Co-Circulation of Qinghai H5N1 RBD Changes in Nile Delta
Recombinomics Commentary
December 23, 2006
The report of a growing H5N1human cluster in the Nile Delta is cause for concern. The first case for this season in the region was a patient who live 12 miles north of the current cluster. That patient was hospitalized at the end of September and was confirmed in the middle of the month. Within days of the confirmation, the HA sequences was deposited at GenBank by US NAMRU3, the US Naval Research lab in Cairo. The sequence produced evidence for evolution via recombination. The Egyptian regional polymorphisms defined last season when human isolates were reported in February. The recent isolate also had a number of additional polymorphism which were in other Qinghai isolates in Europe and Africa.
The acquisition of polymorphisms via recombination creates additional concerns because of the receptor binding changes in Qinghai isolates in the region. PB2 E627K has become fixed in the Qinghai strain. This mammalian polymorphism allows H5N1 to grow more efficiently at lower temperatures, as found in humans (37 C) relative to birds (41 C). The preference for a lower temperature selects for E627K in humans. All human influenza isolates have E627K.However. isolates from last season had a number of additional changes in the receptor binding domain. Lab experiments identified several changes that increase affinity for human receptors. These include S227N was has been detected in human Qinghai isolates in Egypt and Turkey. Similarly, N186K has been found in H5N1 from patients in Azerbaijan. In Iraq the same position is changes to N186S in all human isolates, and two had the additional change of Q196R, which has been shown to synergize with S227N.
Moreover, the recent isolate from Egypt has M230I, which is found in all human flu isolates (H1N1, H3N3, influenza B. Thus, further recombination between co-circulating Qinghai isolates can lead to more efficient human-to-human transmission. In the past, there have been few clusters reported in Egypt. The confirmed cluster of two is the largest in Egypt. If the sister of the index is H5N1 positive, the current cluster will be the largest reported for Egypt. The patients also appear to be developing symptoms sequentially, providing additional evidence for human-to-human transmission. It is unclear if the two additional patients are related to the three described in more detail. However, all five either live or have been hospitalized in a region that is close to the first confirmed case with M230I. These three confirmed and one suspect case all live adjacent to the Nile and have a linkage to ducks.
Last year at this time, low path H5 and Qinghai H5N1 were identified in wild ducks (teal) in Egypt. It is likely that H5N1 is widespread in the region, although only Egypt, Sudan, and Nigeria have reported cases in Africa. None of the countries in the Middle East have reported H5N1, although H5N1 was widespread in Turkey at this time last year and was subsequently found in neighboring countries such was Azerbaijan, Iraq, Iran, and Israel.
The extent of H5N1 spread in these regions in this year is unclear because these countries have not detected or report the H5N1 which is clearly circulating in the area. This lack of transparency in the region, coupled with a confirmed human cluster in Egypt is cause for concern.
One year ago the first human cases of Qinghai infections were reported in Turkey. Neighboring countries subsequently began reporting H5N1 infections In January and February of this year. The first fatality in Egypt did not lead to widespread reporting of H5N1 outbreaks in the area. However, the current cluster may lead to more transparency in the region.
H5N1 does not read press releases or media reports. It continues to acquire new polymorphisms via recombination, and the number of such changes in the receptor binding domain of Qinghai H5N1 co-circulating in the Middle East, including Egypt, remains alarmingly high.
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