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Human Transmission of H5N1 In Indonesia

Recombinomics Commentary

May 16, 2006

The cluster of eight family members with confirmed or suspected H5N1 bird flu has raised pandemic concerns.  Most of the cluster has tested positive in local tests, and samples have been sent to Hong Kong for confirmation.  Local media reports also mention 57 samples sent to Hong Kong for testing.  Usually the samples sent to Hong Kong have generate positive results, but in this case the samples may be sent because of the size of the cluster. Some reports have indicated 11 samples from contacts, including the health care worker with symptoms, have tested negative.

The H5N1 bird flu cluster in North Sumatra is the largest reported to date in Indonesia, and the most deadly, since six have already died.  The two surviving members are now reported to be improving so the number of fatalities in the initial eight patients may remain at six.  However, at least one media report described 12 additional suspect patients at Adam Malik hospital in Medan, although their relationship, if any, to the cluster of eight, has not been described.  Their symptoms have alo not been described, although the treatment has been characterized as intense and patients in the cluster are being treated with 3 X 75 mg Tamiflu.

H5N1 clusters in Indonesia have been common, but most consist of 2-3 family members.  Like the current cluster, most have a 5-10 day gap between the disease onset date of the index case and other family members.  This gap signals human-to-human transmission and is found in most H5N1 clusters dating back to 2004 in Vietnam and Thailand.  Such clusters with gaps have been reported in Cambodia, China, Turkey, Iraq, Azerbaijan, and Indonesia.

The largest cluster was in Turkey.  The seven confirmed cases were in three families of cousins.  Sixteen family members were hospitalized and conformation was reported in all three families.  Members of one or two additional families were hospitalized with symptoms, but were not reported to be H5N1 positive.  The index case in the Turkey cluster had a change (S227N) in the receptor binding domain that was associated with increased affinity for human receptors found in the upper respiratory tract.  This change may have also been identified in H5N1 from the sister of the index case, but the change was not reported in human H5N1 from patients in Iraq or Egypt, suggesting that the change had not become fixed.

Although Indonesia has had the highest number of reported H5N1 fatalities in 2006, sequences from only one human H5N1 isolate from Indonesia has been made public.  This sequences was from the index cluster in July of 2005.  The HA sequence had a new glycosylation site and a novel cleave site, but was most closely related to HA H5N1 from Indonesian poultry.  However, it had acquired polymophisms found in Vietnam, Thailand, wild birds in China, as well as the Qinghai strain of H5N1.  Dues to widespread H5N1 infections in Indonesia, more recent isolates in 2006, including the current cluster, would be expected to have additional changes, which may affect the ease of transmission or the ability of the pandemic vaccine which is being developed against the 2005 isolate to cross react with the 2006 isolate.

Although the size of the cluster in Indonesia is cause for concern, it does not necessarily signal the start of a pandemic.  There are many reasons why human-to-human transmission within families is more efficient than human-to-human transmission outside of families.  H5N1 can be found in many body fluids, and care within homes offers many opportunities for transmission, especially is the care giver, who is usually a family member, is not trained in universal precautions. As noted above, the large clusters in Turkey were not extended to confirmed cases, although data on the 10,000 serum samples that were expected to be collected in January and February has not been released and reported human cases in Turkey stopped abruptly.

In any event, the size of the cluster in Indonesia is cause for concern, and test results on samples sent to Hong Kong as well as additional contacts or suspect cases in North Sumatra would be useful.

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