Medications:

Vaccines are available to prevent influenza (See Viral Influenza Vaccines section in this report).

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. These drugs can shorten symptoms but there is no indication that they can prevent or reduce infections. They do not help if they are started after the first 36 hours of illness. Because of emerging drug resistance, some experts suggest these drugs be reserved for severely ill patients or those at high risk.

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. While effective, their overall benefit is modest.

Important points about the use of these drugs:

• The main benefit of these drugs is a reduction in the the length of symptoms by about one day, and only when started within 48 hours after symptoms become evident. They may be used for treating both A and B strains of influenza.
• They may help reduce transmission of the virus.
• Viral resistance to oseltamivir (Tamiflu) is growing. The CDC therefore recommends that when influenza A (H1N1) infection is suspected, treatment includes zanamivir or a combination of oseltamivir and rimantadine, rather than oseltamivir alone.
• 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. The American Academy of Pediatrics recommends the following: Therapy should be provided to children with influenza infection who are at high risk of severe infection, and to children with moderate-to-severe influenza infection who may benefit from a decrease in the duration of symptoms. Prophylaxis should be provided (1) to high-risk children who have not yet received immunization and during the 2 weeks after immunization, (2) to unimmunized family members and health care professionals with close contact with high-risk unimmunized children or infants who are younger than 6 months, and (3) for control of influenza outbreaks in unimmunized staff and children in an institutional setting.
• 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.

Anti-Viral Drugs: M2 Inhibitors

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 some 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
• 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.

Viral Influenza Vaccines

"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 9 do not develop strong immune responses to one vaccine dose, the CDC recommends two vaccinations given 1 month apart on the first year they receive the vaccine. If children under 9 received only 1 dose of the vaccine on their first immunization year, they should receive 2 doses the following year. Children under 9 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 ages 6 months and 18 years 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.
• Children over age 5 who have a higher risk for serious illness.

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 65 years and older. Older adults who get a flu vaccine have lower hospitalization rates than those who do not. Evidence now suggests that vaccination may help protect against adverse heart events (including those following 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.)
• People of any age who have chronic medical conditions. The U.S. Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 should be vaccinated.
• All health care workers should be vaccinated.
• 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.

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 mild 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 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, it has not been a problem with subsequent vaccines. The risk is far outweighed by the number of severe flu cases prevented by immunization.
• There has been some question concerning influenza vaccinations because of reports that these 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.

Avian Influenza Vaccine

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 doses, 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. The vaccine led to the development of antibodies in 45% of those who received the higher dose studied. The most common side effects reported were pain at the injection site, headache, and muscle pain. Research on the vaccine is continuing.

Antibiotic Resistance

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, may sometimes 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. [For more information, see In-Depth Report # 62: Sinusitis.]
• 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. [For more information, see In-Depth Report # 78: Ear Infections.]
• 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 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 units
• 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.