A drug class called neuraminidase inhibitors are an effective option for treating influenza; the drugs act by blocking an enzyme which usually allows the influenza virus to escape and infect other cells. The neuraminidase inhibitor oseltamivir is widely used, although no research has established the risk of the emergence of viruses resistant to this drug during clinical use.
Yoshihiro Kawaoka (University of Tokyo, Japan) and colleagues investigated oseltamivir resistance in a group of children treated for influenza. Children, being more susceptible to influenza than adults, are thought to be a useful group to study as they could provide a model similar to that of a general population during a flu pandemic.
Influenza A viruses (H3N2) collected from 50 Japanese children before and during treatment with oseltamivir were analysed. Neuraminidase mutations were found in viruses from nine patients (18%). Oseltamivir-resistant viruses were first detected 4 days after the start of treatment and on each successive day of the study.
Dr Kawaoka comments: "Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir".
In an accompanying commentary (p 733), Anne Moscona (Mount Sinai School of Medicine, New York, USA) concludes: "We need more information on the emergence of resistance, especially in oseltamivir-treated patients, and we urgently need to know whether resistant variants, such as those identified in Kiso's study, are transmissible. The development of the neuraminidase inhibitors has been a true success story: protein structural analysis directly applied to preventing and treating a major infectious threat. Let us take Kiso and colleagues' study as an energising mandate to learn more about the incidence and mechanisms of resistance to the neuraminidase inhibitors, so that appropriate strategies can be developed for their use during the next pandemic".
Contact: Dr Yoshihiro Kawaoka, Department of Microbiology & Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan;
T) 81-3-5449-5310;
kawaoka@ims.u-tokyo.ac.jp
Dr Anne Moscona, Department of Pediatrics, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, NY 10029, USA; anne.moscona@mssm.edu
ISSUE: 28 August-3 September 2004
Journal
The Lancet