The unexpected flu vaccine shortage is thrusting a class of powerful virus-fighting drugs into a sudden spotlight.

For more than a quarter century, doctors have turned to antiviral medications, drugs that can halt the sweep of influenza through a nursing home, lessen the severity of the illness in school-age children and clear an infection in a bride or groom who might otherwise miss the big day.On Tuesday, Secretary of Health and Human Services Tommy Thompson offered assurances that enough antiviral drugs are on hand nationwide to treat millions of Americans, even in the event of a pandemic. The drugs act specifically on the replication cycle of influenza viruses and are not effective against other infections caused by viruses.

Influenza antivirals have two uses: preventing a flu infection altogether or, if taken within two days of the first symptoms stopping one in its tracks. Biologically, the difference between getting a flu shot and popping an antiviral pill is as stark as night and day, said Dr. Arnold Monto, an epidemiologist and influenza expert at the University of Michigan´s School of Public Health.

Unlike conventional flu shots - derived from killed influenza viruses, which prompt the body to generate infection-fighting antibodies - antiviral drugs are synthetic compounds designed to disable the microbes at a molecular level. They target a vulnerable protein on the viral surface.

Dr. Dominick Iacuzio, medical director of Roche Pharmaceuticals, which makes one of the newest antivirals, Tamiflu, said the drug effectively halts the replication of influenza pathogens by targeting a protein called neuraminidase. When replication is prevented, the process of infection stops, added Iacuzio, a former director of cold and flu research at the National Institute of Allergy and Infectious Diseases. Two other antivirals, amantadine and rimantadine, act on an influenza protein called hemagglutinin.

"Vaccination is best because that´s real prevention," said Dr. Ira Leviton, an infectious disease specialist at Montefiore Medical Center in the Bronx. "We look at these drugs as adjuncts to vaccines."

A shot with the vaccine protects for an entire flu season - generally November through March. Antiviral pills, however, are taken for several days and provide protection only while the drug is being taken.

Antivirals can be effective in the prevention of influenza´s spread within a household, said Dr. Donald Pearlman, assistant clinical professor of medicine at the University of Medicine and Dentistry of New Jersey. He said in homes with an infant too young to be vaccinated, parents can take an antiviral to prevent infecting a baby with the flu.

Pearlman said he believes doctors and public health officials did not rely enough on the drugs during last year´s severe flu outbreak. "Patients should talk to their doctors about antiviral therapy," he said.

The U.S. Food and Drug Administration has approved four antiviral medications since 1976. Three are used for prevention and treatment, and one is available for treatment only.

For now, makers of the drugs say there are no shortages and, should an emergency arise, there would be enough to aid a major flu-fighting effort.

Last week Dr. Julie Gerberding, director of the U.S. Centers for Disease Control and Prevention, said that millions of doses of one antiviral, rimantadine, sold as Flumadine, will be added to the country´s Strategic National Stockpile, established in 1999 to provide essential medications to states and communities during an emergency, such as a major flu epidemic. The cache already contains about 1 million doses of Tamiflu (oseltamivir), and more are being added.

Thompson said the government stockpile includes amantadine, sold as Symmetrel, and zanamivir, sold as Relenza.

Traditionally, antivirals have been most useful in nursing homes and other institutional settings where influenza can spread quickly and prove deadly. They´re also been useful in hospital wards and on cruise ships, where diseases spread easily. Antivirals, doctors said, also have been a boon to people who are allergic to eggs; flu vaccines are made in eggs, and yolk proteins often make their way into the shot.

But as important as antiviral medications have become, they are not free of side effects.

Leviton said one of the drugs, amantadine, has been known to cause nightmares in some elderly people.

The CDC, which has listed additional side effects on its Web site, notes that in healthy adults and children, rimantadine and amantadine are known to cause nervousness, anxiety, difficulty concentrating, and lightheadedness, as well as nausea and loss of appetite. People with other long-term illnesses who have taken amantadine have experienced delirium, hallucinations, agitation and seizures.

The newer generation of drugs, which includes Tamiflu, also can have side effects, including nausea and vomiting.

Scientists know that influenza viruses come in a variety of strains. Generally, two types of A-strains and a B-strain are included in the vaccine. Tamiflu and zanamivir are effective against A and B. Amantadine and rimantadine are effective only against A.

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A brief written at the spring 2004 demonstrated Roche´s Tamiflu is not suitable for large scale use in China

see attachments

anslysis of China antiviral treatment in the potential avian flu outbreak(1).pdf
antiviralandstrategies.pdf
antiviraldrugs.pdf