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H5N1 Cases in Egypt Raise Tamiflu Resistance Concerns
Recombinomics Commentary 16:51
March 23, 2009

Woman, age 38, began experiencing fever and headache March 14. She was admitted to Assiut Fever Hospital and given Tamiflu on March 14. Infection with avian influenza was confirmed March 18. The woman reported contact with dead and sick poultry. She was reported clinically free and in a good general condition on March 18.

The above detail on the most recent confirmed case in Egypt raises concerns that a mild H5N1 is circulating in Egypt at levels markedly higher than the reported cases.  H5N1 testing is usually limited to symptomatic cases with a recent history of exposure to dead or dying poultry.  Thus, if the above case had denied contact, hospitalization and testing would be unlikely and the symptoms could be mistaken for seasonal flu.  Others may not seek medical attention and assume that the H5N1 infection is a mild infection not requiring medical attention.

None of the eight confirmed cases in 2009 in Egypt have died.  Only one was in critical condition.  The other seven had a mild course.  Milder H5N1 likely leads to more exposure of others, because the patient is not immediately hospitalized and isolated.  The increased exposure would not only the increase the likelihood of infecting others, but would also increase the likelihood of a second infection with H1N1 seasonal flu, which is almost exclusively Tamiflu resistant.

Tamiflu treatment of a patient co-infected with H5N1 and H1N1 carrying H274Y would apply pressure toward the transfer of H274Y from the H1 on H1N1 to the H1 on H5N1, either via reassortment or recombination.  In seasonal flu, both transfers have been reported, raising concerns of similar exchanges between H1N1 and H5N1.

H274Y has been reported to have been independently introduced onto three H1N1 sub-clades that have been recently circulating.  Moreover, the level of H274Y in the most widely circulating sub-clade (clade 2B  - Brisbane/59) has increased to levels approaching 100%.

Thus, the high levels of H274Y in H1N1, coupled with increased circulation of H5N1 in human populations in Egypt raises serious concerns about the emergence of Tamiflu resistant H5N1 that is more efficiently transmitted in human populations.

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