause mucus to be coughed up from the lungs. The most common type used is guaifenesin, which is found in many over-the-counter (OTC) cough syrups as well as prescription products. Expectorants used to be recommended for treatment of sinusitis-associated cough, but some recent guidelines advise against their use. According to the American College of Chest Physicians (ACCP), expectorants and cough suppressants do not help treat cough. The ACCP recommends that adults instead take a decongestant or antihistamine to relieve cough. The ACCP also recommends against OTC cold and cough medicine for children ages 14 years and younger. Parents should talk with their child’s pediatrician for advice on treating cough.

Overview on Antibiotics and Their Overuse. Sinusitis is the fifth most common diagnosis for antibiotic prescriptions. And, there is much evidence that antibiotics are inappropriately prescribed for many patients:

According to a 2007 study of recent treatment patterns for acute and chronic sinusitis, antibiotics are widely overused. The researchers noted that viruses (not bacteria) account for a large percentage of acute sinusitis cases and that most acute sinusitis cases clear up on their own. The study also indicated that inhaled corticosteroids are frequently prescribed for acute sinusitis despite a lack of evidence for their benefit.
A major analysis reported that antibiotics helped only 1 child in 8 who had persistent nasal discharge for at least 20 days. Even when antibiotics were helpful, benefits were modest in reducing duration of the infection. This study supports other research that has found no significant benefit from antibiotics for most children. In a 2001 study, for example, 87% of children improved regardless of their treatment.

The intense and widespread use of antibiotics -- not only for sinusitis but also for other upper respiratory tract infections -- is leading to a serious global problem, which is bacterial resistance to common antibiotics. For example, according to reports in 2002 and 2001, in Canada 15% of S. pneumoniae strains are resistant to penicillin; in the U.S. 30 - 40% are resistant; in Hong Kong 70 - 80% of strains no longer respond to penicillin. Furthermore, in the U.S. about 23% of S. pneumoniae are currently resistant to at least three antibiotics. High rates of resistance strains are even being observed in infants. In general, regions with the highest rate of resistance are those in which antibiotics are the most heavily prescribed. Encouraging studies are now reporting that inappropriate antibiotic prescriptions are on the decline.

When to Use Antibiotics. Because the majority of sinusitis cases resolve on their own, doctors generally wait 10 - 14 days before prescribing antibiotics. However, antibiotics may be prescribed sooner if severe symptoms develop. These symptoms include:

Fever
Facial pain or tenderness
Swelling around the eyes

Antibiotic Regimens

The standard first-line antibiotic treatment for acute bacterial sinusitis is a 10 - 14 day course of amoxicillin. Trimethoprim-sulfamethoxazole is an alternative choice.
If no change occurs within 3 - 5 days, the doctor may prescribe a different type of antibiotic such as amoxicillin-clavulanate, cephalosporin, or a macrolide.
If the patient does not respond after 21 - 28 days, broad-spectrum antibiotics such as amoxicillin-clavulanate, cefuroxime, or cefpodoxime may be used. Other choices include clarithromycin or azithromycin (macrolides) or levofloxacin (a fluoroquinolone).

Side Effects of Antibiotics. Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones):

The most common side effect for nearly all antibiotics is gastrointestinal distress.
Antibiotics double the risk for vaginal infections in women. Taking supplements of acidophilus or eating yogurt with active cultures may help restore healthy bacteria that offset the risk for such infections.
Allergic reactions can also occur with all antibiotics but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening anaphylactic shock.
Certain drugs, including some over-the-counter medications, interact with antibiotics; patients should inform the doctor of all medications they are taking and of any drug allergies.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins and cephalosporins. Their primary action is to interfere with bacterial cell walls.

Penicillins. Amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation) has been the most widely prescribed antibiotic for acute sinusitis. This penicillin is both inexpensive and at one time was highly effective against the S. pneumoniae bacteria. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae, and penicillin is no longer as reliable as it once was.

Amoxicillin-clavulanate (Augmentin) is a type of penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with sinusitis infections that have become resistant to penicillin.

Many people have a history of an allergic reaction to penicillin, but some evidence is suggesting that the allergy may not recur in a significant number of adults. Skin tests are available that could determine if some people previously allergic could use these important antibiotics.

Cephalosporins. These drugs are also effective against S. pneumoniae. They are often classed by generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation include cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation include cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of bacteria.

The later-generation antibiotics cefpodoxime, cefdinir, and cefuroxime are good choices for penicillin-allergic patients with mild-to-moderate sinusitis who have been treated in the previous 4 - 6 weeks. Penems, a type of beta-lactam antibiotic, are also being investigated for sinusitis treatment.

Macrolides and Azalides

Macrolides are a class of antibiotics that are divided into different sub-groups. Azalides are one of those sub-groups. This type of antibiotic is often used to treat mild-to-moderate bacterial sinusitis in patients who are allergic to penicillin. Some of the most common macrolids/azalides are azithromycin (Zithromax), clarithromycin (Biaxin), and roxithromycin (Rulid). An extended-release form of azithromycin (Zmax) was approved in 2005 as a single dose treatment for mild-to-moderate acute bacterial sinusitis. These antibiotics are also effective against many strains of S. pneumoniae and M. catarrhalis, but macrolide-resistance rates doubled between 1995 - 1999 as the number of children treated with the antibiotics increased. Erythromycin is not effective against H. influenzae.

Macrolides have anti-inflammatory actions, which may have benefits for some patients with chronic sinusitis. Investigators are studying long-term low-dose macrolide treatments, which are not intended to eliminate bacteria, but to reduce inflammation. Studies suggest that this approach may be effective without increasing the risk for bacterial resistance.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is another first-line antibiotic for sinusitis. It is less expensive than amoxicillin and particularly useful for patients with mild sinusitis who are allergic to penicillin. It is no longer effective, however against certain streptococcal strains. It should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce.

Newer generation fluoroquinolones, which include levofloxacin (Levaquin), sparfloxacin (Zagam), gatifloxacin (Tequin), and moxifloxacin (Avelox), are currently the most effective antibiotics against the common bacteria that cause sinusitis. They are recommended for adults with moderate sinusitis who have already been treated with antibiotics within 6 weeks or who are allergic to beta-lactam antibiotics.

Some of the newer fluoroquinolones only need to be taken once a day, which make compliance easier. Some, but not all, quinolones cause photosensitivity. S. pneumoniae strains resistant to the quinolones have been uncommon in the U.S. but their numbers are increasing. In fact, levofloxacin was the first drug approved specifically for penicillin-resistant S. pneumoniae. Unfortunately, studies are now finding resistance to this drug as well.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against many S. pneumoniae bacteria but not against H. influenzae.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Ketolides

In February 2007, the FDA withdrew approval of telithromycin (Ketek) for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is now approved only for treatment of community-acquired pneumonia (CAP).

In 2003, research suggested that delivering medications directly to the sinus passages (instead of the bloodstream, like a pill might) significantly increases the amount of time chronic sinusitis patients remain infection free. The treatment, called nebulized antibiotic therapy, requires that patients inhale antibiotics in mist form to topically treat their sinusitis. The study showed that nebulization therapy increased the infection free period for some patients by almost 300% when compared to other treatments.

Patients who show signs that infection has spread beyond the nasal sinuses into the bone, brain, or other parts of the skull require emergency care. High dose antibiotics are administered intravenously, and emergency surgery is almost always necessary in such cases.

Severe Fungal Sinusitis. Sinusitis caused by severe fungal infections is a medical emergency. Treatment is aggressive surgery, and high-dose antifungal chemotherapy with a drug such as amphotericin B can be life saving. The use of oxygen administered at high pressure (hyperbaric oxygen) is showing promise as additional therapy for potentially deadly fungal infections.

Treatment for Chronic Sinusitis

Determining and Treating any Underlying Conditions. A thorough diagnostic work-up should be performed to rule out any underlying conditions, including but not limited to allergies, asthma, any immune problems, gastroesophageal reflux disorder, and structural problems in the nasal passages. If a primary trigger for chronic sinusitis can be identified, it should be treated or controlled if possible.

Initial Treatment of Sinusitis. For treatment of chronic sinusitis itself, some doctors recommend:

A wide spectrum antibiotic (one that can eliminate a wide range of bacteria) taken for at least 30 days.
Alternatively, an antibiotic that attacks anaerobic pathogens.
A corticosteroid nasal spray -- some doctors also recommend oral corticosteroids (such as prednisone) for patients who do not respond to nasal corticosteroids or for those patients who have nasal polyps. Prednisone is also used for patients who have allergic fungal sinusitis.
Saline nasal washes.
The expectorant guaifenesin with a decongestant taken by mouth.
Antihistamines.

If the condition dramatically improves between 1 - 2 months, then the antibiotics are stopped. The patient should continue with both the steroid and saline nasal solutions. If there is no improvement after this time, the surgery may be considered. For some people with chronic sinusitis, however, the condition is not curable, and the goal of treatment is to improve the quality of life.

Chronic sinusitis is often the result of damage to the mucous membrane from a past, untreated acute sinus infection. The aerobic and anaerobic bacteria present in chronic sinusitis are often different from those that cause the acute form. The role of antibiotic treatment for chronic sinusitis is controversial. Special types of antibiotics may be used, and treatment may be needed for a longer time.

Intravenous antibiotic therapy may be required for some patients with chronic sinusitis, particularly those with underlying medical disorders that can worsen the condition. They are typically administered 2 weeks before surgery and continued for about month afterward.

Some studies have reported good results in using antibiotics that are sprayed into the nasal passages using a nebulizer. In one study, patients preferred this method to either oral or intravenous treatments.

Benefits of Corticosteroid Nasal Sprays. Nasal-spray corticosteroids, most commonly called steroids, are effective drugs for treating allergic rhinitis. They also are proving to be very important in the treatment of chronic sinusitis and are sometimes used for acute sinusitis. Some studies have reported that, when combined with antibiotics, they speed recovery and improve healing rates of sinusitis compared to antibiotics alone. Nasal spray steroids are proving to be safe and have the following benefits:

They reduce inflammation and mucus production.
They improve night sleep and daytime alertness in patients with perennial allergic rhinitis.
They appear to be beneficial in treating polyps in the nasal passages.

Nasal-Spray Brands. Corticosteroids available in nasal spray form include:

Triamcinolone (Nasacort). Approved for children over age 6.
Mometasone furoate (Nasonex). Approved for use in patients as young as age 3.
Fluticasone (Flonase, Flounce). Approved for children over age 4.
Beclomethasone (Beconase, Vancenase), flunisolide (Nasalide), and budesonide (Rhinocort). Approved for children over age 6.

Side Effects. Corticosteroids are powerful anti-inflammatory drugs. Although oral steroids can have many side effects, the nasal-spray form affects only local areas, and the risk for wide spread side effects is very low unless the drug is used excessively.

Dryness, burning, stinging in the nasal passage
Sneezing
Headaches and nosebleed (these side effects are uncommon but should be reported to your doctor immediately)

Possible Long-Term Complications. Corticosteroids suppress stress hormones, which are known to produce some serious long-term complications in people who take oral steroids. Researchers have found far fewer concerns with nasal administration or inhaled forms, but there may be certain problems.

Effect on growth. The major concern for children is whether nasal steroids, like other forms of steroids, will adversely affect growth. Studies report either only a temporary and slight (about half an inch) early effect on growth or no effect at all.
Effect on eyes. Glaucoma is a known side effect of oral steroids. Some ophthalmologists have observed higher pressure in the eye (a sign of glaucoma) in some patients taking nasal steroid sprays. Studies have found no increased risk for cataracts in young people who have taken intranasal steroids. All the conditions resolve after stopping the steroid, although periodic eye examinations are advised.
Use during pregnancy. Steroids are most likely safe during pregnancy, but pregnant women should discuss all options carefully before taking them.
Nasal passage injury. Steroid sprays may injure the nasal septum (the bony area that separates the nasal passage) if the spray is directed onto it. This complication is very rare.
Lower resistance to infection. People with any infectious disease or injury in the nose should not take these drugs until the disease or wound has been treated and cured. People should avoid steroids if they have not been vaccinated or have had chicken pox or measles.
In some cases, people become insensitive to the effects of corticosteroids and they stop working.

Leukotriene-antagonists are oral drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), (Ziflo), and pranlukast (Ultair, Onon). They may also be useful in certain cases of chronic sinusitis, including sinusitis due to polyps, when allergies are the cause, or in some cases when the cause is unknown.

Scientists are investigating whether antifungal drugs may help treat chronic sinusitis. One such drug, Amphotericin B (SinuNase), is currently in Phase III trials for patients who have had sinus surgery but are still experiencing recurrent sinusitis. Results from previous clinical trials have been mixed.

Patients often have various combinations of allergies, sinusitis, and asthma. Treating each condition is important for improving them all. In addition to decongestants, pain relievers, and expectorants, other remedies are available for people who suffer from nonbacterial sinusitis during allergy season.

Anti-Inflammatory Drugs. Nasal spray corticosteroids (commonly called steroids) are important for reducing the inflammatory response in the nasal passages and airways. They are important in the treatment of asthma and are now considered to be the most effective measure for preventing allergy attacks. Leukotriene-antagonists are also useful for sinusitis symptoms.
Antihistamines. Antihistamine tablets relieve sneezing and itching and can prevent nasal congestion before an allergy attack. Many brands are available by prescription and over the counter.
Immunotherapy. Immunotherapy, commonly referred to as "allergy shots," may be considered for patients with severe seasonal allergies that do not respond to treatment. Immunotherapy is the only treatment that affects the cause of allergies. In one year-long study using immunotherapy, over half of young patients participating experienced improvement in overall sinusitis symptoms, and nearly all felt better in general. Immunotherapy also may prevent asthma and the development of new allergies in children. Newer immunotherapeutic approaches using specially designed antibodies and vaccines are also showing promise.
All drug treatments have side effects, some very unpleasant and, in rare cases, serious. Patients may need to try different drugs until they find one that relieves symptoms without producing excessively distressing side effects.

Surgery

Surgery is used to unblock the sinuses when drug therapy is not effective or if there are other complications, such as structural abnormalities or fungal sinusitis.

The simplest surgical approach is the insertion of a drainage tube into the sinuses followed by an infusion of sterile water to flush them out.

In the past few years there has been a major advance in the surgical treatment with a minimally invasive technique called functional endoscopic sinus surgery (FESS). The procedure allows correction of obstructions, including any polyp and ventilation and drainage to aid healing.

Candidates for the Procedure.

FESS may be a good choice for people with chronic sinusitis associated with structural abnormalities. In one study, the best results were seen in people with polyps (but not those associated with ASA triad, the combination of polyps in the nose, asthma, and sensitivity to aspirin).
Several studies are finding it to be safe and effective in children with chronic sinusitis or whose sinuses have not developed. It does not have an adverse effect on facial growth.
Surgery may help patients with HIV who have chronic or recurrent sinusitis.
It may benefit appropriate candidates who have both sinusitis and asthma. One study suggested that lung function may improve afterward in some patients.

Surgery may not be as effective for patients with the ASA triad, fungus infections, or severe chronic sinusitis, although endoscopy is proving to be beneficial even for these conditions with the use of more powerful instruments.

Procedure. The surgery generally proceeds as follows:

Adults require only a local anesthetic for the procedure, though a general anesthetic is needed for children.
Before the procedure, a computed tomography (CT) scan is taken for use by the surgeon in planning the procedure and as a guide to the sinuses during surgery. Some doctors are now using a device called a depth of field image (DOFI) video enhancement screen that displays a holographic 3-D image. It allows the surgeon an excellent view of the sinus cavities and may prove to significantly reduce complications.
A flexible tube, a miniature camera, and a fiberoptic light source are inserted through a single small opening.
Instruments are then used to remove diseased bone or tissue and clear obstructions. For instance, shavers are used to gently remove soft tissue. Bone cutters are sometimes employed to open the floor of the frontal sinus and restore drainage (called the modified Lothrop procedure). Lasers are also being investigated to remove bone, coagulate the passageways, or clear obstructions.

Complications. Serious complications of FESS are very rare, but the following have been reported in a few cases:

Cerebrospinal fluid leak is the most common major complication, but it occurs in only 0.2% of cases and is usually easily repaired during surgery.
Other very rare complications include meningitis, hemorrhage, infection, or vision loss.
Patients can develop infections afterward that are very difficult to treat. Interesting studies are reporting good to excellent results in these patients by spraying antibiotics into the nasal passages using a nebulizer.

Postsurgical Care. Postsurgical care involves the following:

The patient will experience a dull ache around the nose and sinus cavity that can be treated with pain medication.
Following surgery, the patient should flush the sinuses twice daily with a saline or alkaline solution.
Antibiotics may be prescribed for several weeks until postnasal drip has stopped, and corticosteroid sprays and antihistamines may be needed.

Success Rates. It may take several months for the mucous membranes to completely recover, but between 85 - 90% of patients experience good to excellent symptomatic relief after surgery. Children may require a second procedure 2 - 3 weeks after the first surgery to remove crusty matter.

A high-pressure water jet (HPWJ) treatment that flushes diseased mucus that remains after FESS surgery is being investigated for those whose symptoms do not clear. One 2000 study found the procedure an effective therapy that may even be safe for children.

A new type of surgical procedure threads a small balloon through the sinus passages. As the balloon is gently opened, the sinus passages expand and drainage occurs. Some experts think that this procedure is only appropriate for select patients with sinusitis disease in the maxillary (behind cheek bones), frontal (behind the sides of the forehead), and sphenoid (behind the eyes) sinus regions. It may not work for patients with disease in the ethmoid (between the eyes) sinuses, even though this a common sinusitis location.

Endoscopy is now used in most cases of chronic sinusitis, but in severe cases, invasive surgery using conventional scalpel techniques to remove infected areas may be required. This may be the case with acute ethmoid sinusitis in which pus breaks through the sinus and threatens the eye, with very severe frontal sinusitis, with invasive fungal sinusitis, or when cancer is present in the sinuses.

Resources

www.entnet.org -- American Academy of Otolaryngology - Head and Neck Surgery
www.aaaai.org --American Academy of Allergy, Asthma, and Immunology
www.acaai.org --American College of Allergy, Asthma, and Immunology
www.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
www.american-rhinologic.org -- American Rhinologic Society
www.cdc.gov/nip -- National Immunization Program

References

Brown CL, Bolger WE. Safety and feasibility of balloon catheter dilation of paranasal sinus ostia: a preliminary investigation. Ann Otol Rhinol Laryngol. 2006 Apr;115(4):293-9.

Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM. Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20.

Ebbens FA, Scadding GK, Badia L, Hellings PW, Jorissen M, Mullol J, et al. Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2006 Nov;118(5):1149-56.

Sharp HF, Denman D, Puumala S, Leopold DA. Treatment of acute and chronic rhinosinusitis in the United States, 1999-2002. Arch Otolaryngol Head Neck Surg. 2007 March;133(3):260-265.

Weschta M, Rimek D, Formanek M, Podbielski A, Riechelmann H. Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):743-7.

Review Date:
3/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Pneumonia

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Prognosis
Risk Factors
Diagnosis
Treatment
Medications
Surgery
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosis:

Diagnosing pneumonia may be difficult, since lab tests to grow the bacteria from samples can take many days to process, and chest x-rays cannot always distinguish between pneumonia and other conditions. New tests have the potential to make diagnosis easier and quicker. One is a blood test that identifies a marker of severe inflammation in the body. A new 15-minute urine test shows promise in identifying Legionella pneumophila and Streptococcus pneumoniae in patients on ventilators. Physicians may now sample fluid from the trachea or lungs to identify the pneumonia-causing bacteria.

Treatment:

Treating pneumonia has become increasingly complex as bacteria develop resistance to widely used antibiotics. New antibiotics and combinations of older antibiotics are proving effective against many hardy strains of bacteria. Moreover, guidelines for the appropriate treatment of patients at high risk for pneumonia -- those with heart disease, diabetes, asthma, HIV infection, leukemia, and other lung diseases, for example -- are improving the ability to prevent pneumonia and reduce deaths from the disease.

Drug Warning:

In February 2007, the Food and Drug Administration (FDA) announced that the antibiotic telithromycin (Ketek) would no longer be approved for acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis, but it would remain on the market for the treatment of mild-to-moderate pneumonia acquired outside of hospitals or long-term care facilities (community-acquired pneumonia, or CAP). In addition to warnings for liver damage, Ketek will now carry warnings of additional drug-related adverse events, including visual disturbances and loss of consciousness.

Introduction

Pneumonia is an inflammation of the lung that is most often caused by infection with bacteria, viruses, or other organisms. Occasionally, inhaled chemicals that irritate the lungs can cause pneumonia. Healthy people can usually fight off pneumonia infections. However, people who are sick, including those who are recovering from the flu (influenza) or an upper respiratory illness, have weakened immune systems that make it easier for bacteria to grow in their lungs.

When air is inhaled through the nose or mouth, it travels down the trachea to the bronchus, where it first enters the lung. From the bronchus, air goes through the bronchi, into the even smaller bronchioles and lastly into the alveoli.

Pneumonia may be defined according to its location in the lung:

Lobar pneumonia occurs in one part, or lobe, of the lung.
Bronchopneumonia tends to be scattered throughout the lung.

Doctors often classify pneumonia based on where the disease is contracted. This helps predict which organisms are most likely responsible for the illness and, therefore, which treatment is most likely to be effective.

Community-Acquired Pneumonia (CAP). People with this type of pneumonia contracted the infection outside a hospital setting. It is one of the most common infectious diseases. It often follows a viral respiratory infection, such as the flu.

One of the most common causes of bacterial CAP is Streptococcus pneumoniae. Other causes include Haemophilus influenzae, mycoplasma, and Chlamydia.

Hospital-Acquired Pneumonia. Hospital-acquired pneumonia is an infection of the lungs contracted during a hospital stay. This type of pneumonia tends to be more serious, because hospital patients already have weakened defense mechanisms, and the infecting organisms are usually more dangerous than those encountered in the community. Hospital patients are particularly vulnerable to Gram-negative bacteria and staphylococci. Hospital-acquired pneumonia is also called nosocomial pneumonia.

A subgroup of hospital-acquired pneumonia is ventilator-associated pneumonia (VAP), a highly lethal form contracted by patients on ventilators in hospitals and long-term nursing facilities.

Click the icon to see an image of hospital-acquired pneumonia.

Pneumonia-causing agents reach the lungs through different routes:

In most cases, a person breathes in the infectious organism, which then travels through the airways to the lungs.
Sometimes, the normally harmless bacteria in the mouth, or on items placed in the mouth, can enter the lungs. This usually happens if the body's "gag reflex," an extreme throat contraction that keeps substances out of the lungs, is not working properly.
Infections can spread through the bloodstream from other organs to the lungs.

However, in normal situations, the airways protect the lungs from substances that can cause infection.

The nose filters out large particles.
If smaller particles pass through, sensors along the airway prompt a cough or sneeze. This forces many particles back out of the body.
Tiny particles that reach the small tubes in the lungs (bronchioles) are trapped in a thick, sticky substance called mucus. The mucus and particles are pushed up and out of the lungs by tiny hair-like cells called cilia, which beat like a drum. This action is called the "mucociliary escalator."

Click the icon to see an image of respiratory cilia.

If bacteria or other infectious organisms manage to avoid the airway's defenses, the body's immune system attacks them. Large white blood cells called macrophages destroy the foreign particles.

Click the icon to see an image of a macrophage.

The above-mentioned defense systems normally keep the lung healthy. If these defenses are weakened or damaged, however, bacteria, viruses, fungi, and parasites can easily infect the lung, producing pneumonia.

The lungs are two spongy organs in the chest surrounded by a thin, moist membrane called the pleura. Each lung is composed of smooth, shiny lobes; the right lung has three lobes and the left has two. Approximately 90% of the lung is filled with air. Only 10% is solid tissue. There are several parts to each lung.

When a person takes a breath (inhales), air travels from the trachea (windpipe) into the lung through the main bronchus, which branches into tiny flexible tubes called bronchi.

The bronchi divide, like the branches of a tree, into smaller airways called bronchioles.

The bronchioles lead to a group of microscopic sacs called alveoli, which look like clusters of grapes. Each healthy adult lung contains millions of tiny alveoli. (Note: The singular of alveoli is alveolus.)

Click the icon to see an image of the lungs.

Each alveolus has a thin membrane that allows oxygen and carbon dioxide to pass in and out of the capillaries, the smallest of the blood vessels. When you take a deep breath, the membrane unfolds and expands. Fresh oxygen moves into the capillaries, and carbon dioxide passes from the capillaries into the bloodstream, where it is carried out of the body through the lungs.

Blood vessels carry the oxygen-rich blood to the heart, where it is pumped throughout the body.

Causes

Bacteria are the most common cause of pneumonia. However, pneumonia can also be caused by viruses, fungi, and other agents. It is often impossible to identify the specific culprit.

Many bacteria are grouped into one of two large categories by the laboratory procedure used to look at them under a microscope. The procedure is known as Gram staining. Bacteria are stained with special dyes, then washed in a special solution. The color of the bacteria after washing determines whether they are Gram-negative or Gram-positive. Knowing which group the bacteria belong to helps determine the severity of the disease, and how to treat it. Different bacteria are treated with different drugs.

Gram-Positive Bacteria. These bacteria appear blue on the stain and are the most common organisms that cause pneumonia. They include:

Streptococcus (S.) pneumoniae (also called pneumococcus), the most common cause of pneumonia. This Gram-positive bacterium causes 20 - 60% of all community-acquired bacterial pneumonia (CAP) in adults. Studies also suggest it causes 13 - 38% of CAP in children.
Staphylococcus (S.) aureus, the other major Gram-positive bacterium responsible for pneumonia, causes about 2% of CAP and 10 - 15% of hospital-acquired pneumonias. It is the organism most often associated with viral influenza, and can develop about five days after the onset of flu symptoms. Pneumonia from S. aureus most often occurs in people with weakened immune systems, very young children, hospitalized patients, and drug abusers who use needles. It is uncommon in healthy adults.
Streptococcus pyogenes or Group A streptococcus.

Gram-Negative Bacteria. These bacteria stain pink. Gram-negative bacteria commonly cause infections in hospitalized or nursing home patients, children with cystic fibrosis, and people with chronic lung conditions.

Haemophilus (H.) influenzae is the second most common organism causing community acquired pneumonia, accounting for 3 - 10% of all cases. It generally occurs in patients with chronic lung disease, older people, and alcoholics.
Klebsiella (K.) pneumoniae may be responsible for pneumonia in alcoholics and other people who are physically debilitated. It is also associated with recent use of potent antibiotics.
Pseudomonas (P.) aeruginosa is a major cause of hospital-acquired pneumonia (nosocomial pneumonia). It is a common cause of pneumonia in patients with chronic or severe lung disease.
Moraxella (M.) catarrhalis is found in everyone's nose and mouth. Experts have identified this bacterium as an uncommon cause of certain pneumonias, particularly in people with lung problems such as asthma or emphysema.
Neisseria (N.) meningitidis is one of the most common causes of meningitis (central nervous system infection), but the organism has been reported in pneumonia, particularly in epidemics of military recruits.
Other Gram-negative bacteria that cause pneumonia include E. coli, proteus (found in damaged lung tissue), enterobacter and acetinobacter.

Atypical pneumonias produce mild symptoms and a dry cough. Organisms that cause atypical pneumonias include:

Mycoplasma (M.) pneumoniae, the most common atypical pneumonia organism. Mycoplasma is a very small bacterium that lacks a cell wall. Pneumonia caused by M. pneumoniae spreads when someone carrying the infection comes in close contact with others for a long period of time. It is most often found in school-aged children and young adults. The condition, commonly called "walking pneumonia," is usually mild.
Chlamydia (C.) pneumoniae is now thought to cause 10% of all CAP cases. This atypical pneumonia is most common in young adults and children, and is usually mild. It is less common, but usually more severe, in the elderly.
Legionella pneumophila causes Legionnaire disease. It is contracted by breathing in drops of contaminated water. Outbreaks are often been reported in hotels, cruise ships, and office buildings, where people are exposed to contaminated droplets from cooling towers and evaporative condensers. They have also been reported in people who have been near whirlpools and saunas. Legionella pneumophila is not passed from person to person. Some experts believe the organism causes 29 - 47% of all pneumonia cases.

Legionnaire disease was first described in 1976 after an outbreak of fatal pneumonia at an American Legion convention. The newly described organism that caused the disease was named Legionella pneumophila, shown in this picture. (Courtesy of the Centers for Disease Control.)

A number of viruses can cause pneumonia either directly or indirectly. They include:

Influenza (Flu). Pneumonia is a major complication of the flu and can be very serious. It can develop about 5 days after flu symptoms start. The flu weakens the body's defense systems, making it easier for bacteria to grow in the lungs.
Respiratory syncytial virus (RSV). Most infants are infected with RSV at some point, but it is most often mild. However, RSV is a major cause of pneumonia in infants as well as adults with damaged immune systems. Studies indicate that RSV pneumonia may be more common in adults, especially the elderly, than previously thought.
Severe acute respiratory syndrome (SARS). SARS is a respiratory infection caused by a newly-described coronavirus, which appears to have jumped from animals to humans. The disease was first reported in China in 2003.
Human parainfluenza virus. This virus is a leading cause of pneumonia and bronchitis in children, the elderly, and patients with damaged immune systems.
Adenoviruses. Adenoviruses are common and usually are not problematic, although they have been linked to about 10% of childhood pneumonia.
Herpesviruses. In adults, herpes simplex virus and varicella zoster (the cause of chickenpox) can cause pneumonia in people with impaired immune systems.
Avian influenza. Type A influenza subtype H5N1 in birds is spreading around the globe. Fortunately, only a few hundred human cases have been identified. Most have resulted from close contact with infected birds. Person-to-person contact is rare. All patients diagnosed with "bird flu" show signs of pneumonia, although symptoms may be mild. Oseltamivir (Tamiflu) is the most effective treatment for this type of influenza, which can be fatal.

The mouth contains a mixture of bacteria that is normally harmless. However, if this mixture reaches the lungs, it can cause a serious condition called aspiration pneumonia. This may happen after head a injury or general anesthesia, or when a patient takes drugs or alcohol. In such cases, the gag reflex doesn't work as well as it should, so bacteria can enter the airways. Unlike other organisms that are inhaled, bacteria that cause aspiration pneumonia do not need oxygen to live. These bacteria are called anaerobic bacteria.

Impaired immunity leaves patients vulnerable to serious, life-threatening pneumonias known as opportunistic pneumonias. They are caused by organisms that are harmless to people with healthy immune systems. Infecting organisms include:

Pneumocystis carinii, renamed Pneumocystis jiroveci in 2002, is an atypical organism. Originally thought to be protozoa, it is now classified as a fungus. P. jiroveci is very common and generally harmless in people with healthy immune systems. It is the most common cause of pneumonia in AIDS patients.

Click the icon to see an image of pneumocystis carinii.

Fungi, such as Mycobacterium avium
Viruses, such as cytomegalovirus (CMV)

Click the icon to see an image of CMV.

In addition to AIDS, other conditions also put patients at risk for opportunistic pneumonia. They include cancers such as lymphoma and leukemia. Long-term use of corticosteroids and drugs known as immunosuppressants also increase the risk for these pneumonias.

Exposure to chemicals can also cause inflammation and pneumonia. Where you work and live can put you at higher risk for exposure to pneumonia-causing organisms.

Workers exposed to cattle, pigs, sheep, and horses are at risk for pneumonia caused by anthrax, brucella, and Coxiella burnetii, which causes Q fever.

Click the icon to see an image of inhalation anthrax.

Agricultural and construction workers in the Southwest are at risk for coccidoidomycosis (Valley fever). The disease is caused by the spores of the fungus Coccidioides immitis.
Those working in Ohio and the Mississippi Valley are at risk for histoplasmosis, a lung disease caused by the fungus Histoplasma capsulatum.

Click the icon to see an image of coccidoidomycosis.

Workers exposed to pigeons, parrots, parakeets, and turkeys are at risk for psittacosis, a lung disease caused by the bacteria Chlamydia psittaci.
Hantavirus, a rare virus carried by rodents, causes a dangerous form of lung disease. It does not spread from person to person. Cases have occurred in New Mexico, Arizona, California, Washington, and Mexico.

Click the icon to see an image of the hantavirus.

Severe acute respiratory syndrome (SARS) is a contagious respiratory infection that was recognized as a worldwide threat in 2003. It was first identified as a new disease by World Health Organization (WHO) physician Dr. Carlo Urbani. Urbani diagnosed SARS in a 48-year-old American businessman, who had traveled from the Guangdong province of China through Hong Kong to Hanoi, Vietnam. The businessman died from the illness. Dr. Urbani died from SARS just a month later, on March 29, 2003 at the age of 46. SARS spread fast. Within 6 weeks of Urbani's discovery, the disease had infected thousands of people around the world on every continent except Antarctica. Schools closed throughout Hong Kong and Singapore, and national economies were affected. The WHO officially identified SARS as a global health threat, and issued an unprecedented travel advisory. It wasn't clear at the time whether SARS would become a global pandemic or settle into a less aggressive pattern. The latter seems to have happened. As of a May 2005, there was no known SARS transmission anywhere in the world, according to the U.S. Centers for Disease Control and Prevention (CDC). The SARS outbreak is a dramatic example of how quickly world travel can spread a disease. According to reports from the CDC and WHO, more than 8,000 people became sick with SARS during the outbreak. Of that group, 774 died. The outbreak is also an example of how quickly a networked health monitoring system can respond to an emerging threat

Causes And Risk Factors. SARS is a serious form of atypical pneumonia that causes acute respiratory distress and sometimes death. It is caused by a new member of the coronavirus family, the family that includes the virus that causes the common cold). The discovery of the SARS-related virus represents one of the fastest identifications of a new organism in history.

SARS is spread by droplet contact. When someone with SARS coughs or sneezes, infected droplets are sprayed into the air. Like other coronaviruses, the SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried. While droplet transmission through close contact has been responsible for most cases of SARS, there is evidence that SARS might also spread by infected droplets carried on hands and other objects the droplets had touched. Airborne transmission was a real possibility in some cases. Live virus had even been found in the stool of people with SARS, where it has been shown to survive for up to 4 days. And the virus may be able to live for months or years when the temperature is below freezing.

With other coronaviruses, re-infection (contracting the same disease after recovery or during initial illness) is common. Preliminary reports suggest that this may also be the case with SARS.

The estimated incubation period is 2 - 10 days, although there have been documented cases where the onset of illness was considerably faster or slower. People with active symptoms of illness are clearly contagious. It is not known, however, how early contagion begins before symptoms appear, or how long contagion might linger after the symptoms have disappeared.

Prevention. The best way to prevent SARS is to avoid direct contact with people who have SARS until 10 days after their fever and other symptoms are gone. Reduce travel to locations where there is an uncontrolled SARS outbreak. The CDC has identified hand hygiene as the cornerstone of SARS prevention. Wash your hands often with soap and water, or use an alcohol-based instant hand sanitizer. Cover your mouth and nose when sneezing or coughing. Consider respiratory secretions infectious. Clean commonly touched surfaces with an EPA-approved disinfectant. In some situations, masks, and goggles may be useful for preventing the spread of airborne or droplet infection. Gloves should be used in handling potentially infectious secretions.

Vaccine. In December 2004, the U.S. National Institutes of Health began a small clinical trial to test a preventive SARS vaccine. Interim results showed the vaccine to be safe and well tolerated. Chinese researchers began testing a SARS vaccine in May 2004.

Symptoms. The hallmark symptoms of SARS are fever of 100.4° F (38.0° C) or higher and a dry cough, with difficulty breathing or other respiratory symptoms. The following symptoms, listed in order of how often they appeared, were found in more than half of the first SARS patients:

Fever
Chills and shaking
Muscle aches
Cough
Headache

Less common symptoms (also in order) include:

Dizziness
Cough that produces mucus (sputum)
Sore throat
Runny nose
Nausea and vomiting
Diarrhea

Signs and Tests. Listening to the chest with a stethoscope (auscultation ) may reveal abnormal lung sounds. In most people with SARS, progressive chest x-ray changes or chest CT changes reveal the presence of pneumonia.

Much attention was given early in the outbreak to the development of a quick, sensitive test for SARS. Specific tests for the SARS virus include the PCR for SARS virus, antibody tests to SARS (such as ELISA or IFA), and direct SARS virus isolation. All current tests have some limitations. General tests used in the diagnosis of SARS might include:

Chest x-ray or chest CT is abnormal.
CBC. People with SARS tend to have a low white blood cell count (leukopenia), a low lymphocyte count (lymphopenia), or a low platelet count (thrombocytopenia).
Clotting profiles. SARS patients often have prolonged blood clotting times.
Metabolic blood tests. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) levels are often high. ALT and LDH are most often measured to evaluate the presence of tissue damage.
CPK blood test. Creatine phosphokinase (CPK) is an enzyme found predominantly in the heart, brain, and skeletal muscle. Levels of the CPK enzyme are sometimes elevated in patients with SARS.
Sodium and potassium blood tests are sometimes below normal levels.

