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Resistant Cluster in Maryland / Virginia USA
The above comments describe a Tamiflu resistant cluster in the Washington, DC area. This cluster follows recent clusters at Duke, Wales and Edinburgh signaling efficient transmission of H274Y. Silent spread of H274Y has been suggested by the short time period between the start of Tamiflu and symptoms. In the spring these examples were relatively rare, which was likely due to the relatively low level of H274Y. In most cases the host immune system would control H274Y positive virus, so most selection was sub-clinical. However, there have been dramatic jumps in reported cases in the past several weeks, suggesting the viral load or circulating levels of H274Y have increased. These increased levels has led to more efficient transmission; leading to more cases and clusters.
In addition to the indirect evidence for mixtures, an upcoming report on the first reported case of resistance in the absence of Tamiflu treatment indicated that the patient was infected with equal levels of wild type and H274Y positive virus. In most cases however, the ratio of H274Y to wild type was lower, allowing H274Y to silently spread.
WHO has issued an update, noting that the number of H274Y reports in the past two weeks has almost doubled from 57 to 96, leaving little doubt that such dramatic increase would continue and likely accelerate, creating a significant public health issue, which WHO has denied.
The denial of the significance of spreading Tamiflu resistance follows a denial that the receptor binding domain change, D225G, reported in all fatal cases in Ukraine, is also not significant. More recent statements have left the significance open, but statements on "spontaneous" changes involving D225G follow similar statements on H274Y in seasonal and pandemic H1N1.
The reliance of spontaneous mutations to explain influenza evolution stems from an outdated paradigm based on random mutations fueled by copy errors, which is not supported by a growing sequence database. However, WHO and consultants, including the CDC continue to base policy and press releases on the fatally flawed concept, which is hazardous to the world's health.
This hazard is increasing daily.