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H1N1 D225G in Lungs of Patients Across Russia
Recombinomics Commentary 21:28
December 31, 2009

Vector labs in Novosibursk, Russia has submitted a full set of sequences from lung isolates from patients at three distinct locations in Russia (A/Salekhard/01/2009, A/Tomsk/07/2009, A/Abakan/02/2009).  Although each isolate represents a seperate H1N1 genetic background, all three have D225G.  Since all three isolates came from lung, it is likely that the three infections were fatal, or at least severe, which extends the linkage of D225G with severe or fatal H1N1 cases.  These are the first public HA sequences from Russia with D225G and raise concerns that the establishment of the polymorphism, and/or the related associated polymorphism D225N raises concerns of a new pandemic wave that is markedly more severe that prior pandemic H1N1 waves.

Recent comments by ECDC on the WHO working hypothesis that these changes were due to random mutations generated by uncorrected copy errors and that H1N1 with these changes do no transmit, are not consistent with public data.  In Ukraine, six of six fatal cases have D225G or D225N.  Since these markers are only reported in about 1% of pandemic H1N1 HA sequences, the chances of these markers randomly appearing in 6 of 6 fatal cases is in the trillion to one range.  Similarly, several recently released sequences have both D225G and D225N, including two samples in San Luis Potosi that were collected within one day of each, again creating an event that would require two independent changes at adjacent codon positions for residue 225 in two individuals in the same location at the same time.  The likelihood of these two sets of changes happening independently, when only four samples in the Genbank and GISAID database have both changes, so also extremely unlikely, once again raising serious questions about the scientific basis for the WHO position that these changes are independently generated and are copy errors.  The only data in support of this hypothesis is an attribution to WHO in the ECDC report, which has no scientific basis.

The movement of D225G from one H1N1 genetic background is consistent with homologous recombination, and the clustering in western Ukraine, Sao Paulo, or San Luis Potosi is consistent with transmission.  These developments continue to raise concerns that H1N1 with these receptor binding domain changes will emerge in the next wave. 

Today's report from Ukraine has 29 more fatalities in the past 24 hours, raising the increase in the past 4 days to 94 fatalities.  The report of D225G in lung patients from three different regions in Russia on three different genetic backgrounds increases concerns of an emerging lethal pandemic H1N1, WHO proclamations notwithstanding

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