Recombinomics: Indonesian H5N1 Cluster and Case Reports Raise Concerns

Commentary
Indonesian H5N1 Cluster and Case Reports Raise Concerns
Recombinomics Commentary 20:18
March 3, 2009

Head of Unicef for the East Java, Bali, NTB, and NTT, Jinung D Kritanto added, Unicef continues to actively participate in prevention efforts to the spread of bird flu. Basic steps are carried out the program within the community to continue cautious spread of the virus is vicious. "We just want to add that local governments in the area of concern that the traditional market becek.Sebab, the spread of bird flu virus is more easily in humid areas and tarnish," he said.

He explains, according to the Ministry of Health of RI 2005-2009, the number of people with bird flu reached 145 inhabitants and 119 patients declared dead.

The above translation is from a media report dated February 11, 2009, indicating that the four confirmed cases being widely reported today had died and had been confirmed in early February. Indeed, media reports on three of the four cases describe their deaths in January. The fourth case, from Bekasi, is not identified in earlier media reports, but inclusion in the above translation suggest that she also died in late January or early February. The translation also strongly suggests that WHO was aware of these confirmed cases weeks ago, yet has still not issued a situation update, more than a month after they died.

When Indonesia announced their news blackout on confirmed cases, WHO offered assurances on timely updates. International Health Regulations require notification within 24-48 hours of confirmation and previously WHO had issued updates within a day or two of the death or discharge of confirmed cases. In Indonesia is abiding by these regulations, then WHO is withholding the data for weeks or months after they are notified. Ironically, when WHO offered its assurances last year, they noted that the Indonesian confirmed cases were not part of a cluster. Yet the news blackout came after the third cluster was confirmed. In each cluster the index died, but was diagnosed with something other than H5N1 (lung inflammation, dengue fever, or typhus) and when a family member was H5N1 confirmed, the misdiagnosis was not upgraded, so the official case count underrepresented both cases in clusters.

This undercount continues today. On Java the past 16 confirmed cases have been fatal. A case fatality rate of 100% signals an under-representation of infected cases that recover. In the latest confirmed cases from Bogor, two siblings died (see updated map). However, a third sibling who survived refused testing. Similarly, three paramedics affiliated with the hospital that treated the confirmed fatality in Surabaya developed symptoms and were in critical condition. At the end of last month they were still hospitalized and unconfirmed, but the likely three cases would create another cluster that included surviving contacts of an H5N1 confirmed case.

These latest likely clusters raise concerns that the H5N1 in Indonesia is evolving toward an H5N1 that is more efficiently spread to humans. The recent WHO report on H5N1 vaccine targets included an HA phylogenetic tree with four isolates from Indonesian patients. These isolates continued to evolve away from this initial 2005 isolate from Tangerang, and raise concerns that vaccines directed against the 2005 isolate will offer limited protection. Moreover, the continued evolution raises concerns of receptor binding domain changes leading to more efficient transmission. Recent H1N1 seasonal flu isolates have had a number of changes in or around the receptor binding domain near position 190 (H3 numbering), including A193T. A193T is in all published clade 2B H1N1 isolates this season which have the Tamiflu resistant polymorphism, H274Y. Moreover A193T was associated with the spread of adamantane resistant S31N in H1N1 clade 2C, and S193F was linked to the spread of S31N in H3N2. Therefore, changes in this area of H5N1 in Indonesia would be a cause for concern.

Thus, the continuing rapid evolution of H5N1 in Indonesia, coupled with frequent larger H5N1 clusters continues to increase pandemic concerns, while the level of WHO transparency on cases and clusters declines.

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