Treatment. People suspected of having SARS should be evaluated immediately by a physician. Antibiotics are sometimes given in an attempt to treat bacterial causes of atypical pneumonia. Antiviral medications have also been used. High doses of steroids have been employed to reduce lung inflammation. In some serious cases, serum from people who have already gotten well from SARS (convalescent serum) has been given. Evidence of general benefit of these treatments has been inconclusive.

Other supportive care such as supplemental oxygen, chest physiotherapy, or mechanical ventilation is sometimes needed.

Prognosis. The overall worldwide death rate due to SARS at the end of the outbreaks was 14 - 15%, although it was up to 50% in infected people over age 65. Many more were sick enough to require breathing assistance from a machine (mechanical ventilation). Many others required ICU care.

Today, intensive public health policies are proving to be effective in controlling outbreaks. Many nations have stopped the epidemic within their own countries. All nations must be vigilant, however, to keep this disease under control.

Complications.

Respiratory failure
Liver failure
Heart failure
Myelodysplastic syndromes (bone marrow abnormalities leading to anemia, low platelet counts, and low white blood cell counts)

Call Health Care Provider. Call your health care provider if you suspect you or someone you have had close contact with has SARS.

Symptoms

General Symptoms. The symptoms of bacterial pneumonia develop very quickly and typically include:

A single episode of shaking chills followed by fever
Chest pain on the side of the infected lung. Severe abdominal pain sometimes occurs in people with pneumonia in the lower lobes of the lung.
Shortness of breath
Rapid breathing and heart beat
Cough, which may be initially dry, but eventually produces sputum
Nausea, vomiting, and muscle aches

Emergency Symptoms. Symptoms of pneumonia indicating a medical emergency include the following:

High fever
Rapid heart rate
Bluish-toned (cyanotic) skin
Labored and heavy breathing.
Mental confusion
Coughing up mucus (sputum) containing pus or blood

Symptoms in the Elderly. It is important to note that older people may have fewer or different symptoms than younger people. Symptoms may come on much more slowly. An elderly person who experiences even a minor cough and weakness for more than a day should seek medical help. Some elderly people may exhibit confusion, lethargy, and general deterioration.

Pneumonia caused by anaerobic bacteria such as prevotella (formerly called bacteroides) can produce dangerous abscesses in the lungs. People with such pneumonias may have prolonged fever and a productive cough. There is frequently blood in the mucus that is coughed up. Blood may indicate dead lung tissue. About a third of these patients experience weight loss.

General Symptoms for Atypical Pneumonias. Atypical pneumonia is most commonly caused by mycoplasma and usually appears in children and young adults.

The disease progresses gradually.

General flu-like symptoms often occur first. They may include fatigue, fever, weakness, headache, nasal discharge, sore throat, earache, and stomach and intestinal distress.
Vague pain under and around the breastbone may occur, but the severe chest pain associated with typical bacterial pneumonia is uncommon.
Patients may have a severe hacking cough, but it usually does not produce sputum.

Symptoms of Legionnaire Disease. Symptoms of Legionnaire disease usually occur more rapidly and include high fever, a dry cough, and shortness of breath. These symptoms are often accompanied by headache, muscle pains, fatigue, gastrointestinal problems, and mental confusion.

Prognosis

More than a million people are hospitalized each year for pneumonia, making it the third most frequent cause of hospitalizations (births are first, and heart disease is second). Although the majority of pneumonias respond well to treatment, the infection kills 40,000 - 70,000 people each year.

Hospitalized Patients. For patients who require hospitalization for pneumonia, the death rate is 10 - 25%. If pneumonia develops in patients already hospitalized for other conditions, death rates range from 50 - 70%, and are higher in women than in men.

Older Adults. Community-acquired pneumonia is responsible for 350,000 - 620,000 hospitalizations in the elderly every year. Older adults have lower survival rates than younger people. Even when older individuals recover from CAP, they have higher-than-normal death rates over the next several years. Elderly people who live in nursing homes or who are already sick are at particular risk.

Very Young Children. About 20% of deaths in stillborn and very young infants are due to pneumonia. Small children who develop pneumonia and survive are at risk for developing lung problems in adulthood.

Pregnant Women. Pneumonia poses a special hazard for pregnant women, possibly due to changes in a pregnant woman's immune system. This complication can lead to premature labor and increases the risk of death during pregnancy.

Patients With Impaired Immune Systems. Pneumonia is particularly serious in people with impaired immune systems. This is particularly true for AIDS patients, in whom pneumonia causes about half of all deaths.

Patients With Serious Medical Conditions. Pneumonia is also very dangerous in people with diabetes, cirrhosis, sickle cell disease, cancer, and in those whose spleens have been removed.

Specific organisms vary in their effects. Mild pneumonia is usually associated with the atypical organisms mycoplasma and chlamydia. Severe pneumonia is most often associated with a wide range of organisms. Some are very virulent (potent) but are extremely curable, while others are difficult to treat.

Mycoplasma and chlamydia are the most common causes of mild pneumonias and are most likely to occur in children and young adults. They rarely require hospitalization when they are appropriately treated, although recovery may still be prolonged. Severe and life-threatening cases are more likely to occur in elderly people with other medical conditions.
Streptococcus pneumoniae is the most common cause of pneumonia and, in fact, all bacterial upper respiratory infections. It can produce severe pneumonia, with mortality rates of 10%. Nevertheless, pneumococcal pneumonia is very responsive to many antibiotics.
Staphylococcus aureus is a Gram-positive bacterium that often causes severe pneumonia in hospitalized and high-risk patients and following influenza A and B. People who get this form of pneumonia may develop pockets of infection in their lungs (abscesses) that are difficult to treat and can cause the death of lung tissue (necrosis). Mortality rates are 30 - 40%, in part because the patients who develop this infection are generally very ill or vulnerable.
Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative bacteria that pose a risk for abscesses and severe lung tissue damage.
Legionella pneumophila is very virulent and can cause widespread damage. Treatments have improved dramatically since it was first identified. However, a 2002 study suggested that many patients experience long-term problems, including coughing, shortness of breath, fatigue, and neurological and muscular complications.
Viral pneumonia is usually very mild, but there are exceptions. Respiratory syncytial virus (RSV) pneumonia rarely poses a danger for healthy young adults, but it can be life-threatening in infants and serious in the elderly.

Abscess. An abscess in the lung is a thick-walled, pus-filled cavity that forms when infection has destroyed lung tissue. It typically occurs as a result of aspiration pneumonia, when a mixture of organisms is carried into the lung. Untreated abscesses can cause hemorrhage (bleeding) in the lung, but targeted antibiotic therapy significantly reduces their danger. Abscesses are more common with Staphylococcus aureus, Pseudomonas aeruginosa, or Klebsiella pneumoniae, and uncommon with Streptococcus pneumoniae.

Respiratory Failure. Respiratory failure is one of the top causes of death in patients with pneumococcal pneumonia. Acute respiratory distress syndrome (ARDS) is the specific condition that occurs when the lungs are unable to function and oxygen is so severely reduced that the patient's life is at risk. Failure can occur if pneumonia leads to mechanical changes in the lungs (ventilatory failure) or oxygen loss in the arteries (hypoxemic respiratory failure).

Bacteremia. Bacteremia, bacteria in the blood, is the most common complication of pneumococcus infection, although it rarely spreads to others sites. Bacteremia is a frequent complication of infection from Gram-negative organisms, including Haemophilus influenzae.

Pleural Effusions and Empyema. The pleura are two thin membranes that line the chest and lungs:

The visceral pleura cover the lungs.
The parietal pleura cover the chest wall.

In some cases of pneumonia the pleura become inflamed, which can result in breathlessness and acute chest pain when breathing.

In about 20% of pneumonia cases fluid builds up between the pleural membranes, a condition known as pleural effusion. Ordinarily, the narrow zone between the two membranes contains only a tiny amount of fluid, which lubricates the lungs.

In most cases, particularly in Streptococcus pneumoniae, the fluid remains sterile (no bacteria are present), but occasionally it can become infected and even filled with pus, a condition called empyema. Empyema is more likely to occur with specific organisms such as Staphylococcus aureus or Klebsiella pneumoniae infections. The condition can cause permanent scarring.

Collapsed Lung. In some cases, air may fill up the area between the pleural membranes, causing the lungs to collapse. This is called pneumothorax. It may be a complication of pneumonia (particularly Streptococcus pneumoniae ) or of the invasive procedures used to treat pleural effusion.

Pneumothorax occurs when air leaks from inside of the lung to the space between the lung and the chest wall. The lung then collapses. The dark side of the chest (right side of the picture) fills with air from outside of the lung tissue.

Other Complications of Pneumonia. In rare cases, infection may spread from the lungs to the heart and possibly throughout the body. This can cause abscesses in the brain and other organs. Severe hemoptysis (coughing up blood) is another potentially serious complication of pneumonia, particularly in patients with lung problems such as cystic fibrosis.

Kidney complications and electrolyte imbalances are common in patients admitted to the hospital with pneumonia. If not treated, these problems cause more severe illness and increase the risk of death. Treatment with intravenous saline can usually resolve the problem.

The pneumonias cased by the atypical organisms mycoplasma and chlamydia are usually mild. Some research suggests, however, that chlamydia may have powerful inflammatory effects in the blood vessels. This effect may have certain adverse long-term consequences even in healthy younger individuals.

Heart Disease and Stroke. Research has suggested that chlamydia may trigger the immune system to react, causing inflammation in the coronary arteries. Over time, this can cause hardening of the arteries (atherosclerosis). Atherosclerosis can lead to heart attacks and strokes. Studies on a causal relationship between chlamydia and heart disease have been mixed.

Click the icon to see an image of arterial plaque.

Chylamydia pneumoniae has been associated with a thickening in the carotid arteries that lead to the brain -- a risk factor for stroke. It is not clear whether the organism poses any significant risk for stroke.

Click the icon to see an image of atherosclerosis of the internal carotid artery.

Asthma. Chlamydia pneumoniae, Mycoplasma pneumoniae, and RSV are becoming suspects in many cases of severe adult asthma. One small Australian study found evidence of previous chlamydia infection in 64% of the asthmatic patients tested.

Risk Factors

Risk factors for pneumonia often depend on the specific type of disease.

CAP is the most common type of pneumonia. It develops outside of the hospital. Each year 2 - 4 million people in the US develop CAP, and 600,000 are hospitalized. The elderly, infants, and young children are at greatest risk for the disease.

Pneumonia that is contracted in the hospital is called hospital-acquired or nosocomial pneumonia. It affects an estimated 5 -10 of every 1,000 hospitalized patients every year. More than half these cases may be due to strains of bacteria that have developed resistance to antibiotics. In fact, methicillin-resistant Staphyllococcus aureus and multidrug-resistant Pseudomonas aeruginosa are leading causes of death from hospital-acquired pneumonia. The elderly, the very young, and those with chronic or severe medical conditions, are at highest risk.

In addition, the following conditions within the hospital put patients at higher risk:

Surgery, particularly in people over the age of 80. Among the surgical procedures that pose a particular risk are splenectomy (removal of the spleen), abdominal aortic aneurysm repair, or operations that impair coughing.
Being in the intensive care unit (ICU). This is particularly true for newborns or patients on breathing machines (mechanical ventilators). In one study, 10% of ICU patients on a breathing machine developed pneumonia. Such patients who lie flat on their backs are at particular risk for aspiration pneumonia. Raising the patient up may reduce this risk.
Sedation. Hospital patients who receive sedatives also have a higher risk of developing nosocomial pneumonia.
Previous use of antibiotics, particularly within 6 months.

Hospitalized patients are particularly vulnerable to Gram-negative bacteria and staphylococci, which can be especially dangerous in people who are already ill.

Chronic Lung Disease. Chronic obstructive lung diseases (COPD), which include chronic bronchitis and emphysema, affect 15 million people in the U.S. This condition is a major risk factor for pneumonia. In patients with COPD, vaccination with the pneumococcal vaccine can substantially reduce the risk of developing pneumonia or decrease its severity.

Bronchitis is the inflammation of the bronchi, the main air passages to the lungs. It generally follows a viral respiratory infection. Symptoms include coughing, shortness of breath, wheezing, and fatigue.

Click the icon to see an image of emphysema.

People With Compromised Immune Systems. People with impaired immune systems are extremely susceptible to pneumonia. It is a common problem in people with HIV and AIDS. In one study, the primary bacteria were found to be Legionella pneumophilia and Streptococcus pneumoniae. Smoking and chemotherapy for cancer were more common in those with legionella pneumonia. The patients tended to have a higher CD4 count, undetectable viral load, and more frequent need for antiretroviral therapy. Their pneumonia was more severe than in HIV patients diagnosed with pneumococcal pneumonia. Those with legionell were more likely to have respiratory failure, need ventilation, have pneumonia in both lungs, and were more likely to die. However, AIDS was more common in the patients with pneumococcal pneumonia.

In addition to AIDS, other conditions that compromise the immune system include organ transplantation, chemotherapy, and adult and pediatric cancers, especially leukemia and Hodgkin's lymphoma. Patients who are on corticosteroids or other medications that suppress the immune system are also prone to infection.

Gastroesophageal Reflux Disease. Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move up into the esophagus. This is called reflux. Current studies indicate an association between GERD and various problems that occur in the sinuses, ears, nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid (aspirates) from the esophagus into the lungs, serious pneumonia can occur. GERD may contribute to these conditions by triggering inflammation in these upper passages.

However, GERD drugs may increase one's risk. Patients at high risk for pneumonia should take gastric acid-suppressing drugs only when necessary and at the lowest possible dose. A 2004 study found that the use of gastric acid-suppressing drugs raises the risk of developing CAP. The highest risks were associated with proton pump inhibitors (PPIs) such as Prilosec and Nexium, but H2-receptor antagonists such as Tagamet and Pepcid also elevated risk. The researchers theorize that reducing levels of germ-killing stomach acid allow germs to spread in the upper gastrointestinal tract and move into the respiratory tract. The risk posed by these medications is highest in the elderly, children, and patients with asthma, COPD, and compromised immune systems.

Acute stroke. Acute stroke is a risk factor for developing pneumonia. In one German study, the incidence of stroke-associated pneumonia (SAP) was 22% in patients admitted to the intensive care following a stroke. Dysphagia, non-lacunal basal-ganglia infarction, or any infection present on admission, and National Institutes of Health Stroke Scale score greater than or equal to 10 were found to be independent risk factors for the development of SAP. Other risk factors included combined brainstem and cerebellar infarction, infarction affecting more than 66% of the middle cerebral arterial territory, hemispheric infarction exceeding middle cerebral artery territory, impaired vigilance, mechanical ventilation, age of 73 or greater, and cardioembolic stroke. Patients with lacunal strokes were found to be at less risk of SAP.

Click the icon to see an image of gastric reflux.

Dormitory or Barrack Conditions. Recruits on military bases and college students living in dormitories are at higher than average risk for Mycoplasma pneumonia. These groups are at lower risk, however, for more serious types of pneumonia.

Smoke and Environmental Pollutants. The risk for pneumonia in people who smoke more than a pack a day is three times that of nonsmokers. Those who are chronically exposed to secondhand cigarette smoke, which can injure airways and damage the cilia, are also at risk. Quitting smoking reduces the risk of dying from pneumonia to normal, but the full benefit takes 10 years to be realized. Toxic fumes, industrial smoke, and other air pollutants may also damage cilia function, which is a defense against bacteria in the lungs.

Drugs and Alcohol. Alcohol or drug abuse is strongly associated with pneumonia. These substances act as sedatives and can diminish the reflexes that trigger coughing and sneezing. Alcohol also interferes with the actions of macrophages, the white blood cells that destroy bacteria and other microbes. Intravenous drug abusers are at risk for pneumonia from infections that originate at the injection site and spread through the bloodstream to the lungs.

Fatty Diet: A diet high in fatty acids such as palm oils appears to increase the risk of CAP in young and middle-aged women by as much as 54%. Higher intake of monosaturated fats appears to decrease the risk of pneumonia.

Certain children have a higher-than-normal risk for pneumonia and recurrence. Conditions that predispose infants and small children to pneumonia include:

Impaired immune system
Leukemia
Infection with the respiratory syncytial virus (RSV)
Gastroesophageal reflux disorder
Inborn lung or heart defects
Abnormalities in muscle coordination of the mouth and throat
Asthma
Certain genetic disorders such as sickle-cell disease, cystic fibrosis, and Kartagener's syndrome, which result in poorly functioning cilia, the hair-like cells lining the airways

Diagnosis

Diagnostic Difficulties in Community-Acquired Pneumonia (CAP). It is important to determine whether the cause of CAP is a bacterium, atypical bacterium, or virus, since they require different treatments. In children, for example, S. pneumonia is the most common cause of pneumonia, but respiratory syncytial virus may also cause the disease. Although symptoms may differ, they often overlap, which can make it difficult to identify the organism by symptoms alone.

Nevertheless, in many cases of mild-to-moderate CAP, the physician is able to diagnose and treat pneumonia based solely on a history and physical examination.

Diagnostic Difficulties with Hospital-Acquired (Nosocomial) Pneumonia. Diagnosing pneumonia is particularly difficult in hospitalized patients for a number of reasons:

Many hospitalized patients have similar symptoms, including fever or signs of lung infiltration on x-rays.
In hospitalized patients, sputum or blood tests often indicate the presence of bacteria or other organisms, but such agents do not necessarily indicate pneumonia.

Doctors making a diagnosis of pneumonia should rule out other conditions, using a chest x-ray, two sets of blood cultures, a urine analysis for legionella, and a lung fluid sample, among other tests.

The patient's history is an important part of making a pneumonia diagnosis. Patients should be sure to report any of the following:

Recent or chronic respiratory infection
Exposure to people with pneumonia or other respiratory illnesses (such as tuberculosis)
History of smoking
Alcohol or drug abuse
Recent travel
Occupational risks

Use of the Stethoscope. The most important diagnostic tool for pneumonia is the stethoscope. Sounds in the chest that may indicate pneumonia include:

Rales, a bubbling or crackling sound. Rales on one side of the chest or heard while the patient is lying down are strongly suggestive of pneumonia.
Rhonchi, abnormal rumblings indicating the presence of thick fluid.
A dull thud obtained by percussion. The physician will also use a test called percussion, in which the chest is tapped lightly. A dull thud, instead of a hollow drum-like sound, indicates certain conditions suggestive of pneumonia. These conditions include including consolidation (a condition in which the lung becomes firm and inelastic), and pleural effusion (fluid build-up in the space between the lungs and the lining around it).

Although current antibiotics can destroy a wide spectrum of organisms, it is best to use an antibiotic that targets the specific one making a person sick. Unfortunately, people carry many bacteria, and sputum and blood tests are not always effective in distinguishing between harmless and harmful kinds.

In severe cases, a doctor needs to use invasive diagnostic measures to identify cause of the infection. Standard lab tests used to help diagnose pneumonia include:

Sputum Tests. The color of the mucus (sputum) sample coughed up from the lungs can reveal the severity of the disease. Only a sputum sample will reveal the infecting organism.

The patient coughs as deeply as possible to bring up mucus from the lungs, since a shallow cough produces a sample that usually only contains normal mouth bacteria. Some people may need to inhale a saline spray to produce an adequate sample. In some cases, a tube will be inserted through the nose into the lower respiratory tract to induce a deeper cough.

The physician will check the sputum for:

Blood, which means an infection is present
Color and consistency: If it is yellow, green, or brown, an infection is likely.

The sputum sample is sent to the laboratory, where it is analyzed for the presence of bacteria and to determine whether the bacteria are gram-negative or Gram-positive.

Blood Tests. The following blood tests may be performed:

White blood cell count (WBC). High levels indicate infection.
Blood cultures. Cultures are done to determine the specific organism causing the pneumonia, but they usually can not distinguish between harmless and dangerous organisms. They are accurate in only 10 - 30% of cases. Their use is generally limited to severe cases.
Detection of antibodies to S. pneumoniae. Antibodies are immune factors that target specific foreign invaders. One type of immunohistochemical test for S. pneumoniae is showing tremendous promise.
Polymerase Chain Reaction (PCR). In some difficult cases, PCR may be performed. A test makes multiple copies of the genetic material (RNA) of a virus or bacteria to make it detectable.
Procalcitonin test. This marker of systemic inflammatory response to infection is increasingly recognized as a valuable method of determining which patients need antibiotics, and when antibiotic therapy can be safely stopped. Such information is critical to preventing the development of antibiotic-resistant bacteria.

Urine Tests. Urinary antigen tests for Legionella pneumophila and Streptococcus pneumoniae may be performed in patients with severe CAP. The S. pneumoniae test takes only 15 minutes and may identify up to 77% of pneumonia cases and rule out S. pneumoniae infection in 98% of patients. It may not be useful in children.

Invasive Tests. In critically-ill patients with ventilator-associated pneumonia, physicians have tried sampling fluid taken from the lungs or trachea. The techniques enabled the physicians to identify the pneumonia-causing bacteria and start the appropriate antibiotics. However, this made no difference in the length of stay in the ICU or hospital, and there was no significant difference in outcome.

Laboratory Tests for Less Common Organisms

If uncommon organisms -- such as legionella, mycoplasma, and chlamydia -- are strongly suspected, more advanced laboratory tests may be used:

Specialized techniques can detect antibodies to the organisms in blood samples, but these antibodies, such as those responding to mycoplasma or chlamydia, are not present early enough in the course of pneumonia to permit prompt diagnosis and treatment.
PCR is useful for identifying certain atypical strains, including mycoplasma and Chlamydiapneumoniae and, possibly, Haemophilus influenzae type b, but it is expensive.
A urine test can be used to diagnose some cases of Legionnaire disease.
Specialized tests called DNA probes are being developed to detect these organisms in respiratory secretions.

X-Rays. A chest x-ray is nearly always taken to confirm a diagnosis of pneumonia.

X-rays are a form of electromagnetic radiation (like light). They are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

A chest x-ray may reveal the following:

White areas in the lung called infiltrates, which indicate infection
Complications of pneumonia, including pleural effusions and abscesses

Other Imaging Tests. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be useful in some circumstances, especially when:

X-ray results are unclear
Patients do not respond to antibiotics
Complications occur
Patients have other serious health problems

Click the icon to see an image of a CT scan.

CT and MRI can help detect the presence of tissue damage, abscesses, and enlarged lymph nodes. They can also detect some tumors that block bronchial tubes. No imaging technique can determine the actual organism causing the infection. However, features on CT scan of patients with certain forms of pneumonia -- for example, that caused by Legionella pneumophila -- are usually different from features produced by other bacteria in the lungs.

Invasive diagnostic procedures may be required when:

Patients have life-threatening complications
Standard treatments have failed for no known reason
AIDS or other immune problems are present

Invasive procedures include:

Thoracentesis. If a doctor detects pleural effusion during the physical exam or on an imaging study, and suspects that empyema (pus) is present, a thoracentesis is performed.

Fluid in the pleura is withdrawn using a long thin needle inserted between the ribs.
The fluid is then sent to the lab for multiple tests.

Complications of this procedure are rare, but can include collapsed lung, bleeding, and introduction of infection.

Bronchoscopy. A bronchoscopy is done in the following way:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The physician inserts a fiber optic tube into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the physician to view the windpipe and major airways and look for pus, abnormal mucus, or other problems.
The doctor removes specimens for analysis and can also treat the patient by removing any foreign bodies or infected tissue encountered during the process.

Click the icon to see an image of bronchoscopy.

Bronchoalveolar lavage (BAL) may be done at the same time as bronchoscopy. This involves injecting high amounts of saline through the bronchoscope into the lung and then immediately sucking the fluid out. The fluid is then analyzed in the laboratory. Studies find BAL to be an effective method for detecting specific infection-causing organisms.

The procedure is usually very safe, but complications can occur. They include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Lung Biopsy. In very severe cases of pneumonia or when the diagnosis is unclear, particularly in patients with damaged immune systems, a lung biopsy may be required. A lung biopsy involves taking some tissue from the lungs and examining it under a microscope.

Lung Tap. This procedure typically uses a needle inserted between the ribs to draw fluid out of the lung for analysis. It is known by a number of names including lung aspiration, lung puncture, thoracic puncture, transthoracic needle aspiration, percutaneous needle aspiration, and needle aspiration. It is a very old procedure that is not done often any more, since it is invasive and poses a slight risk for collapsed lung. Some experts argue, however, that a lung tap is more accurate than other methods for identifying bacteria, and the risk it poses is slight. Given the increase in resistant bacteria, they believe its use should be reconsidered in young people.

Common Causes of Persistent Coughing. Over 30 million people seek medical help each year for persistent coughing, which is nearly always temporary and harmless when other symptoms, such as fever, are not present. The four most common causes of persistent coughing are asthma, postnasal drip, gastroesophageal reflux disease (GERD), and chronic bronchitis. Other obvious common causes of chronic cough include heavy smoking or the use of heart drugs known as ACE inhibitors.

Acute Bronchitis. Acute bronchitis is an infection in the passages that carry air from the throat to the lung. The infection causes a cough that produces phlegm. Acute bronchitis is almost always caused by a virus and usually clears up on its own within a few days. In some cases, acute bronchitis caused by a cold can last for several weeks.

Chronic Bronchitis. Chronic bronchitis causes shortness of breath and is often accompanied by infection, mucus production, and coughing, but it is a long-term and irreversible condition. The same microbes that cause pneumonia can cause chronic bronchitis, and symptoms of the two disorders are often similar. They include fatigue, coughing, fever, and production of sputum. There are significant differences between chronic bronchitis and pneumonia:

Patients with bronchitis are less likely to have wheezing, shortness of breath, chills, very high fevers, and other signs of severe illness.
Those with pneumonia usually cough up heavy sputum, which is also more likely to contain blood.
X-rays of patients with bronchitis do not show fluid or consolidation in the lung.

Asthma. In asthma, the cough is accompanied by wheezing and occurs mostly at night or during activity. Fever is rarely present (unless the patient also has an infection). Asthmatic symptoms from occupational causes can cause persistent coughing, which is usually worse during the work week. Tests -- the methacholine inhalation challenge and pulmonary function studies -- may be effective in diagnosing asthma.

Anthrax. Because of current terrorist concerns, it is important to differentiate between anthrax and community-acquired pneumonia. According to one study, people with inhalation anthrax are more likely to have rapid heart rate and less likely to have headache, nasal symptoms, and muscle aches than those with pneumonia. Blood tests with anthrax also show high hematocrit and low albumin and sodium levels. Certain chest x-ray findings also raise the likelihood of anthrax.

Other Disorders that Affect the Lung. Many conditions mimic pneumonia, particularly in hospitalized patients. They include:

Tuberculosis
Bronchial asthma
Bronchiectasis, an irreversible widening of the airways usually associated with birth defects, chronic sinus or bronchial infection, or blockage
Atelectasis, a collapse of lung tissue
Heart failure. If it affects the left side of the heart, fluid build-up can occur in the lungs and cause persistent cough, shortness of breath, and wheezing.
Severe allergic reactions, such as reactions to drugs
Acute respiratory distress syndrome (ARDS)
Lung cancer
Interstitial pulmonary fibrosis, a non-infectious inflammation of the lung marked by progressive damage and scarring

Ruling Out Causes in Children. Important causes of coughing in children at different ages include:

Asthma
Physical abnormalities in infants under 18 months
Sinusitis in children 18 months to 6 years
Psychologic causes in older children and adolescents

Acute bronchitis is an infection in the passages that carry air from the throat to the lung. In such cases, the airway tubes become inflamed and collect mucus, causing a cough that produces phlegm. In 95% of cases, acute bronchitis is caused by a virus and is spread from person to person through coughing. In some cases, mycoplasma or chlamydia may be responsible.

Symptoms. The cough in acute bronchitis usually lasts for 7 - 10 days. In about half of patients, coughing can last for up to 3 weeks, and 25% of patients continue to cough for more than one month.

Complications. Acute bronchitis is usually temporary. It can last for weeks to months if the airways are not healing properly. Pneumonia should be suspected if coughing is continuous and hacking, if blood appears in the sputum, and if the patient has a high fever and signs of severe illness. These signs include shortness of breath or extreme weakness and fatigue. [See In-Depth Report #94: Colds and the flu. ]

Of particular interest and some concern are the roles of mycoplasma and chlamydia, two of the infectious organisms that cause acute bronchitis. These agents are being investigated for their roles as possible causes of asthma. Chlamydia is also being investigated as a trigger for coronary artery disease.

Treatments.

Bronchodilators. For some patients with acute bronchitis, inhaled medications called bronchodilators may be effective. These drugs relax and open the airways and may relieve symptoms and reduce the duration of the coughing. The most common bronchodilator used for acute bronchitis is albuterol (Proventil, Ventolin). It is called salbutamol outside the US. The drug is a short-acting beta-2 agonist.
Antibiotics. Acute bronchitis almost never warrants antibiotics. (Coughing caused by pneumonia, however, does require antibiotics.) A 5-year study of more than 800 patients found that those with uncomplicated acute bronchitis all recovered within the same time period, regardless of whether or not they received antibiotics. For most patients, coughing lasted an average of 12 days. For a quarter of the patients, coughing lasted 17 days.

Treatment

Patients with pneumonia are generally treated with:

Antibiotics
Respiratory support with oxygen, if needed

Up to 10% of all adult hospitalizations in the U.S. are due to pneumonia. Studies indicate that many patients are hospitalized unnecessarily for pneumonia, and those patients could be released sooner. A number of strategies are being devised to determine when and which patients can be safely discharged. Studies have shown that low-risk patients with mild-to-moderate pneumonia do just as well when treated as outpatients and return to work and normal activities faster than those treated in the hospital.

One approach for determining whether a patient should be hospitalized categorizes patients into 5 classes depending on risk factors for severity, with class 1 being the least severe (having less than a 0.5% risk for death) and class 5 being the most severe (having at least a 10% risk of death).

Ruling out the Least Severe Cases. The procedure for determining the need for hospitalization starts by selecting patients in the lowest risk groups (classes 1 and 2) who can be discharged with outpatient care only. This can often be done with a simple physical examination, which can rule out a severe condition. Patients in low-risk categories have the following characteristics:

Under age 50 and not a patient in a nursing home
No other major illnesses
No serious symptoms such as altered mental state, breathing problems, bluish skin, very low blood pressure, or very high fever

Even these criteria, however, are flexible. Physicians must use their own judgment and take all factors into consideration. As examples, the following young people with signs of pneumonia should be hospitalized, even if they otherwise fit low-risk (class 1) categories:

Any infant under the age of one month
Young adults with alcoholism or severe psychiatric condition
Young adults or children with abnormal heart rhythm
Young adults or children who are vomiting heavily
Children who are dehydrated

Determining The Next Levels of Severity. If a patient is not in a class 1 category or does not appear to need hospitalization, the next step is to determine which of the other 4 higher classes the patient fits into. This step involves assigning points to other findings, including:

Laboratory test results
X-ray findings
Demographics (Is the patient male or female? Does the patient live in a nursing home?)

The points are added and the patients are scored:

Patients who score the lowest are assigned class 2 and 3. They can usually be treated at home or need only to be hospitalized for 24 hours for observation.
Patients with higher scores are placed in classes 4 and 5, and are hospitalized.

Home care may be possible even in severe cases when there is good support and available home nursing services. Often, caregivers can even be trained to administer intravenous antibiotics and chest therapy to patients at home.

Joint guidelines issued in 2007 by the Infectious Disease Society of America and the American Thoracic Society (ITSA/ATS) recommend that mild CAP in otherwise healthy patients be treated with oral macrolide antibiotics (azithromycin, clarithromycin, or erythromycin).

Many patients with heart disease, kidney disease, diabetes, or other comorbid conditions may still be treated as outpatients. However, they should be given a fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin) or a beta-lactam (preferably high-dose amoxicillin or amoxicillin-clavulanate), plus a macrolide, unless they live in an area with high S. pneumoniae resistance to macrolides.

The following tips are also suggested:

Drink plenty of liquids.
Do not suppress a cough. Coughing is an important reflex for clearing the lungs. Some doctors advise taking expectorants, such as guaifenesin (Breonesin, Glycotuss, Glytuss, Hytuss, Naldecon Senior EX, Robitussin) to loosen mucus. However, there is no proof that any of these products make much difference in outcome.
Mild pain can be treated with aspirin (in adults only), acetaminophen (Tylenol), or ibuprofen (Advil, Motrin).
For severe pain, codeine or other stronger pain reliever may be prescribed. It should be noted, however, that codeine and other narcotics suppress coughing, so they should be used with care in pneumonia. Such pain relievers often require monitoring.
A laboratory study reported that aromatic oils containing oregano, thyme, and rosewood destroyed S. pneumoniae. It is not known whether they have any effect on pneumonia in people.
Patients should practice chest therapy.

Treatment. If the pneumonia is severe enough for hospitalization, the standard treatment is intravenous administration of antibiotics for 5 - 8 days. In cases of uncomplicated pneumonia, many patients may require only 2 or 3 days of intravenous antibiotics followed by oral therapy. Antibiotics taken by mouth are prescribed when the patient has improved substantially or leaves the hospital.

ITSA/ATS guidelines recommend patients admitted to the hospital (but not the ICU) be treated with fluoroquinolones or a beta-lactam plus a macrolide (preferably cefotaxime or ceftriaxone and ampicillin).

Duration of Stay. Patients should remain in hospital until all their vital signs are stable. Most patients become stabilized in 3 days. Many experts use 7 variables to measure stability and to determine whether the patient can go home:

Temperature. (Some experts believe that patients can go home when their temperature drops to 101° F. Stricter criteria require that it be at or close to 98.6° F.)
Respiration rate. (Goal is a normal breathing rate, although expert opinion differs on the degree of normality required to be discharged.)
Heart rate. (Goal is 100 beats per minute or less.)
Blood pressure. (Goal is systolic blood pressure of 90 mmHg or greater.)
Oxygenation. (Goal is determined by the physician.)
The ability to eat. (Goal is regular appetite.)
Mental function. (Goal is normal.)

Patients or their families should discuss these criteria with their doctor. In a 2002 study, 42% of patients who had 2 or more signs of instability when they left the hospital were either readmitted or died within 30 days, compared with 10.5% of completely stabilized patients.

Chest therapy using incentive spirometry, rhythmic inhalation and coughing, and chest tapping are all important techniques to loosen the mucus and move it out of the lungs. It should be used both in the hospital and during recovery at home.

Incentive Spirometry. The patient uses an incentive spirometer at regular intervals to improve breathing and loosen sputum. The spirometer is a hand-held clear plastic device that includes a breathing tube and a container with a movable gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible.

Rhythmic Breathing and Coughing. During recovery, the patient performs rhythmic breathing and coughing every 4 hours:

Before starting the breathing exercise, the patient should tap lightly on the chest to loosen mucus within the lung. If available, a caregiver should also tap on the patient's back.
The patient inhales rhythmically and deeply 3 or 4 times.
The patient then coughs as deeply as possible with the goal of producing sputum.

Medications

Dozens of antibiotics are available for treating pneumonia, but selecting the best drug is sometimes difficult. Patients with pneumonia need an antibiotic that is effective against the organism causing the disease. When the organism is unknown, "empiric therapy" is given, meaning the doctor guesses which antibiotic is likely to work based on factors such as the patients' age, health, and severity of the illness.

In determining the appropriate antibiotic, the physician must first answer a number of questions:

How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics, while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
If the organism causing the pneumonia is not known, was the disorder community- or hospital-acquired? Different organisms are usually involved in each setting, and the physician can use this information to guess the most likely organism causing the pneumonia.
If the organism is known, is it typical or atypical? Community-acquired pneumonias, for example, are usually caused by the typical bacteria Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. These antibiotics do not affect atypical organisms, such as legionella, mycoplasma, or chlamydia. These organisms are generally treated with a macrolide or possibly a newer quinolone.
Does the patient have an impaired immune system? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.

Once an antibiotic has been chosen, there are still difficulties:

Individuals respond differently to the same antibiotic, depending on age, health, size, and other factors.
Patients can be allergic to certain antibiotics, thus requiring alternatives.
Patients may harbor strains of bacteria that are resistant to certain antibiotics.

For a more detailed discussion of the different types of antibiotics, see the "Antibiotic Classes" section below.

Many cases of community-acquired pneumonia are caused by S. pneumoniae, Gram-positive bacteria that usually respond to antibiotics known as beta-lactams (which include penicillin,) and to macrolides. However, resistant strains of S. pneumoniae are increasingly common. Most resistant strains respond to fluoroquinolines such as levofloxacin (Levaquin), gemifloxacin (Factive) or moxifloxacin (Avelox), or to ketolides (telithromycin).

