Current and future antiviral therapy of severe seasonal and avian influenza.pdf

Ac p S p v d d u o T i a P K 1 s i d I c g i i c T o r w i 0 dAvailable online at Antiviral Research 78 (2008) 91–102 Current and future antiviral therapy of severe seasonal and avian influenza John Beigel ?, Mike Bray National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Received 27 August 2007; accepted 8 January 2008 bstract The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and hildren (“seasonal influenza”), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral neumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in outheast Asia can cause severe disease when transferred from domestic poultry to previously healthy people (“avian influenza”). Most H5N1 atients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, iral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral issemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza rugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for ncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment ptions may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. his article reviews licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase nhibitors, peramivir and zanamivir; dimeric for