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Bangladesh H5N1 Cluster Raises Pandemic Concerns
Recombinomics Commentary 20:45
March 16, 2011

"We are lucky that the strain (clade 2.2) of H5N1, which circulates in Bangladesh, is less virulent, so it causes less infection to humans," he said.

"But we have to be careful as it has the potential to change into another class (2.1), which was highly infectious to human," he added.

The first human case in May 2008, a 15-month-old boy, got the virus when his mother slaughtered a chicken at home and later cuddled him with unwashed hands.

The above comments from a media report on the current H5N1 cluster in a Dhaka slum (Kamalpur), suggests that the infections were due to clade 2.2 (Qinghai strain), which was true for the case confirmed in 2008 (H5N1 sequence was clade 2.2.3), which was also in Kamalpur.  However, more recent H5N1 reports have described clade 2.3 (2.3.2) in wild birds, which are the likely origin of the current outbreaks (human and avian) in Kamalpur.

In 2005 the Qinghai strain was identified in bar headed geese at Qinghai Lake in China, and this sub-clade spread to Europe, the Middle East, and Africa, as well as south Asia, including Bangladesh, India, and Pakistan.  This sub-clade arrived from locations in southern Russia and northern Mongolia, where clade 2.3 has replaced clade 2.2.  Therefore, it is likely that the H5N1 currently circulating in Bangladesh is clade 2.3, not clade 2.2 (or clade 2.1, which has only been reported in Indonesia).

Clade 2.3.2 has generated more concern based on recent sequences from wild birds collected in 2011.  Sequences from Hokkaido and Fukushima have S227R, which is a concern because changes at position 227 are known to affect the specificity of receptor binding.  In H5N1, S227N was associated with increased affinity for gal 2,6 receptors which is found in human cells located in the upper respiratory tract.  It was predicted to appear in human isolates from the Middle East, which was confirmed in the first case in Turkey in early 2006.

The H5N1 detected in nose and throat swabs from the two Kamalpur toddlers, raising concerns that the H5N1 was more efficiently transmitted in humans.  This concern was increased by two additional RBD changes, V223I and M230I, which were present in the Gharbya cluster, the largest human cluster reported to date in Egypt.  Both of these changes had been reported previously in clade 2.3.2, and M230I is dominant in seasonal H1N1, H3N2, and influenza B.

Moreover, the two recent cases in Bangladesh have much in common with the first two H1N1 cases, reported in southern California in the spring of 2009.  Those two cases had no reported contact with swine or each other, indicating a large number of unreported human cases led to the concurrent detection of the first two confirmed cases who were more than 100 miles apart.

Similarly, there has been not reported link between the two H5N1 cases with birds or each other.  Moreover, both cases were mild, and detection of mild cases is more difficult because most infections will not lead to doctor or hospital visits, and most such visits will not test for H5N1.

Thus, like the H1N1 index cases in 2009, these two H5N1 cases were identified through routine surveillance.  Although these two cases were mild, the presence in two toddlers from the slums of Dhaka, raises concerns for rapid spread and evolution to more virulent versions as the H5N1 adapts to human hosts.  Moreover, the recent wild bird isolates with S227R were from northern Japan, where impacts from the recent earthquake and tsunami could be significant.

Release of the sequences from these two cases as well as symptoms and testing associated with contacts would be useful.

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