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Recombination Drives Duke D225G/N Death Transmission
Recombinomics Commentary 11:30
February 10, 2010

4 oseltamivir-resistant pandemic (H1N1) 2009 viruses emerged at Duke University Hospital in Durham, North Carolina, United States. One male and 3 female patients, ranging in age from 43 years to 67 years, with severely immunocompromised status, were admitted to the same ward.

The above comments describe the death cluster at Duke.  Although WHO has maintained that the causal relationship between the three deaths and the infection of all three by the same virus has yet to be established, even more coincidences are required to maintain its position that the appearance of receptor binding domain changes D225G and D225N are due to independent random copy errors and lack of transmission of such errors.

Although other clusters have nullified WHO’s position on transmission, and the clustering in time, space, and phylogeny in Ukraine and Russian severly weakens WHO’s position.  However, the cluster at Duke is detailed with clear transmission of the same virus, yet three different versions of the receptor binding domain were published in the three patients whose samples were collected between October 14 and October 16.  The detection of three different receptor binding domains on identical genetic backgrounds in a cluster where transmission has been demonstrated makes the random mutation paradigm untenable.

WHO has already put out two releases acknowledging the transmission of Tamiflu resistance.  All four patients had H274Y on NA and the rare polymorphisms, Y223H on HA, establishing infection in all four patiets by the same virus.

However, the earlier announcements fail to note that these sequences have 3 distinct receptor binding domains, which were present in the mid-October collections from the first three patients.  D225G and D225N had not been previously reported in this sub-clade, yet both D225G and D225N were found in the first three infected.  The WHO position would require that a change in the first position of the 225 codon happened in one patient, while changes at the second position happened in a second patient, all shortly after each was infected, when the only differences in these sequences are in codon 225.

The likelihood that random errors would be limited to one codon and appear virtually simultaneously is extremely unlikely.  The presence of all three sequences in all three patients is far more likely.  Moreover, the detected sequence would be dependent on when and where the sample was collected.  Two samples were collected from one patient, one day apart and the earlier sample had D225G as a mixture with wild type, while the second sample only had D225G.

These data support transmission of D225G and D225N within this sub-clade, which also transmitted Y233H in the HA sequence and H274Y in the NA sequence.  This transmission of viruses with receptor binding domain changes as well as H274Y is cause for concern, as is WHO’s failure to acknowledge D225G and D225N when providing an update almost 4 months after the cluster, which included three fatal infections due to H1N1.

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