The WHO Hoarding of Published Azerbaijan H5N1 Sequences
Recombinomics Commentary
November 22, 2006
all specimens were transferred to the WHO Collaborating Centre for Influenza at the National Institute for Medical Research (NIMR), Mill Hill (United Kingdom) for confirmation by RT-PCR for influenza A/H5 virus (Asian lineage), haemagglutination inhibition test, virus isolation in embryonated eggs and MDCK cells, and genomic sequencing.
Virus strains were isolated from three cases from the cluster in Salyan district. Phylogenetic comparison of H5 haemagglutinins at the WHO Collaborating Centre for Influenza shows that all genes were of avian virus origin and closely related to the sequences of the corresponding genes of other ‘Qinghai Lake’ H5N1 viruses isolated from avian species (including viruses isolated from a swan in Azerbaijan in February 2006, A/swan/Italy/179/06, and from a swan in the Islamic Republic of Iran, A/swan/Iran/754/2006, and from humans (in Turkey, Iraq and Egypt).
The above comments are from a published report on two clusters in Azerbaijan earlier this year involving eight confirmed cases and one suspect case. Interest in this cluster has been generated because of recent large die-offs of birds in Azerbaijan, coupled with a recent Nature report on changes in the receptor binding domain that increased binding for human receptors, including positions N186K and Q196R which were said to be in H5N1 from two patients from Azerbaijan and one patient from Iraq.
Currently, there is one public human H5N1 HA sequence from Iraq and one from Azerbaijan. Neither sequence has the changes described in the Nature paper, indicating these sequences are being withheld by The WHO. The Nature paper, as well as a recent PNAS paper, describe sequences that are being withheld by WHO consultants, even though the papers have now been published.
The quotes above, add the Azerbaijan sequences to the list being hoarded by WHO consultants post-publication.
The Azerbaijan clusters were in February / March of 2006 and the time gaps between disease onset dates of cluster members strongly suggested the H5N1 was transmitted human-to-human. The presence of the changes in the receptor binding domain would provide a mechanism for the increase in transmission efficiency. However, only the Azerbaijan sequence without the changes was released. The two sequences with the changes were withheld.
This selective withholding of critical changes in H5N1 isolated from humans is cause for concern. The most recent H5N1 case in Egypt has acquired M230I, which creates a match will all three human flu strains (H1N1, H3N2, and influenza B and creates a match between that Qinghai isolate and the receptor binding domain of position 226-230 (QSGRI) in influenza B.
This lack of transparency by the agency controlling the testing of human H5N1 outbreaks diminishes the credibility of calls for the sharing of samples and sequences from bird and human cases in China. The hoarding of the data after publication violates the basic underpinnings of peer review, which requires disclose of information required for independent confirmation, which in the case of changes in receptor binding domains, requires the deposit of these sequences in a public database, such as Genbank.
Instead, the WHO limits access to the data by creating a private database that has thousands of H5N1 sequences, most of which have been described in peer reviewed journals.
The hoarded data includes partial sequences from H5N1 isolates from 1999 to 2006, as well as full sequences from gene segments. These isolates have already been described in peer reviewed publications.
The excuses of the past, on release requirements or publication requirements, are no longer operative. The samples are collected by public health agencies supported with public funds, yet The WHO and consultants assume they have the authority to withhold such information from the public, even though such information is critical for pandemic preparedness and vaccine production.
These sequences should be released immediately and investigations on the lack of transparency by the WHO and consultants, who are also significantly supported by public funds, should also be initiated
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