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H5N1 Bird Flu Fatality Confirmed In Egypt 

Recombinomics Commentary

March 18, 2006

Police identified the woman as Amal Mohammed Ismail, 35, saying she was admitted to hospital in the governorate's capital Qalyoub, about two weeks ago, and was subsequently transferred to the Cairo Fevers' Hospital where she died Friday.

A US Navy lab in Cairo found that the woman, who died on Friday, had the H5N1 virus….

The above comments confirm another H5N1 fatality in another country.  H5N1 deaths have been confirmed in Turkey and Iraq and H5N1 in birds has been confirmed in Iran, Israel, and Egypt.  This latest result will increase the level of concern throughout the Middle East.

Although the sequence from the cases in Turkey have not been released, media reports indicate the index case had a change, S227N in the receptor binding domain, which increases the affinity of H5N1 for human receptors.  The sequence of HA from the index case in Iraq was released this week and although it did not contain S227N, it did have N186S, another change near the receptor binding domain.  The US Naval Lab in Cairo, released an Iraqi human, cat and goose H5N1 sequence this week.  The involvement of the lab in the fatal Egyptian case suggests sequences will be promptly released.

These sequences are important because H5N1 is evolving and already appears to be using two distinct changes to infect humans with the Qinghai strain of H5N1.  It will be useful to see if either approach is used for the case in Egypt.

In addition, the database of Qinghai H5N1 sequences is increasing because labs in Russia, Italy, France, and Egypt are promptly depositing sequences in a public database.  In contrast, Weybridge and Hong Kong have sequestered sequences in a WHO private database.  The Weybridge sequences include isolates of H5N1 throughout Europe, but are being held until publication.  Since the papers have yet to be written, these sequences could be sequestered for 6-12 months.  Similarly, Hong Kong has withheld the human H5N1 sequences from Indonesia.  One of these sequences has been selected for a new target for a pandemic vaccine, but the relationship between this sequence to other sequences from human cases is not possible because the sequence has not been released.  Similarly, no human sequences from China have been released.

These sequences should be released immediately.  H5N1 is rapidly evolving, and a full dataset is required for proper analysis.  The analysis by WHO and consultants is limited.  Initial efforts have focused on reassortment with human genes, which has never been reported for H5N1.  More recent comments have focused on "random mutations" by a polymerase lacking a proof reading function.  However, recent sequences from swine in Canada contain long stretches of RNA that has been copied with absolute fidelity for over 25 years, effectively destroying the "random mutation" explanation of influenza evolution.

Influenza, including H5N1, evolves via recombination.  WHO and consultants appear to lack the background and understyanding to conduct such an analysis.  Although these consultants have published sequence data in peer reviewed journals, they have failed to acknowledge the obvious examples of recombination in the sequences they have generated.

The sequestered H5N1 should be released immediately so they can be properly analyzed.

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