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Source of Human H5N1 Bird Flu In Indonesia Unclear

Recombinomics Commentary

June 5, 2006

for the source of the spread, 23 percent of the bird flu sufferer had direct contact with with the chicken or the poultry that died, 25 percent contact indirectly (the chicken or the poultry around the sufferer's positive house H5N1), 2 percent contact with fertiliser that came from the waste of the animal and totalling 17 percent was not yet known by the source of his spread.

The "case of bird flu in Indonesia most happened to the man compared to the woman." This illness not only attacked the adult, but also children. Twenty-two percent of the case of bird flu happened to children, twenty percent to the student, eight percent happened to the worker in livestock breeding, four percent happened to the worker in the traditional market, said Steven.

The above translation on human H5N1 bird flu infections in Indonesia raises additional questions about the source of the infections.  As noted above, the majority of confirmed cases are not directly linked to poultry.  Poultry outbreaks are widespread in Indonesia (see map), and don't always coincide with human cases (see map).

The amount of sequence information from H5N1 human cases in Indonesia is limited to two sequences (HA and NA) from one isolate, A/Indonesia/5/2005 (deposited at Los Alamos on August 1, 2005).  WHO updates have descriptions of that isolate as well as the isolate from the second confirmed case, and recent isolates from the north Sumatra cluster.  Additional information in an Effect Measure report, as well as Declan Butler's report in association with a Nature news story suggests there are three distinct H5N1's isolated from human cases and none match the public poultry sequences from Indonesia.

The most common sequence is public.  It has a novel cleavage site as well as a novel glycosylation site.  Although it is closely related to a subset of Indonesian poultry isolates, the cleavage site is not found in any other public H5N1 sequence.  However, it does match most of the human H5N1 in the West Java region and was also present in a cat isolate from the area.  The absence of this sequence from the public H5N1 poultry sequences raises questions about the origin of the human infections.
The second human H5N1 isolate described in the WHO update appeared to be more closely related to bird isolates.  It had a wild-type cleavage sie and was sensitive to both classes of anti-virals.  However, it had PB2 E627K, which allowed H5N1 to grow at lower temperatures and be more virulent, Most humans infected with H5N1 with PB2 E627K died, as did the 2nd confirmed patient.  E627K was not found in bird H5N1 until it was isolated from infected birds at Qinghai Lake.  However, the Qinghai strain was easily distinguished from the Indonesian strain of H5N1.  Thus, the E627K could have been acquired via reassortment, random mutation, or recombination.

The most recent description of human H5N1 from Indonesia is from the large cluster in North Sumatra.  Those isolates also had a wild type cleavage site, but were amantadine resistant.  Moreover the patients were said t have higher levels of H5N1 in their nose and throat, suggesting they had E627K, which could make H5N1 more easily transmissible, which would be consistent with the large number of cases (eight) coupled with the high fatality rate, 87%.

Thus, there at least three distinct versions of H5N1 in humans in Indonesia.  The genetic relationship of these isolates with Indonesia birds is not public.  Only two of the eight gene segments have been released for the isolate from the index case, and no sequences have been released from the other isolates, which remain sequestered in WHO's private database.

Release of the sequences would allow for more detailed analysis of the origins of these isolates and their relationship to local birds.  More isolates from both domestic and wild birds in Indonesia would expand the H5N1 database and make more accurate determination of the source of the human cases in Indonesia.  More detailed analysis would also allow for more accurate predicts of new sequences and better vaccine targets.

The growing number of clusters in Indonesia dictates a more aggressive screening program and release of the existing data being hoarded by WHO.  Recent statements by representatives of the Indonesian government indicated that these sequences could be released, which should be done immediately.

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