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Novel H5N1 Bird Flu Sequence in Garut Cluster?
Recombinomics Commentary

August 17, 2006

two including being positive. This continued to be carried out sequencing

"infection that in Garut was different from that in Karo and Bekasi."

The above translation appears to indicate the sequence of the two isolates from Garut are different than the two major strains of human H5N1 detected in Indonesia.  The recent Karo cluster involved sequences that were more closely related to bird sequences, especially those in north Sumatra.  In contrast, all but one of the remaining human isolates had a distinct sequence that had a novel cleavage site, PQRESRRKKR.  In contrast the Karo sequences and the only other human H5N1 sequence that did not have the novel sequence had the common cleavage site PQRERRRKKR.

The two major strains of  H5N1 outside of southeast Asia are the Qinghai and Fujian strains.  Both have cleavage sites that are readily distinguished from the sequences in Karo or Bekasi. The Qinghai sequence is PQGERRRKKR while the Fujian sequence has dropped a K and chnaged the Q upstream from the cleavage site to L, PLRERRRK_R.  These differences would be easily identified in initial sequencing.

Both of these strains have been identified in wild birds and have been associated with human H5N1 infections.  The Qinghai strain spread throughout Europe, the Middle East, and Africa and has cause confirmed human infections in Turkey, Iraq, Egypt, Azerbaijan, and Djibouti.  The Fujian strain was initially identified in a duck in Fujian province and has been identified in human cases in China in 2005 and 2006 and spread into Laos, Malaysia, and Hong King early in 2006.  Recent reports indicate it is also in Thailand and likely has spread throughout southeast Asia.

Although all isolates from Indonesia thus far have had a Indonesia genetic background, the Qinghai cleavage site has been found in Bali and polymorphisms from both Qinghai and Fuian strains have been found in H5N1 in Indonesia, including both versions found in human cases in Indonesia.

Thus, acquisition of the Indonesian strain in Garut would not be a surprised and the quick comments above suggest this change may involve the HA cleavage site.

The cluster in Garut is alarming.  The number of confirmed or suspect cases has quickly grown to nine and six of the cases have already died.  Moreover,  within the larger cluster are smaller clusters including two cousins in one hamlet and an index case, her mother, and two neighbors in another hamlet.  All secondary cases attended the funeral of the index case for that hamlet.

The epidemiology suggests birds may be causing the initial infections, followed by human-to-human transmission.  Thus, there have been confirmed or suspect cases in four hamlets and clusters within the clusters..

More information on sequence differences, as well as the status of contacts would be useful.

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