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H5N1 Fatality in South Sulawesi Indonesia
Recombinomics Commentary

September 8, 2006

Indonesia's 47th fatality from the virus was a woman called Akira from
South Sulawesi province, said Health Minister Siti Fadillah Supari, adding that infected birds had been found dead in the same area

"We did not send (the samples) to the WHO (World Health Organisation)
because our positive results are usually positive results at the WHO," she added.

Up until now, Indonesia has always sent blood and tissue samples from
suspected human bird flu cases to a WHO laboratory in Hong Kong for

Sari Setiogi, the WHO spokesperson in Indonesia, said that under a new
arrangement Jakarta could confirm infections after two local tests showed the person to have contracted H5N1.

Supari gave no further details other than that the latest bird flu case had been first discovered on June 24.

The above comments detail another confirmed H5N1 bird flu fatality in Indonesia.  The report however raises several additional questions.

Although there was dying poultry in the proximity of the confirmed case, the link to domestic poultry remains weak.  The sequences of H5N1 identify a number of regional changes, as well as changes that are increasing with time.

In 2006, all human H5N1 isolates, other than the cluster from Karo have had a novel HA cleavage site, RESRRKKR.  This change is associated with a number of additional changes in HA as well as the other seven gene segments which are not present in poultry H5N1 isolates.

Recently, an isolate from a duck in Indramyu, A/Duck/Indramayu/BBPW109/2006, did have the novel cleavage site, as well as another nearby change that was found in a limited subset of the human cases that were isolated in 2005 or January 2006.  There were additional changes linked to these earlier isolates, but many of the changes seen in human cases in 2006 were not present in the duck isolate.  These changes include four human isolates from January 2006 that were from patients in Indramyu, A/Indonesia/283H/2006, A/Indonesia/286H/2006, A/Indonesia/292H/2006, and A/Indonesia/304H/2006.

Recently, the CDC released three recent sequences from western Java, including one sample from the Garut cluster.  These recent sequences also had the novel cleavage site as well as the changes that were found in human and cat 2006 isolates, but absent from the duck isolate.

Thus, all human H5N1 isolates from Java have these changes, but they are not found in any of the avian isolates from Java.  The only bird isolate with the novel cleavage site is more closely related to earlier isolates, raising the possibility that the human cases are coming from a source other than domestic poultry.  More sequences from domestic and wild birds would be useful.

The recent isolates also raise questions on future sequences/  In the past, samples positive for H5N1 based on tests in Jakarta have been sent to Hong Kong and the CDC for confirmation and virus isolation and sequencing, since the lab in Jakarta does not have appropriate facilities for sequencing known H5N1 isolates.  In addition, bird samples have been sent to the WHO affiliated lab in Australia for sequencing.

It is important to continue aggressive sequencing because H5N1 is clearly evolving, and there are regional differences that distinguish the H5N1 in Karo from the sequences on Java.  To date there are no human sequences from South Saluwesi, the location of the latest confirmed cases.

Some media reports have suggested human samples were no longer being sent to Hong Kong.  The most recent submitted sequence from Hong Kong is from a patient who died in early July.  The CDC has released three sets of sequences collected from patients after early July, suggesting Hong Kong may no longer be receiving sequences.  In the past, some isolation of H5N1 has been limited to either Hong Kong or the CDC, so isolation attempts by both groups would be useful.

Moreover, the limited matching between human and bird H5N1 indicates sequencing of isolates from Indonesia should be increased, not decreased.

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