The best ways of managing patients with H5N1 infection (avian influenza) are debated by experts in this week's open access journal PLoS Medicine.

Higher than recommended doses of the antiviral drug oseltamivir (Tamiflu) should be used to fight H5N1 influenza, argues Nicholas White (Mahidol University, Bangkok, Thailand). In contrast to the current WHO guidelines recommending that oseltamivir be given at a dose of 75 mg twice daily for five days, Dr. White argues that higher doses should be given for H5N1 infection to avoid any possibility of under-dosing those patients with unusual pharmacokinetics and more resistant organisms. This will come at the expense of increased toxicity, he says, but is necessary given the mortality burden of H5N1 infection and the fact that H5N1 replicates more rapidly than seasonal influenza viruses, reaches much greater viral burdens than do other human influenza viruses, and resistance develops swiftly.

Robert Webster and Elena Govorkova from St. Jude Children's Research Hospital in Memphis, USA, writing in response to Nicholas White's article, disagree. They argue that we must instead consider a multidrug approach to managing patients with H5N1, an approach that is supported by animal data and "can guard against the emergence of resistant strains." Tim Uyeki from the Centers for Disease Control and Prevention in Atlanta, USA, emphasizes theneed for more data to help inform clinical management of patients with H5N1 infections. In the absence of these data, he argues, we need a multipronged strategy: pharmacological strategies including combination antiviral treatment, anti-inflammatory agents, and immunotherapy, and non-pharmacological strategies such as the standardization of optimal ventilator and fluid management, especially for acute respiratory distress syndrome, and management of other complications.

In a 2007 article in PLoS Medicine (PLoS Med 4(5): e119), Holger J. Schünemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a "rapid advice" guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days.

Funding: NJW is a Wellcome Trust Principal Fellow. RGW and EAG are funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200700005C; and by the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in the decision to publish or preparation of the manuscript. TMU received no specific funding.

Competing Interests: NJW is the co-chairman of the World Health Organization antimalarial treatment guidelines committee. RGW reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals and receiving consulting fees from GlaxoSmithKline. EAG reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals.

"What Is the Optimal Therapy for Patients with H5N1 Influenza?"
White NJ, Webster RG, Govorkova EA, Uyeki TM (2009)
PLoS Med 6(6): e1000091.

PLoS Medicine

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