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Fatal D225G / D225N
H1N1 Co-Infections Raise Concerns
The above comment from the ECDC report on D225G and D225N is false. The current data suggests just the opposite and indicates these changes are transmitting and jumping from one genetic background via recombination. The frequency of D225G/N in public HA sequences (about 3000) is near 1% yet in Ukraine D225G/N is in six of six isolates from fatal cases, which has a chance of a trillion to one if events are independent and random. Moreover, the association of H225G/N with fatal or severe cases extends well beyond Ukraine.
In Sao Paulo there are four examples and all four are also from fatal cases. The published sequences have two with D225G and two with D225N. However, recent sequences with D225G and D225N in the same sample in Sweden, Mexico, and the United States have raised the possibility that the mixture is common, but selection in the sample collected or isolation of the virus leads to detection of one or the other.
For the US (Utah) case the CDC published two sequences. One, A/Utah/42/2009, was taken directly from the clinical sample and it contained mixed signals at position 1 and 2 of the codon for position 225. The other sequence was a clone from the sample which had the D225G codon at position 225, indicating the mixed signals were due to two sequences in equal proportions which had D225G and D225N. All five sequences from patients, as well as a sequence from swine in Mexico, have these tandem mixed signals, indicating the hosts are co-infected with sequences containing D225G and D225N.
In Mexico, two patients in San Luis Potosi have the mixed signals in isolates which were collected within a day of each other. The WHO working hypothesis would require that both patients were independently infected by wild type H1N1 and the H1N1 in both patients would make the same two errors in adjacent positions to generate the fatal combination of D225G and D225N. The likelihood of this happening independently in two patients in the same location at the same time is beyond remote.
This combination is also seen in Ukraine samples. Four sequences generated by Mill Hill have D225G, while two sequences generated by the CDC have D225N raising the possibility that all six fatal cases have both D225G and D225N, which would make the WHO/ECDC working hypothesis even less tenable because it would require two changes at position 225 to happen in the same patient and have those two changes as the only non-synonymous changes in these patients relative to sequences isolated from survivors.
The reliance of the WHO and ECDC on such an unlikely explanation of the data raises serious questions about data analysis by consultants so wedded to such an outdated view invoking random mutations, which is not supported by the data.
This reliance is extremely hazardous to the world's health.