H5N1 Receptor Binding Domain Changes In Pakistan?
Recombinomics Commentary
December 21, 2007
All the close contacts and involved healthcare workers remain asymptomatic and have been released from close medical observation."
The WHO sent a team of experts to Pakistan to help investigate the situation, and US Navy Medical Research Unit 3 (NAMRU-3) in Cairo has sent a portable laboratory.
Rainford declined to predict today how soon confirmatory testing in the eight cases, which were identified in preliminary tests by Pakistan's national lab, will be completed. He said some samples from the patients would be sent to London for analysis.
"I hope we'll get some early results but question whether we'll have lab results that are what we need," he said. "We've got, hopefully, samples arriving in London sometime over the weekend that will provide a better environment to assess what we've got."
He said he expected both the NAMRU lab and the one in London will play a role in the testing: "NAMRU staff on site will be able to give us some information, but I guess there's a role for an additional lab to give us a full picture."
The above comments provide additional detail on the H5N1 outbreak in Pakistan. The comments on health care workers are curious. One media report indicated a male doctor had symptoms, but the above report indicates all remain asymptomatic. It is unclear if the asymptomatic comment means none developed symptoms, or all that developed symptoms previously are asymptomatic now. Similarly, the comment on health care workers and contacts did not indicate the tested negative. One female health care worker was said to have tested positive. The above quote only states that contacts are now asymtmatic and have been released. Since it has been over three weeks since the second fatality, release of mild cases would be expected at this time.
The comments on samples going to London are also curious. The NAMRU-3 mobile lab should be able to confirm the positives in Pakistan, since media reports indicate the initial positives have already been confirmed locally. The shipment to London raises the possibility that the sequencing has identified receptor binding changes and samples are being sent to London to see of these changes are associated with receptor binding affinity changes.
The H5N1 in Pakistan is almost certainly the Qinghai Lake sub-clade (2.2) and is likely the Uva Lake strain, which is widespread in Europe and also migrated to South Korea 12 months ago. Two years ago, the Qinghai strain was reported in the outbreak in Turkey. There were many small and large clusters in the Turkey outbreak, and two of the four sequences had S227N. It is likely that all had patients had S227N, but detection in isolates would be dependent on isolation procedures. Isolates from chicken eggs would likely not have S227N.
However, Qinghai isolates had a series of receptor binding domain changes. The clusters in Azerbaijan had N186K. The cluster in Iraq had N186S and Q196R. The cluster in Egypt had V223I and M230I. Other patients in Egypt also had S227N. All of these isolates had PB2 E627K, which has become fixed in Clade 2.2.
The delay in the WHO situation update again points toward serious issues in Pakistan, which may have generated the most sustained H5N1 transmission chain reported to date.
Associated changes in the receptor binding domain would not be a surprise.
Release of H5N1 sequences from Pakistan, which would identify significant receptor binding domain changes, would be useful.
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