New Research on Antiviral Treatment of Influenza
By Eric Toner, M.D., October 13, 2006
Dr. Frederick Hayden presented the John F. Enders Lecture at the Infectious Diseases Society of America’s (IDSA) 44th annual meeting in Toronto this morning. Dr. Hayden is a leading influenza virologist from the University of Virginia currently seconded to the WHO and is a member of the newly formed WHO Ad Hoc Influenza Pandemic Task Force. In his talk, entitled “Antivirals for Influenza: Personal Perspectives on Flu Bugs and Drugs,” he reviewed past and current research on the use of various antiviral agents against influenza.
In particular, Dr. Hayden referred to research by Dr. Allison McGeer and colleagues from Toronto which was presented as an abstract at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco on September 29, 2006. Dr. McGeer showed for the first time that oseltamivir treatment of patients admitted to a hospital with influenza or pneumonia secondary to influenza significantly reduced both complications and mortality. Surprisingly, this was true even for patients in whom oseltamivir treatment was started more than 48 hours after the onset of symptoms, which is usually considered the upper limit of the therapeutic window of opportunity for antiviral treatment in influenza.
Also of interest, Dr. Hayden referred to the study of humans infected with influenza virus H5N1 by Dr. Menno de Jong and colleagues from Vietnam recently published in Nature Medicine. In that study, the researchers found that there was a marked production of pro-inflammatory cytokines and chemokines in patients infected with the H5N1 virus. This finding has been the basis for speculation by some that various immune modulators or anti-inflammatory drugs may have a role in controlling human disease caused by this virus. However, Dr. Hayden suggested that the production of these cytokines and chemokines were directly related to viral replication. As a result, he believes that early antiviral therapy, such as the neuraminadase inhibitors, is central to treatment of influenza since the drugs function to inhibit viral replication. In response to a question at the conclusion of his lecture, Dr. Hayden expressed skepticism that immune modulatory therapy would be beneficial in the absence of antivirals to control viral replication.
Clearly, the work reported by Dr. McGeer should encourage clinicians to use neuraminidase inhibitors in patients with influenza who are ill enough to be admitted to a hospital. Dr. De Jong’s research suggests that whereas immune modulatory therapy theoretically may have a role in the treatment of H5N1 influenza infection in humans, that role is secondary. Early treatment with neuraminidase inhibitors continues to be the primary treatment of choice.
McGeer A, Siddiqi N, Green KA, Low DE, Toronto Invasive Bacterial Diseases Network (TIBDN). Outcomes of influenza requiring hospital admission in Ontario, Canada: Two years of surveillance. Abstract presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco on September29, 2006.
de Jong MD, Simmons CP, Thanh TT, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 2006;12:1203-7. Available at http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm1477.pdf. Accessed October 13, 2006.