Oseltamivir in human avian influenza infection

Abstract

Avian influenza A viruses continue to cause disease outbreaks in humans, and extrapulmonary infection is characteristic. In vitro studies demonstrate the activity of oseltamivir against avian viruses of the H5, H7 and H9 subtypes. In animal models of lethal infection, oseltamivir treatment and prophylaxis limit viral replication and improve survival. Outcomes are influenced by the virulence of the viral strain, dosage regimen and treatment delay; it is also critical for the compound to act systemically. Observational data on oseltamivir treatment in the early stages of disease suggest it is useful for improving survival in patients infected with H5 viruses, and drug-selected resistance has only rarely been reported. The WHO strongly recommends oseltamivir for the treatment of confirmed or suspected cases of human H5 infection and prophylaxis of those at high risk of infection. In addition to oral dosing, nasogastric administration appears to be a viable option for the management of severely ill patients, as is the use of higher doses and prolonged schedules. F. Hoffmann-La Roche Ltd, the manufacturer of oseltamivir, is developing a mathematical model to allow rapid prediction of appropriate dosage regimens for any future pandemic. Roche is also funding the Avian Influenza Registry, an online database that aims to collect information from clinicians worldwide on the course of avian influenza in humans.

Figure 1

Infection and mortality in chickens inoculated with and in contact with influenza A/Chicken/Pennsylvania/1370/83 (H5N2); n = 5 chickens per group. ‘Infection’ refers to systemic infection indicated by virus isolation from the cloaca (with or without tracheal infection). Figure derived from data in Meijer et al.

Figure 2

Survival among H5N1-infected patients treated with oseltamivir. Figure derived from data in WHO Writing Committee, Liem et al. and Hien et al.

Figure 3

Rates of recovery according to time to oseltamivir treatment in patients infected with influenza A/H5N1 in Indonesia from June 2005 to February 2008. Initiation of treatment within 2 days was associated with significantly lower mortality than initiation after 5–6 days or later (P < 0.0001). Figure derived from data in Kandun et al.