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Third Suspect H5N1 Cluster in Sohag Egypt Raises Concerns

Recombinomics Commentary
December 1,  2006

A woman and her two children are suspected of contracting the deadly H5N1 strain of bird flu in Upper Egypt, a veterinary official reportedly said.

The 25-year-old mother, her 12-year-old son and daughter, 10, from a village in Sohag governorate, were hospitalized after showing the first symptoms of the sickness, the province's veterinary services chief Mohammed al-Masri told the official MENA news agency.

They are currently undergoing tests to determine whether they are suffering from H5N1 which has killed seven people in Egypt this year, he added.

The above suspect H5N1 cluster is the third in Sohag, and raises pandemic concerns.  H5N1 re-emerged in Egypt in September.  H5N1 was confirmed in Sohag and Cairo areas.  The confirmed positives in poultry was followed by a cluster involving a mother and son.  The symptoms were described as "haemorrhagic disease". 

A second cluster involved three siblings and a neighbor who were hospitalized on the same day.  Two of the four suspect cases were unconscious at the time of admission and had pneumonia.  The two clusters were followed by reports of a 25 year old Sohag women admitted a week ago.  It is unclear if the 25F admitted last week is the same person described above.  If there is only one 25F patient, then infection of the children by their mother is likely.

The three suspect clusters in Sohag increase pandemic concerns.  Although the human clusters have not been confirmed, the reports of false negatives worldwide are frequent.  Media reports have not provided updates on these patients or described a subsequent diagnosis for these cluster members.

The only confirmed case in Egypt this season was of a fatal infection (39F) near Cairo.  The sequence of HA H5N1 from that patient has been released, and it has a number of changes from H5N1 isolated in Egypt earlier this year, although the isolate clearly has many of the Egyptian associated markers.

One of the changes was M230I.  This polymorphism is in all three human influenza's (H3N2, H1N1, influenza B).  Moreover, the change creates a five amino acid exact match with the receptor binding domain of influenza B for positions 226-230 (QSGRI).  Influenza B is efficiently transmitted human-to-human.  Moreover, recent released sequences of otter Qinghai isolates in the region identify S227N in an Egyptian patient, as well as N186K and Q196R in patients in Azerbaijan and Iraq. The newly release human H5N1 sequences contained two Azerbaijan isolates with N186K and two Iraq isolates with Q196R.  The Iraq isolates are confusing because there were more human HA H5N1 Iraq sequences than confirmed cases in Iraq

Since there have now been four changes at positions in or near the receptor binding domain (N186K, Q196R, S227N, M230I) in human Qinghai isolates in the region, further recombination can bring these changes together in the same sequence.  The recent Nature paper provided synergy data for Q196R and S227N, which were found in one clone from a patient in Vietnam.  The presence of such changes in birds infected with Qinghai H5N1 is unclear, since these isolates are from chicken eggs, which would select away from changes that increase affinity for 2,6 gal (human) receptors.

An increase in affinity for human receptors would lead to more efficient spread of H5N1 which would initially present as familial clusters.  Such clusters were reported in Turkey, where two of the four public sequences have S227N, and Azerbaijan, where two of the public human H5N1 sequences have N186K.  Moreover, all of the human Qinghai isolates have the mammalian polymorphism, PB2 E627K.

Thus, although the three suspect cluster in Egypt have not been confirmed, the clustering of suspect clusters in Sohag increase concern. 

Details on the current status of these patients, regardless of H5N1 results, would be useful.

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