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Biosecurity Briefing
Study: H5N1 Showing Increased Resistance to Oseltamivir By Crystal Franco, August 10, 2007 The journal Emerging Infectious Diseases (EID) released a study online, ahead of print for its September 2007 issue, on findings of reduced H5N1 influenza virus sensitivity to the antiviral drug oseltamivir—commonly known as Tamiflu®. Oseltamivir is currently the “drug of choice for treating [H5N1] infected persons,” and is being stockpiled by governments around the world in anticipation of a flu pandemic. In this study, scientists test the drug sensitivity of H5N1 virus strains to both oseltamivir and zanamivir (another antiviral drug).1 The study tests the “two different strains of highly pathogenic avian influenza A (H5N1)” which “have been circulating since 2003.” The first strain (clade 1) has been found in Southeast Asia and parts of Africa, and the second strain (clade 2) has spread in the People’s Republic of China, Indonesia, and into Europe and Africa. Tests were performed on different avian H5N1 virus samples from clade 1 (2004) in Vietnam and Malaysia, from clade 1 (2004–2005) in Cambodia, and from clade 2 (2005) in Indonesia.1 Scientists found that “despite their origins in different countries and different avian species, all clade 1 and clade 2 viruses had similar sensitivity to zanamavir as the reference [control] influenza (H1N1).” In contrast, sensitivities to oseltamivir differed by clade and country of origin. Clade 1 isolates from Vietnam and Malaysia (2004) were more sensitive than the control human H1N1 virus to oseltamivir. However, clade 1 isolates from Cambodia (2004–2005) showed a sharp “6- to 7-fold decrease” in sensitivity to the drug. Of most concern, were the clade 2 isolates from Indonesia (2005) which “demonstrated a 15- to 30-fold decrease in sensitivity specifically to oseltamivir.”1 The study concluded that “none of the sequence variations” found in the H5N1 isolates “correlate with any mutation known to confer oseltamivir resistance,” suggesting that “the decrease in sensitivities may be due to [genetic] drift” and not due to use of and “exposure to oseltamivir.” The authors of the study find this decrease in sensitivity disturbing “especially since [the virus strains] maintain their pathogenicity and transmissibility in birds and are clearly pathogenic in humans.”1 Although these findings indicate that there may be a dramatic increase in drug resistance to oseltamivir in the Indonesia clade 2 H5N1 strain, according to the authors, it is still unclear whether “this decreased sensitivity occurs only in the Indonesian clade 2 isolates or globally with all clade 2.” However, the authors urge that “because the clade 2 virus [has] now spread through parts of Europe and Africa, continued global collaboration and phenotypic testing of drug sensitivity of circulating highly pathogenic avian isolates…are critical.” They add that “this knowledge is essential for developing appropriate management strategies for pandemic planning.” The findings also suggest that “zanamivir may…play an important role in pandemic stockpiles.”1 References
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