In addition, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (erythromycin, clarithromycin, or azithromycin), to ketolides, or to newer fluoroquinolones.

Antibiotic treatment for CAP is determined by a number of factors, including the patient's history of antibiotic therapy, co-existing diseases (such as COPD, diabetes, and heart failure), and whether the patient is well enough to be treated at home or requires hospitalization or nursing home care. Treatment options can include a single drug, such as levofloxacin or doxycycline, or combination treatment, such as a macrolide administered with a beta-lactam.

Antibiotics taken by mouth are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP. Antibiotic therapy should be given for a minimum of 5 days -- longer if the patient still has a fever and more than one sign of clinical instability.

Gram-Positive Pneumonia. S. aureus is a common cause of hospital-acquired pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases, but certain specialized penicillins such as nafcillin may be effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.

Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from Gram-negative organisms such as Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycoside (entamicin or tobramycin). A pilot study of inhaled (aerosol) tobramycin showed the novel form of this aminoglycoside to be as effective against P. aeruginosa as its intravenous formulation. Multidrug therapy may be necessary, particularly for patients on mechanical ventilators, who are at very high risk for multiple dangerous organisms. A 2006 study of high-dose ampicillin-sulbactam for multidrug-resistant (MDR) Acinetobacter baumannii pneumonia showed the combination to be 66.7 - 77.8% successful in curing critically ill, ventilator-dependent patients of the bacterial infection.

Trimethoprim-sulfamethoxazole is the first choice for both preventing and treating P. Jiroveci (formerly called P. carinii) pneumonia in HIV-positive patients. Clindamycin-primaquine may be used in patients who do not respond to standard therapies.

A study of children with leukemia found atovaquone to be an excellent alternative for preventing P. jiroveci pneumonia in children who cannot tolerate trimethoprim-sulfamethoxazole, the current standard preventing therapy.

Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).

The most common side effect for nearly all antibiotics is stomach problems.
Antibiotics raise the risk of vaginal infections. Taking acidophilus supplements or eating yogurt with active acidophilius cultures may help restore healthy bacteria that offset the risk for such infections.
Overuse of antibiotics can cause infection with Clostridium difficile, a pathogen responsible for causing severe diarrhea, colitis, and abdominal pain. It can be fatal.
Allergic reactions can occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe -- even life-threatening -- anaphylactic shock.
Certain drugs, including some over-the-counter (OTC) medications, interact with antibiotics. Patients should inform the physician of all medications and OTC preparations they are taking and of any drug allergies they might have.

Beta-Lactams

Beta-lactam antibiotics share common chemical features. They include penicillins, cephalosporins, and some newer similar agents. They interfere with bacterial cell walls.

Penicillins. Penicillin was the first antibiotic. There are many forms to this still-important agent:

Natural penicillins include penicillin G (for intravenous use) and V (for oral use).
Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is inexpensive and, at one time, was highly effective against S. pneumoniae. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar and is an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects.
Amoxicillin-clavulanate (Augmentin) is an augmented penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become resistant to penicillin.
Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard drug was methicillin, but it is no longer used routinely due to very high rates of resistance in hospital-acquired pneumonias. Resistance in community-acquired Staphylococcus aureus is also increasing. Alternatives include vancomycin and linezolid.
Certain penicillins used against Pseudomonas aeruginosa include ticarcillin and piperacillin. Piperacillin is more effective that ticarcillin.

Many people have a history of an allergic reaction to penicillin, but research suggests that the allergy may not recur in a significant number of adults. Skin tests are available to help determine if those with a history of penicillin allergies could use these important antibiotics.

Cephalosporins. Most of these agents are not very effective against bacteria that have developed resistance to penicillin. They are classed according to their generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation includes cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid),
Third generation includes cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria. Cefditoren has also been shown to be 85% effective against Haemophilus influenzae and 90% effective against penicillin-resistant strains of S. pneumoniae.

Other Beta-Lactam Agents. Carbapenems include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations (imipenem/cilastatin [Primaxin]). These agents cover a wide spectrum of bacteria. They are now used for serious hospital-acquired infection and for bacteria that have become resistant to other beta-lactams. Imipenem has serious side effects when used alone, so it is given in combination with cilastatin to offset these adverse effects. The newer agents are less toxic, although they may not be as potent.

Sanfetrinem, a novel beta-lactam antibiotic known as a trinem is proving to be effective against S. pneumoniae,H. influenzae, and M. catarrhalis.

Ceftobiprole is an investigational beta-lactam in phase III clinical trials for methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and other Gram-negative pathogens. Other anti-MRSA beta-lactams in clinical development include CS-023/RO-4908463, a carbapenem, and ceftaroline, a cephalosporin (PPI-0903).

Fluoroquinolones

Fluoroquinolones (quinolones) interfere with the bacteria's genetic material to prevent reproduction.

Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa. It is not very effective for Gram-positive bacteria such as Streptococcus pneumoniae.
"Respiratory" quinolones are currently the most effective drugs available for a wide range of bacteria. Such drugs include levofloxacin (Levaquin), sparfloxacin (Zagam), and gemifloxacin (Factive). Some of the newer fluoroquinolones only need to be taken once a day.
The fourth generation quinolones Moxifloxacin (Avelox) and clinafloxacin, which is still under development, are proving to be effective against anaerobic bacteria.

S. pneumoniae -- strains resistant to the "respiratory" quinolones are uncommon in the U.S., but resistance is dramatically increasing.

Many quinolones cause side effects, including sensitivity to light and neurologic, psychiatric, and heart problems. Pregnant women should not take these agents. The drugs also enhance the potency of oral anti-clotting agents.

Macrolides, Azalides, and Ketolides

Macrolides and azalides also affect the genetics of bacteria. They include:

Erythromycin
Azithromycin (Zithromax, Zmax)
Clarithromycin (Biaxin)
Roxithromycin (Rulid)

These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. They are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. All but erythromycin are effective against H. influenzae. Macrolide-resistance rates doubled between 1995 and 1999 as more and more children were being treated with these antibiotics. Some research suggests these agents may reduce the risk of a first heart attack in some patients by reducing inflammation in the blood vessels.

Extended-release (ER) azithromycin (Zmax) is the first anti-pneumonia antibiotic that can be given in a single dose. It is effective against Gram-positive, Gram-negative, and atypical pathogens. Studies have shown the results to be equal (noninferior) to that acheived with 7 days of levofloxacin or clarithromycin ER in patients wtih CAP. A single-dose antibiotic decreases the likelihood that a patient will discontinue taking the antibiotic early, which rapidly contributes to the development of drug-resistant bacteria.

Ketolides. Ketolides are a new class of antibiotic drugs. They are derived from erythromycin and were developed to combat organisms that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, was approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP).

In February 2007, the FDA withdrew approval of Ketek for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is approved for treatment only of CAP. The drug carries a black box warning noting the potentially serious side effects, including liver failure, vision problems, loss of consciousness, and neuromuscular problems.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include skin reactions to sunlight, burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Some are available in inhaled forms or by applying a solution directly to mucous membranes, skin, or body cavities. They can have very serious side effects, including hearing damage, balance problems, and kidney damage.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against S. pneumoniae and S. aureus, but not against H. influenzae.

Glycopeptides

Glycopeptides (vancomycin, teicoplanin) are used for Staphylococcus aureus infections that have become resistant to standard antibiotics. The drug can be taken by mouth or given intravenously. The latest generation of glycopeptides, a derivative of vancomycin, is called telavancin. Currently in phase III studies of hospital-acquired pneumonia, it looks positive for the treatment of Gram-positive pneumonia.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin. It is particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people allergic to sulfa drugs. Allergic reactions can be very serious.

Oxazolidinone

Linezolid (Zyvox) is the first antibacterial drug in a new class of synthetic antibiotics called oxazolidinones. It has been shown to work against certain aerobic Gram-positive bacteria.

Other Agents

Inhaled polymyxin, a drug used in cystic fibrosis patients, is showing efficacy against pneumonia caused by multidrug-resistant Gram-negative bacteria, including pseudomonas and klebsiella.

Prevention of RSV. Two agents have been approved for protecting high-risk infants against RSV pneumonia:

Palivizumab (Synagis) is known as a monoclonal antibody, a genetically engineered antibody that targets the RSV virus. It is given by an injection into the muscle. Early studies of motavizumab, another monoclonal antibody in development, also show potent protection against RSV.
RSV immune globulin (RespiGam) is made up of antibodies to RSV that are obtained from the blood of healthy infants. RespiGam is given as a shot.

Treatment of RSV. Ribavirin is the first treatment approved for RSV pneumonia, although it has only modest benefits. The American Academy of Pediatrics recommends it for children at high risk for serious complications of RSV. In one study, a combination of ribavirin with RSV immune globulin was more effective than either drug used alone.

Drugs called bronchodilators, which open up the airways, are sometimes used to treat RSV infection. However, evidence is conflicting. One study involving albuterol, a common bronchodilator, found that epinephrine may be more effective.

Surgery

Although most patients with pneumonia do not require invasive therapy, it may be necessary in patients with abscesses, empyema, or certain other complications.

Thoracotomy is the standard surgery for pneumonia. It requires general anesthesia and an incision to open the chest and view the lungs. This procedure allows the surgeon to remove dead or damaged lung tissue. In severe cases, the entire lobe of the lung is removed. This is calledalobectomy. Remaining healthy lung tissue re-expands after surgery to make up for tissue that has been removed.

Chest tubes are used to drain infected pleural fluid. Tubes are not typically required for pneumonia or abscesses. The tubes are inserted after the patient is given a local anesthetic. They remain in place for 2 - 4 days, and are removed in one quick movement. This can be very distressing, although some patients experience no discomfort. Complications of chest tubes include infection, accidental injury of the lung, perforation of the diaphragm, and fluid build-up within the lung if the pleural fluid is removed too rapidly. Removing the chest tubes may cause the lung to collapse, requiring the reintroduction of a chest tube to inflate the lung.

Click the icon to see an illustrated series detailing chest tube insertion.

Prevention

The best way to prevent serious respiratory infections such as pneumonia is to avoid those who are sick (if possible), and to practice good hygiene. [See In-Depth Report #94: Colds and influenza.]

Colds and flu are spread primarily from infected persons who cough or sneeze. A very common method for transmitting a cold is by shaking hands. Hands should always be washed before eating and after going outside. Using ordinary soap is sufficient. Alcohol-based gels are also effective for every day use, and may even kill cold viruses. If extreme hygiene is required, alcohol-based rinses are needed.

Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV). Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Bacteria abound in hospitals and long-term care facilities, and are particularly virulent in areas with the sickest patients, such as intensive care units. Health care facilities are revising many of their practices and educating physicians, nurses, and therapists how to reduce the likelihood of transmitting bacteria.

A Swiss study found that coating endotracheal tubes with a solution of silver chloride and silver salts inhibited the growth of bacteria and reduced the transmission of Pseudomonas aeruginosa.
Another more widely adopted method involves the daily use of oral antibiotics to clean the mouths of patients on ventilators. This practice has been shown to lower the incidence of ventilator-associated pneumonia.

Foods Containing Lactobacilli (Good Bacteria). Friendly bacteria inside the intestines may help keep you healthy. Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. One such strain is acidophilus, which is used to make yogurt. According to a Finnish study, children attending day care who drank milk containing the strain lactobacilli GG reduced their risk of respiratory infections by 10 - 20%. More research is needed. (The strain used in the Finnish study was not the kind found in most commercial yogurt products.)

Vitamins. Studies are mixed when it comes to whether or not vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

A review of more than 134,000 Swiss patients found that use of cholesterol-lowering statin drugs was associated with a significantly lower risk of fatal pneumonia and a somewhat lower risk of less-severe pneumonia.

Breast-feeding. Some evidence suggests that women who breast-feed reduce the risk of respiratory infections in their children.

Low Stress and Active Social Life. Several studies have reported that socially active people with low stress have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc appears to have certain important effects on the immune system, and it may have a direct effect on viruses. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. However, research findings regarding the benefits of zinc have varied. (The differing results may be due to different zinc preparations.)

A nasal gel containomg zinc gluconate has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, patients who took the nasal gel within 14 - 48 hours of getting sick had less severe symptoms and felt better faster than those who took a placebo. The finding supports earlier studies reporting that Zicam shortened the duration of a cold by about two days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges (e.g., Fast-Dry, Galzin) may be more effective and have a better taste than other formulations, such as zinc gluconate (Cold-Eeze, Orazinc). On the other hand, a 2002 study reported that zinc gluconate reduced the duration of colds significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective. The reasons for these conflicting results are not clear.
A small 2001 study on a nasal spray preparation found no benefits. The spray preparation had less zinc than the nasal gel.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds.

Side Effects of Zinc. Side effects include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a physician if any of these symptoms occur.
In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or other elements.

It may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
Used in high doses for long periods of time, zinc can cause copper deficiencies.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for colds:

Echinacea. The herbal remedy echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. Studies have been mixed on its effectiveness. It is difficult to test, however, since it is available in different species (notably, E. purpurea and E. augustifolia ), and preparations vary from using extracts to dried forms of the root, the herb, or the whole plant. If echinacea is helpful at all, it may be more effective taken before symptoms develop than during the cold or flu. However, evidence suggests that it is not helpful at all. In addition, allergic reactions have been reported. People with autoimmune diseases or who have plant allergies should avoid taking it. There have also been some reports of a reaction called erythema nodosum associated with echinacea. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal cold and allergy medications may contain trace amounts of aristolochic acid, a chemical that is toxic to the kidneys and considered a carcinogen. Products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China having been laced with potent pharmaceuticals such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals.

Brands and Benefits. Zanamivir (Relenza) and oseltamivir (Tamiflu) are called neuraminidase inhibitors. They are newer agents that have been designed to block a key viral enzyme called neuraminidase, which helps viruses spread (replicate).

Both zanamivir and oseltamivir have the following benefits:

Neuraminidase inhibitors are effective for treating both A and B strains of influenza. M2 inhibitors, which prevent the virus from reproducing, are only effective against type A.
They shorten the duration of the flu by 1 - 3 days.
They may help reduce transmission of the virus, although evidence is needed to confirm these findings.
They may have a lower risk than M2 inhibitors for emerging viral strains that are resistant to their effects. In January 2006, the Centers for Disease Control and Prevention (CDC) released a Heath Alert (the highest level of importance) regarding the use of M2 inhibitors (amantadine and rimantadine) for the prevention or treatment of flu. Due to significant increase in influenza A resistance to this class of antiviral medication, the CDC recommended against its use for the remainder of the 2005 - 2006 flu season.
Oseltamivir has been shown to prevent influenza from progressing to pneumonia in 50% of children who were given the drug within 1 day of being diagnosed with the flu.
They have fewer serious side effects than the M2 inhibitors.
Both have some benefits for preventing influenza. Only oseltamivir has been approved for this purpose, however, and only in people over age 13.

Limitations and Side Effects. Although they have many advantages compared to the M2 inhibitors, they are much more expensive. They also need to be taken within 2 days of symptoms to be effective. There are also some differences between the two agents that could be significant for some individuals:

Zanamivir (Relenza) is administered as a nasal spray or inhaler. People with asthma or other lung disorders may experience airway spasms and should use this drug with caution. Side effects are minor in most patients. Of concern, however, was a 2001 British study, which found that a majority of elderly patients were not able to properly use the zanamivir (Relenza) inhaler device, rendering the medicine virtually ineffective. The study was small, however, and other reports suggest that zanamivir is sill effective in this older group.
Oseltamivir comes in capsule and liquid form. Side effects are also minor, but about 10 - 15% of patients experience nausea and vomiting. Patients with kidney dysfunction should take lower doses.

To date both M2 inhibitors and oseltamivir have been approved for prevention of influenza.

M2 inhibitors. Amantadine and rimantadine protect against the influenza A infection itself in about half of individuals. Rimantadine is preferred for prevention during outbreaks of influenza A because it has fewer adverse side effects. Unfortunately, a majority of influenza A strains are now resistant to both M2 inhibitors.
Neuraminidase Inhibitors. Both zanamivir (Relenza) and oseltamivir (Tamiflu) help prevent both influenza A and B. Only oseltamivir has been approved for this purpose, however, and only in people over 13. Both appear to be very effective in preventing influenza in people who have been exposed to family members with the flu.

Antiviral drugs are not a substitute for vaccines, but they are extremely important add-on therapy for people in certain high-risk groups. They may also be used:

In combination with the flu vaccine during seasons where there is a poor match between the virus and vaccine.
In high-risk individuals who are vaccinated after the flu season has started. In such cases, it takes about 2 weeks (or longer in children) for the vaccine to take effect. The anti-viral drugs offer protection during that period.
As supplementary protection for vaccinated people in high-risk groups, such as the elderly or people with compromised immune systems.
In people who cannot have vaccinations for whatever reason.
For people who provide care for high-risk individuals.
For high-risk individuals who cannot or will not be vaccinated.

Viral Influenza Vaccines (Flu Shot)

Description of Vaccines. Vaccines against the flu (or a "flu shot") use inactivated (not live) viruses. They are designed to provoke the immune system to attack antigens contained on the surface of the virus. Antigens are foreign molecules that the immune system specifically recognizes and targets for attack.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy them.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines must be redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they too vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children who have not developed immunity to the virus will experience severe flu if they are exposed to type B.

A live but weakened intranasal vaccine (FluMist) for healthy people aged 5 - 49 years is approved by the FDA. It is known as a live, attenuated, trivalent, intranasal influenza vaccine (LAIV). The vaccine is engineered to grow only in the cooler temperatures of the nasal passages, not in the warmer lungs and lower airways. It boosts the specific immune factors in the mucous membranes of the nose that fight off the actual viral infections. FluMist is a nasal spray. In one study it protected up to 93% of children against the flu.

Timing and Effectiveness of the Vaccine. Ideally, people should get a flu shot every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the influenza virus usually develop within 2 weeks of vaccination. Immunity peaks within 4 - 6 weeks, then gradually wears off. That is why most people should get a flu shot every year.

In healthy adults, the flu shot reduces the chance of illness by 70 - 90%. The current flu vaccines may be slightly less effective in the elderly and those with certain chronic diseases. Even in people with weak immune systems, however, the vaccine usually protects against serious flu complications, particularly pneumonia. In fact, among the elderly, interesting studies are now suggesting that influenza vaccination may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated.The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children 6 - 23 months of age. The flu shot is not approved for children less than 6 months of age.

In addition, any child over the age of 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell anemia, or immune deficiencies) should also receive a flu shot. Children who are receiving long-term aspirin therapy should also be immunized against the flu, because they are at higher risk for Reye syndrome, a life-threatening disease, if they get the flu.

Children with Asthma. Recent and major studies have found that the flu shot is safe for children with asthma. It is very important for these patients to reduce their risk for respiratory diseases. Unfortunately, 90% of asthma patients remain unvaccinated.

All adults age 65 and older. Older adults who receive a flu shot have lower hospitalization rates than those who don't. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from influenza. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. While there have been concerns about the safety of the vaccinations in certain high-risk patients, such as those with HIV or asthma, studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from influenza outweighs any potential adverse effects from the vaccines.
Adults ages 50 - 64 with chronic medical conditions. The US Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 be vaccinated, although this is not recommendation of the CDC.

Other adults who should consider influenza vaccinations include:

People at risk for flu complications who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for flu complications who will be in their second or third trimester during flu season. (Vaccinations should usually be given after the first trimester.)
Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.

Side Effects. Possible side effects include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two-thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 - 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include cough, wheezing, tightness in the chest, and sore throat. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last up to 2 days. These symptoms are not the flu itself, but are an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Isolated cases of Guillain-Barre syndrome occurred in about one of every 100,000 people vaccinated with the swine-flu vaccine in 1976, but it has not been a problem with subsequent vaccines. Guillain-Barre disease can cause paralysis.

The pneumococcal vaccine protects against S. pneumoniae bacteria, the most common cause of respiratory infections. There are two effective vaccines available: One called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults, and another called 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

Click the icon to see an image of pneumococcal pneumonia.

Pneumococcal Vaccine in Young Children. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Evidence suggests that this vaccination, plus the vaccination against Haemophilus influenzae (an important cause of meningitis), has led to 25,000 fewer cases of serious bacterial infections each year.

The pneumococcal vaccine is now recommended by many experts for the following groups:

All children up to age 2. The pneumococcal vaccine (Prevnar or PCV7) has now been added to the Recommended Childhood Immunization Schedule. The pneumococcal vaccine (Prevnar or PCV7) is very effective in children. Studies are suggesting that it prevents common ear infections as well as serious infections such as pneumonia. In one study, a similar vaccine under investigation protected not only children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as those with sickle-cell disease, immune deficiencies, or chronic medical conditions.
Other children aged 2 - 5 who are higher risk for serious pneumococcal infections should be considered for vaccinations. They include African-Americans, Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year. (In one study, the vaccine reduced the number of ear infections episodes by 6%.)

The recommended schedule of immunization for Prevnar (PCV7) is four doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have three doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to help reduce the rate of pneumonia in young adults, although not to the degree that it protects young children. Its benefits for the elderly, other than protection against bloodstream infection, are unclear. Still, pneumonia is declining among adults, which may be due to fewer infections transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over age 65. (Anyone vaccinated more than 5 years previously should be revaccinated.) The vaccination is protective against pneumococcal bacteremia (blood infection) in this group, but it does not appear to protect against community-acquired pneumonia itself.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease, chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies, such as HIV, or those undergoing treatments to suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies suggest the vaccine may not be as effective in these patients as it is in those with healthy immune systems. Nevertheless they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics (especially those with cirrhosis).
People living in long-term care facilities.
Alaska Natives or Native Americans who may be at increased risk for pneumonia.

Because the vaccine is inactive, it is safe for pregnant women and people with immune deficiencies. In fact, when the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although it may wear off faster in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

Side Effects. Pain and redness at the injection site, fever, and joint aches are possible with the pneumococcal vaccine. Children are more likely to have fever side effects within 48 hours if they receive other vaccines at the same time. They are also likely to have fewer side effects after the second dose. In rare cases, such local reactions can be severe. Even if a person is mistakenly re-vaccinated before the effects of the first vaccination have worn off, the risk for severe side effects is very low. Allergic reactions are very rare.

Resources

www.lungusa.org -- American Lung Association
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov -- Centers for Disease Control and Prevention

References

Alperovich M, Neuman MI, Willett WC, Curhan GC. Fatty acid intake and the risk of community-acquired pneumonia in U.S. women. Nutrition. 2007;23(3):196-202.

Barr CE, Schulman K, Iacuzio D, Bradley JS. Effect of oseltamivir on the risk of pneumonia and use of health care services in chidlren with clinically diagnosed influenza. Curr Med Res Opin. 2007;23(3):523-531.

Bast DJ, Dresser L, Duncan CL, et al. Short-course therapy of gemifloxacin effective against against pneumococcal pneumonia in mice. Chemother. 2006;18(6):634-640.

Betrosian AP, Franzeskaki AF, Xanthaki A, Georgiadis G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multi-drug resistant Acetinobacter baumannii. Scand J Infect Dis. 2007;39:38043.

Bush K, Heep M, Macielag MJ, Noel GJ. Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demontrate clinical efficacy. Expert Opin Investig Drugs. 2007;16(4):419-429.

Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med.2006;355(25):2619-2630.

Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007. Mar 26; [Epub ahead of print].

Christ-Crain M, Soltz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia. Am J Respir Crit Care Med. 2006;174:84-93.

Digiandomenico A, Rao J, Harcher K, et al. Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc Nat Acad SciUSA. 2007;104(11):4624-4629.

Gastmeier P, Sohr D, Geffers C, Behnke M, Ruden H. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the krankenhaus infektions surveillance system. Infect Control Hosp Epidemiol. 2007;28(4):466-472.

Granizo JJ, Gimenez MJ, Barbarean J, Coronel P, Gimeno M, Aguilar L. The efficacy of cediftoren pivoxil in the treatment of lower respiratory tract infections, with a focus on the per-pathogen bacteriologic response in infections caused by Streptococcus pneumoniae and Haemophilus influenzae: a pooled analysis of seven clinical trials. Clin Ther. 2006;28(12):2061-2069.

Guarner J, Packard MM, Nolte KB, et al. Usefulness of immunohistochemical diagnosis of Streptococcus pneumoniae in formalin-fixed, paraffin-embedded specimens compared with culture and Gram stain techniques. Am J Clin Pathol. 2007;127(4):612-618.

Hallal A, Cohn SM, Namias N, et al. Aerosol tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt ). 2007;8(1):73-82.

Labarere J, Stone RA, Obrosky DS, et al. Comparisons of outcomes for low-risk outpatients and inpatients with pneumonia: a propensity-adjusted analysis. Chest. 2007;131(2):480-488.

Laohavaleeson S, Kuti JL, Nicolau DP. Telavancin, a novel lipoglycopeptide for serious Gram-positive infections. Expert Opin Investig Drugs. 2007;16(3):347-357.

Lawrence SJ, Puzniak LA, Shadel BN, Gillespie KN, Kollef MH, Mundy LM. Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure. Infect Control Hosp Epidemiol. 2007;28(2):123-130.

Lee TA, Weaver FM, Weiss KB. Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. J Gen Intern Med. 2007;22(1):62-67.

Lodise TP Jr, Pypstra R, Kahn JB. Probability of target attainment for ceftobiprole as derived from a population pharmacokinetic analysis of 150 subjects. Antimicrob Agents Chemother. 2007. Mar 26; [Epub ahead of print].

Madden RM, Pui CH, Hughes WT, Flynn PM, Leung W. Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. Cancer. 2007. Mar 7; [Epub ahead of print].

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72.

Mesaros N, Nordmann P, Plesiat P, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect. 2007. Jan 31; [Epub ahead of print].

Muller B, Harbath S, Stolz D, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.

Nair V, Niederman MS, Masani N, Fishbane S. Hyponatremia in community-acquired pneumonia. Am J Nephrol. 2007;29(2):184-190.

Nisar N, Guleria R, Kuman S, Chand Chawla T, Ranjan Biswas N. Mycoplasma pneumoniae and its role in asthma. Postgrad Med J. 2007;83:100-104.

Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, efficacy, safety and effectiveness of penumococcal conjugate vaccines (1998-2006). Vaccine. 2007;25(12):2194-2212.

Pedro-Botet ML, Sopena N, Garcia-Cruz A, et al. Streptococcus pneumoniae and Legionella pneumophila pneumonia in HIV-infected patients. Scand J Infect Dis. 2007;39(2):122-128.

Pereira GH, Muller PR, Levin AS. Salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli with inhaled polymyxin B. Diagn Microbiol Infect Dis. 2007. Mar 8; [Epub ahead of print].

Ramstedt M, Houriet R, Mossialos D, Haas D, Mathieu HJ. Wet chemical silver treatment of endotracheal tubes to produce antibacterial surfaces. J Biomed Mater Res B Appl Biomater. 2007. Mar 23; [Epub ahead of print].

Sakai F, Tokuda H, Goto H, et al. Computed tomographic features of Legionella pneumophila pneumonia in 28 cases. Comput Assist Tomogr. 2007;31(1):125-131.

Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR. Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy. 2007;27(3):325-332.

Spaude KA, Abrutyn E, Kirchner C, Kim A, Daley J, Fisman DN. Influenza vaccination and risk of mortality among adults hospitalized with community-acquired pneumonia. Arch Intern Med 2007;167(1):53-59.

Swainston HT, Keam SJ. Azithromycin extended-release: a review of its use in acute bacterial sinusitis and community-acquired pneumonia in the U.S. Drugs. 2007;65(5):773-792.

Thorpe C, Edwards L, Snelgrove R, et al. Discovery of a vaccine antigen that protects mice from Chlamydia pneumoniae infection. Vaccine. 2007;25(1):2252-2260.

Tolentino-Delos Reyes AF, Ruppert SD, Shiao SY. Evidence-based practice: use of the ventilator bundle to prevent ventilator-associated pneumonia. Am J Crit Care. 2007;16(1):20-27.

Verhamme KM, DeCoster W, DeRoo L, et al. Pathogens in early-onset and late-onset intensive care unit-acquired pneumonia. Infect Control Hosp Epidemiol. 2007;28(4):389-397.

Viejo Banuelos JL. Respiratory manifestations of avian influenza. Arch Bronchoneumol. 2006;42(Suppl 2):12-18.

Walter U, Knoblich R, Steinhagen C, Donat M, Benecke R, Kloth A. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. J Neurol. 2007. Mar 14; [Epub ahead of print].

Wu H, Pfarr DS, Johnson S, et al. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007. Feb 20; [Epub ahead of print].

Review Date:
4/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Review provided by VeriMed Health Network.

A.D.A.M. Copyright

adam.com

Non-Hodgkin's lymphoma

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Staging and Treatment Guide...
Chemotherapy
Biologic Therapy (Immunothe...
Radiation
Transplantation
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, which include epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.

In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels have stronger warnings and updated dosing-related safety information.

The FDA advises that for treating anemia associated with chemotherapy, dosing should increase hemoglobin levels to no more than 12 g/dL. Treatment with these drugs should stop as soon as the chemotherapy course is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists. The FDA is currently reviewing additional data concerning the safety of these drugs.

Positron Emission Tomography (PET) Scans and Lymphoma

PET scans are used to help diagnose and stage lymphoma, and they may also be helpful in assessing treatment outcomes for some types of lymphoma. In 2007, an international team of cancer specialists drew up new guidelines for evaluating how well lymphoma responds to treatment in clinical trials. The guidelines now recommend that PET scans be used to help determine if a patient has achieved remission.

Introduction

Lymphomas are malignancies of the lymph system that are generally subdivided into two groups, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Hodgkin's disease accounts for about 15% of all lymphomas. [For more information, see In-Depth Report #83: Hodgkin's disease.]

Non-Hodgkin's lymphomas is a term for malignancies that range from a very slow disease to an extremely aggressive but curable condition. They have certain features in common.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if they are enlarged include the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

Lymphomas, such as non-Hodgkin's lymphomas and Hodgkin's disease, represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, important cells involved in defending the body against infectious organisms. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation, and its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.

Lymphocytes. The lymphatic system is involved in the production and transportation of lymphocytes, white blood cells that are a primary component of the immune system. Among other vital functions, certain lymphocytes are responsible for producing antibodies, factors that can target and attack specific foreign proteins (antigens). To understand the lymphatic system, it is helpful to track part of the life cycle of these lymphocytes:

Lymphocytes develop in the bone marrow or thymus gland and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
T cells also start out in the bone marrow but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it atrophies (shrinks).
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Some lymphocytes, along with fluid, proteins, and other substances, migrate out of the capillaries into the surrounding tissues. A proportion of these lymphocytes and other substances then enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes and lead to larger lymphatic ducts and branches until they drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.

Lymph Nodes. In the lymph node, lymphocytes receive their initial exposure to foreign substances (antigens), such as bacteria or other microorganisms, activating the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are in clusters located throughout the system. Important node clusters are found in the neck, lower arm, armpit, and groin.

Other Structures in the Lymphatic System. The tonsils and adenoids are secondary organs composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.

Click the icon to see an animation about lymph nodes.

Click the icon to see an image of lymph nodes in the head and neck.

Click the icon to see an image of the immune system structures.

Non-Hodgkin's lymphomas occur most often in lymph nodes in the chest, neck, abdomen, tonsils, and the skin. NHLs may also develop in sites other than lymph nodes such as the digestive tract, central nervous system, and around the tonsils.

About 85% of non-Hodgkin's lymphomas (NHLs) arise in B cells; the rest occur in T cells. Activation of a gene called BCL-2 is believed to be partly responsible for many B-cell lymphomas. This defect prevents apoptosis (a natural process whereby cells self-destruct) in the lymphoma cells.

There are more than 20 distinct types of non-Hodgkin's lymphomas. Most first arise in the lymph nodes, but about 20 - 30% of cases are now found outside the nodes, most often in the stomach, small intestine, skin, and brain.

Even experts disagree about the exact groupings. Lymphomas are categorized in a number of ways.

Classification by Cell Type, Appearance, and Genetic Make-up: The REAL System. Different classification systems for lymphoma have been proposed. The system used in this report is called REAL (Revised European-American Lymphoma Classification). It classifies all lymphomas by appearance, cell type, and genetic make-up:

Non-Hodgkin's lymphomas are first grouped as B cell or T cell.
Next, they are categorized by whether the B-cell and T-cell lymphomas were derived from immature (precursor) cells or mature (peripheral) cells.
The peripheral B and T cells are then classified by their appearance, genetic make-up, and specific chemical "markers," which further identify them.

T-cell lymphomas, Hodgkin's disease, and certain leukemias and aggressive lymphomas are covered in the REAL classification but are not discussed in any depth in this report.

Groups by Slow or Fast Growth. Each non-Hodgkin's lymphoma is further defined by its grade, or how aggressive it is:

Indolent (slow-growing), also called low-grade
Aggressive (fast-growing), also called intermediate- or high-grade

According to one report, half of new cases are now intermediate-grade lymphomas. Low-grade makes up 30%, while high-grade makes up 10% of all lymphomas.

Groups by Properties. Lymphomas are also grouped by certain properties:

Size (large versus small)
Shape (round versus irregular)
Whether they are or resemble blood plasma cells
Whether they are follicular (organized in round clusters) or diffuse (spread evenly throughout the lymph node)

Staging. Staging the disease is the next important step in classifying lymphomas. The stage (I - IV) of an NHL is determined by the number of tumors and whether they are still localized or have spread beyond the lymph node. In general, the higher the stage, the poorer the outcome, but other factors are important for a precise prognosis.

Indolent (Slow-Growing) Lymphomas (also Called Low-Grade Lymphomas)

Follicular lymphomas (FLs). Follicular small cleaved cell lymphoma (grade I) and follicular mixed small and large cell lymphoma (grade II). FLs account for 70% of indolent tumors and 20% of all NHLs in industrialized countries. It is very rare in developing countries and in Asia.

Lymphoplasmacytoid/Waldenstrom's macroglobulinemia. Often found in bone marrow, lymph nodes, and spleen. Can cause blood to become viscous and "sticky."

Marginal zone lymphomas (MZL). MZLs often occur as a result of a pre-existing disorder such as hepatitis C, bacterial infection in the stomach (H. pylori ), or an autoimmune disorder (Sjögren syndrome in the salivary glands or Hashimoto's thyroiditis in the thyroid gland). They may be classified as:

Monocytoid B-cell lymphoma, which involves only lymph nodes
Splenic marginal zone lymphoma, which affects the spleen, blood, and bone marrow
Mucosa-associated lymphoid tissue (MALT) lymphoma, which usually involves the gastrointestinal tract, thyroid, lung, breast, or skin

There is some controversy over whether MALT is a variation of MZL or a completely separate type of lymphoma that is more suitably classified as a separate low-grade lymphoma. At this time, it is classified as an MZL.

Aggressive Lymphomas (also Called Intermediate- and High-Grade Lymphomas)

Diffuse large-cell lymphomas (DL). DLs are the most common NHLs, accounting for about 40% of all cases. Subtypes include the following:

Primary mediastinal large B-cell lymphoma
Follicular large cell lymphoma
Anaplastic large cell lymphoma
T-cell lymphomas (not covered in this report)

In about 40% of cases, these DL lymphomas appear in areas outside lymph nodes, including digestive tract, skin, bone, thyroid, and testes.

Burkitt's lymphoma/diffuse, small noncleaved cell lymphoma. This is the most common childhood NHL. In African children, it often involves facial bones and is associated with Epstein-Barr infection.

Mantle cell lymphoma. Mantle cell lymphomas are found in lymph nodes, the spleen, bone marrow, blood, and sometimes the gastrointestinal system (lymphomatous polyposis). This lymphoma is similar to indolent lymphomas at the time of diagnosis, but it is more aggressive.

Lymphoblastic lymphoma. This lymphoma often occurs in young people. It is associated with a large mediastinal mass (occurring in chest cavity between the lungs) and carries a high risk for spreading to bone marrow and central nervous system.

Risk Factors

About 63,000 Americans were diagnosed with non-Hodgkin's lymphomas in 2007, and nearly 19,000 people died of the disease. For the past 25 years, the incidence in NHL has increased continuously. Most of this increase has occured in people over age 65.

Part of the reason for the dramatic rise was AIDS, which increases the risk for high-grade lymphomas. However, even after eliminating changes in diagnosing NHLs and known causes (such as AIDS), the incidence over the past 40 years is 40% higher. The number of cases in which lymphomas first occur outside the lymph nodes has also increased compared to those limited to the nodes. (This observed increase, however, may in large part be due to different methods of diagnosing lymphomas).

