Influenza (cont.)

What is the bird (avian) flu?

The bird flu, also known as avian influenza, is an infection caused by avian influenza A. Bird flu can infect many bird species, including domesticated birds such as chickens. In most cases, the disease is mild; however, some subtypes can be pathogenic and rapidly kill birds within 48 hours. Rarely, humans can be infected by these bird viruses. People who get infected with bird flu usually have direct contact with the infected birds or their waste products. Depending on the viral type, the infections can range from mild influenza to severe respiratory problems or death. When this virus (H5N1) infects human, it is highly pathogenic and although only about 700 people worldwide have been infected, about 10% died. Fortunately, this virus does not seem to be easily passed from person to person. The major concern among scientists and physicians about bird flu is that it will change (mutate) its viral RNA enough to be easily transferred among people and produce a pandemic similar to the one of 1918.

Do antiviral agents protect people from the flu?

Vaccination is the primary method for control of influenza; however, antiviral agents have a role in the prevention and treatment of mainly influenza type A infection. Regardless, antiviral agents should not be considered as a substitute or alternative for vaccination.

Currently, there are four antiviral agents available in the United States. They are amantadine (Symmetrel), rimantadine (Flumadine), zanamivir (Relenza), and oseltamivir (Tamiflu). In 2006, the CDC recommended that neither amantadine nor rimantadine be used for prevention of influenza A as resistance to these drugs had developed. This resistance problem and additional adverse reactions to the drugs (behavioral changes, seizures) have limited their subsequent use. Oseltamivir has had a similar FDA label warning about behavioral changes.

The 2007-2008 Advisory Committee on Immunization Practices (ACIP) recommends that only zanamivir and oseltamivir be used in the U.S. for treatment or prevention until influenza A susceptibility to the other drugs is reestablished. In general, infected people need to begin taking the antiviral medications within two days of developing the initial symptoms of influenza. This may reduce the symptoms and shorten the illness by one or two days. However, in high-risk people, these drugs may either prevent the flu disease symptoms (both conventional and novel H1N1) or, once established, prevent the flu from becoming severe. There is a high potential for overuse of these drugs so the CDC has put out the following guidelines to be used with clinical judgment:

• Uncomplicated febrile illness typically does not require antiviral treatment unless individuals are at higher risk for influenza complications.



• Treatment is recommended for all hospitalized patients with confirmed, probable, or suspected novel influenza (H1N1).



• Clinical judgment should be used when evaluating children; caregivers should be aware that the risk for severe complications from seasonal influenza among children younger than 5 years of age is highest among children younger than 2 years of age and may require antiviral medication.

In early September 2009, CDC officials further modified the antiviral guidelines for the interim guidelines for use of Tamiflu and Relenza as follows:

1. People with high risk factors should discuss flu symptoms and when to use antivirals; doctors should provide a prescription for the antiviral for the patient to use if the patient is exposed or develops flu-like symptoms without having to go in to see the doctor.

2. "Watchful waiting" was added as a response to taking antiviral drugs with the emphasis on those people who develop fever and have a preexisting health condition should then begin the antiviral medication.

3. The antivirals are the first-line medicines for treatment of novel H1N1 swine flu, and most current cases of flu are novel H1N1 and are, to date, susceptible to Tamiflu and Relenza.

Prevention of influenza (both A and B) is possible with both zanamivir and oseltamivir. While zanamivir was approved for people 7 years of age or older and oseltamivir was approved for people 1 year of age and older for the conventional flu, the CDC has published guidelines for antiviral use against novel H1N1 in late September 2009 that includes children under 2 years of age and pregnant women:

• People with more severe illness, such as those hospitalized with suspected or confirmed influenza



• People with suspected or confirmed influenza who are at higher risk for complications



• Children younger than 2 years of age



• Adults 65 years of age and older



• Pregnant women



• People with certain chronic medical or immunosuppressive conditions



• People younger than 19 years of age who are receiving long-term aspirin therapy

Prevention rates vary from about 68%-89% when these antiviral medications were given to individuals before they developed symptoms of the conventional flu or were exposed to infected people; data are not yet available for novel H1N1. Treatment usually consists of a five-day schedule of antiviral medication, while prevention usually requires 10 days of medication. For example, duration of antiviral chemoprophylaxis (prevention) post-exposure is 10 days after the last known exposure. However, recommended treatment and prevention schedules vary according to age, weight, drug formulation, and if the individual is hospitalized. Details about dosing in adults, pregnant women, children, and infants are available and updated on both the CDC and FDA web sites: http://www.cdc.gov/H1N1flu/antiviral.htm and http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm183870.htm. Gastrointestinal symptoms (nausea, vomiting) are some of the most common side effects of these drugs. Influenza viruses are known to develop resistance to both drugs but at a much lower rate than to the other antiviral drugs. These drugs and others that are in development (such as peramivir, favipiravir, and ligand epitopes) are being studied to determine if they can be used to prevent or treat new influenza strains such as novel H1N1 and bird flu.

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