Terapong Tantawichien, M.D.
Antiviral agents
form an important part of a rational approach to epidemic influenza
and are critical to planning for a pandemic. The M2 ion channel-blocking
drugs adamantanes (amantadine and rimantadine) and the newer generation,
more expensive antiviral compounds (neuraminidase inhibitors) nebulised
zanamivir (Relenza?) and oral oseltamivir (Tamifu?) have anti-infuenza
activity. Earlier research had shown that all four antiviral medications
were similarly effective in reducing the duration by 1 or 2 days
of illness caused by influenza A viruses, when used for treatment
within the first 2 days of illness. The adamantanes interfere with
viral uncoating inside the cell. They are effective only against
influenza A and are associated with several toxic effects and with
rapid emergence of drug-resistant variants. Recent evidence indicates
that a high proportion of currently circulating influenza A viruses
in the United States have developed resistance to adamantine and
rimantadine, so these drugs will not have reliable efficacy in regions
where there is substantial activity of influenza A (H3N2) or influenza
B. The neuraminidase inhibitors zanamivir and oseltamivir interfere
with the release of progeny influenza virus from infected host cells,
a process that prevents infection of new host cells and thereby
halts the spread of infection in the respiratory tract. The current
avian influenza (H5N1) outbreak in Asia, which has a high case-fatality
rate, indicates the need for decisive action. These circulating
H5N1 strains are fully resistant to these the M2 inhibitors. Oseltamivir
is effective against H5N1 and is used as treatment in Vietnam and
Thailand. As for the circulating avian H5N1 viruses that constitute
pandemic threats, national preparedness plans have become essential.
In a pandemic hastened by globalization, vaccination is not a viable
initial solution because vaccine production requires an estimated
6 months. Instead, neuraminidase inhibitors are influenza-specific
antiviral agents that figure strongly in preparedness plans. Many
nations are acquiring stockpiles of these drugs because of their
effectiveness in influenza treatment and prophylaxis. The decision
to stockpile requires predetermined objectives; non-economic, moral,
and ethical implications should be considered. Policymakers have
to act decisively, and determine the subpopulations to be given
priority, to enable preparedness plans to succeed. Antiviral resistance
to neuraminidase inhibitors has been clinically negligible so far
but is likely to be detected during widespread use during a pandemic.
There have now been several reports that oseltamivir-resistant influenza
A (H5N1) viruses with the H274Y mutation have been isolated from
humans with avian influenza infection who were treated with oseltamivir.
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