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German H1N1Tamiflu Resistance Cluster Raises Concerns
Recombinomics Commentary 17:34
December 20, 2009

For the first time in Germany when swine flu patients - a ten year old and a 31-year-old man - resistance to the influenza drug Tamiflu has been demonstrated.

Both had come with pre-existing conditions and a "weak defense" to the University Hospital of Munster, said the clinic on Friday. They were already infected with swine flu in the reception.

The above translation describes the first to H274Y confirmed cases in Germany.  Although Germany has a strong surveillance system and has reported H1N1 since the spring, the first reported cases of H274Y come at a time when reported cases are exploding in the United States, Japan, and the Netherlands, suggesting H274Y is transmitting. This is further supported by the presence of H274Y in two patients from the same hospital.  Hospital outbreaks have been reported in Wales and North Carolina in immuno-compromised patients and in North Carolina, three of the four died.

The sudden appearance of H274Y in Germany supports the phylogenetic analysis of recently released sequences from the US and Japan.  This analysis shows clustering of H274Y confirmed sequences, and suggests other sequences which are in the same sub-clades also have undetected H274Y.

In one of these clusters, the H274Y is associated with D225E, raising concerns linkage between H274Y and receptor binding domain changes.  In another cluster, one isolate has D225G paired up with H274Y, raising concerns that H274Y could be paired with RBD changes linked to fatal or more severe cases.

Thus, the two cases in Germany suggest H274Y is widespread and transmitting, and in some circumstances, the widespread appearance of H274Y may be linked to receptor binding domain changes

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