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Receptor Binding Domain Changes In Egypt
The above comments, from “Characterization of conserved properties of hemagglutinin of H5N1 and human influenza viruses: possible consequences for therapy and infection control” describe a subset of H5N1 sequences from Egypt that have chacteristics that match H1N1 seasonal flu. These matches include sequences from the Ghabiya cluster, as well as two Qena siblings with mild H5N1 in the spring of 2007. The sequences from the siblings had a 3 BP deletion that produce S129del, which is within the region listed above, Although the disease onset date of the index case was withheld from the WHO update, the hospital admission dates were four days apart, signaling the infection of the brother (4M) by his sister (6F). The sequences from the Qena siblings were identical, further supporting H2H transmission. Moreover, additional family members had symptoms, but tested negative.
This year there has been another cycle of mild cases in Egypt, but instead of affecting children between the ages of 3 and 10, like the siblings above, 10/12 cases are toddlers. However, like the cases in the spring of the 2007, the case fatality rate is low (in 2007 only 1/17 died, and this year 0/12 have died) and most patients did not develop pneumonia. These mild cases, coupled with the younger age group, raise concerns that H5N1 spread in the past two year was far more extensive than indicated by the confirmed cases, and were missed by current testing, which requires a poultry contact for H5N1 PCR testing.
Although NAMRU-3 has not released any human or poultry sequences this year, the first two human isolates were represented in a recent HA tree of vaccine targets. Although public sequences are not on the branch with the 2009 isolates, the location of the branch suggests these isolates also have the 3 BP deletion and are closely related to the sequences in the siblings from 2007.
The four day gap in admission dates for the Qena siblings, matches the four day gap in the disease onset dates for two cousins (both 2M) from Beheira. The cousins are next door neighbors, and the four day gap also indicated human to human transmission, further supporting the spread of mild H5N1.
The 3 BP deletion produces S129del and position 129 is in the receptor binding domain. This deletion maps to the region in H5N1 with similarities with H1N1, suggesting more efficient transmission, consistent with the clusters in Qena and Beheira.
Release of the sequences from the H5N1 cases this year would be useful. If these sequences have the same deletion as seen in the Qena cluster, an extensive screening of toddlers without a poultry connect is critical.
The failure to recognize the significance of the mild cases in 2007 is cause for concern. The failure to aggressively act at this time is beyond scandalous, and is hazardous to the world’s health.