The cancer can develop in people at all ages, including children, although it is most common in those ages of 45 - 60. In general, the incidence of NHL is 50% higher in men than in women. This higher rate has been observed in many countries. Nevertheless, recent reports suggest that the rate is leveling off or even declining in men, but is increasing in women, particularly African-American women. Overall, the risk is slightly higher in Caucasians than in African-Americans.

The risks for NHL among men versus women and among African-Americans versus Caucasians may vary by lymphoma subtype. For example, follicular lymphomas were significantly higher in Caucasians than in African-Americans, and there was little gender difference. High-grade lymphomas were the most rapidly increasing type, particularly among men, with follicular lymphomas increasing most rapidly in African-American men.

Other studies have also reported ethnic differences by specific lymphoma subtypes. For example, follicular lymphomas constitute 20% of all NHLs in Western nations but are very uncommon in Asia and in developing countries.

The brother or sister of a person with the disease has more than twice the risk of developing NHL than the general population. Some cases of NHL in such cases are due to inherited disorders of the immune system. Studies suggest, however, that such family clusters are more likely to be due to environmental conditions that trigger the genetic factors.

Because of the rapid rise in NHL, investigators are looking for lifestyle factor that may contribute to this increase. No real association between lymphomas and body weight or shape or amounts of exercise has been found.

A number of reports suggest an influence of diet in the development of non-Hodgkin's involvements. However, for the most part a strong association remains speculative. Some of the possible dietary risk factors include:

A number of studies have observed an association between an increased risk for non-Hodgkin's lymphomas and high consumption of red meat (beef, pork, and lamb).
A higher risk for lymphoma has also been suggested for trans fatty acids (hydrogenated polyunsaturated fats, which are contained in hard margarines and commercial baked goods and fast foods). There appears to be no higher risk with natural polyunsaturated fats (found in most vegetable and fish oils).
Fish may be protective.
Some evidence suggests that milk may also be protective.
One major study observed a reduction in risk with high intake of vegetables. Another found no protection from vegetables, but did with diets rich in fruit.
Vitamin supplements have no effect on NHL.

Despite these kinds of reports, the influence of diet on the development of non-Hodgkin's lymphomas remains speculative.

Alcohol Use. Studies on alcohol have been mixed, with some showing a higher risk, some a lower risk, and some no difference at all.

Smoking. There is no evidence that smoking increases the risk for NHL itself, although it has been linked with high-grade and follicular NHLs in people with lymphomas.

Viruses or other microorganisms also play a role in some lymphomas. A number are being investigated:

Epstein-Barr virus, the cause of mononucleosis, is highly associated with Burkitt's disease and NHLs associated with immunodeficiency diseases. It is also a risk factor for Hodgkin's disease
Adult T-cell leukemia-lymphoma, which appears to be caused by a virus known as HTLV-I, has been found in southwestern Japan, the Caribbean, and the southeastern United States.
People who have stomach inflammation due to Helicobacter pylori or H. heilmannii bacteria are at increased risk for mucosa-associated lymphoid tissue lymphomas (MALT). (The use of antibiotics to get rid of the bacteria may cause remission in some patients who have an early stage form of lymphoma in an early stage.)
Human herpes virus 8 has been associated with NHL.
Borrelia burgdorferi, the bacteria that causes Lyme disease, has been associated with primary B-cell lymphoma.
Heavy antibiotic use during adulthood may increase risk. A 2005 study found that adults who used antibiotics more than 10 times had 1.8 times the risk of developing NHL than nonusers. However, researchers were not certain if antibiotics themselves, or the underlying infections they treated, were responsible for the increased risk.

Click the icon to see an image of Lyme disease.

Studies are reporting a higher prevalence of viral hepatitis C and B in patients with lymphomas, although such viruses do not appear to play a major role in triggering lymphoma.

Patients with diseases or conditions that affect the immune system may be at higher risk for lymphomas:

HIV-positive patients and those with full-blown AIDS are at higher risk for NHL, and the disease is more likely to be widespread in these patients than in those without the immune disease. Most AIDS-related NHLs are high-grade lymphomas. Burkitt's lymphoma is often seen in patients with AIDS. Although these patients have had a very poor prognosis, advances in antiviral therapy for HIV now allow better management of NHL with some success in achieving favorable outcomes. Part of the dramatic increase in NHL incidence over the past decades can be traced to AIDS.
Patients with a history of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, Hashimoto's thyroiditis, Crohn's disease, and Sjögren syndrome, are at an increased risk for certain NHLs, such as marginal zone lymphomas.
People who have organ transplants are at higher risk for NHL, probably due to multiple factors, including the drugs used to suppress the immune system and the transplanted organ itself.
Patients who have had high-dose chemotherapy with stem-cell transplantation are at higher risk.
Other immunodeficiency syndromes that put people at risk for NHL include Chediak-Higashi syndrome, ataxia-telangiectasia, B-cell lymphoproliferative syndrome, Bruton agammaglobulinemia, common variable immunodeficiency, and Wiskott-Aldrich syndrome.

Note on Allergies: There appears to be no association between NHL and allergies, overactive responses of the immune system. Allergies are the most common immune disorder.

Overexposure to a number of industrial and agricultural chemicals has been frequently linked to an increased risk for lymphomas. The data, however, are not consistent.

Organochlorines are chemicals produced when solid waste is burned. These by-product chemicals include dioxin, polychlorinated biphenyls (PCBs), and furans. Many studies have indicated that exposure to these chemicals increases the risk of developing NHL.
A number of studies have found an association between NHL and certain pesticides and herbicides, although more research is needed to confirm any definitive risk.
White spirits, thinners, phenoxy herbicides, wood preservative, aviation gasoline, plastic, and rubber chemicals have been associated with a higher risk for lymphomas. Specifically, in one study, painters and lumberjacks had a higher risk for NHL, while office and house workers had a lower risk.
Some studies have found an association with long duration and early use of permanent dark hair dyes. There is no consistent evidence, however, that hair dye increases the risk for lymphomas.

Symptoms

The most common first sign of lymphomas is painless enlargement of one or more lymph node, usually in the neck, armpits, or groin. Patients should see their doctors if these symptoms do not go away within 2 - 3 weeks.

The most common lumps or swellings in the neck are enlarged lymph nodes. They can be caused by bacterial or viral infections, cancer, and other rare causes.

Lymphomas sometimes cause systemic symptoms -- symptoms that affect the whole body, rather than a specific location. Some systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.

B systemic symptoms include:

Drenching night sweats and weight loss
Fever (may occur sporadically and only at night)

Other systemic symptoms include:

Itching all over the body caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of NHL, this is due to abnormalities in the immune system. Although this is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
In late stages, some patients develop a skin rash.
Tumor masses in the chest can cause coughing or breathlessness.
Lymphomas in the stomach can cause nausea and vomiting.

Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as "swollen glands"). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.

Infections. In the great majority of cases, swollen glands are caused by an infection:

Enlarged lymph nodes in the neck are much more likely to be a sign of strep or other throat infection than NHL.
Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
Travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
Other infections that cause swollen glands include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.

Hodgkin's Disease. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin's disease under some circumstances. [For more information, see In-Depth Report #83: Hodgkin's disease.]


Characteristics	Hodgkin's Disease	Non-Hodgkin's Lymphomas
Age and Prevalence	Average age is 28 with two age peaks, the major one occuring between 15 - 24, anda lesser peak after age 55. It is less common than NHL.	Average age is about 67. It is more common than HD.
Location	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases.	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.
Symptoms	More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis.	Less likely to have systemic symptoms (27%) at the time of diagnosis.
Progression	Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.	More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread.

Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.

Very serious causes of enlarged lymph nodes include disorders of the lymph system, such as Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #83: Hodgkin's disease or Report #86: Acute lymphocytic leukemia.]

Exposure to Medications. Exposure to certain medications such as phenytoin (Dilantin) may cause enlarged nodes. Other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash, which may resemble Hodgkin's disease.

Diagnosis

The doctor will first ask questions about the patient's medical history and perform a physical examination to detect any node enlargements. If these steps point to lymphoma, additional tests will be done to rule out other diseases or to confirm the diagnosis and extent of the lymphoma.

It is sometimes reasonable to wait a little while for the swelling and symptoms to go away before deciding that additional testing is necessary. In some cases, lymph node swelling may be due to a temporary infection. However, some lymphomas cause off and on lymph node swelling. This is particularly true with small cleaved cell lymphoma (the most common NHL). Lymph nodes should be checked periodically for any return of swelling.

The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node sometimes indicates certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma. Soft nodes suggest infection or inflammatory conditions.

Blood tests help rule out infection and other diseases. Such tests include those blood counts and blood chemistries for kidney and liver function, uric acid, calcium, and phosphate levels. In a patient already diagnosed with lymphoma, blood tests that measure the enzyme lactate dehydrogenase are important in determining the prognosis. High levels indicate bulkier tumors. The presence of anemia may indicate specific NHLs, such as diffuse, small lymphocytic lymphoma.

A biopsy is the most important test for diagnosing lymphomas and can be used to tell the difference between non-Hodgkin's and Hodgkin's disease. A biopsy has risks and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually go away on their own if a temporary infection is causing the swelling. (However, some lymphomas may go away and appear to be benign, only to reappear at a later time.)

The Procedure. The doctor removes the node and checks the surrounding areas. The tissue in the node is then examined under a microscope for signs of infection and abnormalities indicating cancer or other conditions.

Results. Even if biopsies do not show any problems, disease may still be present in some cases. The doctor should continue to observe the patient until swelling or other signs of disease are gone. Biopsied tissue samples should be frozen in case special tests are later required. Such tests may include detection of particular antibodies, genetic and immune factors, and certain markers (substances that may indicate disease) located on the surface of the cells. If lymphoma has been diagnosed, the tissue will be examined for its histology, the cellular structures that will determine the lymphoma type.

Bone marrow aspirate and biopsy are routinely performed to determine whether the disease has spread. With bone marrow aspirate, bone marrow cells are sucked out through a special needle. A biopsy may be performed before or after the aspiration. In this procedure, a special needle removes a core of the marrow that is structurally intact.

Click the icon to see an image of bone marrow aspiration.

Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area. It is particularly useful in detecting Hodgkin's disease and enlarged lymph nodes.

Click the icon to see an image of an x-ray machine.

Computer Tomography. Computed tomography (CT) scans are more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, monitor response to treatment, and evaluate when the symptoms occur. A CT scan is also often used in detecting lymphomas in the abdominal and pelvic areas, the brain, and chest area.

Click the icon to see an image of a CT machine.

Magnetic Resonance Imaging (MRI). MRIs may be used to detect the spread of the disease to the brain, spine, chest, pelvis, and abdomen.

Click the icon to see an image of a MRI machine.

Positron Emission Tomography (PET). PET scans can help tell whether or not an enlarged lymph node is benign or cancerous. PET scans are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.

Tests of lymphoma's DNA are in use or are being developed to detect particular genetic abnormalities that help determine outlook and may eventually lead to new treatments. Examples of such abnormal genetic arrangements are those that affect normal cell death, resist chemotherapy, or trigger aggressive cancer growth.

An advanced approach called the microarray technique uses chips that contain up to thousands of DNA sequences that represent specific normal and abnormal genes. Such sequences have been compiled for lymphomas. Eventually, experts may be able to match a patient's DNA to these patterns and identify specific subtypes.

Biologic markers, also called biomarkers, are high levels of substances released by tumors. They indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), and growth factors. Some under investigation include:

CD44. This molecule binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
BCL-6. This cancer gene is implicated in diffuse large B-cell lymphoma. High levels of this gene in these patients indicate a better outlook after treatment.

Outlook

Five-year survival rates for NHL range from 20 - 95%, depending on the lymphoma type, stage, age of the patient, and other variables. Because the outlook varies so widely, making a definite prognosis is very difficult. For example, patients with very slow growing (indolent) lymphomas can live many years. However, they are usually diagnosed at a late stage, after the cancer has spread, thus reducing the survival rate. Aggressive lymphomas are more likely to cause rapid death, but they are also often curable. New drugs that target specific factors in the tumor cells are improving survival rates.

Follicular lymphomas, the most common indolent (slow-growing) NHLs, are potentially curable in early stages I and II. Unfortunately, however, these slow-growing malignancies produce no symptoms until they are in advanced stages. In most cases, these lymphomas are not diagnosed until they have spread to other sites, including the spleen and bone marrow. In such cases, they are difficult to cure. Predicting outcome for indolent follicular lymphomas is more difficult than for aggressive lymphomas. Even if treatment achieves a response, these tumors almost always recur. Even after relapse, however, the tumors can be treated again if they are still very slow-growing.

In general, the average survival rate for follicular lymphoma is 7 - 10 years, depending on other risk factors. New drug treatments, particularly monoclonal antibodies, have significantly improved survival rates. According to a 2005 study, 91% of patients with follicular lymphoma now survive the first 4 years after diagnosis, compared with 69% of patients treated in the past with older types of drugs. The research team found the best 4-year survival rates for patients treated with the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy regimen followed by monoclonal antibody biologic drugs (rituximab or iodine-131 tositumomab).

Factors for Predicting Outlook in Indolent Lymphomas. Six risk factors are proving to be useful for predicting outlook:

Being male
Being older
Having stage III or IV disease
Elevated levels of the enzyme lactate dehydrogenase (LDH)
The presence of B symptoms
Erythrocyte sedimentation rate over 30

Patients with a good chance for a positive outcome (65% chance for survival rates of 10 years or greater) have one or none of these factors. Those with intermediate risk (23%) have two factors, and those likely to have a poor outcome (11%) have three or more factors. MALT lymphomas generally have a good prognosis. Primary gastric lymphomas have a 3-year survival rate of 89%.

High-grade aggressive lymphomas are often symptomatic early on and are potentially curable with aggressive treatments. Diffuse large-cell lymphomas, the most common aggressive non-Hodgkin's lymphomas, while fatal if not treated, are often curable with intensive chemotherapy combinations. If relapse occurs after chemotherapy, it usually does so within 2 years.

Most other aggressive lymphomas respond to aggressive chemotherapy. Mantle cell lymphoma is less responsive to chemotherapy. The average survival time is 3 - 5 years.

Factors for Predicting Outlook in Aggressive Lymphomas: A scoring system called the International Prognostic Index has proved to be fairly accurate for predicting outcome in patients with most aggressive B-cell lymphomas. It uses five risk factors to help predict whether the disease will be aggressive:

Being older than 60 -- this age group tends to have other medical conditions, which contribute to the poorer prognosis
Having a disseminated tumor (stage III or IV)
Disease that has spread to more than one site beyond the lymph nodes
A poor performance status
Having elevated levels of lactate dehydrogenase (LDH)

Having one or none of these risk factors indicates the best outlook. Two factors indicate a low-to-intermediate likelihood of a poor outlook. Three factors predict an intermediate-to-high likelihood of poor outlooks. Finally, four or five factors pose the highest likelihood of poor survival.

Lymphoma can spread to the central nervous system, or it can appear there first. Called primary CNS lymphomas (PCNSL), this condition is a very serious, particularly if it occurs at relapse.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

Risk Factors for CNS Involvement After a Diagnosis of NHL. AIDS-related lymphomas often involve the central nervous system (CNS), including the brain and spinal column. CNS involvement also occurs with aggressive lymphomas, such as Burkitt’s lymphoma.

Risk Factors of Primary CNS Lymphomas. PCNSL used to account for only about 2% of lymphomas, but the incidence is on the rise in all age groups and in both. The reason for the increase is not known.

Medical Problems. The radiation and chemotherapies used in treating NHL can have long-term effects on many organs in the body and can increase the risk for serious illnesses, including heart disease and certain cancers.

Negative Emotional Problems. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Many patients also suffer from fatigue and aches and pains, called somatic symptoms, which have no apparent physical basis. In one study, such symptoms were more highly associated with intensive chemotherapy. Women and people in lower social and economic groups are at higher risk for depression and somatic symptoms -- just as they are in the general population.

Staging and Treatment Guidelines

Treatment for non-Hodgkin's lymphoma is highly specific for each patient and is determined by the tumor classification. It includes the following factors:

Stage
Grade
Histologic type (cellular structure)
Location
Other factors, such as blood levels of lactate dehydrogenase

Treatment for lymphomas has been primarily dependent on chemotherapy (particularly intensive regimens using several drugs) or a combination of chemotherapy and radiation. For advanced or refractory lymphomas and for relapse, patients may undergo bone marrow or stem cell transplantation. New treatments, especially those known as immunotherapies, or biological response modifier (BRM) therapies, are showing promise. Some experts recommend that patients ask their doctors about getting into well-designed clinical trials as early as possible.

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

In assessing the success of a clinical trial, experts often refer to the tumor response. A complete response, for example, means that there is no longer any evidence at all of the disease by examination, blood tests, or x-ray studies. It does not necessarily mean, however, that the disease is cured. It may still recur later on.

In judging the success of a treatment for NHL, the most important criteria are overall survival and the duration of time until the disease progresses or the patient dies.

In Stage I, lymphoma is found in only one lymph node area or in only one area or organ outside the lymph nodes. Either of the following indicates stage II:

Lymphoma is found in two or more lymph node areas on the same side of the diaphragm.
Lymphoma is found in only one area or organ outside the lymph nodes and in the lymph nodes around it. Other lymph node areas on the same side of the diaphragm may also have lymphoma.

Early Stage Indolent (Low-Grade) Lymphoma. Below are the general treatment options:

Radiation therapy. Radiation to local areas can achieve a cure in 40 - 50% of patients.
Chemotherapy. Chemotherapy uses drugs to kill cancer cells.
Watchful waiting. Patients who choose watchful waiting must be aware of signs and conditions indicating the need for treatment. These include B symptoms, endangered organs, massive bulky tumors, or a steady progression that lasts at least 6 months.
Investigative treatments, such as conjugated and unconjugated monoclonal antibodies or radiation plus chemotherapy. In one study, a combination of therapies worked better than radiation alone.

The following are treatment options for some specific low-grade lymphomas:

Mucosa-associated lymphoid tissue (MALT) lymphoma. When disease is in the stomach (gastric MALT) and the patient is infected with H. pylori bacteria, antibiotics can cause regression in a significant number of patients with stage I lymphoma. In certain patients where antibiotics fail, or are not appropriate, radiation alone can achieve significant cure rates. Surgery with or without radiation, or chemotherapy with or without radiation, are possible options. Treatment options for patients with MALT localized in other sites depend on the location of the specific disease and range from radiation to chemotherapy to biologic therapies, such as interferon.
Primary gastric lymphoma (indolent). Radiation is the typical treatment for this lymphoma, which is located only in the stomach, small intestine, or other nearby regions. Surgery is being reconsidered since it seems to offer no advantage.

Click the icon to see an image of the digestive system.

Early Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options include:

Chemotherapy alone
Combinations of chemotherapy (usually CHOP) plus radiation therapy
Radiation alone (rarely)
Chemotherapy alone or with surgery for lymphoma in the gastrointestinal region
Immunotherapies (rituximab, Bexxar) with or without chemotherapy (usually CHOP), or high dose chemotherapy and bone marrow or stem cell transplantation

In stage III, lymphoma is found in lymph node areas on both sides of the diaphragm (for instance, in both the chest and the abdomen). The lymphoma may also have spread to the spleen. In stage IV, lymphoma has spread via the bloodstream to organs outside the lymph system, such as the bone marrow or brain. Lymphoma cells may or may not be in the lymph nodes near these organs.

Advanced Stage Indolent (Low-Grade Lymphomas). Treatment options are controversial because of the low-cure rate and yet slow-growing nature of these lymphomas. Patients without symptoms are often managed by watchful waiting, in which the disease is monitored closely for development of symptoms or bulky tumor masses, particularly if they threaten major organs. At such times, treatment is started. Treatment may include:

Chemotherapy combinations (CHOP, CVP, CMOPP)
Nucleoside analogs (for example, fludarabine) alone or with chemotherapy
Oral alkylating chemotherapy drugs such as cyclophosphamide or chlorambucil with or without steroids
Monoclonal antibodies (MAbs) such as rituximab alone or in combinations with CHOP or nucleoside analogs
Chemotherapy plus interferon
Clinical trials involving intensive chemotherapy and radiation followed by bone marrow or stem cell transplantation

Advanced Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options may include:

Doxorubicin-based combination chemotherapy with or without rituximab
Chemotherapy plus radiation therapy
Immunotherapies with or without chemotherapy
Treatments to prevent disease from spreading to the central nervous system in high-risk patients
Clinical trials for patients at high risk for relapse, involving intensive chemotherapy, high dose chemotherapy, and bone marrow or stem cell transplantation

Indolent-Lymphomas Relapses. Nearly all patients with indolent lymphomas relapse after initial treatment, with length of remission after a first treatment averaging 18 - 50 months. Successful retreatment is often possible, but disease-free periods become increasingly shorter with each subsequent treatment.

Older patients may choose watchful waiting. Other treatment options may include:

Radiation alone or with chemotherapy -- in one study low-dose involved-field radiotherapy was very effective in recurring indolent lymphoma
Chemotherapy
High-dose chemotherapy with autologous stem cell transplant
Clinical trials involving monoclonal antibodies, radioimmunotherapy, nucleoside analogues alone or in combination with other drugs, or stem cell transplantation followed by biologic therapies

Aggressive Lymphomas Relapse. After initial treatment, more than half of patients with aggressive lymphomas are cured, while about 20% progress, and the other 30% relapse after a disease-free period. Among those who relapse, many can still be cured with aggressive treatments.

Treatment options:

Bone marrow or peripheral stem cell transplantation
Bone marrow transplantation with radiation
Clinical trials that involve continuous infusion chemotherapy, biologic therapies (monoclonal antibodies) alone or in combination with transplantation

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Treating Lymphoma Restricted to the Central Nervous System. Treatment options may include:

High-dose methotrexate regimens alone or in combination with radiation
Corticosteroids and radiation
Clinical trials that involve biologic therapies, such as rituximab or interferon alpha administered directly into the spinal fluid (intrathecal administration) for meningitis related to central nervous system lymphoma

Preventing (Prophylactic Treatment) Lymphomas in High-Risk Patients. Treatment to prevent the spread of NHL to the central nervous system may be appropriate in some patients. It is not recommended for patients with low-grade NHL. Preventive treatment may be appropriate for certain patients with high-grade NHL, such as those with lymphoblastic and Burkitt's lymphoma or if they have 4 - 5 of the following risk factors: Elevated levels in the blood of the enzyme acetate dehydrogenase and albumin (a common protein), being older than 60, and having lymph nodes beyond the peritoneum (the lining of the abdomen) and involvement of more than one site outside a lymph node.

Chemotherapy

Chemotherapy plays a role in the treatment of nearly all lymphoma patients and has achieved remarkable results, even in late stages. It uses drugs to kill cancer cells. Such drugs are called cytotoxic drugs. Chemotherapy is referred to as bodywide or systemic therapy because the drugs travel throughout the bloodstream to the entire body.

Studies indicate that chemotherapy as sole treatment is adequate for most children and young adults in early, and perhaps in many advanced, stages. (Radiation has been commonly used for these patients but can be particularly dangerous for children.)

A chemotherapy cycle is usually 21 - 28 days. Patients take the drugs for a few days, then have a period of rest. The drugs may be taken by mouth or given by injection. Chemotherapy is injected into the spinal fluid if the cancer has spread to the brain. This is called intrathecal chemotherapy. Intrathecal chemotherapy is also used as a preventive measure in patients at high risk for central nervous system involvement. Chemotherapy may be administered at a medical center or in a doctor's office. Some patients receiving chemotherapy need to remain in the hospital for several days so the effects of the drug can be monitored. Patients with lymphoblastic lymphoma may need long-term maintenance chemotherapy. Such therapy does not seem to benefit patients with small-noncleaved-cell and large-cell lymphomas.

CHOP. The current standard chemotherapy regimen for NHL is CHOP. CHOP is a combination of cyclophosphamide, doxorubicin hydrochloride (Adriamycin), vincristine (Oncovin), and prednisone. It is proving to be particularly effective for many stages of lymphoma when used in combination with rituximab (Rituxan), a monoclonal antibody. (See Biologic Therapy section.) Some studies of this combination in low-grade lymphomas have reported response rates of 70 - 100%. CHOP alone is still preferred for HIV patients, who tend to have a toxic response to rituximab.

CVP. This stands for cyclophosphamide, vincristine, and prednisone. It may be used with CHOP in certain cases.

Fludarabine and Nucleoside Analogues. Fludarabine (Fludara) is a type of drug called a nucleoside analogue. It is one of the most active drugs for treating low-grade lymphomas and may be effective for other NHLs, including mantle cell lymphomas. Promising regimens containing fludarabine are under investigation. For example, FND (fludarabine, mitoxantrone, and dexamethasone) may be helpful in combination with rituximab for certain patients, including those with indolent NHL. Other nucleoside analogues include gemcitabine and cladribine. Toxicities and infection rates from high dose nucleoside analogues have been high. Fludarabine also has been associated with a risk for leukemia.

Bendamustine. This potent drug has shown to be effective for indolent NHLs and possibly aggressive lymphomas. One study suggested that a single dose of low-dose etoposide, taken by mouth, may be beneficial for elderly patients.

Antibiotics. Antibiotics, such as doxycycline, may cure or put into complete remission about half of mucosa-associated lymphoid tissue (MALT) lymphoma cases. MALT lymphoma is a type of lymphoma that sometimes affects the eyes. It is associated with the bacterium Helicobacter pylori (H. pylori ), which also causes stomach ulcers. Recent studies indicate that antibiotics are a good alternative to chemotherapy or radiation for patients with this type of lymphoma. Patients most likely to respond positively to antibiotics are those with MALT lymphoma in its early stages.

Vorinostat. Vorinostat (Zolinza) was approved in 2006 for treatment of cutaneous T-cell lymphoma (CTCL), a rare form of NHL.

Side effects and complications of any chemotherapeutic regimen are common. They are more severe with higher doses. Side effects may increase over the course of treatment.

Common Side Effects. Common side effects include:

Nausea and vomiting -- Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Hair loss
Weight loss
Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps a few days a month.

Serious Side Effects. Serious chemotherapy side effects can also occur and may vary depending on the specific drugs used. They include:

Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta), can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to treat only anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
Liver and kidney damage
Abnormal blood clotting (thrombocytopenia)
Allergic reaction

Long-Term Complications.

Fatigue and Somatic Symptoms. Chemotherapy has been associated with long-term somatic symptoms, which are general conditions, such as fatigue and aches and pains that have no apparent physical basis. Fatigue is especially common after chemotherapy and can even last for years.
The most serious long-term complications from chemotherapy are secondary cancers, particularly in people over age 40.
Infertility is a risk, particularly with the use of cyclophosphamide.
Some patients get osteoporosis (bone thinning) and damage in bone cells.
Regimens containing certain drugs, particularly doxorubicin or mitoxantrone, increase the risk for future heart failure.

Click the icon to see an image of the uterus and ovaries.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Doctors are particularly concerned about the effects of combinations of chemotherapy with radiation, especially leukemia and heart problems. Interestingly, in one study on patients with intermediate- and high-grade NHL, those on chemotherapy alone had more toxic effects than those on combined modality, most likely because it employed fewer cycles of chemotherapy. Better radiation techniques are also reducing the risks of combined modality treatments.

Biologic Therapy (Immunotherapy)

Biological response modifier therapy, also called immunotherapy, uses the body's own immune system to fight cancer using natural or laboratory-developed factors. These drugs are often combined with other treatments.

Monoclonal antibodies (MAbs) are designed in the laboratory to produce the same effects as natural antibodies and are exciting new weapons in the anti-cancer armament. They bind to specific proteins called antigens and make them vulnerable to attack by other factors in the immune system. Lymphomas carry antigens that provoke strong immune responses and so are believed to be particularly good candidates for MAb therapy.

MAbs are called either unconjugated or conjugated, depending on how they are designed to destroy the cancer cell.

Unconjugated monoclonal antibodies rely on a strong natural immune system. The antibody builds up at the tumor site until it is able to trigger an immune response against the cancer. A possible downside to this form is the potential development of tolerance to the antibody so that it loses its effectiveness. Rituximab is an unconjugated form and the first MAb to be approved for any cancer.
Conjugated monoclonal antibodies are linked to a plant or bacterial toxin or radioisotope. The antibody specifically attacks the antigen on the lymphoma cell, and the toxin or radioactive material from the isotope kills it.

Unconjugated MAbs (Rituximab). Rituximab (Rituxan) was the first monoclonal antibody approved for cancer. This drug targets the CD-20 antigen, which is found on most B-cell lymphomas.

First approved in 1997 for treatment of relapsed or refractory NHL, rituximab has received several expanded indications since that time. As of 2006, rituximab is approved for:

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, NHL
First-line treatment of diffuse large B-cell (DLBC), CD20-positive, NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens
First-line treatment of follicular, CD20-positive, B-cell NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy
Low-grade, CD20-positive, B-cell NHL in patients with stable disease or patients who have been partially or completely helped by first-line treatment with CVP chemotherapy

Rituximab in combination with CHOP (a regimen called R-CHOP, or CHOP-R) is used for first-line treatment for aggressive lymphomas, with studies reporting 3-year event-free survival of 53% compared to 35% with CHOP alone. A 2006 study also indicated that rituximab provides benefits when used as maintenance treatment after CHOP or R-CHOP induction therapy. Rituximab plus CHOP is also showing promise as a first-line treatment for mantle cell lymphoma.

Rituximab is given by infusion. The treatment has mild-to-moderate short-term side effects, including nausea, fever, chills, hives, dizziness, and headache. Uncommon and more serious side effects are severe allergic reactions, very low blood pressure, blood abnormalities, wheezing, infections, and sudden heart events.

Rituximab has also been associated with cases of progressive multifocal leukoencephalopathy (PML), a rare and potentially deadly brain infection. Patients who experience any of the following symptoms should immediately contact their doctors:

Vision problems or unusual eye movements
Confusion
Dizziness or loss of balance
Difficulty talking or walking

Patients who have previously had hepatitis B, or who are at high-risk for this viral infection, should be tested before taking rituximab because the drug has been linked to reactivation of the hepatitis B virus. Patients who are HIV-positive may experience more adverse effects from rituximab than with CHOP.

Conjugated Monoclonal Antibodies with Radioimmunotherapy. Conjugated MAbs with radioimmunotherapy contain tiny amounts of radioactive materials. When the drug is injected, the monoclonal antibody targets an antigen (protein) on the surface of the tumor. The radioisotope is then delivered directly into the tumor where it kills the cancer. Ibritumomab and tositumomab both target the CD-20 antigen. Treatment with these drugs takes about 7 - 9 days to complete, compared to several months for traditional chemotherapy treatments.

Ibritumomab (Zevalin) is approved for patients with relapsed or refractory low-grade, follicular or transformed B-cell NHL. It is also approved for patients with follicular NHL who have not responded to rituximab (Rituxan). Research indicates it may also be safe for patients with advanced NHL who have had stem cell transplantation. Zevalin uses an yttrium-90 (90-Y) radioactive isotope.
Tositumomab and Iodine I-131 (Bexxar) combines the monoclonal antibody tositumomab with the radioisotope I-131. The Bexxar treatment is approved for treatment of relapsed or refractory low-grade, follicular, or transformed B-cell NHL. Overall response rates of 56% have been reported with Bexxar, with up to 30% being complete responses (no evidence of cancer). Recent studies suggest that when Bexxar is used as a first treatment, it may produce long-term complete remission in patients with advanced stage follicular lymphoma. In a 2005 New England Journal of Medicine study, 95% of previously untreated patients with advanced follicular lymphoma responded to Bexxar, and 75% had complete responses. Seventy percent who had complete responses from Bexxar treatment were still disease-free 4 - 7 years later.

In general, these drugs cause fewer side effects than traditional chemotherapy. However, serious complications may include skin infections, severe allergic reactions, and temporary lowering of blood counts.

Other Monoclonal Antibodies. Other MAbs are being developed that target other antigens on lymphomas. For example, epratuzumab targets CD-22 and is showing promise in early studies. Some are being studied in both conjugated and unconjugated forms and also in combination with MAbs that target different antigens.

Interferon alpha (Intron A) is used as an antiviral drug that also has properties that are effective against some common forms of NHL, particularly low-grade, follicular NHL in advanced stages. It is usually combined with chemotherapy regimens such as CHOP that contain an anthracycline drug (usually doxorubicin). The combination is toxic, however, and outcomes vary. Interferon is also being studied for lymphomas in the central nervous system. It may be useful after autologous stem cell transplantation.

Side Effects. Side effects of interferon include flu-like symptoms, severe depression, irritability, weight loss, vomiting, general weakness and loss of strength, and fever. About a third of patients have a severe drop in white blood cells. About 10% of patients cannot tolerate the drug's side effects.

Cytotoxic Deoxyguanosine Analogue Prodrugs. Nelarabine (Arranon) is approved for treating T-cell lymphoblastic lymphoma (T-LBL). T-LBL is a rare form of lymphoma that accounts for less than 2% of all cases of NHL.

Proteasome Inhibitors. In 2006, bortezomib (Velcade) was approved for treatment of mantle cell lymphoma in patients who have received at least one prior therapy.

Cyclin-Dependent Kinase Inhibitors. Flavopiridol, a drug known as a cyclin-dependent kinase inhibitor, is showing some effect in patients with mantle-cell lymphoma. This drug is designed to block enzymes that regulate cell cycles and help block their growth.

Vaccines. Although still experimental, lymphoma vaccines are used to treat -- not prevent -- cancer. They are part of an immunotherapy approach called personalized medicine; each vaccine is individually tailored to the genetic composition of the patient’s tumor. The vaccine is usually given a few months after a patient receives chemotherapy. Several different vaccines, including the BiovaxID and MYVax, are in late-stage clinical trials.

Radiation

Radiation is commonly used to treat indolent lymphomas. The dose administered ranges from 35 - 50 Gy and depends on a number of factors: The type of lymphoma, the age of the patient, whether the intent is to cure or relieve symptoms, how close sensitive organs are to the diseased area, and whether radiation is being combined with chemotherapy.

Radiation is tailored to the individual and usually limited to the diseased areas and possibly nearby regions:

If the lymphoma is confined to tissues above the diaphragm, radiation is delivered to the neck, chest, and under arms (called the mantle-field) and sometimes to lymph nodes in the upper abdomen or spleen or both.
If the lymphoma is below the diaphragm, subtotal nodal radiation may be used, which is directed to other regions, including lymph nodes in the upper abdomen, spleen, and pelvis, in addition to the mantle-field.
Radiation to the brain is called cranial radiation.
Total body irradiation is sometimes performed, although it is not clear whether its high toxicity outweighs any advantages.

Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.

Side effects and complications of radiation generally depend on the target site in the body. They include:

Dental problems
Inflammation in the lungs -- with carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.
Hypothyroidism
Infections
Long-term risk for heart disease
Long-term risk for certain cancers -- of particular concern is a possible increased risk for breast cancer. Studies indicate that young women and adolescent girls are at highest risk, with the incidence increasing significantly 15 years after treatment. The risk is greater in those who had higher radiation doses. Radiation may also increase the risk over time for other cancers, including lymphoma and thyroid, lung, and colon cancers, although the risk is still low. Smoking, of course, increases the risk for lung cancer. Radiation of bone marrow increases the risk for leukemia.
Impaired bone growth -- children and adolescents are at special risk for bone problems caused by radiation. Experts are finding that radiation for many children and young adults in early stages or NHL is no more effective and has more serious long-term effects than chemotherapy. Some believe that radiation should play no role in the treatment of young people, except in special cases, such as lymphomas that require radiation to the brain.
Infertility -- the negative effects on fertility may be worse in women than in men; sperm usually recover within 5 years. To protect the ovaries, a technique called ovarian transposition is sometimes used. Transposition may sometimes be performed through a laparoscope, a thin tube containing tiny instruments and cameras, which is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.

Click the icon to see an image of the lungs.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of the uterus and ovaries.

Transplantation

Stem cell procedures have proven to produce long-term survival and even cures in some patients with intermediate- and high-grade non-Hodgkin's lymphomas.

Stem cell transplantation involves removing and replacing stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them from the donor into the patient.

Sources of Cells. Stem cells must first be collected in one of the following ways:

Directly from blood, called peripheral blood stem cell transplantation
From bone marrow, called bone marrow transplantation
From umbilical cords or placentas -- this procedure uses donor cells, but has a lower risk for immune system rejection of the cells than with a standard donor transplant. It takes longer to restore blood cells with this process, so it is generally used for children and sometimes adults with low weight.

Some evidence suggests that both stem cell and bone marrow procedures produce similar benefits in terms of response rates and duration of remission. However, in one study, stem cell transplantation was associated with better overall survival rates. It also seems to be superior in terms of cost, quality of life, and the need for less supportive care.

