Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?

Influenza A(H5N1) virus is one of many avian influenza viruses and was identified as the cause of 18 hospitalizations and 6 deaths in Hong Kong in 1997; the slaughter of 1.5 million poultry is credited with aborting the outbreak [1–3]. The concern that this event provoked for an occurrence of an H5N1 pandemic was reinforced when H5N1 infections were detected in 2003 in children in Vietnam; exposure to poultry was documented for 8 of 9 cases [4]. Expanded surveillance recorded H5N1 outbreaks in poultry throughout Asia and in other parts of the world [3, 5]. These occurrences in poultry led to recognition of H5N1 infections and disease in humans exposed to infected poultry , a circumstance that has continued to date [6]. Most H5N1 infections in humans result in a severe pneumonia with a high mortality rate, but with little ability to spread among humans [4, 6]. It is proposed that pneumonia is the characteristic H5N1 disease in humans because the avian influenza virus receptor is prevalent on terminal bronchioles and lung alveolar cells, and not on the epithelial cells of the respiratory passages [7]. Unless the feared mutation(s) leading to a typical influenza virus infection of the respiratory passages occurs, H5N1 will likely remain primarily an uncommon severe pneumonia caused by exposure to infected poultry. Nevertheless , this threat of a change leading to a pandemic has caused an extensive worldwide effort to develop preventive vaccines [8, 9]. As of 1 June 2010, the World Health Organization (WHO) has documented 498 cases of H5N1-induced disease and 295 (59%) deaths [10]. The bulk of documented cases (79%) have been in In-donesia, Vietnam, and Egypt, with a mortality rate of 82%, 50%, and 31%, respectively. Clinical descriptions of H5N1 cases have indicated that the viral load is usually much higher than those seen in cases of H3N2 or H1N1 seasonal influenza, and is higher in fatal cases than in nonfatal cases; moreover, levels of several cytokines and chemokines were also higher among cases of H5N1 than in cases of H3N2 or H1N1, and among fatal cases than among non-fatal cases [11, 12]. Although cytokine dis-regulation has been proposed for the so-called cytokine storm, it seems primarily attributable to a " viral load storm, " and the sequence of high viral load leading to high cytokine load frequently leads to development of the acute respiratory distress syndrome, respiratory failure, and death. The …