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Colds and the flu

Description

An in-depth report on the diagnosis, treatment, and prevention of colds and flu.

Alternative Names

Influenza; Strep throat; Bird flu; Avian influenza

Medications

For mild influenza, symptom relief is similar to that for colds. Vaccines are available to prevent influenza (See section on Viral Influenza Vaccines ).

Two classes of antiviral agents have been developed to treat both influenza A, B, or both: M2 inhibitors and neuraminidase inhibitors. The CDC recommended in January 2006 that the M2 inhibitors should no longer be used to treat flu during the 2005 – 2006 season because many strains of influenza A have become resistant to these drugs. In November 2006, the National Institute of Allergy and Infectious Diseases recommended against using M2 Inhibitors during the 2006 – 2007 flu season, again because of influenza A virus resistance . M2 inhibitors have never been active against influenza B, a milder infection. Until recently, these agents were considered appropriate for prevention and treatment of the flu.

Anti-Viral Drugs: M2 Inhibitors

Brands and Benefits. Amantadine (Symmetrel) and rimantadine (Flumadine) are M2 inhibitors. They have the following benefits against 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 National Institute of Allergy and Infectious Diseases now recommends that M2 inhibitors should not be used during the 2006 – 2007 flu season in the U.S.
• M2 inhibitors are not effective against influenza B.
• Neither has proven to reduce the risk for complications, including pneumonia and bronchitis.

Side Effects. Both agents 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.

Anti-Viral Drugs: Neuraminidase 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.

These drugs have the following benefits:

• Neuraminidase inhibitors are effective for treating both A and B strains of influenza. (M2 inhibitors are effective only against type A.)
• They shorten the duration of the flu by 1 - 3 days.
• They may help reduce transmission of the virus.
• They may have a lower risk than M1 inhibitors for emerging viral strains that are resistant to their effects.
• 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 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, they are much more expensive. They also need to be taken within 2 days of symptoms to be effective. Neither is effective against influenza-like illness. 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 generally 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, making the medicine virtually ineffective in these cases. 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.

Candidates. Their current use in different age and patient groups are as follows:

• Adults. Both 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. 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 they are safe and effective in patients with serious medical problems or other conditions that put them at risk for complications of flu.

Comparing Anti-Viral Medications for the Flu

	Amantadine (Symmetrel) and rimantadine (Flumadine)	Oseltamivir (Tamiflu) and Zanamivir (Relenza)
Type of Drug	M2 inhibitor	Neuraminidase inhibitor
Treats infection with Influenza type A?	Yes	Yes
Treats infection with Influenza type B?	No	Yes
Useful for 2006 - 2007 flu season?	No -- many strains of influenza A have become resistant to these drugs.	Yes
Shortens duration of flu symptoms?	Yes	Yes
Reduces transmission of the virus (nasal shedding)?	No	Yes
Prevents respiratory complications of the flu such as pneumonia and bronchitis?	No	Maybe
Sources: CDC, The Lancet

Antiviral Drugs for Prevention of Influenza

Antiviral drugs are not a substitute for vaccines. Oseltamivir and Relenza may be important as add-on protection agents during a serious epidemic or pandemic, when used in conjunction with public health measures such as quarantine and rigorous hygiene practices.

Oseltamivir is the only drug studied for protection against avian flu. 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. Further study is necessary.

Viral Influenza Vaccines

Description of Vaccines. Vaccines against influenza employ 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 so targets for attack.)

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 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 chickens, and undergo major genetic reassortments.
• 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.

A live but weakened intranasal vaccine (FluMist) is proving to be effective and safe in healthy people aged 5 - 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 employed using a nasal spray. In one study , FluMist provided protection against the flu in up to 93% of children. According to a broad Canadian study in 2004, one to two doses of the intranasal spray gave children better protection than injected vaccines.

Timing and Effectiveness of the Vaccine. 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 influenza 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 one dose, the CDC recommends two 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 one month apart. Further study is ongoing.
• 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, according to a 2004 Canadian analysis of multiple studies.

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 months and 2 years of age. 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 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.

Of note: 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. Still, 90% of asthma patients remain unvaccinated.

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 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.)
• Adults age 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 the recommendation of the CDC.) People (such as household members or health care workers) in contact with individuals who are at high-risk for complications from influenza.
• All health care workers should be vaccinated, according to ACIP’s 2005 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.)
• People such as firemen or policemen who are critical for public safety.

Negative Effects. Possible negative responses 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. Isolated 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, but it has not been a problem with subsequent vaccines.

Pneumococcal Vaccines

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. This has created a great sense of urgency in the medical community to find effective measures for preventing infection.

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 years old. 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 children with sickle disease, immune deficiencies, or chronic medical conditions.
• Other children age 2 - 5 years who are 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. (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 two doses. And those who are over 2 years old need only one dose.

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. Its benefits 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. (Anyone who received the vaccine more than 5 years ago should be revaccinated.) Of note, the vaccination is protective against pneumococcal bacteremia (invasive 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 (such as heart failure or cardiomyopathies), 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 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 should be vaccinized.
• Alcoholics (especially those with cirrhosis) should receive a pneumococcal vaccine.
• People living in long-term care facilities should be vaccinized.
• Alaska Natives or Native Americans, who may be at increased risk for pneumonia, also should receive this vaccine.

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 over 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.

Side Effects of the Pneumococcal Pneumonia Vaccine. 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. Rarely, 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.

Antibiotic Resistance The intense and widespread use of antibiotics is leading to a serious global problem of antibiotic resistance. According to 2001 - 2002 reports, between 30 - 40% of S. pneumoniae strains no longer responded to penicillin in the U.S. The problem is much worse in Hong Kong, where 70 - 80% of strains no longer respond to penicillin. High rates of resistance strains are even being observed in infants. High-Risk Regions. In general, regions and institutions with the highest rate of resistance are those in which antibiotics are heavily prescribed. The inappropriate use of powerful newer antibiotics for conditions, such as colds or sore throats, poses a particular risk for resistant strains of bacteria. In a 2003 study, of adult patients with upper respiratory infections, such antibiotics were prescribed in 33% of antibiotic prescriptions for sore throats and 65% for ear infections. Patients who lived in the Northeast and South were more likely to be given the potent antibiotics than those in the Midwest and West. When Antibiotics Are Needed for Upper Respiratory Infections. Antibiotics do not affect viruses and, in healthy individuals, these agents 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 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 (which is caused by the Streptococcal bacteria) or severe sore throat that involves fever, swollen lymph nodes, and absence of cough. (Strep throat makes up only about 12% 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. As of yet, the average person is not endangered by this problem. Some patients are at greater risk for developing an infection resistant to common antibiotics. 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 are those who attend day care, who are exposed to cigarette smoke, who were bottle-fed, and who had siblings with recurrent ear infections. On a positive note, a small study in Israeli suggested that antibiotic-resistant pneumococcal strains carried by children in a day care center were not passed on to the adults in their household. What the Health Care Community Is Doing. Prescribing antibiotics only when necessary is most important step in restoring bacterial strains that are susceptible to antibiotics. Encouraging studies are reporting that inappropriate antibiotic prescriptions are on the decline. In one study, there was a 47% reduction in prescriptions for otitis media since 1989. Prescriptions for other common respiratory infections also decreased for sore throat, acute bronchitis, and colds and flus. Rates for sinusitis were unchanged. 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.

• Review Date: 3/6/2007
• Reviewed By: A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (12/4/2006).

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