Nov. 3, 2005 In the absence of a specific avian flu vaccine, could antiviral drugs thwart a pandemic should the virus spread from birds to humans? One person with a detailed knowledge of that subject is Dr. Anne Moscona, an infectious-disease expert at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
In a review in the New England Journal of Medicine (Sept. 29), Moscona suggests that the right antiviral drugs and response plan will make a life-or-death difference should the avian virus spread to humans.
Moscona's review examines the four drugs currently available to treat influenza and outlines how antiviral drugs could be used to prevent a pandemic.
So far, avian flu has occurred mostly among Asian poultry workers who had direct contact with infected birds. However, in one possible case in Thailand researchers have suspected human-to-human transmission of the virus. And as infected birds continue to migrate, public health officials worry that an avian strain could become better at spreading between humans, making it uncontrollable.
If the virus does spread between people, doctors believe that antiviral drugs could reduce the severity of the influenza and protect those exposed from getting sick. Still, antiviral drugs need to be distributed and used cautiously, or an outbreak of influenza can actually be made much worse.
The Four Drugs to Combat Influenza
According to Moscona, the two classes of drugs to treat influenza are adamantanes and neuraminidase inhibitors.
"Adamantanes, the class of drugs that includes amantadine and rimantadine, are cheaper and more readily available," she says. "But they have some major drawbacks and would likely not be useful in an avian pandemic." Adamantanes are not effective against most of the avian flu viruses that have been isolated, and they can have serious side effects, such as seizures. Use of adamantanes can also encourage drug-resistant strains to emerge, and these strains can transmit from person to person.
"In most cases," says Moscona, "neuraminidase inhibitors are a better bet."
The class of neuraminidase inhibitors contains the drugs zanamivir and oseltamivir, although most consumers know them by their commercial names, Relenza and Tamiflu.
These drugs prevent the release of influenza virus from infected cells to healthy ones. They must be administered early before the virus infects too many cells, but they are highly effective at treating and protecting against all strains of influenza, including avian influenza.
Neuraminidase inhibitors are also associated with very little toxicity and are far less likely to promote the development of drug-resistant variants or strains. In a pandemic caused by avian influenza, neuraminidase inhibitors would likely be the only useful drug.
Neuraminidase inhibitors would have been effective against the virus that caused the 1918 influenza pandemic in which an estimated 25 million people worldwide died, and are effective against the avian viruses of 1997 to 1999, the avian viruses of 2004 and this year's avian viruses. The avian viruses are largely resistant to adamantanes.
But, there is also bad news about neuraminidase inhibitors. "There are not enough available to stop a pandemic, and there is little capacity to increase production in a time of need," says Moscona. She calls on agencies or nations to create stockpiles of neuraminidase inhibitors that can be quickly delivered to an outbreak. One idea is to develop international stockpiles managed by the World Health Organization.
Like water quenches a fire, neuraminidase inhibitors would be given to the sick as well as those who might have come in contact with them, creating "rings of prophylaxis" around outbreaks. Moscona prefers this to other responses, such as treating only the sick and health-care workers, or offering drugs as a prevention to those at high risk.
Why Not Vaccines?
With traditional influenza, health officials have become adept at anticipating what strains will surface and manufacturing vaccines accordingly. However, in a rapidly spreading pandemic caused by an unknown strain, vaccination is not a realistic plan.
For starters, vaccines require months to create. Scientists need to identify a virus and grow antibodies against it. Plus, the vaccine needs to be distributed, which takes time. A vaccine for the avian virus is being developed but none is yet available.
"In 2005, the tools to detect and diagnose an influenza outbreak are better than they have ever been," says Moscona. "Doctors now have highly effective drugs to treat existing cases and safeguard against others developing."
Unfortunately, individuals can still carry and spread influenza before showing any symptoms, and with modern transportation, an infected person in country "A" can board a flight, mingle with other passengers, and soon countries "B," "C" and "D" have cases to deal with.
"Rapid transit makes curbing an outbreak harder," says Moscona, who thinks a pandemic is likely to happen some year, but is less gloomy about the outcome. She thinks that many people can be protected if scientists keep developing new antiviral drugs and governments improve their public health infrastructure. "But this has to be made a priority in every country because what's 'over there' is no longer so far away."
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