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Commentary
H1N1 D225G Transmission In Duke Death Cluster
Recombinomics
Commentary 11:48
March 24, 2010
The above comments are from the Saturday presentation at the Fifth Decennial meeting of the International Conference of Healthcare-Associated Infections. The detail above, coupled with the associated Gantt chart and collection dates for samples submitted to GISAID by the CDC, indicates HA sequences from two of two isolates from the index case (43F) had D225G. However, the presence of D225G in the index case or D225N in the isolate from a second fatal case (61M) was not mentioned in the abstract or two prior descriptions by WHO (in a Dec 2 briefing report and a Feb 5 WER report), even though the D225G positive sequences were from isolates from Oct 15, A/North Carolina/39/2009, and Oct 16, A/North Carolina/49/2009 collections. These collection dates correspond to the first collection from the index case on Oct 15. Two other samples, A/North Carolina/41/2009 and A/North Carolina/42/2009, were collected on Oct 14, which would correspond to initial collection dates for the other two fatal cases (67F and 61M, respectively).
H1N1 from all four patients were linked by a rare HA polymorphism, Y233H, and Tamiflu resistance, H274Y. Thus, although all four patients were infected with the same H1N1, D225G was only detected in the index case. However, the first collection was a mixture with wild type, while the second collection was on the date of death, and therefore may have been collected at autopsy. The collections from the other two fatal cases were on Oct 14, while both patients were alive and prior to treatment, so these samples were likely from the upper respiratory tract since one patient had already been discharged, and the other patient survived for 3 days after collection (assuming the date of death corresponds to the last October data point on the Gantt chart). Although all three fatal cases were infected with the same H1N1 and died between Oct 15-17, the Feb 5 WER maintained that the causes of deaths were uncertain.
Thus, the detection of D225G in two of two isolates from the index case strongly suggests that D255G was transmitted to the three other patients and the failure to detect D225G in these cases was simply due to the timing and location of samples collected. The Oct 14 collections were prior to treatment and at dates that were 4 or 7 days post initial symptoms, while the D225G positive samples from the index case were at days 9 and 10 post initial symptoms. Moreover, the clean D225G sequence was collected on the date of death, and therefore may have been an autopsy sample. However, the direct sequence from this sample was not released.
The surveillance of D225G remains abysmal. The recently released sequences from India failed to find D225G in a patient that was D225G positive when tested by the CDC. However, for the Duke death cluster the CDC failed to find D225G in direct sequencing of the original sample from the index case, and failed to release the sequence from the sample collected on the date of death. Similarly, no subsequent sequences from the other two fatal cases were released. D225G in these samples would destroy the WHO/CDC working hypothesis that D225G is “sporadic” , spontaneous, and due to random mutations.
These inconsistencies and lack of transparency continue to raise pandemic concerns. Release of the sequence from the Oct 16 collection from the index case and more recent collections from the other two fatal cases would be useful.
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