H5N1 S227N Re-emergence in Qena Cluster in Egypt?
Recombinomics Commentary
April 3, 2007
Human to human transmission of the H5N1 virus between a brother and sister in Egypt cannot be ruled out yet, although both siblings seem to have been exposed to sick birds, the World Health Organization (WHO) said on Tuesday.
A four-year-old boy, from Qena province around 670 km (400 miles) south of Cairo, was among three human cases announced by the health ministry at the weekend. His six-year-old sister was one of two children diagnosed with the virus late last week.
"Human to human transmission cannot yet be ruled out. We are continuing investigations," WHO spokesman Gregory Hartl said in Geneva. "But we know all the children had exposure to sick or dead birds."
The above comments describe a familial cluster in Qena and raise concerns about increased transmission of Qinghai H5N1. The first confirmed cluster of Qinghai H5N1 in humans was in Turkey in January, 2006. That cluster was linked to the acquisition of S227N, which increases the affinity for human receptors and decreases the affinity for avian receptors. In Turkey, S227N was in the sequence from the index case, A/Turkey/12/2006, but was not in the sequence from the sister of the index case, A/Turkey/15/2006. However, S227N was also present in A/Turkey/65596/2006, suggesting the lack of detection of S227N in the sister of the index case was due to mixtures of H5N1 in the sister, rather than de novo creation of S227N in the two isolates listed above.
Similarly, S227N was found in Egypt last year. The isolate, A/Egypt/2947-NAMRU-3/2006, was from a patient in Kafr El Sheikh. At the same time, two additional H5N1 positive siblings were identified in Kafr El Sheikh, A/Egypt/2991-NAMRU-3/2006 and A/Egypt/2992-NAMRU3/2006. The NA sequence from A/Egypt/2991-NAMRU3 was presented at the Northern California American Society for Microbiology meeting on Saturday. It contains C976T (see slide 54), which is also present in A/Egypt/1394-NAMRU-3/2007, which is from a patient in Fayyoum. The NA sequence the index case in the Qena cluster, A/Egypt/2621-NAMRU3/2007, also has C976T. The HA sequence from the Fayyoum patient also has S227N. Similarly, the HA sequence of the index case sequence has the 3 BP deletion, as does A/Egypt/1394-NAMRU3/2007 and A/Egypt/0626-NAMRU3/2007.
This 3 BP deletion in HA is associated with G257A in NA, indicating these sequences are evolving by recombination, and not segregating by reassortment.
S227N in A/Egypt/1394-NAMRU3/2007 was in a mixture, raising the possibility that S227N is present at low levels in the other isolates from this sub-clade, which includes the index case for the Qerna cluster, A/Egypt/2621-NAMRU3/2007.
These data indicate more cloning should be done of 2007 samples with the 3 BP deletion, as well as the two siblings from Kafr El Sharif last year.
Detection of S227N in 2007 isolates would be expected, if the 3BP deletion found in 2007 isolates was on the same sequence as the S227N found in A/Egypt/1394-NAMRU3/2007.
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