Commentary
Recombinomics Commentary 01:18
April 21, 2009
However uncertainty remains and it will be important to investigate further. It is very welcome that the Egyptian authorities have invited WHO to send senior staff to Egypt next week to assess the current epidemiological situation.
It is especially reassuring that despite the low CFR and apart from two of the cases in the most recent report there have been no clusters in the cases suggesting more easy human to human transmission.
However it would be hoped that this would be investigated in Egypt with serological surveys to look for milder and asymptomatic cases and any suggestion of clustering since even though the seeming lack of significant change in the sequence of the virus is reassuring the changes can be subtle and its how the viruses behave that is most important.(7)
A good example of such investigations were recently published in the Weekly Epidemiological Report of joint National / WHO work done in Pakistan in 2007.(8)
The above comments from the European Centre for Disease Prevention and Control report on the low case fatality rate in Egypt were published last week when there was only one cluster, the Beheira cousins in the Kom Hamada district. However, there were 3 subsequent cases in the past three days, which created two more clusters. One is in the Kellin district of Kafr el Shiekh where case #64 (33F) and #66 (1.5F) were confirmed over the weekend. The other is in northern Cairo, where case #65 (25F) and #63 (6M) are located. Both were admitted to the same hospital, where treatment was delayed in both cases, presumably because the patients denied a poultry contact. Thus, the above comment on hints of one cluster have already grown to three clusters.
Similarly, the WHO phylogenetic tree suggests that many of the new 2009 cases willl have the same genetic markers, S129del and the associated I152T, which was identified in escape mutants in the Webster lab. Both of these markers are in all thirteen public H5N1 sequences in this sub-clade, which included the Qena cluster (6F and 4M) from 2007, a liely in the first two human H5N1 isolates from 2009.
Although Egypt has provided samples of the cases to NAMRU-3, none have been released. The finding of S129del and I152T in the 2009 would provide a genetic signature for these cases and the similarities of the sequences with H1N1 is cause for concern.
This season the cases have not just been focused in children, but have been in toddler (11 of the 12 confirmed cases in childfren. This concentrayion in this narrow age group (1 ½ to 2 ½) raises additional concerns that the PCR testing of suspect cases in Egypt lacks sensitivity.
Such a lack of sensitivity was seen in the Paksitan cluster mentioned above. Although four brothers were symptomatic and had x-ray confirmed pneumonia, only one was PCR positive. One was not tested, but the other two were negative in spite of high H5 antibody levels (titers of 2560 and 320). Moreover, another brother who was asymptomatic and PCR negative also had an H5 titer of 320.
Thus, the Pakistan study demonstrated the limitations in PCR testing and raises concerns that many of the PCR negatives among the 99% of suspect hospitalized patients in Egypt are false negatives.
Therefore, antibody testing of these suspect cases, as well as toddlers that have symptoms but lack a poultry contact, are welcome and necessary and shoudl be addressed by the WHO investigation.
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