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More H5N1 Match Failures in Indonesia

Recombinomics Commentary
December 2,  2006

H5N1 sequences from the two most recent confirmed cases in Indonesia were released today.  The most recent case (35F), from Tangerang, died November 28.  The earlier case (2.5M) from Karawang died November 13.  H5N1 was isolated from both patients on Nov 10 and 13 respectively.  Although the WHO update indicated poultry had died in the Karawang neighborhood, the sequences from the two patient failed to match H5N1 from poultry.

The match failure is not a new development, but the two recent cases indicate that H5N1 continues to evolve in reservoirs that are not closely linked to most of the H5N1 from poultry.  The first human H5N1 sequences was generated in July, 2005.  It had the novel cleavage site RESRRKKR.  All human H5N1 isolates from, the island of Java have had this cleavage site, except the second confirmed case, who was thought to have been infected by H5N1 in fertilizer in August, 2005.  Thus, for well over a year, every human H5N1 isolate, including the sequences released today, have had the novel cleavage site.

In contrast, there has only been one bird isolate from Java that has had the cleavage site.  It was from a duck in Indrmayu, but that isolate matched a small subset of human cases from the end of 2005.  The duck isolate did not match human isolates from Indramayu, or any of the more recent human isolates.

The sequences from the most recent fatality is most closely related to H5N1 from a one year old girl from West Java who died in the spring of 2006 (A/Indonesia/CDC523/2006).  The sequence of the 2 1/2 year old boy is closely related to more recent human H5N1 sequences, from the Jakarta are over the summer.  Both sequences had some additional polymorphisms from Fujian isolates, as well as those in the Karo cluster indicating continued evolution via recombination.

However, these most recent sequences are most closely related to the other human sequences from Indonesia, which are readily distinguished from the poultry isolates.

Although the match failure is clear, WHO updates continue to mention dead poultry in the neighborhood of many cases even though the matching of a sequence from a bird with a nearby human case has never been demonstrated in Indonesia, even though the number of official deaths is at 57.  Moreover, H5N1 testing is largely limited to patients who have some association with dead or dying poultry.

Thus far the only Java match with the H5N1 human sequences has been a cat isolate from Indramayu.  Media reports have suggested additional H5N1 positive cats have been identified, but no sequences have been published other than the one cat sequence described above.

The continued match failures with poultry, couple with a lack of sequences from other H5N1 sources, remains a cause for concern.

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