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Second H5N1 Fatality in Gharbiya Cluster in Nile Delta
Recombinomics Commentary
December 25, 2006

A 15-year-old girl has died from the H5N1 strain of bird flu, the second such death in as many days in Egypt, the health ministry in Cairo said.

The above comments describe the death of the second family member and third H5N1 fatality this season.  This increased fatality rate coupled with the largest cluster to date in Egypt, are cause for concern. Last season, Egypt reported fourteen confirmed H5N1 cases, including six fatalities.  This season the first case was hospitalized on Sept 30.  She was H5N1 confirmed on October 11 and US NAMRU-3 deposited the HA sequences at Genbank on October 13.

The sequence had many polymorphism found in human and bird cases from the earlier cases in the spring.  However, there were also a number of additional polymorphisms found in recent Qinghai isolates in Europe and Africa, indicating the new isolate had recombined with other Qinghai isolates in the area and acquired the new polymorphisms.

Most alarming was the acquisition of M230I, which is found in human H1N1, H3N2, and influenza B strains.  This acquisition created a region of identity between positions 226-230 (QSGRI) of the influenza B receptor binding domain.  Influenza B is efficiently transmitted human-to-human.  Moreover, Qinghai isolates have PB2 E627K, which is another mammalian polymorphism that increases polymerase activity at lower temperatures.  This polymorphism is present in all human isolates, including the 1918 pandemic strain, and has become fixed in the Qinghai strain..

The death of the cousin of the index case keeps the case fatality rate at 100% in Egypt this season.  This increased CFR may be related to the genetic changes seen in the HA sequence from the earlier case.  The recent cases lived 12 miles from the October case (with M230I). Release of the sequences from the three recent cases would be useful.

US NAMRU-3's rapid release of the sequence from the first cases is to be commended.  Similar timely releases from the current cluster would be useful.  Additional receptor binding domain changes in Qinghai isolates from the region, including S227N in Egypt and Turkey, N186S and Q196R in Iraq, and N186K in Azerbaijan, were reported in human cases from last season. 

Acquisition of these changes by H5N1 isolates from Egypt would be cause for additional concern.

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