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For papers that will be published online on 10 September 2006
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Understanding why H5N1 is so lethal - Nature Medicine
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 Understanding why H5N1 is so lethal
A study of patients who became infected with H5N1 in Vietnam reveals clues as to why the avian influenza virus is so virulent, according to research to be published in the October issue of Nature Medicine.
Menno de Jong and colleagues compared viral levels and effects on the immune system in one group of patients infected with H5N1 and another group infected with two types of human flu virus. The patients with H5N1 infection had much higher levels of viral load in the throat than the patients infected with the human virus; markers of viral load were highest in the H5N1 patients who died. Virus could also frequently be detected in the blood of H5N1 patients but only in those who died. The authors found that high levels of H5N1 virus triggered a release of some inflammatory cytokines; levels of cytokines correlated with levels of viral load and were highest in the patients who died. Fatal H5N1 infection was also associated with a loss of lymphocytes in the peripheral blood.
The authors suggest these findings support the view that the H5N1 virus replicates to much higher levels than the human virus and that the high levels of the virus trigger an overwhelming inflammatory response that contributes to lung dysfunction and eventual death. They also propose that it will be important to diagnose H5N1 infection early and administer antivirals quicky, nipping viral replication in the bud and preventing the intense inflammation.
Menno de Jong (Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam)
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