Re: Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines
Commentary
WHO Hoarding of H5N1 Sequences Raise Pandemic Concerns
Recombinomics Commentary 01:55
February 23, 2009
Of the most recent isolates from China, A/Guangxi/1/2009 belongs to clade 2.3.2, the first human isolate from this clade. A/Hunan/2/2009, belonging to clade 2.3.4, shows genetic divergence from other viruses of this clade. Both viruses should be considered as potential vaccine strains pending further characterization.
The above comments are from the latest version of the WHO publication on H5N1 vaccine targets, ?Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as human vaccines?, which was released earlier this month.
Although the comments, in conjunction with the HA phylogenetic tree at the end of the document, provide insight into the rapid evolution and divergence of H5N1 clades and sub-clades, the report is more notable for the data withheld than the data released.
In recent months, the increasing lack of transparency in reports on H5N1 outbreaks has reached an alarming level. China created concern when 8 confirmed cases of H5N1 were reported in January, this year. The concerns were increased because China has not reported associated outbreaks in poultry. Prior to the spike in human cases, China reported two outbreaks of asymptomatic clade 7 H5N1 in poultry in Jiangsu in December, raising concerns that the human cases were also clade 7.
The WHO report is glaringly silent of six of the eight cases. As noted above, the two disclosed cases involve the Funjian strain (clade 2.3). One is linked to a more divergent clade 2.3.4. Previously, almost all human cases in China were clade 2.3.4. The other case is a different Fujian sub-clade, 2.3.2, which led to the first human isolate. However, this sub-clade has been isolated from wild birds in Hong Kong for the past three seasons, and was also isolated in Japan and southern Russia in the spring of 2008. South Korea has also isolated clade 2.3.2 from poultry, but has not released any sequence data. Moreover, a soldier / culler involved in the spring Korean outbreak developed bird flu symptoms and was PCR H5 confirmed. However, South Korea did not file a WHO report because they could not isolate the clade 2.3.2 virus. They argued that the soldier wasn?t clade 2.3.2 positive because the sub-clade had not previously been reported in human cases. The current WHO report shows that the sub-clade can fatally infect humans, which increases concerns because the virus is widespread in wild birds migrating along the East Asian flyway.
However, of greater concern is the WHO silence on the other 6 confirmed human cases in China. The virus isolated from the first case, A/Beijing/1/2009 was said to not have any human flu gene segments, indicating all eight gene segments had been sequenced in early January. Moreover, the sequences were characterized as having small differences with prior isolates from China. The likelihood that the sequence was clade 7 was increased when officials in Hong Kong indicated that the dead birds there were infected Fujian strains. Calde 2.3.2 was in the wild birds, while clade 2.3.4 was in the poultry washing ashore, signaling additional unreported outbreaks in China. However, the officials also said that the human cases in China were due to a strain from the north, strongly suggesting that the human infections were clade 7.
In the WHO report above, clade 7 was discussed because more outbreaks were reported in Vietnam, and the newer clade 7 isolates in Vietnam were distinct from earlier clade 7 isolates, although all isolates were from 2008. Moreover, the isolates in Vietnam were distinct from the previosuly reported clade 7 isolates in China, raising concerns that this clade was rapidly evolving and causing widespread human infections in China.
However, WHO failed to comment on the other isolates from China, and these isolates, including A/Beijing/1/2009 were also not in the phylogenetic tree. The tree had an unprecedented number of recent isolates of interest that were lacking public disclosure of the underlying sequence. This lack of transparency has created concerns because it is well known that H5N1 transmission can be dramatically affected by a very small number of changes in the receptor binding domain, such as those seen in public clade 7 sequences.
In addition to withholding the sequences of the six isolates from China that are not on the tree, WHO regional labs are withholding an unprecedented number of sequences.
Prior to being designated a WHO regional lab, NAMRU-3 would promptly release human H5N1 sequences. However, this season there have been no sequences released, even though two 2009 isolates, A/Egypt/0001-NAMRU-3/2009 and A/Egypt/0585-NAMRU-3/2009 are listed on the WHO tree. These isolates are related to the vaccine resistant sequences reported last season, and raise concerns that there are additional receptor binding domain changes in the human isolates.
Similarly, NAMRU-3 has not released the sequence, A/Pakistan.540-NAMRU-3/2008 from the outbreak in Pakistan at the end of 2007. This outbreak involved one of the most extended human to human transmission chains reported to date for H5N1, yet the sequence of the only recovered isolate has been withheld. It is in the phylogenetic tree and is the first reported human case linked to the Uvs Lake strain the Qinghai sub-clade, 2.2.3, and was said to not have receptor binding domain changes, which would also be a first for a clade 2.2 extended human to human transmission chain. Moreover, the second reported human Uvs Lake isolate, A/Bangladesh/ 2070095/2008, has also been withheld.
In addition to the withholding of human isolates from China, Egypt, Pakistan, and Bangladesh, the novel clade 2.2.3 isolate from western Africa, A/chicken/Togo/CHEK2/2008 is also in the tree, but withheld.
In addition to the withholding of the human and bird clade 2.2 isolates, WHO has also withheld the various clade 7 isolates from Vietnam, A/chicken/Vietnam/NCVD-016/2008, A/chicken/Vietnam/NCVD-093/2008, and clade 7 vaccine target, A/chicken/Vietnam/NCVD-03/2008.
This withholding of important sequences, including those selected or recommended as vaccine targets is without precedent. Even Indonesia, which has a glaring lack of transparency in reporting H5N1 cases, has placed four recent human isolates, A/Indonesia/7379/2008, A/Indonesia/7272/2008, A/Indonesia/7261/2008, and A/Indonesia/8228/2008 on deposit at GISAID.
Thus, the increased hoarding of H5N1 sequences by WHO raises pandemic concerns and these scandalous actions are increasingly harder to justify.
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