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Growing H5N1 Transmission Chain in Indonesia Raises Concerns

Recombinomics Commentary

May 22, 2006

The growing H5N1 bird flu transmission in Medan, Indonesia has raised transmission and transparency concerns.  The cluster has now grown to eight, and seven members of the cluster have died.  H5N1 has been confirmed in all except the index case and the disease onset dates indicate there have been three generations of human-to-human (H2H2H) or possibly four generations (H2H2H2H).

The index case developed symptoms on April 27.  There was a family barbeque on April 29 and other family members began showing symptoms in early May.  This gap between the disease onset date of the index case and additional family members indicates human-to-human transmission (H2H). Seven family members developed symptoms, and six were confirmed to be H5N1 positive.  However, the last member to develop symptoms died on May 13 (the index case died on May 4 followed by deaths on May 9, 10, 12, 13, 14).  That family member was the nephew of the index case and may have been infected by other family members, which would represent H2H2H.

Today his father died and has been H5N1 confirmed, suggesting the transmission chain has grown to H2H2H2H, which would represent the longest H5N1 transmission chain to date.

The cluster was described in the WHO update of May 18.  The update described the index case and seven family members who had symptoms, including the uncle who is still alive and the nephew who had tested negative.  Although the disease onset date fro the index case was given, the update withheld the disease onset dates for the family members.

Moreover, the update failed to mention the father of the nephew who died on May 13.  The uncle had symptoms, had been given Tamiflu, and had left the hospital.  He refused further treatment and died.  However, this travel into the community prior to his death raises concerns about additional transmissions.  The WHO update indicate that there was no evidence of spread beyond the immediate family, but did not reveal the release of the uncle and potential spread.  The status of additional family members with early symptoms remains unclear.

The spread of H5N1 across three or four generations of infections is cause for concern.  Sequences of H5N1 from the patients has been said to contain no mutations, but there is no indications that the sequences will be released.  Sequences from only one Indonesian patient has been released. The sequence was deposited on August 1, 2005, but was withheld from the public until March 26, 2006.  It has a novel cleavage site, which is shared by most of the sequestered human sequences from Indonesia.  At least one sequence has a wild type cleavage site, but it has not been released.  The sequences in this cluster would significantly increase the number of  H5N1 human sequences from Indonesia, and should be done as soon as accuracy of the sequences has been determined.  The other H5N1 sequences at the private respiratory should be released immediately.

The withholding of disease onset dates and the status of the family member who died today reduces credibility and dictates release of the sequestered sequences.

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