Donor or Patient Cells. The marrow or blood stem cells can be taken from the patient (autologous) or from a matched donor (allogeneic):

In an autologous transplant, the marrow or blood cells used for replacement are taken from the patient. There is some danger, however, that these cells may contain tumor cells, and that the cancer can regrow. It is unclear if this approach improves survival compared to standard chemotherapy for newly diagnosed disease. However, it clearly has benefits in the treatment of some forms of relapsed non-Hodgkin's lymphomas. There is also a higher risk for leukemia. (This risk is lower in peripheral stem cells transplants than in bone marrow transplants.)
In an allogeneic transplant, bone marrow or stem cells are taken from a donor. Siblings are the best donors. Relapse rates can be very low with this approach, and cure may be possible in some cases. However, it is highly toxic and donor and recipient must be matched as closely as possible to avoid rejection by the immune system, a serious complication called graft-versus-host disease. Advances in techniques are reducing the toxicities associated with this approach. Older patients who cannot tolerate the preparatory treatment required for a standard allogeneic transplant may be able to receive a non-myeloblative transplant (“mini-transplant), which uses lower doses of chemotherapy and radiation.

The Blood Stem Cell Collection Procedure. With peripheral blood stem cell transplantation:

The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim, pegfilgrastim) to stimulate stem cell growth.
The patient (or donor in an allogeneic procedure) then undergoes apheresis. With this process the blood is withdrawn from one of the patient's veins, then passes through a machine that filters out the white cells and platelets, which contain the stem cells. The blood is returned through another vein. The entire procedure takes 3 - 4 hours but needs to be repeated several times.
The stem cells are treated to remove contaminants and then are frozen to keep them alive until the patient is ready to receive them back.

Blood is the only fluid tissue in the body. Blood transports oxygen and nutrients to body tissues, and returns waste and carbon dioxide. Blood distributes nearly everything that is carried from one area in the body to another place within the body. For instance, blood helps transport hormones from the endocrine organs to their target organs. Blood also helps maintain body temperature. The protective functions of blood include clot formation and the prevention of infection.

Allogeneic transplants are preceded by chemotherapy treatment known as conditioning. The point of this treatment is to inactivate the immune system and to kill any residual malignant cells. It is extremely toxic since it also destroys non-malignant marrow cells. Drugs used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning to reduce toxicity includes total-body radiation plus drugs. Monoclonal antibodies, such as rituximab, are promising drugs, since they have low toxicity and may add benefits for all stages of transplantation.
A few days after treatment, the patient given the stored stem cells, which are administered through a vein. This may take several hours. Patients may have a fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
The patient may be treated with granulocyte colony-stimulating factor after chemotherapy. The goal is to stimulate the growth of infection-fighting white blood cells. Adding thrombopoietin may help enhance stem cell production.
The patient is kept in a protected environment to minimize infection. Patients who have received an allogeneic transplant may need blood cell replacement, nutritional support, and drugs to treat graft-versus host disease. They usually can leave the hospital within 3 - 5 weeks.

Candidates. These procedures are typically used for patients with relapsed aggressive lymphoma who are still sensitive to the effects of chemotherapy. The procedures do not work for patients whose tumors are not responsive to drugs. Some evidence suggests that certain primary (non-relapsed) lymphomas initially unresponsive to a first round of chemotherapy but who respond to a second round may benefit from combination of high-dose chemotherapy and radiation followed by transplantation. Transplantation is also being investigated as first-line therapy for patients with aggressive lymphomas, although at this time evidence does not support its use.

Success Rates. Success rates vary depending on many factors. The following are survival rates reported by a few studies of patients with different lymphomas:

In patients with refractory or relapsed intermediate grade NHL who received autologous transplantation, 5-year survival rates averaged 34%.
In a study of allogeneic bone marrow transplantation, 58% of patients with late-stage low-grade lymphoma had survived after an average of 29 months.
Patients with anaplastic large-cell lymphoma were treated with autologous stem cell transplantation with intensified chemotherapy as first line-therapy. Survival rates were 87% at 5 and more years afterward. (Survival was much lower with other lymphomas.)
Patients with diffuse aggressive NHL who did not achieve a first remission but who are still sensitive to chemotherapy achieved a 5-year survival rate of up to 37% after autologous stem cell transplantation.
In one study, 35% of patients with an initial poor prognosis were still alive 5 years after an allogeneic stem cell transplantation, although mortality probability from the treatment itself was very high (48%).

Common side effects include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.

Infection resulting from a weakened immune system is the most common side effect. Because the stem cell procedure is done more swiftly, the risk period is shorter than with bone marrow transplantation. The risk for infection is most critical during the first 6 weeks following the transplant, but it takes 6 - 12 months post-transplant for a patient’s immune system to fully recover. Immune systems of patients with graft-versus-host disease can take even longer to function normally.

Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

It is very important that patients take precautions to avoid infections. Guidelines for post-transplant infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about handwashing and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. Mild cases of GVHD can actually be helpful as they can cause graft-versus-lymphoma where the immune system kills remaining lymphoma cells. Still, severe GVHD can pose serious complications.

To reduce the risk for GVHD, doctors remove some immune T-cells from the donor’s stem cells before the transplant. Researchers are investigating new techniques to refine this process of T-cell depletion.

Acute GVHD occurs in 30 - 50% of allogeneic transplants, usually within 25 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). The first sign of acute GVHD is a rash, which typically develops on the palms of hands and soles of feet and can then spread to the rest of the body. Other symptoms may include nausea, vomiting, stomach cramps, diarrhea, loss of appetite and jaundice (yellowing of skin and eyes). To prevent acute GVHD, doctors give patients immune-suppressing drugs such as steroids, methotrexate, cyclosporine, tacrolimus, and monoclonal antibodies.

Chronic GVHD can develop 70 - 400 days after the allogeneic transplant. Initial symptoms include those of acute GVHD. Skin, eyes, and mouth can become dry and irritated, and mouth sores may develop. Chronic GVHD can also sometimes affect the esophagus, gastrointestinal tract and liver. Bacterial infections and chronic low-grade fever are common. Chronic GVHD is treated with similar medicines as acute GVHD.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Secondary cancers. There is a small long-term risk for leukemia after transplantation in young people. Use of newer chemotherapeutic drugs, however, may not pose as high a danger as older treatments.

Other potentially serious complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)

Surgery

Surgery is sometimes used to remove as much malignant tissue as possible before administering chemotherapy. This is particularly useful for bulky tumors that occur in the stomach.

Surgery is sometimes performed for primary gastric lymphoma, but its advantages are uncertain. Some studies indicate that chemotherapy alone or with radiation may be sufficient and could spare many patients from surgery.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.leukemia.org -- The Leukemia and Lymphoma Society
www.canceradvocacy.org -- National Coalition for Cancer Survivorship
www.marrow.org -- National Marrow Donor Program
www.asco.org -- American Society of Clinical Oncology
www.lymphoma.org -- Lymphoma Research Foundation
www.plwc.org -- People Living with Cancer
www.oncolink.org -- Cancer information
www.fhcrc.org/science/clinical/ltfu/patient -- Fred Hutchinson Cancer Research Center -- Transplant Infection Guidelines for Patients
www.lymphomainfo.net -- Lymphoma Information Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Boffetta P, de Vocht F. Occupation and the risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2007: 16(3):369-72.

Ferrara JL. Novel strategies for the treatment and diagnosis of graft-versus-host-disease. Best Pract Res Clin Haematol. 2007. 20(1):91-7.

Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma. V.3.2007.

Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood. 2007 Nov 15;110(10):3507-16. Epub 2007 Aug 20.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Lyme disease and related tick-borne infections

FitSugar — Wed, 08 Oct 2008 17:35:15 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diseases with Similar Sympt...
Diagnosis
Treatment
Prevention
Human Granulocytic Anaplasm...
Babesiosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lyme Disease Rates Double in Past 15 Years

The annual number of people newly infected with Lyme disease has doubled from around 10,000 cases per year in the early 1990s to about 20,000 cases per year now. Improved diagnosis and reporting probably contribute to this increase. In the United States, Massachusetts, New Jersey, and Pennsylvania have reported the highest number of Lyme disease cases in recent years. People ages of 5 - 14 years and 45- 54 years are at highest risk for contracting Lyme disease.

New Guidelines for Treatment of Neurological Lyme Disease

Most cases of Lyme disease can be prevented or cured with prompt antibiotic treatment following a deer tick bite. However, neurological complications can later develop in some patients. In 2007, the American Academy of Neurology released new guidelines for the treatment of nervous system Lyme disease. The guidelines recommend that patients with severe disease receive a 2 - 4 week course of intravenous antibiotics (penicillin, ceftriaxone, or cefotaxime). Patients with milder neurological cases may do well with a 2 - 4 week course of oral doxycycline. No guidelines currently recommend long-term antibiotic treatment for any stage or complication of Lyme disease.

Introduction

Lyme disease is the most commonly reported vector-borne disease in the United States. Vector-borne infections are transmitted by insects.

The Lyme disease infection in the U.S. is caused by a spirochete called Borrelia (B.) burgdorferi. A spirochete is a bacteria-like organism with a cylinder-like shape surrounded by an outer membrane.

Lyme researchers have the completion of DNA encoding of B. burgdorferi. Researchers learned that certain proteins coat its outer surface. These proteins, collectively called Osp, are responsible for attaching the spirochete to cells in humans and other mammals.

The vector that carries B. burgdorferi in the U.S. Northeast and North Central states is the Ixodes scapularis tick. The Ixodes scapularis tick goes through three stages over the course of about two years:

It is born from eggs as a larva.
It develops into the nymph stage.
It develops into the adult stage.

Cycle of Infection in the Northeast and North Central U.S. For Lyme disease to exist in these regions, three factors must come into close contact:

The Borrelia (B.) burgdorferi spirochete
The spirochete's host, the Ixodes scapularis tick
The mammal for the tick to bite

The following describes the most common cycle in the Northeast and North Central U.S. by which the Lyme disease infection eventually reaches a person:

The cycle of infection is related to the tick's life cycle, which requires 2 years to complete. The tick typically first picks up the spirochete during its larva stage, when it needs a blood meal to mature further.
The tick's initial meal is typically blood from the white-footed mouse, which is commonly infected with Borrelia burgdorferi. After it dines on the infected blood, the tick then becomes a carrier of this spirochete.
Borrelia burgdorferi lodges in the tick throughout one of both of its following life stages, nymph and adult. It is during these stages that the infection is passed on to other animals, including humans. Nymph ticks emerge around mid-June and can be about the size of poppy seeds. They are very difficult to spot and are estimated to be responsible for 90% of all Lyme disease cases. Adult ticks can be as large as a raisin after feeding, and easy to spot, but they usually prefer their dinner on the white-tailed deer.
The infected nymph or adult tick crawls (it does not fly or jump) onto another animal, which can be mice or larger animals, such as deer, birds, or humans. If the tick bites these animals, it may then infect them with the B. Burgdorferi spirochete. (It should be noted that infected humans cannot pass the spirochete on to other humans by any means, including infected blood or urine or sexual contact.)
A tick can feed for several days while being imbedded in the skin, after which it falls off. The tick's bite is painless, however, so only about half of people with Lyme disease recall being bitten.

Cycle of Infection in the Northwest. In the Northwest, the infecting insect is the Western blacklegged tick, Ixodes Pacificus. Here, the frequency of Lyme disease is much lower than in the other two regions because the animal carrier of the infection is the dusky-footed wood rat. This animal is bitten and infected by the Ixodes neotomae tick, which does not bite humans. The actual tick that spreads B. burgdorferi to people is Ixodes pacificus, which must feed first on an already infected wood rat.

The two other important infections carried by the Ixodes scapularis tick are human granulocytic anaplasmosis (HGA) and babesiosis. Although they are both borne by the same tick as Lyme disease, all three of these infections are entirely different diseases.

Risk for Coinfection. Because Lyme disease, HGA, and babesiosis can all be carried by the same tick, there is some risk for co-infection with two or more of these organisms. The risk, however, is not wholly known. Studies have reported that 2 - 25% of ticks in several high-tick locations carry both HGA and Lyme. In one study of patients located in high-risk areas in New England, 39% had more than one of these infections transmitted by the Ixodes tick. There is no evidence that co-infection with one or more of these infections causes a more severe condition than either infection separately.

Symptoms

Symptoms of Lyme disease are diverse and often occur in early and late phases. They vary widely from person to person. Any one symptom may fail to appear, and symptoms may overlap in various combinations. Death from Lyme disease is very rare and occurs only in a few cases in which the heart is severely affected.

Stage 1. In the majority of cases, the first sign of early Lyme disease is the appearance of a bull's-eye skin rash. It usually develops about 1 - 2 weeks after the bite, although it may appear as soon as 3 days, and as late as 1 month. In some cases, it is never detected. Flu-like symptoms (joint aches, fever, and general fatigue) commonly develop.
Stage 2. Untreated, the infection spreads through the bloodstream and lymph nodes within days to weeks, involving the joints, nervous system, and possibly the heart. Multiple rashes may erupt in other places. If the infection affects the nervous system in stage 2, it most often causes weakness or paralysis in the nerves of the face (Bell's palsy) or in nerves of the spine.
Stage 3. If the disease remains untreated, a persistent infection can occur after a few weeks or months, leading to prolonged bouts of arthritis and neurologic problems, such as concentration problems or personality changes. Fatigue is a prominent feature of both early and late stages.

Evidence suggests that up to 90% of patients with Lyme disease exhibit a rash a few days to a month after a tick bite. The rash, known as erythema migrans, usually first appears on the thigh, buttock, or trunk in older children and adults, and on the head or neck in young children.

The bull's eye rash, which is commonly believed to be the classic sign of Lyme disease, may take the following course:

It can first appear as a pimple-like spot, which expands over the next few days into a purplish circle. The circle may reach up to 6 inches in diameter with a deeper red rim. In some cases the ring is incomplete, forming an arc rather than a full circle.
The center of the rash often clears or may turn bluish. Or secondary concentric rings may develop within the original ring, creating the bull's-eye pattern. Over the next several weeks, the circular rash may grow to as large as 20 inches across.
Patients often describe the sensation of the rash as burning rather than itching.

It is important to note that in one study, only 9% of patients diagnosed with Lyme disease exhibited this classic pattern. Nearly 60% had a rash that was more general in appearance and 32% had a circular dense red rash.

In most patients, any rash fades completely after 3 - 4 weeks, although secondary rashes may appear during the later stages of disease.

A flu-like condition is the most common sign of Lyme infection, and it can occur with or without a rash. Symptoms can last from 5 - 21 days and may include:

Fatigue
Chills and fever (100 - 103° F)
Headache (usually most prominent at the back of the head)
Joint aches (usually in the large joints)
Stiff neck
Backache
Swollen glands (in the area around the tick bite or elsewhere)
Less often, nausea, vomiting, and sore throat occur

Some experts recommend that children in high-risk areas be tested for Lyme in the summer months if they have the most common Lyme symptoms (fever, headache, joint aches) -- even if they have no tell-tale rash. Severe and sustained flu symptoms without the rash in such patients may indicate the presence of human granulocytic anaplasmosis (HGA) or babesiosis -- the other infections carried by the Ixodes tick.

Joint pain can arise at any time after the appearance of a skin rash. In the absence of a rash, arthritic symptoms may be the first indication of Lyme disease. Or, as suggested by some studies, it can develop months after the disease has been diagnosed. Arthritic symptoms may occur as follows:

Aches, stiffness, and swelling, sometimes massive, of large joints, such as the knee, elbow, or shoulder. One or both knees are affected most often. The ankle, wrist, jaw, and finger joints are involved less often.
Typically, no more than three joints are affected during the course of the disease. If several joints are involved, they tend to be asymmetrically distributed.
Joint pain flare-ups are often accompanied by muscle pain.
Arthritis symptoms usually last for a few days or weeks and are interspersed with longer periods during which the joints feel fine.
The severity and frequency of attacks peak within 1 - 2 years then decrease and usually resolve, even without treatment.

About 15% of untreated patients develop neurologic symptoms. They can occur in all stages of the disease and can affect any part of the nervous system.

Common Early Neurologic Symptoms. Most often, neurologic symptoms first appear while the initial skin rash is still present or within 6 weeks after its disappearance. Sometimes they are the first symptoms that the patient experiences. The most common neurologic symptoms may be headaches, sleep problems, and mood disturbance. Memory problems can also occur. Neurologic symptoms typically improve or resolve within a few weeks or months, even in untreated patients.

Bell's Palsy. In 5 - 10% of untreated Lyme patients, the facial nerve is affected, which results in Bell's palsy. This is a sudden weakness and drooping of the facial muscles and eyelid on one side of the face. Nerves around the facial area may also cause numbness, dizziness, double vision, and hearing changes. Another common neurologic problem is pain in the lower spine. It resembles low back pain from arthritis (although in the case of Lyme disease the skin near the spine may have abnormal sensations). Of note, Lyme disease has been observed in more than half the children who develop Bell's palsy.

Symptoms of Meningitis. In about 10 - 15% of patients, the infection takes place in the membranes that surround the brain and spinal cord (called meningitis). This can cause:

Episodes of headache not relieved by over-the-counter medication
Mild stiff neck
Sensitivity to light

Symptoms of Lyme Encephalopathy. In some cases of untreated disease, the infection causes a condition called Lyme encephalopathy or neuroborreliosis. This causes the following symptoms:

Unexplained mood changes
Depression
Trouble concentration and remembering
Irritability
Feelings of "pins and needles" or numbness in the arms or legs

Other Neurologic Symptoms.

If the infection affects the white brain matter, symptoms resemble multiple sclerosis.
If the infection occurs in the nerves affecting the skin, some patients experience pricking, tingling, or creeping feelings.
Children have a higher risk than adults for neurologic effects on the eye. (This is still rare, however.)

The infection may affect electrical conduction to the heart and cause symptoms suggesting heart rhythm disturbances:

Palpitations
Shortness of breath
Chest pain
Dizziness
Fainting can occur if the infection affects the heart

These symptoms almost never produce serious problems in people without other types of heart disease.

Symptoms in the eyes have been reported at every stage. Conjunctivitis ("pink eye") may be a symptom in the early stages. In late, untreated Lyme disease, neurologic problems can affect the eye, causing pain and sensitivity to light.

Risk Factors

Since 1991, when Lyme disease became a reportable disease, annual cases have doubled. (This increase is probably both due to increased infection rates as well as better diagnosis.) In general, about 21,000 cases of Lyme disease are now reported in the U.S. each year.

Anyone exposed to ticks is at risk for Lyme disease and other tick-borne diseases. Pets are also at risk. Naturally, anyone who is regularly outside in areas where tick rates are high has a greater than average risk for becoming infected.

Age. The highest reported incidence of Lyme disease occurs among children 5 - 14 years old and adults 45 - 54 years old.

Sex. Men and women are equally at risk.

In general, the risk for developing Lyme disease after a tick bite is only between 1 - 3%. The risk varies depending on different factors:

The longer the tick has fed, the greater the risk. In fact, in one study, no individuals developed Lyme disease after being bitten by a nymph tick for fewer than 72 hours. The risk was 25% in people on whom the tick had been feeding for longer than 72 hours.
Nymph ticks carry a greater risk than adult ticks, probably because they are often too small to be detected (about the size of a pinhead). In addition, only nymph ticks that are at least partially swollen when removed pose any significant risk. (This suggests that they have feeding for a prolonged period.)

Locations in the U.S. Lyme disease has been reported in nearly all U.S. states. However, most Lyme disease cases are concentrated in the northeastern, mid-Atlantic, and north central states. Although Lyme disease was named for a town in Connecticut where the first American cases of the disease were described, in recent years Massachusetts, New Jersey, and Pennsylvania have reported the greatest number of cases.

Worldwide Locations. Pockets of Lyme disease exist around the world. The disease is common in Europe, particularly in forested areas of middle Europe and Scandinavia. The Borrelia family is also responsible for tick infections in Europe, but different subspecies (B. garinii and B. afzelii) may be more common there and cause slightly different symptoms. The infection has also been reported in Russia, China, and Japan.

Deer ticks thrive in grassy areas that have low sunlight and high humidity. Woodlands and fields are prime habitats, but these ticks can also be found in the long grasses adjacent to beaches. The ticks are not confined to rural settings. In suburban areas, they can live in overgrown lawns, groundcover plants, and leaf litter.

The exact time of year for risk depends on a geographic region’s seasons and how they affect the tick’s breeding cycle. In general, the highest risk for Lyme disease onset is from June through August, and the lowest risk is from December through March.

Complications

Prompt treatment with antibiotics is very effective in curing Lyme disease in nearly all infected people, including children. One study showed that the long-term outcome of patients with Lyme disease who are treated with antibiotic therapy is excellent. However, even if Lyme disease has been successfully treated, it may be possible to become reinfected with Lyme disease again at a later date. The risk appears to occur only in patients who had been treated for the rash. In those who also developed arthritic symptoms, the antibody response appears to persist and prevent reinfection.

People at highest risk for persistent symptoms are those who go the longest before treatment. Fortunately, public vigilance has significantly reduced the rates of late-stage Lyme disease. Antibiotics given at late stages will relieve symptoms in most people, although about 5% may continue to have problems. Also at risk for persistent symptoms are those who show evidence of having severe infections. Retreatment at later stages has been shown to be effective in about three quarters of these patients.

Left untreated, Lyme disease can spread (disseminate). The infection may affect almost any part of the body and cause the following complications:

Severe arthritis
Persistent fatigue
Mood disturbances and loss of concentration
Neuropathy (numbness, tingling, or other odds sensations in the hands, arms, feet or legs)
Life-threatening disorders affecting the heart, lungs, or nervous system can occur, but are very rare.

Arthritis. Without treatment, 60% of patients develop intermittent joint inflammation, especially in the knees. Lyme arthritis usually responds to a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime). A small number of patients may require intravenous antibiotics.

If the arthritis persists or joint swelling recurs after several months, patients may be treated by another 4-week course of oral antibiotics or 2 - 4 weeks of intravenous antibiotics (ceftriaxone). If symptoms still persist, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, or disease-modifying antirheumatic drugs may be recommended by a rheumatologist. In severe cases, patients may require surgery (synovectomy) to reduce joint inflammation.

Persistent Neurological Disorders. In general neurological problems persist in 5% of patients, although some studies have reported much higher rates of up to 50%. Persistent symptoms usually include headache, attention and memory problems, and depression. Patients may also experience neurologic pain, numbness, or abnormalities in the face. Neurologic symptoms generally resolve and improve within a year.

Heart Problems. About 5% of untreated patients experience acute heart events from electrical conduction problems caused by the infection. Heart symptoms can appear within a few days to several months after the onset of disease. They include:

Arrhythmias (irregular heartbeats)
Pericarditis (inflammation of the lining of the heart), which occurs in about 5% of patients

Lyme-related heart problems almost always resolve without serious consequences within a week. About 30% of patients may need a temporary pacemaker, however. In very rare cases, these heart rhythm abnormalities have been fatal. There is some debate about whether there are any long-term consequences to the heart, such as the development of heart failure in some patients. One study of patients who had Lyme-related heart effects reported no greater long-term risk for heart problems than in people without a history of Lyme disease.

Miscellaneous Complications. Other complications reported include:

Problems in the eye, including swelling that can cause pain and sensitivity to light
Hepatitis (inflammation in the liver)
Respiratory difficulties

Infections in the Pregnant Patient. The occurrence of any infection during pregnancy is of special concern. While the current research indicates that complications during pregnancy due to Lyme disease are very rare, pregnant women should still adhere scrupulously to preventive measures.

Some studies indicate that Borrelia burgdorferi may be transmitted to the fetus during pregnancy, with the risk highest during the first trimester. If this occurs, however, it is likely to be very rare and not an issue of great concern. There is no evidence of any severe effects in the offspring of infected pregnant women.
There are no reports of human infant Lyme disease infection from breast-feeding. Studies on animals, however, have reported transmission of the organism to infant mice through breast milk, but these findings do not appear to be applicable to people.

Lyme disease is a curable condition. Nearly all patients (95%) improve after a short course of antibiotics. In very rare cases, patients continue to complain of persistent non-specific symptoms, such as fatigue, muscle aches, cognitive problems, and headache lasting years after completing antibiotic treatment for the initial infection.

This syndrome, which resembles chronic fatigue syndrome (CFS) or fibromyalgia, is referred to as post-Lyme disease syndrome. In the past, it has been called “chronic Lyme disease.” However, based on many reviews of scientific literature, experts strongly believe that Lyme disease does not have a chronic state. According to the 2006 guidelines from the Infectious Diseases Association of America, post-Lyme disease syndrome is the preferred name for this condition.

Patients are considered to have this syndrome if they still have symptoms 6 months after treatment. Most importantly, there must be definitive evidence that the patient was originally infected by the B. burgdorferi spirochete. If there is no documented evidence of infection, it could be that the patient never had Lyme disease, or may be experiencing a new or different type of illness. If the patient did have Lyme disease, symptoms should eventually resolve without additional antibiotic treatments.

Experts strongly advise against prolonged antibiotic treatment. There is no evidence that long-term antibiotics help treat post-Lyme disease syndrome symptoms. In addition, long-term antibiotic treatment carries its own serious risks, such as the development of antibiotic-resistant superbugs.

Diseases with Similar Symptoms

Many other illnesses can mimick various features of Lyme disease. Depending on the symptoms, a doctor may be able to perform the evaluations necessary to rule out other conditions.

Other infections can produce fever, headache, muscle aches, fatigue, and some of the neurologic or cardiac features of early Lyme disease. Some are transmitted by the same tick as Lyme disease.

Co-Infections Transmitted by the Ixodes Tick. Babesiosis and human granulocytic anaplasmosis (HGA) are transmitted by the same tick that carries Lyme disease. People may be co-infected with one or more of these infections, all of which can cause flu-like symptoms. If these symptoms persist and there is no rash, it is less likely that Lyme disease is present. Still, diagnosing a co-infection is difficult.

Other Spirochete Infections. Leptospirosis is a spirochete infection spread through animals or contaminated water that most often affects young people during the summer or fall.

Other Tick-Borne Infections. A number of other tick-borne diseases may resemble Lyme disease, although they are more common in parts of the U.S. where Lyme disease is less prevalent.

Tick-borne relapsing fever (TBRF), a flu-like illness that occurs in mountainous areas of the West during the summer, may be misdiagnosed as Lyme disease. The antibiotic doxycycline may be prescribed to patients who have been bitten by ticks suspected of carrying TBRF, to help prevent development of the disease.
Rocky Mountain spotted fever, which is also transmitted by ticks, is most prevalent in the south central and southeastern parts of the United States, but occurs throughout North and South America. The most characteristic symptom is a spotty rash that appears 5 - 10 days after infection. The disease is caused by ticks that carry the bacterial organism Rickettsia rickettsii, and is considered the most severe tick-borne illness in the United States. Unlike Lyme disease, which is rarely fatal, Rocky Mountain spotted fever causes death in 10% of all cases. Recent outbreaks of Rocky Mountain spotted fever have been linked to increases in wild dog populations.
A tick-borne infection called by human monocyte ehrlichiosis (HME), carried by the Lone Star tick, strongly resembles Lyme disease, including a similar rash. It is not caused by the Lyme spirochete, however, and has been identified in patients who live in the southern United States.

Researchers speculate that ticks may be responsible for other diseases not previously thought to be carried by these vectors. For example, the Bartonella family of bacteria causes cat-scratch fever (which is transmitted from cat to cat by fleas) and trench fever (historically transmitted by lice).

Allergic Reaction to the Tick. If a rash, even ring-shaped, appears hours rather than days after a tick bite, it is most likely an allergic reaction to the tick, not a symptom of Lyme disease.

Other Insect Bites. Not every rash seen in regions where Lyme disease is common is caused by a tick. The bites of many insects and spiders can cause a skin reaction.

A number of autoimmune diseases have chronic and low-level symptoms that may be confused with Lyme disease.

Systemic lupus erythematosus (SLE) produces a rash (usually on the face), flu-like symptoms, and arthritis, but they usually develop very slowly over time.
Rheumatoid arthritis or Reiter syndrome causes pain, swelling, or stiffness of the joints that may be confused with post-Lyme disease syndrome.
Scleroderma has a limited form of the disease called morphea, which produces hard patches of skin. Some studies have even reported an association between B. burgdorferi and some cases of morphea. However, the evidence is weak and if it exists it is possibly limited to a specific variant in Europe and Asia. There is no association between severe scleroderma and Lyme disease.
In children, juvenile rheumatoid arthritis or rheumatic fever, which follows strep throat, should be considered.

A number of conditions cause chronic fatigue and joint and muscle aches that resemble descriptions of post-Lyme disease syndrome:

Mononucleosis -- this viral infection is common in adolescents
Chronic fatigue syndrome (CFS)
Fibromyalgia
Depression (may include persistent fatigue and vague aches and pains)

The early neurologic symptoms of Lyme disease (headache, stiff neck, and fatigue) can easily be mistaken for viral meningitis. Children with viral meningitis are more likely to have a higher fever. Patients with Lyme disease often have other symptoms, such as the bull's-eye rash.

Diagnosis

Proper diagnosis of Lyme disease is important. A diagnosis of Lyme disease is straightforward if the patient meets the following criteria:

Lives in an area of tick-infestation
Has the tell-tale bulls-eye rash
Has other symptoms (headache, joint aches, malaise, flu-like symptoms)

If the patient meets all the criteria, except the rash, the doctor may undertake the enzyme-linked immunosorbent assay (ELISA) or the Western Blot test.

In some cases, if the patient seeks a diagnosis within the first 2 - 3 weeks, the doctor may take a sample of the skin or of the blood. If Lyme spirochete is present, it may be identified in the laboratory in a culture medium (a substance in which the organism can thrive and reproduce). This is necessary only if a doctor suspects Lyme but the diagnosis is not clear.

If the infection is not obvious from the patient's history and physical symptoms, but Lyme disease is suspected, the doctor may run tests for evidence of specific factors that suggest infection with B. burgdorferi. Such factors include:

Proteins referred to as Osps. These proteins (referred to as Osp A through F) coat the outer surface of the B. burgdorferi spirochete and then attach to human cells after infection.
Antibodies that attack these Osps. Antibodies are the weapons of the immune system that are launched when foreign invaders (called antigens) are detected. In the case of Lyme disease, these antigens are the Osps.

Specific Tests.

The U.S. Centers for Disease Control (CDC) recommends a two-step process for Lyme disease blood tests:

ELISA and Other Initial Tests. The first tests used are either enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test. ELISA is the immune test used most often for Lyme disease. (The IFA test is less accurate but may be used when ELISA isn't available.) ELISA measures antibodies that are directed against the B. burgdorferi spirochete. A newer variant is a rapid test (PreVue) that can provide results within an hour. Positive results from any of these tests still require confirmation with a Western blot test. Negative results do not require further testing.
Western Blot. If any of these tests is positive or uncertain, they are followed by the Western immunoblot (WB). This test is more accurate and is very helpful in confirming the diagnosis. The Western blot creates a visual graph showing bands of different colors or shading that experts use to interpret the immune response.

The CDC recommends only these tests. In 2005, the CDC warned against tests -- such as urine antigen, immunofluroescent staining, and lymphocyte transformation -- that do not have enough scientific evidence to support their use.

Accuracy of the Tests. These tests are very expensive, and none are completely accurate in either identifying Lyme or ruling it out. They should never be used to make a primary diagnosis of Lyme disease in patients who do not have obvious symptoms of the disease.

Both false positive and false negative results are common with these tests.

False positive results occur when the test suggests the presence of the disease, but the person does not actually have an active infection. This may occur in different ways:

The antibodies to the infectious organism triggering the antibodies are not the Lyme spirochetes. Other organisms that can trigger such antibodies include syphilis and relapsing fever. Dental infections may trigger a false positive response.
The patient may have been infected with Lyme disease previously and harbor antibodies to the disease.

False negative results miss the actual presence of the disease. These results are also common. (If the results are negative but Lyme disease is highly suspected, the doctor will probably prescribe antibiotics anyway.) False negative results occur for a number of reasons:

The test is taken too early in the course of Lyme disease. In such cases, the antibodies that fight the spirochete might not have reached a level that is high enough to be detected. (Only about 20 - 30% of patients can be identified using immune system tests in the first 2 - 4 weeks. By the fourth week, up to 80% of patients will have detectable antibodies.)
The patient has taken certain medications, such as steroids or certain anti-cancer drugs, which reduce the immune system's ability to produce antibodies, including those in response to Lyme disease.
There are too many infection-fighting antibodies attached to the bacteria. In this case, there are not enough loose antibodies in the blood sample to trigger a response.
The laboratory itself has set its sensitivity point too high. Some laboratories establish a standard of very high antibody levels before the test results will trigger a finding of Lyme disease. (They do this to avoid too many false-positive responses.) In so doing, however, their tests may miss the disease in patients with lower antibody levels. A related diagnostic problem concerns the possibility of missing persistent Lyme disease after antibiotic treatments, when antibody levels would be low.

All of this means that a negative blood test does not rule out a diagnosis of Lyme disease, particularly if symptoms strongly suggest its presence. Conversely, a weakly positive blood test does not prove that Lyme disease is causing the symptoms. A second blood test, taken several weeks later, may help.

The polymerase chain reaction (PCR) test detects the DNA of the bacteria that causes Lyme disease. However, it requires technical expertise and expensive equipment, and can be performed only in a few laboratories in the country. The test also has a high risk of false-positive results. Research indicates that blood or urine samples do not provide accurate results, but skin biopsies may be useful in some cases. At this point, the PCR test is reserved for certain patients with specific diagnostic problems. For most patients, standard antibody tests are preferred.

Analysis of Spinal Fluid. In patients who have neurologic symptoms, a lumbar puncture (a spinal tap) may be used to test for the bacteria in spinal fluid and may be useful for an early diagnosis of Lyme disease.

Treatment

Antibiotics are the drugs of choice for all phases of Lyme disease. In nearly all cases they can cure Lyme, even in later stages.

According to the 2006 guidelines from the Infectious Diseases Society of America (IDSA), people bitten by deer ticks should not routinely receive antibiotics to prevent the disease.

A single dose of the antibiotic doxycycline may be given in situations that meet all of the following conditions:

The tick is still attached to the patient and is positively identified as an adult or nymphal I. scapularis (the tick that carries the Lyme disease B. burgdorferi spirochete).
Doxycycline treatment can be started within 72 hours of the tick bite.
There is proof that at least 20% of ticks in that geographic area are infected with B. burgdorferi.
It is safe for the patient to receive doxycycline (this drug should not be given to pregnant women or children younger than 8 years of age).

In general, the risk of developing Lyme disease after being bitten by a tick is only 1 - 3%. However, patients who have removed attached ticks from themselves should inform their doctors. Patients who have been bitten by a tick should be monitored for up to 30 days to make sure they do not develop symptoms of Lyme disease, especially the tell-tale bull’s-eye rash. If you do develop a skin lesion or flu-like illness during this time, be sure to tell your doctor.

The early stages of Lyme disease usually involve classic bull’s-eye rash (erythema migrans) and flu-like symptoms of chills and fever, fatigue, muscle pain, and headache. In rare cases, patients develop an abnormal heartbeat (Lyme carditis).

All of these conditions are treated with 10 - 28 days of antibiotics. The exact number of days depends on the drug used, and the patient’s response to it. Antibiotics for treating Lyme disease generally include:

Doxycycline. This antibiotic is effective against both Lyme disease and human granulocytic anaplasmosis (HGA) and so is the standard antibiotic for any patient over 8 years old (except pregnant women). Doxycycline cannot be used routinely in children under 8 years old. It is a form of tetracycline and as such discolors teeth and inhibits bone growth. It can also cause birth defects, so it should not be used during pregnancy.
Either amoxicillin (one of the penicillins) or cefuroxime (Ceftin) -- a drug known as a cephalosporin -- are the alternative treatments for young children and some adults. Amoxicillin is the first choice and also probably the best antibiotic for pregnant women. Unfortunately, many people are allergic to penicillin. In addition, strains of bacteria are emerging that are resistant to penicillins.
Intravenous ceftriaxone -- another cephalosporin -- may be warranted if there are signs of infection in the central nervous system (the brain or spinal region) or heart problems.
Other types of antibiotics, such as macrolides, are not recommended for first-line therapy.

Side Effects of Antibiotics. The most common side effects of nearly all antibiotics are gastrointestinal problems, including cramps, nausea, vomiting, and diarrhea. Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening, anaphylactic shock. Some drugs, including certain over-the-counter medications, interact with antibiotics. Patients should report to their doctors all medications they are taking.

Most cases of Lyme disease involve a rash and flu-like symptoms that resolve within 1 month of antibiotic treatment. However, some patients go on to develop late-stage Lyme disease, which includes Lyme arthritis and neurologic Lyme disease.

