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Transport of Effient Human Transmission of H5N1 Via S227N
Recombinomics Commentary
February 10, 2006
"They're all basically the same. Nothing new and unusual,'' Michael Perdue, a scientist with the WHO's global influenza program, said from Geneva.
"That mutation just showed up in that one patient,'' said Perdue.
Genetic analysis of the viruses showed they are closely related to a group or clade of H5N1 viruses that caused a massive die-off of wild birds at a wildlife reserve last May in western China. These Qinghai Lake viruses have been found in dead wild birds in Russia, Turkey, Romania and a number of other spots in western Asia and Eastern Europe.
They are believed to be responsible for Africa's first outbreak of H5N1, in Nigeria.
The above comments concerning the close relationship between a chicken H5N1 isolate in Nigeria and earlier isolates from Qinghai Lake in China and isolates in Turkey and Croatia are of conern. On a recent NPR broadcast it was noted that a string of H5N1 isolates - Turkey, Turkey, Croatia, China, Croatia, Turkey, Croatia, China were between 99.4% and 100% homologous to the chicken isolate from Nigeria. These data leave little doubt that the H5N1 that caused outbreaks at Qinghai Lake in China, Chany Lake, Tula, Kurgen, and Askatran in Russia, Mongolia, Kazakhstan, Romania, Croatia, Bulgaria, Greece, Cyprus, Ukraine, Azerbaijan, Turkey, Iraq, and Nigeria is transmitted and transported by migratory birds carrying closely related H5N1.
However, the comment that the alteration in the receptor binding domain, S227N (also called S223N), described in a sequences from the index case from Turkey is limit to the one patient is clearly misleading. It is well known that isolation of H5N1 in different cell types can alter receptor binding domain sequences and isolation in chicken eggs selects for sequences with avian receptor binding domains. S227N is an alteration that favors receptors on human cells, which leads to more efficient transmission to humans. Media reports on the detection of S227N in the index case in Turkey mentioned isolation of H5N1 from Turkey using chicken eggs as well as MDCK cells (dog kidney). S227N would be selected for on MDCK cells, and selected against in chicken eggs. Thus, isolates from chicken eggs would have reduced levels of S227N.
The data from Turkey, as well as northern and southern Iraq, identified clusters of patients. The size and number of patients indicated H5N1 became more efficient at infecting humans. Prior to Turkey, there were no verified reports of the Qinghai strain infecting humans. In Turkey the human cases exploded, indicating the H5N1 had changed, and the acquisition of S227N was a clear indicator of such a change.
The clusters in northern and southern Iraq indicate that the S227N polymorphisms is transported by wild birds, and the initial reports out of Nigeria suggest it is being carried by long range migratory birds.
Statements by WHO indicating that S227N was limited to the index case require more detail. In the WHO updates on H5N1 positive cases in Turkey, more detail was glaringly absent. Disease onset dates and relations between H5N1 patients were withheld. These data demonstrated extensive human-to-human transmission.
These commissions by omission by WHO are cause for concern.
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