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United States Pledges Increase in H5N1 Support in Indonesia
Recombinomics Commentary
November 20, 2006

The two Presidents discussed the grave threat posed by Avian Influenza (AI), and President Yudhoyono reiterated his Government's firm commitment to combating its spread. He briefed President Bush on Indonesia's completion of a unified national response plan, increase in the AI budget for 2007, and active participation in the International Partnership on Avian and Pandemic Influenza. President Bush announced the United States would increase its AI assistance to Indonesia to expand animal surveillance and response efforts and strengthen nation-wide public awareness. President Bush confirmed that the U.S. Centers for Disease Control and Prevention and Animal and Plant H
ealth Inspection Service would assign permanent staff to Indonesia to build more effective partnerships with their counterparts in Indonesia. President Yudhoyono thanked President Bush for the United States' work in support of the Indonesian Ministry of Health's efforts to identify human AI cases and investigate AI outbreaks. The two Presidents stressed the imperative of continued and enhanced cooperation between Indonesian and American health workers and medical scientists to fight infectious diseases, including through the Naval Medical Research Unit (NAMRU-2), which has been in operation since 1968. They agreed that negotiations to extend the research work of NAMRU-2 should be expedited.

The above comments reaffirm the concerns about H5N1 bird flu in Indonesia and pledge additional support and expanded testing.  However, after more than a year of analysis of H5N1 human patients in Indonesia, major questions on the origin and spread of human H5N1 remain.

The first human H5N1 was isolated in July of 2005 and had a novel cleavage site, RESRRKKR, as well as a number of associated genetic changes.  From July 2005 to the present, the vast majority of human H5N1 has had these sequences.  There have only been two exceptions, the second confirmed human H5N1 Indonesian case, and the Karo clusters.  Isolates from the remaining cases have come from areas throughout Java, but primarily in regions of western Java, including the Jakarta area.

These human H5N1 sequences have failed to match poultry H5N1.  The match failure was noted in the H5N1 meeting in Jakarta in July, 2006.  Since the failure might have been due to collection dates, 91 samples were sent to a WHO-affiliated lab in Australia.  The vast majority of the poultry isolates, collected between the fall of 2005 and spring of 2006 also failed to match the human sequences.  On isolate on the island of Java from a duck in Indramayu had the novel cleavage site, but only matched a small subset of human cases from late 2005.  They only two avian matches for the human cases on Java were from two chickens on Sumatra.  The only non-human match on Java for the cases there was from a cat in Indramayu, which matched the human cases on Java, including the cases from Indramayu.

The match failures in poultry suggest H5N1 is evolving in a separate reservoir, which likely involves wild birds and a mammalian reservoir on Java. 

Recent data has pointed toward the acquisition of mammalian polymorphisms that affect receptor binding.  Although these changes have been found in H5N1 in human cases in Vietnam and Thailand, as well as human cases in the Middle East, they have not been found in human isolates from Indonesia.  However, human samples from H5N1 patients have been sent to the CDC and Hong Kong, but the human H5N1 has been isolated in chicken eggs, which would select against mammalian specific changes in the receptor binding domain.

Determining the source of human H5N1 in Indonesia as well as the isolation of human H5N1 on mammalian cells, should be top priorities of the increased effort described above.

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