Slightly more than half of patients infected with B. burgdorferi develop Lyme arthritis. About 10 - 20 % of patients develop neurologic Lyme disease. A very small percentage of patients may develop acrodermatitis chronica atrophicans, a serious type of skin inflammation. These conditions are treated for up to 28 days with antibiotic therapy. If arthritis symptoms persist for several months, a second 2 - 4 week course of antibiotics may be recommended. Oral antibiotics (doxycycline, amoxicillin, or cefuroxime) are used for Lyme arthritis and acrodermatitis chronica atrophicans. (In rare cases, patients with arthritis may need intravenous antibiotics.)

A 2 - 4 week course of intravenous penicillin, ceftriaxone, or cefotaxime is used for treating severe cases of neurological Lyme disease. For milder cases, 2 - 4 weeks of oral doxycycline is an effective option.

In about 5% of cases, symptoms persist after treatment, a condition referred to as post-Lyme disease syndrome. The treatment of post-Lyme disease syndrome is a controversial issue. Most experts do not recommend continuing antibiotic therapy beyond 30 days. Scientific studies do not show any evidence that the benefits of long-term antibiotic treatment outweigh its risks. Long-term antibiotic treatment can lead to a serious and difficult-to-treat infection called Clostridiumdifficile, and can also cause the patient to become resistant to all types of antibiotics.

Experimental and alternative remedies are also not recommended. However, some patients may benefit from learning pain control and cognitive behavioral techniques to help them cope with and manage their symptoms.

Some people use vitamin B complex, omega-3 and omega-6 fatty acids (found in primrose oil and fish oils), and magnesium supplements (magnesium L-lactate dihydrate) to help relieve symptoms. No evidence suggests that they are beneficial. Any such therapies should be discussed with a doctor. Newsletters and Internet sites have cropped up in recent years advertising untested treatments to patients with symptoms of Lyme disease who are frustrated with traditional medical channels. Some remedies are dangerous, and most are ineffective.

In 2006, the Food and Drug Administration (FDA) warned people not to use an alternative medicine product called bismacine (also known as chromacine). This injectable product contains high amounts of bismuth, a heavy metal that can be poisonous. People who have taken bismacine have experienced heart and kidney failure, and one death has been reported. Although some people claim that bismacine can help treat Lyme disease, it is not approved for the treatment of any illness or condition.

Prevention

Everyone should avoid specific tick-infested areas, including tall grass, woods, and bushes where ticks tend to congregate. If this is not possible, people should take additional preventive measures. The U.S. Centers for Disease Control (CDC) also recommends:

Use of tick repellant.
Routine tick checks -- removal of infected ticks within 48 hours of attachment substantially reduces the likelihood of transmission.
Prompt antibiotic prevention for tick bites -- although this method is controversial, the CDC concludes that it is probably beneficial.
Removing brush and leaves -- such landscaping measures can reduce transmission rates by 50 - 90%.
Applying pesticides to yards once or twice per year, which can decrease the number of ticks by 68 - 100%

Mowing the grass regularly, clearing away leaves, and placing wood chips as a barrier around a lawn can help greatly reduce the tick population.

Permethrin for the Lawn. Insecticides can reduce tick infestation by 90%. Insecticides should be applied in late spring or early fall in a strip a few feet wide along the perimeter of the lawn where small animals are likely to enter or live.

The most commonly used insecticides are pyrethrins, which are compounds derived from the Chrysanthemum family. They are available as natural products or in synthetic forms (permethrin). They are poisons that affect the nerve system of insects. They are safe, particularly the natural products, for humans and pets. All pyrethrins are highly toxic for certain fish and slightly toxic for birds, such as mallard ducks. Some people do experience an allergic reaction to them. As with all insecticides, there is some concern about the possible consequences of long-term exposure, but to date there is no evidence of any harm.

Damminix, available in hardware stores, consists of cardboard tubes stuffed with permethrin-treated cotton. The tubes are placed where mice can find them (dense, dark brush) and collect the cotton for lining their nests. The pesticide on the cotton kills any immature ticks that are feeding on the mice. Best results are obtained with regular applications early in the spring and again in late summer. As many neighbors as possible should use it to be effective.

Other Pesticides. Other tick-killing spray pesticides that have been used include those containing diazinon, chlorpyrifos, and carbaryl. Animal studies have reported severe toxic effects associated with these chemicals. Some of these chemicals are being phased out for home use. Parents should balance the effects of a very negligible risk for a highly treatable infection versus excessive use of possibly harmful chemicals.

Fencing. Deer fencing, a wire fence about 3 - 4 yards high, or electrified fencing can be helpful, but it is costly to put up and maintain.

Ivermectin. Corn that is laced with the anti-parasite medication ivermectin (Ivomec and others) and then eaten by deer helps prevent ticks from feeding on them. Ivermectin is present in a number of products used by veterinarians to control parasites, such as heartworm. It has potential toxic effects in collie or collie mixed breeds, however.

Hiking and camping in the Northeastern woods carries a significant risk for tick bites and Lyme disease (3% in one study). Anyone out in the woods during tick season should wear protective clothing, including:

Light-colored clothing -- makes it easier to spot ticks
Long-sleeved shirts and long pants with cuffs tucked into shoes or socks
High boots, preferably rubber boots
Tick-collars for small dogs -- can be worn around a person's ankles over socks or pants

Simply washing clothes will not kill ticks. After venturing outdoors, people should run their clothes through a dryer at high temperature for a half hour. Spraying clothes with solutions containing permethrin (Permanone, Duranon, Permakill) affords additional protection. Keep in mind that these sprays should not be applied to the skin. Clothes should not be retreated with permethrin for 48 hours unless they are washed.

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Experts recommend that most adults and children over 12 years old use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

DEET products should never be used on infants younger than 2 months. According to the Environmental Protection Agency, DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions.

If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. In deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

Do not use on the face, and apply only enough to cover exposed skin on other areas.
Do not over apply and do not use under clothing.
Do not apply over any cuts, wounds, or irritated skin.
Parents or an adult should apply repellent to a child and not let the child apply it. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
Wash any treated skin after going back inside.
If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied inside or directly on anyone's face.

Other Insect Repellent Products. In 2005, the CDC added two new mosquito repellents to its list of recommended products:

Picaridin. Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breastfeeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.
Oil of lemon eucalyptus. In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Self-Inspection. The tick is unlikely to transmit the infection within 3 days of the bite, but prompt removal is still important. The following tips are important for self-inspection:

Ticks responsible for Lyme disease are very small and may resemble freckles or scabs.
People spending time in tick-infested locations should inspect themselves several times a day, including at bedtime.
Check nonexposed areas, such as the back of the knee, as well as exposed areas. Someone else should check the scalp, back of the neck, and other difficult to reach areas.
Check clothing as well as skin. A tick on can be hidden in folds or creases.

Tick Removal. If an attached tick is discovered, there is no reason to panic. Do not put a hot match to the tick or try to smother it with petroleum jelly, nail polish, or other noxious substances. This only prolongs exposure time and may cause the tick to eject the Lyme organism into the body.

The safest and most effective way to remove an attached tick is:

Grasp the tick's mouth area with clean tweezers as close to the skin as possible. (Take care not to handle it with bare fingers as this can also spread infection.)
Next, pull upward with a steady even pressure. Do not twist, crush, or squeeze the body area of the tick, because this region contains the infectious organism. In fact, do not be alarmed if some of the mouth parts remain in the skin. They are not infectious.
Put the tick in a jar or container of alcohol, which will kill it. Some people lay a piece of adhesive tape to the top of the tick and fold it over, without touching the insect. Then they simply throw it away. Tape is also effective for trapping a tick that has not yet attached to the skin.
Once the tick is removed, wash the bite area with soap and water or with an antiseptic to destroy any contaminating microorganisms. Wash hands as well.

The LYMErix Vaccine. The LYMErix vaccine, previously approved, was taken off the market because of poor sales and because of problems encountered with its use. A primary limitation was that the vaccine was effective only in about 75% of cases, and the effects were not long lasting. There were also reports of arthritic and neurologic symptoms in a few vaccinated people. There is no definitive evidence, however, that the vaccine was responsible for these symptoms.

Other Vaccines. Deer ticks lay their eggs on mice and other small rodents. These eggs develop into larvae that feed on these small animals. When the larvae develop into nymphs, they seek a larger host like a deer or human. Scientists are exploring the idea of vaccinating mice and other rodents against B. burgdorferi. Inserting an oral vaccine into these animals’ food supply helps reduce the number of nymph ticks and may be a more effective preventive strategy than vaccinating humans. Recent studies suggest that vaccination of mice produces 89 - 100% protection from B. burgdorferi infection.

Since dogs, cats and even horses can get Lyme disease, inspect pets for ticks regularly. Symptoms in animals include lameness and lethargy. Dogs are much more likely to get Lyme disease than cats, but both are susceptible. In dogs, symptoms occur 2 - 5 months after a tick bite and include fever, lameness, and lack of appetite. In rare cases, Lyme disease can cause kidney damage in dogs if it is left untreated.

Preventive Products. Products containing permethrin (Bio Spot, EXspot), amitraz (Preventic), or fipronyl (Frontline) can be used safely on dogs. Not all of these products are safe in cats. Only permethrin is also effective against fleas. Some veterinarians suggest that the combination of BioSpot and Preventic is very effective. [Another product-- selamectin (Revolution) --is sold for flea and tick control, but it appears to have very limited effect against ticks.]

Pet Vaccines. Lyme disease vaccines are available for dogs, but they do not offer total protection. Veterinarians vary in their use of the vaccines.

Treatment. As with people, antibiotics almost always cure the infection in animals.

Human Granulocytic Anaplasmosis (HGA)

In addition to Lyme disease, I. scapularis deer ticks can carry other types of infections that cause disease in humans. Human granulocytic anaplasmosis (HGA) is another illness spread by the deer tick. (HGA was formerly called human granulocytic ehrlichiosis. Another type of ehrlichiosis, human monocytic ehrlichiosis, is carried by a different type of tick.)

Typical HGA symptoms appear very suddenly within 4 - 14 days of being bitten by an infected tick. Symptoms include headache, fever, chills, headache, and muscle pains. Vomiting, diarrhea, and loss of appetite are also common. Blood tests may indicate a low blood platelet count, low white blood cell count, and increased liver enzyme levels.

HGA is caused by a species of bacteria called Anaplasma phagocytophilum. A blood test can identify the presence of this bacterium.

All patients who show signs of symptoms should be treated with doxycycline to reduce the risk of complications. Another type of antibiotic, rifampin, is an alternative option for pregnant women, children younger than 8 years of age, or patients who are allergic to doxycycline. Treatment is not recommended for people who do not exhibit symptoms, even if they test positive for antibodies to A. phagocytophilum.

Babesiosis

The tick that carries Lyme disease and human granulocytic anaplasmosis (HGA) can also carry babesiosis. Babesiosis is caused by a parasite called protozoa. It has been detected in about 10% of Lyme disease patients, and has been reported in Massachusetts, New York, Connecticut, Rhode Island, New Jersey, Minnesota, Wisconsin, Georgia, California, and Washington.

When babesiosis is acquired from ticks, the infection occurs only in the summer. However, unlike in Lyme disease, blood transfusions have also been known to transmit babesiosis, so it can also occur other times of the year. The disease is still very rare, but people in tick-infested areas should be aware of it.

Symptoms of babesiosis occur 1 - 4 weeks after a tick bite and are similar to those of malaria. Most cases are very mild and nearly unrecognizable. More severe symptom may resemble those in malaria and include:

Headache
Fever and chills, with night sweats
Nausea and vomiting
Muscle aches
Anemia

In healthy people, babesiosis generally causes only mild and temporary problems, but research indicates that the infection might persist in some people and may be spreading faster than previously reported. In rare cases, it can be severe and even life-threatening, particularly in elderly people or those with chronic health problems or compromised immune systems. In such cases, the infection can cause altered mental states, anemia and other blood abnormalities, very low blood pressure, respiratory distress, and kidney insufficiency. Coinfection with Lyme disease may also increase its severity. Unfortunately, it is very difficult to diagnose.

Babesiosis is caused by a protozoon parasite, not a bacteria, so antibiotics alone won’t cure the disease. Treatment involves a two-drug combination of an anti-malaria medication and an antibiotic. The standard drug combinations are atovaquone (Mepron) plus azithromycin (Zithromax, Zmax) or clindamycin plus quinine. About 25% of patients cannot tolerate quinine. Adverse effects associated with quinine include hearing loss, tinnitus, stomach upset, diarrhea, and dizziness.

Resources

www3.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
www.cdc.gov/ncidod/dvbid/lyme -- Centers for Disease Control
www.idsociety.org -- Infectious Diseases Society of America
www.aldf.com -- American Lyme Disease Foundation
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation

References

Centers for Disease Control and Prevention. Lyme disease -- United States, 2003-2005. MMWR Morb Mortal Wkly Rep. 2007 Jun 15;56(23):573-6.

Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; Ad Hoc International Lyme Disease Group. A critical appraisal of "chronic Lyme disease." N Engl J Med. 2007 Oct 4;357(14):1422-30.

Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Cholesterol

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Cholesterol's Effect on the...
Cholesterol's Effect on the...
Risk Factors
Symptoms
Diagnosis
Lifestyle Changes
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Children and Adolescents

In 2007, the American Heart Association (AHA) established new guidelines for assessing and treating high cholesterol in children and adolescents. According to the AHA’s scientific statement:

LDL (“bad") cholesterol goals for children should be 190 mg/dL or less for children without heart disease risk factors and 160 mg/dL or less for children with heart disease risk factors.
Children who are overweight or obese, as well as those with a family history of high cholesterol and heart disease, should get their cholesterol levels checked.
For overweight and obese children with cholesterol imbalances, diet changes and exercise should be tried before drug treatment. For children with cholesterol imbalances who have a family history of cholesterol and heart problems, statins are the best first-line drug therapy.

Herbs and Supplements

Garlic, whether raw or in supplement form, does not help lower LDL in patients with moderately high LDL levels, according to a 2007 Archives of Internal Medicine Study.
Policosanol, a dietary supplement derived from sugar cane, has no effect on cholesterol, indicates a 2006 Journal of the American Medical Association (JAMA) study.

Diet Plans

In a 2007 JAMA comparison study of four diet plans (Atkins, Ornish, Zone, and LEARN), the low-carbohydrate Atkins diet was best at raising HDL (“good cholesterol”) levels and lowering triglyceride levels, but did not affect LDL levels. The low-fat Ornish diet was best at lowering LDL levels.
The Mediterranean diet works better than a low-fat diet in quickly lowering cholesterol as well as blood pressure and blood sugar, suggests a 2006 Annals of Internal Medicine study.

Drug Research

In contrast to research findings released last year, rosuvastatin (Crestor) does not appear to reverse heart disease, according to a 2007 JAMA study. However, the statin drug did help slow the progression of arterial thickening.

Introduction

Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.

Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:

Repairing cell membranes
Manufacturing vitamin D on the skin's surface
Producing hormones, such as estrogen and testosterone
Possibly helping cell connections in the brain that are important for learning and memory

Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products, meat, and dairy products.

Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, coconut, and coconut butter -- are also high in saturated fats.

Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants.

Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the information about the effects of cholesterol and triglyceride actually concerns lipoproteins.

Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.

Cholesterol-Carrying Lipoproteins. These are the lipoproteins commonly referred to as cholesterol.

Low density lipoproteins (LDL). (Often called the "bad" cholesterol.)
High-density lipoproteins (HDL), the smallest and most dense. (Referred to as the "good" cholesterol.)

Triglyceride-Carrying Lipoproteins.

Intermediate density lipoproteins (IDL). They tend to carry triglycerides.
Very low density lipoproteins (VLDL). These tend to carry triglycerides.
Chylomicrons (largest in size and lowest in density).

Lipoprotein(a). Lipoprotein(a), or lp(a) has a size and density somewhere between LDL and HDL. The molecules carry a protein that may interfere with the body's ability to dissolve blood clots. Lipoprotein(a) is being investigated as a possible marker or cause of heart disease.

Remnant Lipoproteins. Remnant lipoproteins are byproducts of chylomicrons, very low-density lipoproteins (VLDL), or both. Some research indicates that high levels may be an important risk factor for coronary artery disease, particularly in patients who have otherwise normal cholesterol levels.

Reducing LDL and total cholesterol levels, while at the same time boosting HDL levels, can prevent heart attacks and death in all people (with or without heart disease). Reducing LDL is the primary goal of most cholesterol therapy.

Blood tests can easily measure both HDL and overall cholesterol levels. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by subtracting HDL and triglyceride levels from total cholesterol. The exact formula is:

LDL = TOTAL CHOLESTEROL - HDL - TRIGLYCERIDES/5.

In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

The risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Two or more of these risk factors increases by 20% the chance of having a heart attack within 10 years.

The LDL cholesterol level is one of the most important factors in determining whether a patient needs cholesterol therapy and whether the treatment is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Risk Level	Goal (d/L)	OptimalGoal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

The following chart summarizes all goals.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dL is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dL or below for people with two or more risk factors; 100 mg/dL is an optimal goal. 160 mg/dL or below for people at less risk (one or zero risk factors); 130 mg/dL is an optimal goal. Anything above 160 is high, with levels above 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/dL are optimal.	Below 150 mg/dL is normal. 150 - 199 is borderline high. 200 - 499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men (before age 65 for women), smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dL. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Although current guidelines as described in the table are extremely useful, they do have pitfalls. For example, the following cholesterol levels pose some dilemmas:

Low LDL levels (protective) accompanied by low HDL, high triglycerides, or both (harmful)
High total cholesterol (harmful) accompanied by high HDL (protective)

Would individuals with these cholesterol balances be at high risk or low risk for developing heart disease? To resolve this dilemma, experts have devised a calculation for a risk ratio by dividing the total cholesterol by either total HDL or LDL. It is not clear at this point which ratio is a better predictor of heart disease, although the HDL ratio may be superior. Using this ratio, the following results indicate better to worse outlook:

The ideal ratio is 3.5 or below.
A ratio of 4.5 carries an average risk.
Ratios of 5 or higher are potentially dangerous.

For example, if a person has a high total cholesterol of 280 mg/dL but a high HDL level of 70 mg/dL, the risk ratio is 4, which actually carries a lower than average risk. The use of this ratio may predict coronary artery disease more accurately than using total cholesterol levels alone. Still, the primary goal of lipid-lowering therapy is reducing LDL levels. Evidence strongly suggests that the lower the LDL levels, the lower the risk for heart disease.

Cholesterol's Effect on the Heart

Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

As many as half of these deaths were probably due to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

Click the icon to see an image of the developmental process of atherosclerosis.

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, the risk is compounded.

The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.

On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.

The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.

Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.

When LDL collects on arterial walls these oxidants are released from the wall membranes.
Oxidants are missing an electron and tend to bind with other molecules in the body, a process called oxidation.
When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.

Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:

White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.

Click the icon to see an image of the cut section of an artery.

Immune factors that increase the risk for blood clots are also mobilized.
Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels and allow blood to flow freely.

High density lipoprotein (HDL) appears to benefit the body in two ways:

It removes cholesterol from the walls of the arteries and returns it to the liver.

Click the icon to see an image of the liver.

It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.

HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.

Triglycerides are major troublemakers for the heart. They appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.

The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.

Some evidence also suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), also known as or lp(a). This lipoprotein falls somewhere between HDL and LDL in density and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, few experts recommend drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences.

Cholesterol's Effect on the Brain

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. A 2002 study suggested that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.

Evidence points to high cholesterol levels, along with high blood pressure and a family history of the disease, as independent risk factors for AD. A major research target for common factors between cholesterol levels and AD has been apolipoprotein E (ApoE). ApoE plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD.

High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. Some studies report that cholesterol is important within the brain for cell communication and memory.

Risk Factors

About half of all American adults have total cholesterol levels over 200 mg/dL. Over 25% have been told by doctors that they have unhealthy levels. Total cholesterol levels have been declining over the last several decades, at least among middle-aged and older adults. This decline may be partly due to the increased use of statins and other lipid-lowering medications. However, total cholesterol levels are getting higher among younger adults (ages 25 – 34 years). The major risk factor for these high rates may be the Western lifestyle. The typical high-fat/low-fiber American diet coupled with sedentary habits is largely responsible for this unfortunate trend.

Men. Heart disease is the major cause of death in men. On average, men develop coronary artery disease 10 - 15 years earlier than women do and have a greater risk for dying of heart disease at a younger age. A 2006 study suggested that high total cholesterol may also contribute to the development of high blood pressure in men.

Women. Coronary artery disease is also the number one killer of women. Women between the ages of 20 and 34, and after menopause (around age 55), have higher cholesterol levels than men. Some evidence suggests that HDL levels may be more significant in women than in men. In one study, at total cholesterol levels above 200, women with HDL levels below 50 had a higher death rate than those with levels above 50, regardless of their LDL cholesterol levels. Women also appear to be more susceptible to the high-triglyceride low-HDL syndrome, which may be a particular risk factor for heart disease.

Children and Adolescents. Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish “normal” cholesterol levels in children. Changes in cholesterol levels occur between the ages of 8 - 18, and vary between genders and population groups. Cholesterol levels tend to naturally rise sharply until puberty, then decrease sharply, and then rise again.

In 2007, the American Heart Association established general LDL goals for children that take into account these fluctuations. The association’s LDL goals are 190 mg/dL or less for children with no additional heart disease risk factors and 160 mg/dL or less for children with additional risk factors (such as family history of high cholesterol, heart disease, and diabetes).

It is also clear that children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Studies have confirmed that childhood LDL levels and body-mass index (BMI) are strongly associated with cardiovascular risk during adulthood. The American Heart Association recommends that children who are overweight and obese, as well as those with a family history of high cholesterol, undergo cholesterol screening. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.

As in adults, the primary source of unhealthy cholesterol levels in children comes from diets high in unhealthy fats: Saturated fats (found mainly in animal and dairy products) and trans fatty acids (found in commercial food products). Over-consumption of unhealthy fats increases the risk for both obesity and heart disease.

Less common causes of unhealthy cholesterol levels in children include:

Low-birth weight (associated with low HDL levels)
Low thyroid levels (hypothyroidism)
Kidney or liver diseases
Homozygous familial hypercholesterolemia. This is an uncommon inherited condition that causes severe cholesterol imbalances and can result in very early heart disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane)

Young and Middle-Aged Adults. The strongest evidence of unhealthy cholesterol levels and heart disease is in adults over age 45. However, a 2006 analysis found that while total cholesterol levels are decreasing among older adults, they are increasing in those age 25 - 34 years. Research strongly suggests that the younger a person is when unhealthy cholesterol levels develop, the greater the chance for serious heart and blood vessel problems in the future. A 2006 study in the New England Journal of Medicine indicated that keeping LDL levels low from an early age can help prevent heart disease later in life. In one important study, young men (ages 16 - 34) who had cholesterol levels at or above 240 mg/dL had two to four times the risk of dying from heart attack or other cardiac problems than did men whose cholesterol was lower than 200 mg/dL. Young men without cholesterol problems had a higher life expectancy, by up to 8 years. Other studies have suggested similar risks from unhealthy cholesterol in young women as well.

Elderly Adults. About 85% of people who die from coronary artery disease are over the age of 65. Because high cholesterol is an important risk factor for heart disease, experts strongly recommend statin or other lipid-lowering therapy for elderly people with high cholesterol levels. Surveys indicate that total cholesterol levels have been declining in older people over the last few decades. Many experts believe this is due in part to increased use of statin drugs.

In the U.S., obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, obese individuals tend to have high triglyceride levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects (high blood pressure, increase in inflammation) that pose major risks to the heart.

Obesity is a particularly hazard when it is one of the components of the metabolic syndrome, formerly known as syndrome X. This syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Many experts recommend that patients with metabolic syndrome should be aggressively treated with high-dose statin therapy to lower LDL levels.

Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.

Low thyroid levels (hypothyroidism) are associated with unhealthy lipid levels. (Lipids are fat molecules). Specifically, people with hypothyroidism are at higher risk for high total and LDL cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition can significantly reduce cholesterol levels. Some experts suggest that patients with high cholesterol should be evaluated for thyroid function before they are given cholesterol-lowering drugs. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels. [See In-Depth Report #38: Hypothyroidism.]

Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.

Genetics play a major role in determining a person's blood cholesterol levels. Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old. Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a).

Some inherited disorders and genetic abnormalities have been identified:

Familial hypercholesterolemia causes dangerous increases in cholesterol. It may be more common than previously thought. One European study reported familial hypercholesterolemia in 1 out of every 400 people.
Familial lipoprotein lipase deficiency is a very rare disorder that causes depletion of lipoprotein lipase. This is an enzyme that appears to be important in the removal of lipoproteins that are rich in triglycerides. People who are deficient in it have high levels of cholesterol and fat in their blood. A very low-fat diet is essential and is an effective treatment for these individuals.
Several studies have found a genetic mutation affecting neuropeptide Y in people with high total cholesterol and LDL levels. Neuropeptide Y is a compound in the brain that regulates appetite.
Researchers have identified a gene called APOAV, which may help detect patients at risk for elevated levels of triglycerides.

Other medical conditions strongly associated with unhealthy cholesterol levels include:

Polycystic ovarian syndrome. Women with this disorder, particularly those who are obese, appear to be at increased risk for high triglyceride and low HDL levels. This risk may be due to higher levels of the male hormone testosterone in these women.

Click the icon to see an image of a polycystic ovary.

Kidney disease

Symptoms

There are no warning signs for high LDL cholesterol levels. When symptoms finally occur, they usually take the form of angina or heart attack in response to the buildup of atherosclerotic plaque in the patient's arteries. This is definitely a condition where it pays to invest in preventive medicine before dangerous complications occur.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Diagnosis

A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated using total cholesterol and HDL levels.

To obtain a reliable cholesterol reading, experts advise:

Avoid strenuous exercise for 24 hours before the test.
Do not eat or drink anything but water for 12 hours beforehand.
If the test results are abnormal, a second test should be performed between 1 week and 2 months after the first test.

Home Tests. Tests are available for home use and in public locations, such as shopping malls and pharmacies. For example, the CholesTrak Test can be taken at home with results in 10 minutes, but it measures only total cholesterol. The BioSafe Cholesterol Panel Test is also a home test, but it needs to be sent to a laboratory. This test, however, is very accurate and provides a full lipid profile.

Certain blood tests for factors associated with inflammation in the arteries indicate a higher risk for heart disease, even in people without unhealthy lipids:

C-reactive protein (CRP). CRP is regulated by a very potent immune factor called interleukin-6. Elevated levels have been strongly associated with the inflammatory response and a higher risk for heart attack, even in people with normal cholesterol levels. CRP is also associated with high blood pressure, insulin resistance (the primary problem in type 2 diabetes), and obesity.
A high white blood cell count.
Elevated fibrinogen (a factor responsible for blood clotting).
Lipoprotein-associated phospholipase A2 may prove to be another marker for inflammation and heart disease. Studies suggest that it may play some causal role in coronary artery disease.

A new type of test measures cholesterol levels in the skin. High skin levels may indicate an increased risk for atherosclerosis and serious heart disease.

General Screening Recommendations. Experts groups differ slightly on when screening should start, but the following are generally accepted recommendations:

Periodic cholesterol testing in all adults starting at age 20. Adults with normal cholesterol levels do not need to have the test repeated for 5 years unless changes occur in lifestyle (including weight gain and diet). Adults with risk factors for heart disease or stroke should be rechecked every 2 years.
Selective screening of children who are at risk for high cholesterol and heart disease or familial hypercholesterolemia, which is genetically elevated cholesterol. Risk factors include having parents with total cholesterol levels greater than 240, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger.
Patients already being treated for high cholesterol should be checked every 2 - 6 months.

Lifestyle Changes

Although most studies that prove that lowering cholesterol saves lives are done using drug therapy, the absolute mandate for improving cholesterol levels is to first make changes in lifestyle (both diet and exercise). Even when drugs are used, healthy diet and physical activity are critical companions.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:·

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. Walnuts in particular have cholesterol-lowering properties and are a good source of antioxidants and alpha-linolenic acid.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart healthy food choice.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After embarking on any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce heart risk factors.

Therapeutic Lifestyle Changes (TLC) from the National Cholesterol Education Program. Guidelines from the National Cholesterol Education Program include these recommendations for preventing and managing high cholesterol levels in adults:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains, legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides, low HDL, or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (Benecol, Take Control). Avoid trans fatty acids found in commercial baked products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit dietary cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

Mediterranean Diet. The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Olive oil also contains polyphenol, which are phytochemicals that may help boost HDL levels.

A 2006 study that compared several types of Mediterranean diets to a low-fat diet found that Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season with garlic, onions, and herbs. Unfortunately, garlic does not appear to help lower cholesterol, but it may have other heart benefits. [See Herbs and Supplements in this section.]

Low-Carbohydrate Diets. The Atkins, South Beach, The Zone, and other diet restrict carbohydrate intake include. A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels.

In contrast, a 2007 Journal of the American Medical Association study that compared four different low-carbohydrate and low-fat diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet was best at raising HDL levels and reducing triglyciderides. In terms of LDL reduction, the low-fat Ornish diet produced the best improvements while the Atkins diet had no effect on LDL. The Atkins diet did result in better moderate weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors.

Glycemic Index. Low-carb diets -- such as South Beach, The Zone, and Sugar Busters -- rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. (These low-glycemic foods are also important components of low-fat diet plans.) A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

Low Fat Diets. Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories. In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).

The DASH Diet. The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure).
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein (from mostly plant sources) or monounsaturated fats may help reduce heart disease risk factors.

Calorie Restriction. Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).

Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Inactivity is one of the four major risk factors for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program.

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than sedentary people. Even moderate exercise reduces the risk of heart attack. One study of women found that just 1 hour of walking a week was associated with a lower risk for heart disease. The effects were similar even in women at high risk for developing heart disease.
Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to offer the greatest protection against coronary artery disease, most likely because it raises HDL ("good cholesterol") levels. Moderate exercise has little effect on HDL.
Aerobic exercise helps to open up blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit to aerobics by reducing LDL ("bad cholesterol") levels.
Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Cigarette smoking lowers HDL and is directly responsible for approximately 20% of all deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels in people exposed to cigarette smoke.

A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all.

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following natural remedies are of interest for cholesterol control:

Garlic. Contrary to popular belief, garlic does not significantly reduce cholesterol, according to a 2007 Archives of Internal Medicine study. Researchers tested raw garlic and two types of garlic supplements in 192 patients with moderately high LDL levels. None of the forms of garlic had any effect on LDL levels. However, the researchers note that garlic may still help people with very high LDL levels and it may contain other heart-protective properties.

Policosonol. Policosanol is a nutritional supplement derived from sugar cane that has been promoted as having lipid-lowering benefits. In a randomized, placebo-controlled trial published in 2007 in the Archives of Internal Medicine, policosanol was no better than placebo in reducing LDL levels.

Treatment

In 2004, the National Cholesterol Education Program issued its latest recommendations for cholesterol control and management. These guidelines increase the number of Americans who should be taking LDL-lowering medication.

Starting Medications. Even modest lowering of high cholesterol levels, whether through drug therapy or lifestyle changes, reduces the risk of disability and death from heart disease. Most experts now focus on lowering LDL ("bad") cholesterol. Reducing LDL levels is particularly critical for patients with diabetes.

The doctor will start or consider medication when:

LDL cholesterol is 190 mg/dL or higher.
LDL cholesterol is 160 mg/dL or higher AND patient has one risk factor for heart disease.
LDL cholesterol is 130 mg/dL or higher AND patient has either diabetes or two other risk factors for heart disease.
LDL cholesterol is 100 mg/dL or higher AND patient has heart disease. (If patient has diabetes, even without heart disease, medication may be considered for an LDL cholesterol of 100 mg/dL.)
LDL cholesterol is greater than 70 mg/dL AND patient has had a recent heart attack or has known heart disease along with diabetes, current cigarette smoking, poorly controlled high blood pressure, or the metabolic syndrome (high triglycerides, low HDL, and obesity).

Risk factors for heart disease include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Recent studies have found that aggressive lipid lowering with high-dose statin therapy is more beneficial than standard statin therapy in patients with existing heart disease. The Pravastatin or Atorvastatin Evaluation and Infection Trial (PROVE-IT) and the Reversal of Atherosclerosis with Aggressive Lipid-Lowering trial (REVERSAL) compared the benefits of standard statin therapy (pravastatin, 40 mg) with intensive statin therapy (atorvastatin, 80 mg) in treating patients with heart disease.

Results from PROVE-IT demonstrated that for high-risk patients, intensive statin therapy is more effective than standard therapy in lowering LDL cholesterol and C-reactive protein (CRP) levels, and that CRP levels predict risk even when LDL cholesterol has been lowered substantially. The REVERSAL data suggest that intensive statin therapy produces greater reductions in LDL and CRP levels, and that the more that statins can lower LDL, the more effective they are in reducing the progression of atherosclerosis.

An important 2006 study found that aggressive treatment with rosuvastatin (Crestor):

Helped lower LDL to below guideline levels
Moderately increased HDL levels
Reduced fatty plaque in the arteries

Experts hoped that these results suggested that statin therapy might have the potential to reverse coronary atherosclerosis. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue and to explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than other statins, but it also carries greater risks for more serious side effects (see Adverse Effects section). Many experts believe that the more that LDL is reduced through statin therapy, the greater the reduction in risk for heart disease, heart attack, and stroke.

It is important to emphasize that cholesterol-lowering medications are used along with healthy lifestyle habits, not in place of them.

Choosing the Correct Lipid-Lowering Medication. Experts now recommend that drug treatments be tailored for raising or lowering specific lipids, depending on the patient's blood lipid picture:

Statins are now the standard drugs for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. If LDL goals are not achieved, combinations of a statin with a bile-acid resin or niacin should be considered.
Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

Considerations for Children and Adolescents. In 2007, the American Heart Association (AHA) issued a scientific statement addressing the use of cholesterol drugs in children and adolescents. The AHA recommends that for children who are overweight or obese, lifestyle modifications (diet, exercise) are preferred over drug therapy and should be the first step in lowering cholesterol.

For children and adolescents who have high-risk cholesterol imbalances -- and have a family history of high cholesterol, heart attack, stroke, and diabetes -- the AHA now recommends statins as the first-line drug therapy.

Considerations for People with Diabetes. At this time, statins are recommended as the best drugs for improving cholesterol and lipid levels in people with diabetes. Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Furthermore, in one study, a statin was shown to reduce the risk of developing diabetes by 30% in people with high cholesterol. Fibrates may also be useful for people with type 2 diabetes. Niacin (nicotinic acid) has the best effect on the cholesterol profile of people with diabetes but it also increases blood sugar levels. One well-controlled study, however, found that people with diabetes who used niacin had little trouble with glucose control, and some experts believe it now may be used as an alternative to or in combination with statins.


	Effect on High LDL	Effect on Low HDL	Effect on High Triglycerides	Effect on Lp(a)
Statins	Decrease (18 - 55%)	Modest increase (5 - 15%)	Decrease (7 - 30%)	No change
Nicotinic acid (Niacin)	Modest decrease (5 - 25%) In combination with statins, may convert more dangerous LDL type to less dangerous.	Increase (15 - 35%) Drugs of choice for improving HDL levels	Decrease (20 - 50%) Drug of choice for lowering triglycerides	Decrease
Fibrates	Effect varies, but in general has little effect or modest decrease (5 - 20%)	Modest increase (6 - 20%)	Decrease (20 - 50%)	No change
Bile acid-binding resins	Decrease (15 - 30%)	Very modest increase (3 - 5%)	No change	No change

Statins are the most effective drugs for the treatment of high cholesterol, and may even prove important drugs for many people at risk for heart disease who have normal cholesterol levels. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks, in both adult women and men of any age with unhealthy cholesterol levels. Experts estimate a 25 - 30% reduction in mortality rates when patients take statins after a heart attack. (Some believe the decrease may even be greater.) These drugs may also help improve the outcome in patients with heart disease who have had angioplasty.

Important studies have reported lower rates of heart attack, stroke, and mortality rates from all causes in statin users who were at high risk for heart disease, even if they had normal or low cholesterol levels. Benefits were similar in these people regardless of gender, age, or the presence of specific heart risk factors, such as diabetes or peripheral artery disease.

