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.

<<back