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Paradigm Shift Intervention Monitoring
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Spike in H1N1
Fatalities in Romania Raises Concerns
The above comments reflect a dramatic rise in the number of deaths in the past six week in Romania (see map). The above rate is likely linked to lab confirmed cases and over-represents the true fatality rate, but the dramatic rise is likely linked to the spread of D225G. Six weeks ago samples were sent to Mill Hill, which has likely confirmed D225G. The increase in activity in November was near the Ukraine border, and mutations like those in Ukraine have been cited in media reports. Recent reports also described a cluster of severed cases that involved hospitalization of three from the cluster, followed by the death of two (42F and 21M). These fatalities led to a run on vaccine in Olt County.
These media reports provide further support for the spread of D225G/N. Sequences from Ukraine, Moldova, and Russia with D225G/N have been made public and all appear to be from fatal cases. The sequences are from the same clade, adding addition support for the transmission of these receptor binding domain changes at position 225.
These data do not support the WHO working hypothesis that D225G and D225N are due to independent random mutations. The low frequency of D225G/N in public sequences places the changes of 8 of 8 fatal cases with D225G/N in Ukraine at a trillion to one, and the recent results significantly raise those odds because all of the recently released sequences from fatal cases in Russia also have these changes.
The spread of these sequences raise concerns that these changes will be present at higher frequencies in the next wave of infections. Mill Hill assigned a "low reactor" characterization of a Ukraine isolate, and the sequences had D225G as the only non-synonymous HA change, raise concern for selection of these changes.
Release of sequences from Romania would be useful.