WHO Sending Team to Egypt To Investigate H5N1 Clusters
Recombinomics Commentary 18:01
April 20, 2009
According to Dr. Nasr's Assistant Minister of Health, and Dr. Amr Kandil Undersecretary for Preventive those tests are conducted for all the positive cases to ensure full identification of the type of infection and the virus and the genetic makeup of it. He said Dr. Abdel Rahman Shahin, official spokesman of the ministry that all the tests proved that there are no changes or mutations in the virus.
The translation above described a WHO investigation of H5N1 in Egypt scheduled to begin on Thursday. Egypt has reported mild H5N1 cases in toddlers this year. To date there have been 15 confirmed cases, including three in the last three days. So far none have died, although several of the older recent cases have been reported as being in critical condition and on ventilators. All three of the recent confirmed cases belong to geographic clusters, which increases concerns of more efficient H5N1 transmission to humans.
The absence of "mutations" referenced in the above translation merely refers to the lack of reassortment involving human flu genes (as reported to Egypt by Weybridge/Mill Hill, CDC, and NAMRU-3. However, such natural reassortment including H5N1 genes has not been reported anywhere, although there have been multiple descriptions of human to human transmission between close contacts. These examples of H2H2H or H2H transmissions did not involve H5N1 that had acquired human genes. However, for most clusters involving clade 2.2, which is present in Egypt, there have been changes in the receptor binding domain of H5N1 isolates from human clusters.
One such cluster in Egypt involved two siblings from Qena in the spring of 2007. Both sequences had a 3 BP deletion (S129del) and the sequences from the siblings were identical supporting human to human (H2H) transmission based on the 4 day gap in hospital admission dates. These cases well mild and the siblings quickly recovered. Symptomatic contacts tested negative. This 3 BP deletion has been reported in 13 public sequences from Egypt, including human and poultry in 2007 and 2008.
A recent paper on similarities between a subset of H5N1 isolates in Egypt, and H1N1 seasonal flu included the sequences with the 3 BP deletion. Moreover the two examples used in the table and figure in the paper used a human and chicken sequence with the deletion.
The association of position 129 with the receptor binding domain, raises concerns that this change could increase the efficiency of human H5N1 transmission. The WHO phylogenetic tree in the report of vaccine target for 2009 includes the first two HA sequences from Egypt in 2009. Both sequences were similar to each other and appeared to map to the same position as prior public sequences with the deletion. Although WHO has used prior examples of the deletion in reports in 2007 and 2008, no such public sequences were include in the 2009, which makes the assignment of the deletion to the 2009 cases less certain.
The lack of certainty would be removed however if the sequences were released. The WHO tracking system indicates NAMRU-3 has the samples from the 2009 cases, but no sequences have been made public from the 2008/2009 season (human or poultry). The presence of the deletion in some or all of the 2009 would raise significant concern.
These sequences should be made public immediately.
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