Brands. Statins are currently categorized into four groups:

So-called natural statins, including lovastatin (Mevacor, generics), pravastatin (Pravachol), and simvastatin (Zocor, generics). These are the most studied statins and have proven effectiveness and good safety record.
Synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor). Studies using atorvastatin suggest they may reduce LDL more effectively than natural statins. In 2007, Lipitor was approved for additional indications to reduce the risk of heart attacks, strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is also approved for children.
The newer statins include rosuvastatin (Crestor), which was approved in 2003. Trial results have suggested that rosuvastatin is more effective in improving lipid profiles than atorvastatin, simvastatin, or pravastatin. However, like all statin drugs, rosuvastatin can cause serious side effects (see the Adverse Effects section in this report). The risks may be higher for Asian patients; this population should be started on the lowest rosuvastatin dose (5 mg).
Fixed-dose combination statins, which combine two drugs in one pill, first appeared on the market in 2004. Ezetimibe/simvastatin (Vytorin) combines two cholesterol medications that work in different ways. Simvastatin blocks cholesterol production in the liver, while ezetimibe (a non-statin cholesterol medication) blocks cholesterol absorption in the digestive tract. A 2005 study found that Vytorin was more effective than atorvastatin in lowering LDL and increasing HDL levels. Amlodipine/atorvastatin (Caduet) is a dual-therapy medication that combines the antihypertensive calcium channel blocker amlodipine with atorvastatin. It is used to treat simultaneously high blood pressure and high cholesterol.

Statins are generally administered once a day, typically in the evening because most cholesterol synthesis occurs between midnight and 3 a.m. (Atorvastatin and rosuvastatin, however, can be taken in the morning.) Statins are often prescribed along with other cholesterol-lowering drugs such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.

Beneficial Effects on the Heart and Circulation.

Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs. (The newer statins appear to produce more significant increases in HDL.) Evidence now strongly suggests that statins may offer other health benefits beyond lowering cholesterol:

Statins may improve the function of the endothelium (the lining of blood vessels), thereby improving blood flow. (This benefit apparently does not extend to people with diabetes.)
Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
Some evidence suggests that statins may help prevent blood clotting, a major factor in heart attacks.

Beneficial Effects Outside the Heart. Studies also suggest that the benefits of statins go beyond the heart. At this time, nearly all studies on the following conditions have used natural statins:

Stroke. Statins may reduce the risk for ischemic stroke in high-risk patients with a wide range of cholesterol and lipid levels. (Ischemic strokes occur from blockage in the blood vessels that lead to the brain.) In 2003, statin therapy was shown to reduce both fatal and non-fatal stroke in patients with hypertension and at least three additional cardiovascular risk factors. A 2004 study of stroke patients found that those who were receiving statin therapy at the time of their stroke had more favorable long-term outcomes than patients who were not on statin therapy, suggesting that statin therapy may provide additional benefits to patients who develop stroke.
Diabetes. Statins may have a number of effects that are helpful for patients with diabetes, and may even prevent diabetes in some people with high cholesterol. Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients. A major 2003 study found that statin therapy helped prevent cardiovascular events including coronary death, heart attack, stroke, and the need for revascularization therapy in patients with diabetes, even in those who did not have high cholesterol levels or established coronary disease.
High Blood Pressure. In an important 2002 study, patients with high blood pressure but normal hMG-CoA reductase or slightly high cholesterol levels had fewer heart attacks and strokes when they took the statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study showed similar benefits with the statin simvastatin.
Alzheimer's Disease. A number of studies have reported a significantly lower risk for Alzheimer's disease in people who take specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Statins showing the greatest promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor.) These statins appear to reduce levels of beta-amyloid. Other statins have not been associated with a lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.
Kidney Disease. Statins may prove to protect against heart disease development in patients with mild kidney disorders. According to a 2004 study, statins may also help slow the progression of existing kidney disease.
Eye Disease. Studies are investigating whether statins can help prevent macular degeneration, an age-related eye disease that can lead to blindness. Research is still preliminary, and results have been mixed.

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more common and is characterized by the thinning of the retina and drusen, small white deposits that form within the retina. The dry form of macular degeneration is usually mild. Wet macular degeneration can happen more quickly and be more serious. It occurs when vessels under the retinal layer hemorrhage and cause the retinal cells to die, creating blind spots or distorted vision in the central vision. The disease becomes increasingly common among people in each succeeding decade over 50.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. A specific myopathy, called rhabdomyolysis, can lead to kidney failure. Reports of rhabdomyolysis prompted the recall of cerivastatin (Baycol) in 2001. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.

In 2005, the FDA issued a public health advisory for rosuvastatin (Crestor), noting that this drug, like other statins, increased the risk for myopathy and rhabdomyolysis. The risks were greatest at the highest dose level (40 mg). The FDA advises that patients should not start therapy at this dose. In addition, the FDA reported the results of a post-marketing study that found that people of Asian heritage had twice the blood levels of the drug as Caucasians who had taken the same dose. Because of this difference in drug metabolism, the FDA advises that Asian Americans should start treatment at the lowest rosuvastatin dose (5 mg). In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.

Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. Similarly, high statin doses increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).

Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.

Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is the first choice for patients with low HDL levels. Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin drugs. Although niacin is available over the counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.

Benefits. When used in high doses, it has the following benefits:

Raises HDL levels higher than other anti-cholesterol drugs
Reducing triglyceride levels very effectively
Lowers LDL-cholesterol and lipoprotein(a)
Costs less than other anti-cholesterol drugs

Combinations with other drugs, particularly statins, may add significant benefits.

Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of nicotinic acid. About a quarter of patients who use rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They usually occur between 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does eventually become tolerant to these effects, and they generally subside.

The following may reduce flushing and itching:

Starting with low doses taken at mealtime and gradually working up to the prescribed dose.
Taking low-dose aspirin about 30 minutes before taking nicotinic acid. This may help prevent flushing.
Avoiding hot drinks.
Choosing an extended release form. (Even with this form, it is wise to gradually increase the bedtime dose over time and take a low-dose aspirin a half-hour beforehand.)

Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 30% of patients who take niacin experience elevated levels in blood glucose, which can be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies report that people with diabetes who use niacin have little trouble with blood sugar control.

Potentially Serious Complications. About 3 - 5% of people taking nicotinic acid develop liver problems, which disappear after the medication is discontinued. The extended form (Niaspan) appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should also avoid nicotinic acid because it elevates uric acid.

Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:

Bile is made in the liver and is used as one of the body's primary manufacturing components.

Click the icon to see an image of the gallbladder.

Once the resins bind to bile in the digestive tract, the bile is excreted in feces.
As the resins eliminate bile from the body, the liver takes more cholesterol from the bloodstream in order to produce more bile.
As cholesterol is taken out of the bloodstream, LDL levels drop.

When used in combination with dietary control, LDL levels are reduced by 15 - 20%. Combinations with nicotinic acid are even more effective, with reductions of 40 - 60% observed.

Brands. The bile-acid binding resins and similar drugs include cholestyramine (Questran, Questran Light). They are commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form.

Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. One study found that only half the standard dose of colestipol was needed when psyllium, (a soluble fiber supplement found in Metamucil, Fiberall, and Perdiem), was added to the drink. In addition, bloating and constipation were reduced. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.

Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.

Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.

Drug Interactions. Bile-acid binding resins may also interfere with other medications, including digoxin (Lanoxin), warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.

Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Newer fibrates, including fenofibrate (Lofibra, Tricor, Triglide), may be more effective in lowering cholesterol than gemfibrozil.

Benefits. Most fibrates have been shown to lower the risk of heart attack. In a 2001 study, men with both low HDL and LDL levels had a slightly lower risk of stroke after taking gemfibrozil. Fibric acid derivatives, or fibrates, have the following effects on cholesterol, lipids, and other factors:

They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take drugs ordinarily used for these purposes, such as nicotinic acid. In one study gemfibrozil, the standard fibrate, reduced the risk for adverse heart events by 22%.
Fibrates can produce modest reductions in LDL levels, although not as effectively as statins or other drugs. LDL may actually increase in patients with very high triglycerides who take these drugs. (The newer fibrates are much more effective in lowering LDL than gemfibrozil.)
A study on bezafibrate suggested it might have anti-inflammatory effects in patients with high triglyceride levels. Inflammation in the blood vessels is now recognized as a major contributor to the process leading to heart disease. However, according to a 2004 study, patients with diabetes or impaired fasting glucose levels were less likely to benefit from bezafibrate.
A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout). Another study, published in 2004, demonstrated that like bezafibrate, fenofibrate has significant anti-inflammatory properties in patients with high triglyceride levels.

Concerns. Fibrates do not appear to reduce mortality rates. In one study, people who took gemfibrozil had higher rates of death from other causes, including cancer. Some evidence suggests that fibrates may affect receptors involved in cancer development. However, a number of studies have found no higher incidence of cancer.

Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs.

Click the icon to see an image of gallstones in the gallbladder.

The drugs may cause abnormal heart rhythms and can affect the liver and kidney.

Drug Interactions. Fibrates interact with a number of drugs and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. In 2004, the FDA approved Vytorin, which combines ezetimbe and the statin simvastatin into a single pill.

In 2006, the FDA approved the use of ezetimbe in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone. Fenofibrate is a cholesterol drug that is used along with diet to reduce LDL and triglycerides.

CETP Inhibitors. Cholesteryl ester transfer protein (CETP) inhibitors, such as the experimental drug torcetrapib, are a new drug class that is being investigated for its effect on raising HDL ("good" cholesterol) levels while lowering LDL ("bad") cholesterol levels. Torcetrapib was the most widely studied of these drugs. However, in December 2006, the drug’s manufacturer abruptly stopped late-stage clinical trials after discovering that torcetrapib significantly increased blood pressure and risk of death.

Several studies published in 2007 in the New England Journal of Medicine revealed that while torcetrapib does greatly boost HDL levels (by 61% in one study) and lower LDL, it has no effect on arterial plaque. Scientists are trying to understand why this drug did not work. One theory is that torcetrapib may have increased the quantity of HDL, but not the quality. It is still not clear whether the failure of trocetrapib is specific to this drug or the entire CETP drug class. Given the current findings, it is also unclear whether research will continue on other CETP drugs.

Selective Estrogen-Receptor Modulators(SERMs). Selective estrogen-receptor modulators (SERMs) have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They include tamoxifen (Nolvadex), raloxifene (Evista), and droloxifene. Any beneficial effects of the SERMs on cholesterol and the heart are still unclear. SERMs pose a risk for deep vein blood clots, which may have implications for people with heart problems. Longer studies are needed on possible risks and benefits.

Recombinant ApoA-I Milano. ApoA-I Milano is a type of HDL protein that is found in people with very low levels of HDL. A 2003 study showed that treating patients with a synthetic form of HDL, derived from ApoA-I Milano, caused a significant regression of atherosclerosis. Ongoing trials will evaluate whether this drug can prevent cardiovascular events such as heart attack or death.

Plasmapheresis and Familial Hypercholesterolemia. Plasmapheresis is a blood-filtering procedure that is used to dramatically reduce triglycerides and may also be used to remove LDL. The procedure may be beneficial for patients with severe hereditary forms of high cholesterol who do not respond to other therapies. Studies suggest, for example, that plasmapheresis is particularly useful for patients with familial hypercholesterolemia. The process takes about 3 hours. If not performed regularly, its benefits last only about 2 weeks. People using this procedure are still advised to maintain a healthy diet and continue to take any prescribed medications to control cholesterol.

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

References

Berthold HK, Unverdorben S, Degenhardt R, Bulitta M, Gouni-Berthold I. Effect of policosanol on lipid levels among patients with hypercholesterolemiaor combined hyperlipidemia: a randomized controlled trial. JAMA. 2006 May 17;295(19):2262-9.

Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41.

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006 Sep 9;368(9539):919-28.

Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006 Jul 4;145(1):1-11.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.

Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006 Sep 5;114(10):1056-62. Epub 2006 Aug 28.

Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Review Date:
7/23/2007
Reviewed By:
Alan Greene, MD, FAAP, Chief Medical Officer, A.D.A.M., Inc.; and Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Urinary tract infection

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Urinary Tract Infections (UTIs) in the United States

According to Urologic Diseases in America, a report published in 2007 by the U.S. National Institutes of Health:

UTIs are the most expensive of all urologic diseases, accounting for about $3.5 billion a year in medical costs, including $96.4 million in prescriptions.
Over 60% of women will experience a UTI at least once in their lifetime. At least a third of women experience a UTI by the time they are 24 years old.
Only 20% of UTIs occur in men. However, men are far more likely than women to be hospitalized for an infection.
Childhood risk for UTIs is 2% for boys and 8% for girls. Vesicouretereal reflux, a condition in which urine backs up into the kidneys, affects about 10% of all children.

Circumcision Prevents UTIs

Baby boys who are uncircumcised are 10 - 12 times more likely than circumcised boys to develop UTIs during their first year of life, indicates the Urologic Diseases in America report.

High Doses of Zinc Increase UTI Risk

People who take very high daily doses of zinc supplements may face an increased risk for UTIs and other urologic problems, suggests a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc.
In general, the upper limit for zinc supplements should not exceed 40 mg/day. Eight mg/day for women and 11 mg/day for men are the recommended average doses. However, very high doses of zinc are sometimes prescribed for certain medical conditions, such as age-related macular degeneration.

Introduction

A urinary tract infection (UTI) is a condition where one or more structures in the urinary tract become infected after bacteria overcome its strong natural defenses. In spite of these defenses, UTIs are the most common of all infections and can occur at any time in the life of an individual. Almost 95% of cases of UTIs are caused by bacteria that typically multiply at the opening of the urethra and travel up to the bladder (known as the ascending route). Much less often, bacteria spread to the kidney from the bloodstream.

The male and female urinary tracts are relatively the same except for the length of the urethra.

Different classifications have been devised to help doctors choose treatments and determine the causes of UTIs.

Primary or Recurrent UTIs. UTIs are classified as primary or recurrent, depending on whether they are the first infection or whether they are repeat events.

Community- or Hospital-Acquired. UTIs are also sometimes grouped according to where they are acquired:

Community-Acquired Infections. Most UTIs are thought to develop in the community at large. It is unclear how primary community-acquired infections occur or how they are spread. Although most cases have been thought to arise sporadically, a rare outbreak in 1996 - 2000 caused by drug-resistant bacteria suggests epidemic spread of community-acquired infections could be more common than previously thought and may be spread via contaminated food. Most community-acquired infections are not serious and probably develop when the intestines become colonized with bacteria that are also predisposed to infecting the urinary tract.
Hospital-Acquired Infections. UTIs are also commonly acquired in the hospital, often due to contaminated urinary catheters. Hospital-acquired infections (known as nosocomial infections) tend to be more serious because the bacteria that cause them are often resistant to drug treatment and patients are often in poor general health.

Uncomplicated and Complicated. UTIs are also sometimes further defined as either being uncomplicated or complicated depending on the factors that trigger the infections.

Uncomplicated infections are only associated with bacterial infection, most often Escherichia coli (E. coli). They affect women much more often than men.
Complicated infections, which occur nearly as often in men as women, are also caused by bacteria but they occur as a result of some anatomical or structural abnormality. Often they are associated with catheter use in the hospital setting, bladder and kidney dysfunction, or kidney transplant (especially in the first three months after transplant). Recurrences occur in up to 50 - 60% of patients with complicated UTI if the underlying structural or anatomical abnormalities are not corrected.

Classifications Based on Symptoms and Levels of Infection. UTIs can also occur without symptoms and with symptoms but very low bacterial levels.

When bacteria are present and there are no symptoms it is called asymptomatic UTI or also bacteriuria.
Some patients can also have symptoms of infection with very low bacterial counts. In such cases, the condition is called acute urethral syndrome.

Cystitis. Cystitis is the most common urinary tract infection and is sometimes referred to as acute uncomplicated UTI. It occurs in the lower urinary tract (the bladder and urethra) and nearly always in women. In most cases, the infection is brief and acute and only the surface of the bladder is infected. Deeper layers of the bladder may be harmed if the infection becomes persistent, or chronic, or if the urinary tract is structurally abnormal.

Pyelonephritis (Kidney Infection). When infection spreads to the upper tract (the ureters and kidneys) it is called pyelonephritis, or more commonly, kidney infection. As many as half of all women with cystitis may have infections of the upper urinary tract at the same time as cystitis.

Click the icon to see an image of the kidney.

Urethritis. When infection is limited only to the urethra, the infection is known as urethritis. This is a common sexually transmitted disease in men.

Complicated UTIs may develop because of any one of a number of physical problems and affect any gender and age group. The common feature in most complicated UTIs is the inability of the urinary tract to clear out bacteria because of a physical condition that causes obstruction to the flow of urine or problems that hinder treatment success.

Most women who have had an uncomplicated UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one. Between 3 - 5% of women have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode.

Recurrence is often categorized as either reinfection or relapse:

Reinfection. About 80% of recurring UTIs are reinfections. A reinfection occurs several weeks after antibiotic treatment has cleared up the initial episode and can be caused by the same bacterial strain that caused the original episode or a different one. The infecting organism is usually introduced through the rectal region from fecal matter and moves up through the urinary tract.
Relapse. Relapse is the less common form of recurrent urinary tract infection. It is diagnosed when a UTI recurs within 2 weeks of treatment of the first episode and is due to treatment failure. Relapse usually occurs in kidney infection (pyelonephritis) or is associated with obstructions such as kidney stones, structural abnormalities or, in men, chronic prostatitis.

When a person has no symptoms of infection but significant numbers of bacteria have colonized the urinary tract, the condition is called asymptomatic UTI (also called asymptomatic bacteriuria). (In general, there must be at least 100,000 bacteria per milliliter of urine.) The condition is harmless in most people and rarely persists, although it does increase the risk for developing symptomatic UTIs.

Screening for asymptomatic bacteriuria is not necessary during most routine medical examinations, with the following exceptions:

Pregnant women. Pregnant women with asymptomatic bacteriuria have a 30% risk for acute pyelonephritis in their second or third trimester. Therefore, they need screening and treatment for this condition.
People undergoing urologic surgery (such as prostate surgery in men). The presence of an infection during surgery can lead to serious consequences.

Some groups recommend screening women with diabetes for asymptomatic bacteriuria. However, a 2003 study suggested that treating women who test positive for this condition does not reduce their risk of complications from UTIs. Asymptomatic bacteriuria may be an indicator for serious health problems in the elderly, but screening for the condition is not warranted in this group.

Some people have symptoms of cystitis but have a bacterial count lower than that ordinarily found in UTI. Such patients are sometimes diagnosed with acute urethral syndrome. This condition is usually caused by E. coli or other bacteria that cause cystitis, but in lower numbers, or by a sexually transmitted disease such as Chlamydia or gonorrhea.

Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. The average age of patients with IC is 40 years, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. These women often complain of experiencing pain during sex. Pelvic pain, depression, and stress may intensify symptoms. Women with IC also frequently suffer from other conditions, including allergies, urinary incontinence, sinusitis, and irritable bowel syndrome (IBS). Some doctors think that IC may be related to autoimmune diseases such as fibromyalgia and lupus.

IC is difficult to diagnose and treat. Pentosan (Elmiron) is the most frequent drug treatment, but doctors prescribe other medications as well (see Medications section). Some evidence suggests that diet can worsen IC symptoms. For instance, patients should avoid coffee (both caffeinated and decaf), alcohol, cola, vinegar, citrus fruits, tomatoes, chili, strawberries, pineapple, onions, pizza, chocolate, and apples, according to research presented at the 2006 American Urological Association scientific meeting.

The Urinary System. The urinary system helps maintain proper water and salt balance throughout the body and also expels urine from the body. It is made up of the following organs and structures:

The two kidneys, located on each side below the ribs and toward the middle-back, play the major role in this process. They filter waste products, water, and salts from the blood to form urine.
Urine passes from each kidney to the bladder through thin tubes called ureters.
Ureters empty into the bladder, which rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine, which is then eliminated from the body via another tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)

Defense Systems Against Bacteria. Infection does not always occur when bacteria are introduced into the bladder. A number of defense systems protect the urinary tract against infection-causing bacteria:

Urine itself functions as an antiseptic, washing potentially harmful bacteria out of the body during normal urination. (Urine is normally sterile, that is, free of bacteria, viruses, and fungi.)
The ureters are structurally designed to prevent urine from backing up into the kidney.
The prostate gland in men secretes infection-fighting substances.
The immune system in both sexes continuously fights bacteria and other harmful micro-invaders. In addition, immune system defenses and antibacterial substances in the mucous lining of the bladder eliminate many organisms.
In normal fertile women, the vagina is colonized by lactobacilli, beneficial microorganisms that maintain a highly acidic environment (low pH). Acid is hostile to other bacteria. Lactobacilli also produce hydrogen peroxide, which helps eliminate bacteria and reduces the ability of E. coli to adhere to vaginal cells. (E. coli is the major bacterial culprit in urinary tract infections.)
Some interesting research suggests that when bacteria infect the bladder, the cells that line the bladder literally sacrifice themselves and self-destruct (a process called apoptosis). In so doing, they fall away from the lining, carrying the bacteria with them. This eliminates about 90% of the E. coli.
Some researchers have identified a possible natural antibiotic called human beta-defensin-1 (HBD-1), which fights E. coli within the female urinary and reproductive tracts.

Click the icon to see an image of the prostate gland.

Causes

The bacterial strains that cause UTIs include:

Escherichia (E.) coli is responsible for 75 - 90% of uncomplicated cystitis cases in younger women and in more than half the cases in older women (over age 50). In most cases of UTI, E. coli, which originates as a harmless microorganism in the intestines, spreads to the vaginal passage, where it invades and colonizes the urinary tract. Some bacteria may be able to invade into deeper tissue in the bladder, where they survive to reinfect the patient after resolution of the previous infection.
Staphylococcus saprophyticus accounts for 5 - 15% of UTIs, mostly in younger women. Infections caused by this bacterium tend to have a seasonal variation, with a higher incidence in the summer and fall than in the winter and spring.
Klebsiella, Enterococci bacteria, and Proteus mirabilis account for most of remaining bacterial organisms that cause UTIs. They are generally found in UTIs in older women.
Rare bacterial causes of UTIs include ureaplasma urealyticum and Mycoplasma hominis, which are generally harmless organisms.

The bacteria that cause kidney infections (pyelonephritis) are generally the same bacteria that cause cystitis. There is some evidence, however, the E. coli strains in pyelonephritis are more virulent (able to spread and cause illness).
Complicated UTIs that are related to physical or structural conditions are apt to be caused by a wider range of organism. E. coli is still the most common organism, but others have also been detected, including Klebsiella, P. mirabilis, and Citrobacter.
Fungal organisms, particularly Candida species. (Candida albicans, for example, causes the so-called "yeast infections" that also occur in the mouth, digestive tract, and vagina.)
Other bacteria associated with complicated or severe infection include Pseudomonas aeruginosa, Enterobacter, and Serratia species, gram-positive organisms (including Enterococcus species), and S. saprophyticus.

Recurring infections are often caused by different bacteria than those that caused a previous or first infection.

Even if the reinfecting bacterium is still E. coli, it may be a variant of the original infecting E. coli strain. Such strains produce substances, such as one called P fimbriae, which tend to make the bacteria more infectious. Uncommon causes of reinfection include Ureaplasma and Mycoplasma hominis, which are sometimes associated with acute urethral syndrome.

The bacteria that cause most UTIs are very common. Nearly everyone harbors them. It is not clear how they proliferate and break down the natural defenses of the body. Among the possible ways this occurs are:

Changes in the Acid-Alkaline Balance of the Urinary Tract. Changes in the amount or type of acid within the genital and urinary tracts are major contributors to lowering the resistance to infection. For example, beneficial organisms called lactobacilli increase the acidic environment in the urinary tract. Reductions in their number (which, for example, occurs with estrogen loss after menopause), increases pH and therefore the risk of infection.

Biofilm. One theory, called the biofilm mode of growth, suggests that sometimes bacteria form capsules that adhere to the urinary tract, protecting them from many of the body's normal defenses.

Symptoms

Symptoms of lower urinary tract infections usually begin suddenly and may include one or more of the following signs:

The urge to urinate frequently, which may recur immediately after the bladder is emptied.
A painful burning sensation. (If this is the only symptom, then the infection is most likely urethritis.)
Discomfort or pressure in the lower abdomen. The abdomen can feel bloated.
Cramping in the pelvic area or back.
The urine often has a strong smell, looks cloudy, or contains blood. This is a sign of pyuria, or a high white blood cell count in the urine, and is a very reliable indicator of urinary tract infections.
Occasionally, fever develops.

Symptoms of kidney infections tend to affect the whole body and be more severe than those of cystitis. They may include:

Symptoms of lower UTIs that persist longer than a week. (Sometimes lower UTI symptoms may be the only signs of kidney infection. People at highest risk for such "silent" upper urinary tract infections include patients with diabetes, impaired immune systems, or a history of relapsing or recurring UTIs.)
An increased need to urinate at night.
Chills and persistent fever (typically lasting more than 2 days).
Pain in the flank (pain that runs along the back at about waist level).
Vomiting and nausea.

UTIs in infants and preschool children tend to be more serious than those that occur in young women, in part because they are more likely to occur in the kidneys and upper urinary tract. (Older children are more likely to have lower urinary tract infections and standard symptoms.) Infants and young children should always be checked for UTIs if the following symptoms are present:

A persistent high fever of otherwise unknown cause, particularly if it is accompanied by signs of feeding problems and debility, such as listlessness and fatigue. (Studies have reported that up to 5% of infants and toddlers who are brought to the emergency room with fevers have UTIs. Scarring is a risk so very young children with UTIs need to be screened.)
Painful, frequent, and foul smelling urine. (Parents are generally unable to identify a UTI just by the smell of their child's urine. Medical tests are needed.)
Cloudy urine. (If the urine is clear, the child most likely has some other ailment, although it is not absolute proof that the child is UTI-free.)
Abdominal and low back pain may be present.
Vomiting and abdominal pain (usually in infants).
Jaundice (yellowing of the skin and the whites of the eyes) in infants, particularly if it develops after 8 days of age.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing the skin and whites of the eyes to have a yellowish appearance. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older patients with UTIs. In one study, only 20% of these patients had new urinary complaints, and many have no symptoms at all.

Symptoms of UTIs that may occur in seniors but not in younger adults may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. Concomitant illness may further confuse the picture and make diagnosis difficult.

Risk Factors

After the flu and common cold, urinary tract infections (UTIs) are the most common medical complaint among women in their reproductive years. Women are 30 times more likely to have UTIs than men. At least a third of American women are diagnosed with a UTI by the time they are 24 years old. Every year, 11% of American women have at least one such infection, and up to 60% of all women will develop a UTI at some time in their lives. A third of these women will have a recurrence within a year. Furthermore, each year about 250,000 women develop kidney infections (pyelonephritis) and 100,000 are hospitalized for treatment.

According to a 2007 report from the U.S. National Institutes of Health, urinary tract infections in both women and men are the most expensive of all urologic problems. Nationally, UTIs account for about $3.5 billion a year in medical costs.

Structure of the Female Urinary Tract. In general, the higher risk in women is mostly due to the shortness of the female urethra, which is 1.5 inches compared to 8 inches in men. Bacteria from fecal matter can be easily transferred to the vagina or the urethra.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Sexual Behavior. Frequent or recent sexual activity is the most important risk factor for urinary tract infection in young women. Nearly 80% of all urinary tract infections occur within 24 hours of intercourse. (Sexual activity is less associated with cystitis in women after menopause.)

UTIs are very rare in celibate women. It is important to stress, however, that UTIs are NOT sexually transmitted infections, although these infections ( Chlamydia trachomatis, gonorrhea, or herpes simplex virus) may increase the risk for UTIs.

In general, however, it is the physical act of intercourse itself that produces conditions that increase susceptibility to the UTI bacteria, with some factors increasing the risk:

Women having sex for the first time or who have intense and frequent sex after a period of abstinence are at risk for a condition called "honeymoon cystitis."
A sudden increase in the frequency of sexual intercourse poses a significant risk for UTI, particularly if a diaphragm is used.
Sexual position (such as the woman on top) can contribute to the risk.

Click the icon to see an image of a diaphragm.

Contraceptives may also contribute to risk in a number of ways:

The spring-rim of the diaphragm may bruise the area near the bladder neck, making it susceptible to bacteria.
Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections. (Using a sterile water-based lubricant, such as KY jelly, may help reduce this risk. Petroleum-based lubricants should be avoided because they weaken latex condoms.)
Some women experience UTI as an allergic reaction to latex in condoms or to oral contraceptives.
Use of spermicide, such as nonoxynol-9, doubles or triples a women's risk for UTI, regardless of whether it is used with a condom or diaphragm. Spermicides also pose a risk for sexually transmitted infections, and experts warn against their use.

Pregnancy. Although pregnancy does not increase the rates of asymptomatic bacteriuria, it does increase the risk that it will progress to a full-blown infection. About 2 - 11% of pregnant women have asymptomatic bacteriuria and, of those, 13 - 27% will develop a kidney infection late in their term. (However in early pregnancy, frequent urination -- a common symptom of UTI -- is most likely due to pressure on the bladder.)

Although all pregnant women should be tested for UTIs, women at highest risk have the following conditions or situations:

Diabetes
Sickle cell trait
Low-income
Have had many children
History of childhood UTIs
Have undergone a cesarean section with catheterization of the bladder
Have received epidural anesthesia

Women who have had a UTI before or during pregnancy also have a higher risk of developing recurrent urinary tract infections after delivery. About 25 - 33% of women who experience bacteriuria during pregnancy will have another urinary tract infection, sometimes as many as 10 - 14 years later.

Menopause. The risk for UTIs, both symptomatic and asymptomatic, is highest in women after menopause. Studies indicate that between 20 - 25% of women over 65 years old have UTIs, and 10 - 15% have asymptomatic bacteriuria (compared to 2 - 5% of young women). Sexual activity plays a lesser role in UTIs in older women than in younger women. In general, biologic changes due to menopause put older women at particular risk for primary and recurring UTIs:

With estrogen loss, the walls of the urinary tract thin, weakening the mucous membrane and reducing its ability to resist bacteria. The bladder may lose elasticity and fail to empty completely.
Estrogen loss has also been associated with reduction in certain immune factors in the vagina that help block E. coli from adhering to vaginal cells.
Levels of lactobacilli (protective bacteria) decline after menopause, perhaps also due to drops in estrogen.

Some women carry the blood group P1, which, as they get older, is associated with high levels of specific cells in the vagina and urethra that bind to a specific strain of E. coli that is resistant to normal infection-fighting mechanisms.

Other Risk Factors in Women. Women who have skin allergies to ingredients in soaps, vaginal creams, bubble baths, or other chemicals that are used in the genital area are at high risk for UTIs. In such cases, the allergies may cause small injuries that can introduce bacteria.

Most women who have had one UTI have occasional recurrences. About 25 - 50% of these women can expect another infection within a year of the previous one.

Between 3 - 5% of women, however, have ongoing, recurrent urinary tract infections, which follow the resolution of a previous treated or untreated episode. The major groups of women who are at highest risk for recurrent infections are young highly sexually active women and postmenopausal women. It might be argued that nearly all women who have a urinary tract infection are at risk for another, particularly if they are not treated for the first one.

Lifestyle Factors Increasing the Risk for Recurrence. Why urinary tract infections become chronic and recurring in many women is not entirely clear, but researchers are identifying certain lifestyle factors that may increase the risk in specific women:

Engaging in sexual intercourse more than four times a month.
Recent changes in sexual partners.
Having a mother with a history of UTIs.
Having a first UTI before age 15.
Use of spermicides.
Smoking and taking tub baths may also increase the risk for recurrent urinary tract infections, but they are less significant than other risk factors.

Biologic and Physical Factors. Some women may also have certain biologic or anatomical factors that increase the risk for recurring UTIs:

Having a shorter than average distance between the urethra and the anus.
Certain women may carry a compound called sialosyl galactosyl globoside (SGG) on the surface of kidney cells, which is a highly powerful receptor for E. coli bacteria.
Certain women have a genetic susceptibility to becoming infected in the vaginal area with greater numbers of disease-causing organisms that adhere to the lining.
Certain women may be deficient in human beta-defensin-1 (HBD-1), believed to be a naturally occurring antibiotic.

Risk Factors for Recurrence in the Aging Woman. In addition to menopause, other very strong risk factors for recurrences in older women include urinary incontinence and previous operations on the genital or urinary tracts. Additional risk factors for UTIs in older women include diabetes, vaginal itching or dryness, having had children, and poor overall health.

Each year, about 3% of American children develop urinary tract infections. During the first few months of life, UTIs are more common in boys than in girls. Boys who are uncircumcised are about 10 - 12 times more likely than circumcised boys to develop UTIs by the time they are 1 year old. After the age of 2 years, UTIs are far more common in girls. Throughout childhood, the risk of UTIs is about 2% for boys and 8% for girls. As with adults, Escherichia coli (E. coli) is the most common cause of UTIs in children.

Vesicoureteral Reflux (VUR). Vesicoureteral reflux (VUR) affects about 10% of all children. It is the source of urinary tract infections in 30 - 50% of childhood cases. This is a structural defect of the valve-like mechanism between the ureter and bladder that allows urine to flow backward, carrying infection from the bladder up into the kidneys. VUR also puts children at risk for recurrence. Such recurrences nearly always occur within the first 6 months after the first UTI.

Click the icon to see an image of vesicoureteral reflux.

Men become more susceptible to UTIs after 50 years of age, when they begin to develop prostate problems. Benign prostatic hyperplasia (BPH), enlargement of the prostate gland, can produce obstruction in the urinary tract and increase the risk for infection. In men, recurrent urinary tract infections are also associated with prostatitis, an infection of the prostate gland that is caused by E. coli. Although only about 20% of UTIs occur in men, these infections can cause more serious problems than they do in women. Men with UTIs are far more likely to be hospitalized than women. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Hospitalizations and Catheters. About 40% of all infections that develop in hospitalized patients are in the urinary tract. The organisms that cause infections in hospitals (called nosocomial infections) are usually different from those that commonly cause UTIs. They are also more likely to be resistant to standard antibiotics. Hospitalized patients at highest risk for such infections are those with in-dwelling urinary catheters, patients undergoing urinary procedures, long-stay elderly men, and patients with severe medical conditions.

About 80% of UTIs in the hospital are due to catheters. Nearly all patients who need urinary catheters develop high levels of bacteria in their urine, and the longer the catheter is in place, the higher the risk for infection. Catheterized patients who develop diarrhea are nine times more likely to develop UTIs than are patients without diarrhea. In most cases of catheter-induced UTIs, the infection produces no symptoms. Because of the risk for wider infection, however, anyone requiring a catheter should be screened for infection. Catheters should be used only when necessary and should be removed as soon as possible.

Nursing Homes. All older adults who are immobilized, catheterized, or dehydrated are at increased risk for UTIs. Nursing home residents, particularly those who are incontinent and demented, are at very high risk. Up to 40% of elderly patients who live in nursing homes will contract a urinary tract infection.

Some people have structural abnormalities of the urinary tract that cause urine to stagnate or flow backward into the upper urinary tract. Such conditions include:

A prolapsed bladder (cystocele) can result in incomplete urination so that urine collects, creating a breeding ground for bacteria.
Tiny pockets called diverticula sometimes develop inside the urethral wall and can collect urine and debris, further increasing the risk for infection.

Click the icon to see an image of a cystocele.

Antibiotics often eliminate lactobacilli, the protective bacteria, along with harmful bacteria. This causes an overgrowth of E. coli in the vagina. In one study, the risk for UTI increased during the 15 - 28 days that women were taking antibiotics. In fact, some research suggests that taking antibiotics for a urinary tract infection increases the risk for a subsequent infection.

Diabetes. Diabetes puts women at significantly higher risk for asymptomatic bacteriuria. The longer a woman has diabetes, the higher the risk. (Control of blood sugar has no effect on this condition.) The risk for UTI complications is also higher in people with diabetes. In fact, certain UTI-related abscesses are reported only in patients with diabetes. These patients are also at higher risk for fungal-related UTIs.

Kidney Problems. Nearly any kidney disorder increases the risk for complicated UTIs.

AIDS and Immunosuppressed Patients. Any infection is dangerous in people whose immune systems are damaged, and UTIs are no exception, particularly pyelonephritis.

Sickle-Cell Anemia. Patients with sickle-cell anemia are particularly susceptible to kidney damage from their disease, and UTIs put them at even greater risk.

Kidney Stones. In some cases, kidney stones can cause urinary tract obstruction that leads to infection, particularly pyelonephritis. Symptoms of severe urinary tract infection in people with a history of kidney stones may indicate obstruction, which is a serious condition.

Click the icon to see an image of kidney stones.

Zinc. High doses of zinc supplements may increase the risk for urinary tract infections and other urologic problems, according to a 2007 study. Researchers found that hospitalizations for urinary complications were far more common among patients who took high doses of zinc than those who did not take this mineral supplement. Patients in the study took 80 mg of zinc daily. In general, the recommended daily amount for zinc is 8 mg/day for women and 11 mg/day for men. Higher doses of zinc are sometimes prescribed for people with certain medical conditions, such as age-related macular degeneration (an eye disease). However, no one should take more than 40 mg/day of zinc without talking to a doctor.

Complications

Urinary discomfort and emotional distress are the primary concerns in most women with recurrent UTIs. One study reported significant impairment of a woman's quality of life during symptom periods, which affected social function, vitality, and emotional well-being.

