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H5N1 Cluster in Gharbiya Egypt Cause Concern
Recombinomics Commentary
December 30, 2006

Clinical specimens from the three cases were tested positive for avian influenza A(H5N1) virus by Egyptian Central Public Health Laboratory. The virus was also detected in specimens from two of the three patients by US Naval Medical Research Unit No.3 (NAMRU-3). The samples will be sent to WHO Collaborating Centre for further testing including virus characterization.

The above comments from the WHO update suggest sequence data on the Gharbiya cluster will be public soon.  US NAMRU-3 submitted the HA`sequence,
A/Egypt/12374-NAMRU3/2006(H5N1) from the first Egyptian H5N1 case for this season on October 13, two days after confirmation.  The HA sequence was cause for concern because it included M230I, a change that extended the identity with influenza B to positions 226-230 (QSGRI).  This region of identity is cause for concern because influenza B is efficiently transmitted human-to-human and increased efficiency of transfer generates clusters such as the one described above, which is the largest reported to date in Egypt.  Moreover, these cases are much earlier than last season, when the first reported case in Egypt was in February.

Large clusters involving the Qinghai strain are cause for concern because there were several clusters in Turkey, Azerbaijan, and Iraq last season.  Changes in the receptor binding domain were found in each cluster.  In Turkey, clusters had S227N.  In Azerbaijan, clusters had N186K.  In Iraq, clusters had N186S and Q196R.  All of these changes were in the Qinghai strain, which can readily transport and transmit changes over long distances because the strain is found in long range migratory birds.

Additional receptor binding domain changes have been found in other H5N1 strains,  In China, Shanxi isolates has as many as five changes in or near the receptor binding domain (A188E, A189T, T192I, L194I, R220K, K222Q).  Hunan isolates had four changes (D187N, A189E, T192I, L194I).  Shantou isolates had three changes (K222R, V223I, S227R).  One of these changes (V223I) was in a Qinghai isolate from Mongolia, A/bar-headed goose/Mongolia/1/05.  Sequence from this isolate have already been traced from Mongolia to Egypt, so these changes could fly into the Middle East and generate additional combinations of receptor binding domain changes via recombination.

Therefore, it will be useful to quickly release the recent sequences from the large cluster in Gharbiya.

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