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Indonesian H5N1 Swine and Bird Sequences Are Similar

Recombinomics Commentary

July 4, 2006

The recent meeting on human H5N1 bird flu in Indonesia included phylogenetic trees of HA and M genes.  The HA tree identified two separate groupings of the human isolated, color coded in green.  The Karo cluster was related to avian isolates.  This group is shaded in pink.  Another human isolate, IDN/06/05 is the second confirmed Indonesian human case and it is located on a nearby branch.  However, the remaining human cases formed a separate branch, located at the bottom of the tree.  The only non-human isolate on this branch is an H5N1 isolate from a cat, feline/IDN.CDC1/06.  Like the other isolates on the branch, it had a novel cleavage site, RESRRKKR.

The presence of the novel cleavage site in human and cat isolates raised the possibility that the source of the human infections was mammalian rater than human.  This first human isolate in Indonesia was in Banten in July 2005.  At the time H5N1 was found in swine in Banten and a recent presentation included two H5N1 swine isolates from Banten, as well as 19 chicken isolates from locations throughout Indonesia.  These are listed in a phologenetic tree and show that the swine sequences are similar to bird sequences in Indonesia.  Moreover, the swine sequences have the common HA cleavage site RERRRKKR, which is in all but two 2003 isolates on the phylogenetic tree.  Similarly, most of the Indonesian bird isolates in Indonesia are RERRKKR.

These data indicate the H5N1 in the swine in Banten are not the source of the H5N1 in humans in and around the Jakarta area.  In the past year, the human isolates continue to point away from an avian source.  There are now over 50 avian isolates collected between 2003 and 2005 in Indonesia.  There are a few isolates with novel cleavage sites of RERRRIKR, RERRRIKK, RERRRK_R, and GERRRKKR.  However, the vast majority of the bird sequences are RERRRKKR.  In contrast, other than the Karo cluster and the second human isolate in Indonesia, all other human isolates form a separate branch on the tree and virtually all have an RESRRKKR cleavage site.

The failure to find a matching source for these sequences, other than one cat isolate, is cause for concern. This failure raises serious surveillance issues in Indonesia and  raises doubts concerning transparency in WHO updates, which continue to point toward bird interactions, but fail to identify H5N1 in contact poultry and fail to find matching sequences in a growing number of bird isolates.

The human sequences continue to evolve, yet the sequences of the isolates remain sequestered in a WHO private database.  The only HA sequence made public is the sequence from the first human case confirmed in Indonesia.  That sequence was placed in the WHO database on August 1, 2005.  The phylogenetic tree lists human sequences from over 25 individuals. 

The time for release of these data has past.

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