Nearly all urinary tract infections are mild, treatable, and have no long-term consequences. Serious physical complications can occur in some cases, however, most often in hospitalized patients.

Obstruction and Widespread Infection. Very severe upper urinary tract infections may cause obstruction that results in widespread and even life-threatening infection. Patients who develop UTIs in the hospital are at higher risk for such infections than those outside the hospital. In one particularly dangerous form of kidney infection that obstructs the ureter, mortality rates exceed 40%. This specific condition should be suspected in people with diabetes who have severe UTIs.

Kidney Damage. In high-risk adults, recurrent UTIs may cause scarring in the kidneys, which over time can lead to hypertension and eventual kidney failure. People with UTIs who develop serious kidney disease from UTIs are likely to have other predisposing diseases or structural abnormalities. (Recurrent urinary tract infections, even in the kidney, almost never lead to progressive kidney damage in otherwise healthy women.)

Urge Incontinence. Recurrent UTIs may increase the risk for urge incontinence after menopause. (People with urge incontinence experience leakage and the need to urinate frequently.) [See In-Depth Report #50: Urinary incontinence.]

Kidney Stones. Kidney stones can be caused by urinary tract infections (as well as increase the risk for UTIs in the first place). Those known as struvite stones are almost always caused by urinary tract infections due to bacteria that secrete certain enzymes. These enzymes raise urine concentrations of ammonia, which composes the crystals forming struvite stones. The stone-promoting bacterium is usually Proteus, but others include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci.

Urinary tract infections during pregnancy pose particular risks for both mother and child:

If asymptomatic bacteriuria is not detected and treated promptly in pregnant women, as many as 25% develop kidney infection (pyelonephritis), which in turn increases the risk for premature birth, infant mortality, and later chronic kidney disease.
Even if kidney infection does not develop, untreated UTIs occurring in the first and third trimester of pregnancy slightly increase the risk for mental retardation and developmental delay in the infant.
Certain strains of E. coli can increase the risk for complications during pregnancy, including miscarriage or premature delivery, even if pyelonephritis does not develop.
Infants of women who harbor Ureaplasma urealyticum also have an increased risk for respiratory infections.

Urinary tract infections are a major cause of hospitalization in children. Untreated, they can be very serious, particularly in children under 4 years old. Fortunately, with prompt treatment, childhood cases of upper urinary tract infections rarely cause any serious consequences.

Spread of Infection. Widespread infection is a major complication of a primary infection. Although laboratory tests in some infants with UTI may suggest the presence of meningitis (inflammation of the spinal column), in most of these UTI cases the outcome is good with treatment, and there appear to be no neurological symptoms afterward.

Kidney Scarring. Kidney scarring is the major concern in children who develop serious or recurrent UTIs. Scarring in young growing kidneys is much more serious than in the mature kidney. Over the years, it increases the risk for hypertension and kidney failure. In one study, evidence of scarring developed in 6% of children who had been hospitalized for a urinary tract infection. Children most at risk for this complication include:

Children with vesicoureteral reflux (VUR). (Carefully managed vesicoureteral reflux without scarring is not associated with serious complications.)
Abnormally structured urinary tracts
Recurrent kidney infections
A delay in treating an acute UTI

One encouraging study followed children with evidence of kidney scarring for 16 - 26 years. On average, their total kidney function was well preserved, although the scarred kidney had signs of lower function and patients with scarring in both kidneys were at higher risk for future problems. Earlier studies have shown poorer results, which suggests that outcomes are now improving with early detection and better follow-up.

Women with diabetes have more frequent and more severe UTIs than women without the disease. They also are more frequently hospitalized for kidney infections. In fact, the most serious, but rare, complications of urinary tract infections (pyelonephritis, widespread infections, abscesses, inflammation of the bladder wall) occur mostly in patients with diabetes.

Diagnosis

In younger women, UTI symptoms plus positive results on an over-the-counter dipstick test are often enough to make a diagnosis. Symptoms include frequent urination and vaginal burning, without other complications such as fever, chills, and pain in the kidney. In such cases, young women can usually receive treatment by calling a health professional (usually a nurse) who will prescribe antibiotics. A good response to antibiotic therapy usually eliminates the need for further tests.

This course is recommended only for nonpregnant women at low risk for recurrent infection who do not have symptoms suggesting other problems, such as vaginitis. In some centers, women who are treated over the phone have to be younger than 55 years old; other patients need to see a doctor for evaluation. Pregnant women should be screened for E. coli because of the risk of complications, including miscarriage, from certain strains of these bacteria.

About half of women with symptoms of a UTI actually have some other condition, such as irritation of the urethra, vaginitis, interstitial cystitis, or sexually transmitted diseases (STDs). Some of these problems may also accompany or lead to UTIs.

Vaginitis. Vaginitis is a common vaginal infection that can be caused by a fungus (candidiasis) or bacteria. Occasionally, the infection causes frequent urination, mimicking cystitis. The typical symptoms of vaginitis are itching and an abnormal discharge.

Sexually Transmitted Diseases. Women with painful urination whose urine does not exhibit signs of bacterial growth in culture may have a sexually transmitted disease. The most common culprit is the organism Chlamydia trachomatis. Other STDs that may be responsible include gonorrhea and genital herpes.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost predominantly in women. The average age of patients with IC is 40 years old, but 25% of cases occur in women under age 30. Symptoms are very similar to cystitis, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Bladder Cancer. Bladder cancer is a rare cause of painful urination and is more common in men than in women.

Kidney Stones. The pain of kidney stones along with blood in the urine can resemble the symptoms of pyelonephritis. There are no bacteria present with kidney stones, however.

Thinning Urethral and Vaginal Walls. After menopause, the vaginal and urethral walls become dry and fragile, causing pain and irritation that can mimic a UTI.

Disorders in Children that Mimic UTIs. Problems that might cause painful urination in children include reactions to chemicals in bubble bath, diaper rashes, and infection from the pinworm parasite.

Prostate Conditions in Men. Prostate conditions, including prostatitis (inflammation of the prostate) and benign prostatic hyperplasia, can cause symptoms similar to urinary tract infections.

Click the icon to see an image of benign prostatic hypertrophy.

During an exam, the doctor should examine the pelvic and vaginal area in women. Men require a digital rectal examination to determine if prostate enlargement is present. The doctor will also examine the male genitals for signs of infection. In both men and women, the doctor should also check the abdomen and areas around the kidneys for swelling and tenderness.

With the exception of skin cancer, prostate cancer is the most common type of cancer among men in the United States. Early detection may result from a blood test called a PSA (prostate-specific antigen) or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness found during the exam might be a sign of prostate cancer.

Dipstick tests, available over the counter, are quite reliable in making a reasonable diagnosis of UTIs in women with symptoms. Dipstick tests may also be useful for identifying UTIs in children and infants. The test uses a chemical on a stick that when dipped in urine reacts to nitrites, substances produced by many of the bacteria that cause UTIs. A positive test (which indicates that an infection is present) often eliminates the need for urine cultures, a more expensive test used to detect bacteria. A negative dipstick test helps to avoid unnecessary antibiotics, which are contributing to the growing problem of antibiotic resistance. These tests are not entirely accurate, however, and studies report that they may miss up to 25% of actual UTIs. If a woman has persistent UTI symptoms, and the dipstick test is negative, she should check with her doctor to see if more accurate tests are needed.

A urine sample is needed for most extensive testing. In most cases, the doctor requests a clean-catch sample. There are also other methods for collecting urine, depending on the patient's condition.

Clean-Catch Sample. A clean-catch sample for UTI depends on a sample free of contaminants normally present at the opening of the urethra (white blood cells and bacteria unrelated to UTIs). To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the following steps are taken:

Patients must first wash their hands thoroughly, then wash the penis or vulva and surrounding area four times, with front-to-back strokes, using a new soapy sponge each time.
The patient must then begin urinating into the toilet and stop after a few drops.
The patient then positions the container to catch the middle portion of the stream. Ideally, this urine will contain only the bacteria and other evidence of the urinary tract infection.
The patient then urinates the remainder into the toilet.
The patient securely screws the container cap in place without touching the inside of the rim.

The sample is generally given to the doctor or sent to the laboratory for analysis.

Incontinence Pads. Testing and diagnosing UTIs in elderly patients who are incontinent is especially difficult, because of the similarities in symptoms. Researchers have found that pressing a dipstick into an incontinence pad is an effective way to screen for urinary tract infections in incontinent patients.

Collection with a Catheter. Some patients (small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample.

A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. A urinalysis offers a number of valuable clues for an accurate diagnosis:

Color and cloudiness of urine
Acidity
White blood cells (leukocytes). A high count of white cells in the urine is referred to as pyuria. (A leukocyte count over 10 per microliter is considered to indicate pyuria.) Pyuria is usually sufficient for a diagnosis of UTI in nonhospitalized patients if other standard symptoms (or just fever in small children) are also present.

Treatment can be started without the need for further tests if the following urinalysis results are present in patients with symptoms and signs of UTIs:

A high white cell count
Cloudy urine

A urine culture uses a urine specimen that is placed on an agar plate, then incubated in the laboratory for 24 - 48 hours. It is then examined for the presence of bacterial growth. Urinary tract infection is nearly always caused by a single species of bacteria, notably E. coli. Cultures have limitations, however. If a mix of different species is found, the test is considered contaminated and is redone. In addition, even if E. coli is identified, researchers are also looking for variants of these bacteria. Certain types may indicate a higher risk for a second infection, while others may even be protective against recurring infections. Furthermore, some organisms, such as Chlamydia, which is a sexually transmitted organism, may not be detected.

A urine culture is usually performed if the dipstick results are positive, but even if the results are negative, a culture may still be helpful under certain circumstances:

If urinalysis or dipstick is negative but the patient has UTI symptoms, particularly if the patient has recurring infections or is in a high-risk group.
If the doctor suspects complications.
In girls less than 2 years of age with a high fever of unknown origin that lasts 2 days or more.

Even if bacteria are present in the culture, a diagnosis of UTI depends on symptoms and gender:

The presence in a culture of at least 100,000 bacteria per milliliter of urine usually provides conclusive evidence of infection in women with symptoms.
A count of 100,000 bacteria per milliliter in a woman without symptoms indicates asymptomatic bacteriuria. The decision to treat depends on the woman's risk factors for complications.
In young women with symptoms of cystitis, a diagnosis of infection can reasonably be made with counts as low as 1,000 bacteria per milliliter.
Men are considered to have an infection with a count of only 1,000.

If doctors suspect that bacteria other than E. coli may be present, a Gram stain is used to help predict the species. This is a staining procedure used to make bacteria visible through a microscope. Many bacteria are categorized by the terms Gram-positive and Gram-negative.

Bacteria that turn pink from staining are called Gram-negative
Those that turn blue are called Gram-positive

Escherichia coli bacteria are Gram-negative and the most common cause of UTIs. If doctors suspect that bacteria other than E. coli are causing a UTI, a Gram stain is useful for identifying other species.

Because of the expense and the limited accuracy of imaging procedures, these techniques are used only for the following:

Serious and recurrent cases of pyelonephritis
When structural abnormalities are suspected
If infections do not respond to treatment
If a doctor suspects obstruction or an abscess
After a first urinary tract infection in children age 2 - 24 months to detect possible obstruction or vesicoureteral reflux. Tests include ultrasound and a voiding cystourethrogram and possibly scans. Some evidence suggests that ultrasound is probably not necessary, but at this time it is recommended by major medical groups.

Ultrasound. Ultrasound is a noninvasive, risk-free imaging test that can be used to screen for hydronephrosis (obstructions of the flow of urine), kidney stones that predispose to infection, and kidney abscesses. In men, ultrasound can detect enlargement or abscesses of the prostate and, when combined with x-rays, is an accurate method for detecting incomplete emptying of the bladder, a common cause of UTI in men over age 50. In children with urinary tract infections, it also can be used to detect vesicoureteral reflux, the defect of the valve-like mechanism between the ureter and bladder. Ultrasounds are not as accurate as voiding cystourethrograms.

Nuclear Scans. Imaging techniques called nuclear scans may be useful in certain complicated cases, such as detecting kidney scarring after pyelonephritis in children. They produce better images and expose the patient to far less radiation than x-rays. One such scan called dimercaptosuccinic acid (DMSA) scintigraphy uses injections of tiny amounts of radioactive tracers. A scanning machine (scintillation or gamma camera) is then used to detect pictures of the tracer in the kidney. This information is recorded on a computer screen or on film.

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Magnetic resonance imaging (MRI) and computed tomography (CT) scans are noninvasive advanced imaging techniques that are sometimes used when nuclear scans are inconclusive. A CT scan is useful for ruling out kidney stones or obstructions in women with recurrent UTIs.

X-Rays. Special x-rays can be used to screen for structural abnormalities, urethral narrowing, or incomplete emptying of the bladder, which can cause stagnation of urine and predispose to infection.

Voiding cystourethrogram is an x-ray of the bladder and urethra. To obtain a cystourethrogram, a dye, called contrast material, is injected through a catheter inserted into the urethra and passed through the bladder.
An intravenous pyelogram (IVP) is an x-ray of the kidney. For a pyelogram, the contrast matter is injected into a vein and eliminated by the kidneys. In both cases, the dye passes through the urinary tract and reveals any obstructions or abnormalities on x-ray images. Due to the possible risks to the fetus, x-rays are not performed on pregnant women.

Click the icon to see an image of a voiding cystourethrogram.

Click the icon to see an image of an intravenous pyelogram.

Cystoscopy. Cystoscopy is used to detect structural abnormalities, interstitial cystitis, or masses that might not show up on x-rays during an IVP. The patient is given a light anesthetic, and the bladder is filled with water. The procedure uses a cystoscope, a flexible, tube-like instrument that the urologist inserts through the urethra into the bladder.

Click the icon to see an image of cystoscopy.

No noninvasive test will differentiate between upper and lower urinary tract infections. This is a particular problem because of the high percentage of women whose cystitis symptoms mask infections that also exist in the upper tract.

Antibiotic Trial. The best current test for pyelonephritis is the short-term antibiotic therapy given for cystitis. If the infection returns within 2 weeks after treatment, upper urinary tract infection is usually present.

Blood Cultures. If symptoms are severe, blood cultures will be taken to determine if the infection is in the bloodstream and threatening other parts of the body.

Treatment

Although antibiotics should be used as a cure for most urinary tract infections, severe symptoms can persist for several days until treatment effectively eliminates the bacteria. A number of options are available for relieving symptoms until the antibiotics take action.

Important Note. All of the drugs discussed below treat only symptoms and are not cures. They should never be used to replace antibiotics.

Phenazopyridine (Pyridium, Uristat, Barodium, Eridium, AZO Standard) relieves pain and burning caused by the infection. It should not be taken for more than 2 days and should be discontinued when symptoms are relieved.

Side effects include headache and stomach distress. The drug turns urine a red or orange color, which can stain fabric and be difficult to remove. In rare cases, it can cause serious side effects, including shortness of breath, a bluish skin, a sudden reduction in urine output, shortness of breath, and confusion. In such cases, patients should immediately call the doctor.

Methenamine (Atrosept, Prosed, Urised) or flavoxate (Urispas) reduce bladder spasms, which may occur with some UTIs. These drugs can have severe side effects, however, that the patient should discuss with the doctor.

Medications

Antibiotics are the mainstay treatment for all UTIs. A variety of antibiotics are available, and choices depend on many factors, including whether the infection is complicated or uncomplicated or primary or recurrent. Treatment decisions are also based on the type of patient (man or woman, a pregnant or nonpregnant woman, child, hospitalized or nonhospitalized patient, person with diabetes). Treatment should not necessarily be based on the actual bacteria count. For example, if a woman has symptoms, even if bacterial count is low or normal, infection is probably present and antibiotic treatment should be considered.

Bacterial Resistance to Antibiotics. Antibiotic-resistant strains of E. coli, the most common cause of UTIs, are increasing. The prevalence of such bacteria has dramatically increased worldwide, in large part due to widespread use of antibiotics in humans and animal feed. In a 2003 report, 42% of E. coli were resistant to one or more of the 12 antibiotics that researchers investigated. As more bacteria have become resistant to the standard UTI treatment trimethoprim-sulfamethoxazole (TMP-SMX), more doctors have been prescribing quinolone antibiotics to treat UTIs. A 2006 study found that quinolones have now overtaken TMP-SMX as the most commonly prescribed antibiotic for UTIs. Experts are concerned that resistance may develop to these drugs as well.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins, cephalosporins, and some newer similar drugs. Their primary actions to interfere with bacterial cell walls. Many have been important in the treatment of urinary tract infections.

Penicillins (Amoxicillin). Until recent years, the standard treatment for a UTI was 10 days of amoxicillin, a penicillin antibiotic, but it is now ineffective against E. coli bacteria in up to 25% of cases. A combination of amoxicillin-clavulanate (Augmentin) is sometimes given for drug-resistant infections. Amoxicillin or Augmentin may be useful for UTIs caused by Gram-positive organisms, including Enterococcus species and S. saprophyticus.

Cephalosporins. Antibiotics known as cephalosporins are also alternatives for infections that do not respond to standard treatments or for special populations. They are often classed as:

First generation, including cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation, including cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation, including cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of Gram-negative bacteria.

Other Beta-Lactam Drugs. Other beta-lactam antibiotics have been developed. For example, pivmecillinam (a form of mecillinam), is commonly used in Europe for UTIs. It appears to be safe during pregnancy.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

The typical treatment is a 3-day course of the combination drug trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). A 1-day course is somewhat less effective but poses a lower risk for side effects. Longer courses (7 - 10 days) work no better than the 3-day course and have a higher rate of side effects. TMP-SMX should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious. Trimethoprim (Proloprim, Trimpex) is sometimes used alone in those allergic to sulfa drugs. TMP-SMX can interfere with the effectiveness of oral contraceptives. High rates of bacterial resistance to TMP-SMX exist in many parts of the United States. Still, even when regional rates approach 30%, cure rates with TMP-SMX reach 80 - 85%.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) are now becoming as widely used as TMP-SMX. These drugs interfere with the bacteria's genetic material so they cannot reproduce. They are the standard alternatives to TMP-SMX. Examples of quinolones include ofloxacin (Floxacin), ciprofloxacin (Cipro), norfloxacin (Noroxin), levofloxacin (Levaquin), gatifloxacin (Tequin), and sparfloxacin (Zagam). These antibiotics are effective against a wide range of organisms but are expensive and, in general, used in the following circumstances:

In patients with complicated or catheter-induced UTIs
In patients who do not respond or who are allergic to TMP-SMX
In communities where there are high rates of bacteria resistant to TMP-SMX
In elderly patients. A 2001 study of older women with UTIs (mean age 80), about half of whom were living in nursing homes, found that 96% responded to ciprofloxacin, compared with 87% to TMP-SMX.

Pregnant women should not take fluoroquinolone antibiotics. They also have more adverse effects in children than other antibiotics and should not be the first-line option in most situations.

Antibiotics Used Specifically for UTIs

Nitrofurantoin. Nitrofurantoin (Furadantin, Macrodantin) is a relatively inexpensive antibiotic that is used specifically for urinary tract infections. It is an effective alternative to TMP-SMX or a quinolone. Unlike many of the other drugs, however, it must be given 7 - 10 days, even in cases of simple cystitis. (Shorter course treatments are being investigated.) It is not useful for treating kidney infections. Nitrofurantoin frequently causes stomach upset and interacts with many drugs. Other chronic or serious medical conditions may also affect its use. It should not be used in pregnant women within 1 - 2 weeks of delivery, in nursing mothers, or in those with kidney disease.

Fosfomycin. The antibiotic fosfomycin (Monurol), which comes in an orange-flavored, soluble powder, is proving to be another good alternative. It can be an effective 1-dose treatment for many women, including those who are pregnant. To date, bacterial resistance rates to this antibiotic are very low.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Long-term treatment with tetracycline or doxycycline may be used for infections that are caused by Mycoplasma or Chlamydia. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Aminoglycosides

Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Gentamicin is the most commonly used aminoglycoside for serious UTIs. They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.

UTIs in low-risk women can often be successfully treated over the phone. In such cases, a health professional provides the patients with 3-day antibiotic regimens without even requiring an office urine test. This course is recommended only for women at low risk for recurrent infection and who do not have symptoms suggesting other problems, such as vaginitis.

Antibiotic Regimen. Oral antibiotic treatment cures 94% of uncomplicated urinary tract infections, although the rate of recurrence remains high. The following antibiotics are commonly used for uncomplicated UTIs:

The standard regimen has traditionally been a 3-day course of trimethoprim-sulfamethoxazole, commonly called TMP-SMX (Bactrim, Cotrim, Septra). TMP-SMX combines an antibiotic with a sulfa drug. A single dose of TMP-SMX is sometimes prescribed in mild cases, but cure rates are generally lower than with the 3-day regimens.
Fluoroquinolone antibiotics, also called quinolones, have usually been a second choice. However, in geographic areas that have a high resistance to TMP-SMX, quinolones are now the first-line treatment for UTIs. Ciprofloxacin (Cipro) is the quinolone antibiotic most commonly prescribed. Quinolones are usually given over a 3–day period. Pregnant women should not take these drugs.
Nitrofurantoin (Furadantin, Macrodantin) is a third option. This drug must be given for longer than 3 days.
Fosfomycin (Monurol) is not as effective as other antibiotics but may be used during pregnancy. Resistance rates to this drug are very low.
Many other effective antibiotics are available, including amoxicillin (with or without clavulanate) and cephalosporins. Doxycycline is often effective but cannot be given to children or pregnant women.

After a week of antibiotic treatment, most patients are free of infection. If the symptoms do not clear up within the first few days of therapy, doctors generally suggest that women discontinue their antibiotic and provide a urine sample for culturing in order to identify the specific organism causing the condition.

Treatment for Relapsing Infection. A relapsing infection (caused by treatment failure) occurs within 3 weeks in about 10% of women. Relapse is treated similarly to a first infection, but the antibiotics are continued for at least 2 weeks. (Relapsing infections may be due to structural abnormalities, abscesses, or other problems that may require surgery, and such conditions should be ruled out.)

Preventive antibiotics may be required for women who experience two or more symptomatic UTIs within 6 months or three or more over the course of a year. A woman's own perception of discomfort can generally guide her decisions on whether to use preventive antibiotics or not. All women should use lifestyle measures to prevent recurrences.

Intermittent Self Treatment. Many, if not most, women with recurrent UTIs can effectively self-treat recurrent UTIs without going to a doctor. In general, this requires the following steps:

As soon as the patient develops symptoms, she takes the antibiotic. Infections that occur less than twice a year are usually treated as if they were an initial attack, with single-dose or three-day antibiotic regimens.
At that time, she also performs a clean-catch urine test and sends it to the doctor for culturing to confirm the infection.

A doctor should be consulted under the following circumstances:

If symptoms have not completely resolved within 48 hours
If there is a change in symptoms
If the patient suspects that she is pregnant
If the patient has more than four infections a year

Women who are not good candidates for self-treatment are those with impaired immune systems, previous kidney infections, structural abnormalities of the urinary tract, or a history of infection with antibiotic-resistant bacteria.

Postcoital Antibiotics. If recurrent infections are clearly related to sexual activity and episodes recur more than two times within a 6-month period, a single preventive dose taken immediately after intercourse is very effective. Antibiotics for such cases include TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (such as ciprofloxacin). (Fluoroquinolones are not appropriate during pregnancy.)

Continuous Preventive Antibiotics (Prophylaxis). Continuous preventive (prophylactic) antibiotics are an option for some women who do not respond to other measures. With this approach, low-dose antibiotics are taken continuously for 6 months or longer.

Typical prophylactic regimens include one dose of nitrofurantoin (50 mg), 1/2 tablet of TMP-SMX, or cephalexin (250 mg) daily. Taking the antibiotic at bedtime may be most effective. Studies suggest that continuous prophylactic antibiotics reduces recurrences by up to 95% and may prevent kidney infection.

Adverse effects mostly include gastrointestinal problems and yeast infections. (Taking probiotic supplements or eating yogurt may help prevent yeast infections.) Although there is concern that continuous risk increases the risk for bacteria that are resistant to the antibiotics, studies to date have not reported any significant risk even up to 5 years of use.

Treating Uncomplicated Kidney Infections. Patients with uncomplicated kidney infections (pyelonephritis) may be treated at home with oral antibiotics. Such patients are healthy and nonpregnant. They typically are experiencing fever, chills, and flank pain. However, they are not nauseous or vomiting and show no symptoms or signs of kidney involvement or complicated infection.

The standard treatment for uncomplicated pyelonephritis is a 14-day course of oral antibiotics, usually trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone. Sometimes patients with uncomplicated pyelonephritis are first given an antibiotic injection, if indicated.

Oral amoxicillin or amoxicillin-clavulanate (Augmentin) may be prescribed for women with bacteria (Gram-positive organisms, including Enterococcus species and S. saprophyticus) that do not respond to standard regimens.

A urine culture may be obtained within 1 week of completion of therapy and again 4 weeks later.

Treating Moderate-to-Severe Kidney Infections. Patients with moderate-to-severe acute kidney infection and those with severe symptoms or other complications may need to be hospitalized. In such cases, antibiotics (ceftriaxone and gentamicin) are usually given intravenously for 3 - 5 days or until symptoms are relieved and patients have not shown any signs of fever for 24 - 48 hours.

If fever and back pain persist after 72 hours of antibiotic administration, the doctor will usually order imaging tests to see if abscesses, obstructions, or other abnormalities are present.

Treating Chronic Kidney Infections. Patients with chronic pyelonephritis are often treated with long-term antibiotics, even during periods when they have no symptoms.

The two approved treatments for interstitial cystitis are pentosan polysulfate (Elmiron), and dimethyl sulfoxide (DMSO). Patients generally prefer Elmiron because it can be taken by mouth. A DMSO solution is instilled into the bladder through a catheter. Elmiron is a type of blood thinner that helps to coat the bladder lining and prevent infections. It may take several months before having an effect on symptoms, but the benefits increase the longer the drug is used.

Doctors sometimes also prescribe other types of medications to help interstitial cystitis symptoms. These drugs include antihistamines, such as hydroxyzine (Atarax), and low doses of the tricyclic antidepressant amitriptyline (Elavil). Drugs that reduce bladder spasms (hyoscine, oxybutynin) are also sometimes used. Other treatments are being investigated, including hyperbaric oxygen therapy. This treatment involves having a patient breathe pure oxygen inside a sealed pressurized chamber.

Some doctors think that interstitial cystitis may be related to immune disorders. Researchers are investigating various drugs that block immune and inflammatory responses.

Treating the Pregnant Woman. Pregnant women should be screened for UTIs, since they are at high risk for UTIs and their complications. The antibiotics used during pregnancy are amoxicillin, ampicillin, nitrofurantoin, or an oral cephalosporin. Fosfomycin (Monurol) is not as effective as others but may be used during pregnancy. Pregnant women should not take fluoroquinolones.

Pregnant women with even asymptomatic bacteriuria (evidence of infection but no symptoms) have a 30% risk for acute pyelonephritis in their second or third trimester. They need screening and treatment for this condition. In such cases, they should be treated with a short course of antibiotics (3 - 5 days). For an uncomplicated UTI, pregnant women may need longer-term antibiotics (7 - 10 days).

Treating Women with Diabetes. Women with diabetes have more frequent and more severe UTIs than women without the disease. Many experts recommend that patients with diabetes and UTI, even an uncomplicated infection, be treated with antibiotics for 7 - 14 days. People with diabetes have higher than average rates of asymptomatic bacteriuria, but it is unclear whether they should be screened and treated for this condition. A 2003 study indicated that treating this condition had little value in these women and did not prevent complications.

Treating Urethritis in Men. Urethritis in men has typically been treated with a 7-day regimen of doxycycline. Some research suggests that a single dose of azithromycin may be just as effective while causing fewer side effects. One-dose treatment also improves compliance, so cure rates may even be better than with a long-term regimen. However, once an infection spreads to the prostate gland it is harder to treat, so most doctors still prefer the longer regimen. Patients with urethritis should also be tested for an accompanying sexually transmitted disease such as gonorrhea.

Treating Children with UTIs. Children with UTIs are generally treated with TMP-SMX or cephalexin (Keflex). These drugs are usually taken by mouth in either liquid or pill form. Doctors sometimes give them as a shot or IV. Children usually respond to treatment within a few days. Antibiotic resistance to cephalosporin antibiotics such as cephalexin is increasing, and some doctors prefer to prescribe an aminoglycoside antibiotic. Gentamicin (Garamycin) is the aminoglycoside antibiotic that is most commonly used. It is given intravenously.

Vesicoureteral reflux (VUR) is a concern for children with UTIs. About a third of children with UTIs develop this condition, in which urine backs up into the kidneys. VUR can lead to kidney infection (pyelonephritis), which can cause kidney damage. Either long-term antibiotics or surgery are options to correct vesicoureteral reflux (VUR) and prevent infection. Many experts recommend surgery over antibiotics, especially due to concerns of antibiotic resistance. Antibiotic treatment usually continues for years with the idea that the condition will resolve when the child has grown. However, a 2006 study suggested that long-term antibiotics are not useful for preventing VUR. Furthermore, the study found that mild-to-moderate VUR does not increase the likelihood of UTIs or pyelonephritis.

Children with acute kidney infection are treated with oral cefixime (Suprax) or a short course (2 - 4 days) of an intravenous (IV) antibiotic (typically gentamicin, given in one daily dose). An oral antibiotic then follows the IV.

Preventing Catheter-Induced Infections

Catheter-induced urinary tract infections are very common, and preventive measures are extremely important. Catheters should not be used unless absolutely necessary, and they should be removed as soon as possible. Reducing the risk for infections during long-term catheter use, however, remains problematic.

Catheter Coatings. Catheter coatings, such as silver nitrate, antibiotics, and other substances, are being tested and are showing some benefits, but the problem is still not resolved. One promising catheter (LoFric) uses a so-called hydrophilic coating consisting of PVP (polyvinyl pyrrolidone) and salt. It attracts water to the catheter surface, putting up a water barrier to reduce friction. In a 2003 study, it was associated with significantly fewer UTIs.

Intermittent Use of Catheters. If a catheter is required for long periods, it is best to use it intermittently if possible (as opposed to an indwelling catheter). Some doctors recommend replacing it every 2 weeks to reduce the risk of infection and irrigating the bladder with antibiotics between replacements.

Daily Hygiene. A typical catheter is one that has been preconnected and sealed and uses a drainage bag system. To prevent infection, some of the following tips may be helpful:

Drink plenty of fluids, including 3 glasses of cranberry juice a day.
The catheter tube should be free of any knots or kinks.
Clean the catheter and the area around the urethra with soap and water daily and after each bowel movement. (Women should be sure to clean front to back.)
Wash hands before touching the catheter or surrounding area.
Never disconnect the catheter from the drainage bag without careful instructions from a health professional on strict methods for preventing infection.
Keep the drainage bag off the floor.
Stabilize the bag against the leg using tape or some other system.

Antibiotics for Catheter-Induced Infections

Patients using catheters who develop UTIs with symptoms should be treated for each episode with antibiotics and the catheter should be removed, if possible. A major problem in treating catheter-related UTIs is that the organisms involved are constantly changing. Because there are likely to be multiple species of bacteria, experts generally recommend an antibiotic that is effective against a wide variety of microorganisms. These medications include those in the fluoroquinolone group and drug combinations such as ampicillin plus gentamicin or imipenem plus cilastatin.

Although high bacteria counts in the urine (bacteriuria) occur in most catheterized patients, administering antibiotics to prevent a UTI is rarely recommended. Many catheterized patients do not develop symptomatic urinary tract infections even with high bacteria counts. If bacteriuria occurs without symptoms, antibiotic therapy has little benefit if the catheter is to remain in place for a long period.

Catheterization is accomplished by inserting a catheter (a hollow tube, often with an inflatable balloon tip) into the urinary bladder. This procedure is performed for urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured. Catheterization in males is slightly more difficult and uncomfortable than in females because of the longer urethra.

Other Treatments

The following are hygiene tips. Although there is no evidence that good hygiene makes a real difference in preventing UTIs, it is always a wise practice.

Clean the genital and urinary areas from front to back with soap and water after each bowel movement.
Keep the genital and anal areas clean before and after sex. Urinate before and after intercourse to empty the bladder and cleanse the urethra of bacteria.
Avoid tight-fitting pants.
Wear cotton-crotch underwear and panty hose, changing both at least once a day. (Mild detergents are best for washing underwear.)
Take showers rather than baths.
Avoid bath oils, feminine hygiene sprays, douches, and powders. As a general rule, do not use any product containing perfumes or other possible allergens near the genital area. Douching in is never recommended. It may destroy the natural antiviral organisms normally present in the vagina, making women more susceptible to human papillomavirus (HPV), a risk factor for cervical cancer.
Choose sanitary napkins instead of tampons (which some doctors believe encourage infection). Napkins and tampons, in any case, should be changed after each urination.
Urinate frequently.

Appropriate hygiene and cleanliness of the genital area may help reduce the chances of introducing bacteria through the urethra. Females are especially vulnerable to this, because the urethra is in close proximity to the rectum. The genitals should be cleaned and wiped from front to back to reduce the chance of dragging E. coli bacteria from the rectal area to the urethra.

The following recommendations may reduce the risks from sexual activity:

In women using contraceptives, consider alternatives, particularly if exposed to spermicides from condoms or diaphragms. Discuss the best contraceptive choice with a doctor.
Avoid sex with multiple partners. This can cause many health problems, including sexually transmitted diseases and UTIs.

Postmenopausal women with recurrent UTIs may consider the use of an estrogen vaginal cream or estrogen-releasing vaginal ring (Estring). Estrogen may resist infection by increasing the number of lactobacilli, the microorganism that fights infection by lowering the vaginal pH levels and preventing E. coli from adhering to vaginal cells. Estrogen creams and estrogen-releasing rings may help reduce the risk of recurring urinary tract infections. Oral hormone replacement therapies that contain estrogen do not seem to provide the same benefit as the topical forms. Estrogen HRT carries many health risks, including an increased risk for breast cancer and heart disease. It is not clear if vaginal forms of estrogen are associated with these risks.

Many doctors believe that emptying the bladder frequently will help prevent bladder irritation and therefore recommend drinking plenty of water daily and urinating often.

Cranberries, blueberries, and lignonberry, a European relative of the cranberry, are three fruits that may have protective properties. Researchers are finding that red pigments in these closely related fruits called tannins (or proanthocyanadins) prevent E. coli bacteria from adhering to cells in the urinary tract, thereby inhibiting infection. Fructose, which is commonly used to sweeten fruit juices, may also interfere with bacterial adhesion.

Cranberry juice offers well-known protection against urinary tract infections. In one study, only 15% of elderly women who drank cranberry juice daily for 6 months experienced UTIs, compared with 28% of women who did not drink the juice. Its effects were stronger in helping the body rid itself of infections than in preventing them in the first place, but it showed benefits in both situations.

Studies suggest that for protection, it is necessary to drink at least one to two cups of 30% cranberry or lignonberry juice daily, or to take at least 300 - 400 mg in tablet form twice daily.

Important research has targeted probiotics (essentially friendly organisms), which may protect against infections in the genital and urinary tracts. They may have other health benefits as well. The best-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products (kefir). The probiotics bifidobacteria and GG lactobacilli may prove to be even more important. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Lactobacilli have the potential to help protect women from UTIs in a number of ways:

Maintain a low pH environment
Hinder E. coli growth
Produce hydrogen peroxide, which produces an environment hostile for bacteria

In a 2003 study, drinking fermented milk reduced the risk for UTIs. Not all studies show benefits from drinks containing lactobacilli, but more research is warranted.

Researchers are studying several different herbal treatments for urinary tract infections. Studies on these herbs have only been conducted on animals and cell samples -- not in humans:

Forskolin, an extract from the Indian coleus plant, may help flush out bacteria hiding in the lining of the bladder.
Green tea contains compounds that may help prevent inflammation in bladder cells.
St. John’s wort, a popular herbal remedy for depression, may help relieve pain associated with interstitial cystitis.

It is important to inform your doctor of any herbs, dietary supplements, or vitamins and minerals that you take or are considering taking. Some of these remedies may actually increase your chance of developing urinary tract infections. For example, high doses of zinc have been associated with increased risk of UTIs.

Biofeedback is a technique that provides visual and auditory clues in response to specific exercises. Some research indicates that biofeedback teaches children who are prone to UTIs to relax and control their pelvic muscles, resulting in fewer recurrences of infection.

Resources

http://kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Clearinghouse
www.urologyhealth.org -- American Urological Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.ichelp.com -- Interstitial Cystitis Association

References

Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30. Epub 2007 Apr 8.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com