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All 2011 H5N1 Cases In Egypt Are Clade 2.2.1 G
Recombinomics Commentary 22:30
February 24, 2012

The recently released WHO update on pandemic vaccines contained additional information on human H5N1 cases in Egypt.  Although Egypt has the second highest number of confirmed H5N1 cases in the world (the 161 is 24 fewer than Indonesia), the most recent sequence, A/Egypt/N04434/2010, is from a March 31, 2010 collection.  It was released with 18 additional sequences from 2009 and 2010 (collection dates between June 16, 2009 and March 31, 2010.  The sequences were remarkable since all 19 sequences were clade 2.2.1 G (labeled as clade 2.2.1 in WHO updates). 

Although this sub-clade, which included a 3 BP deletion (S133del), was first detected in late 2006, it attracted interest because of association with mild cases in the spring of 2007.  The interest increased in early 2009 when a large series of mild cases in toddlers was reported, which lowered the case fatality rate for cases in the 2009 calendar year to almost 10% (4/39), in marked contrast to an earlier rate of approximately 40% in Egypt.  Moreover, a bioinformatic analysis of H5N1 in Egypt noted similarities between clade 2.2.1 G sequences and seasonal H1N1.

The presence of clade 2.2.1 G in all 19 cases was surprising, because poultry cases had evolved into two major sub-clades (2.2.1 G and 2.2.1 F).  Clade 2.2.1 F (labeled as in WHO updates) emerged in late 2007 in vaccinated flocks.  However, although the frequency of this sub-clade in chickens has increased, there is only one reported human case, A/Egypt/3300-NARMRU3/2008.

In 2010 and 2011 the H5N1 CFR increased to 40% in Egypt, which generated additional interest in recent cases.  The table in the latest WHO report lists 5 new human cases, and all were designated as clade 2.2.1.  Four (A/Egypt/N09966/2011, A/Egypt/N10621/2011, A/Egypt/N11126/2011, A/Egypt/N11470/2011) were listed in the phylogenetic tree, and all four mapped with clade 2.2.1 G sequences, including 7 additional isolates listed in the prior WHO report (A/Egypt/N0423/2011, A/Egypt/N0544/2011, A/Egypt/N6322/2011, A/Egypt/N6774/2011, A/Egypt/N6828/2011, A/Egypt/N7562/2011, A/Egypt/N7724/2011).  In addition, a prior WHO update also included an additional isolate, A/Egypt/N010360/2011, collected after the samples that yielded the public sequences, which was also clade 2.2.1 G.

The most recent 31 public sequences have all been clade 2.2.1 G, even though clade 2.2.1 F has been detected since late 2007, and only one clade 2.2.1 F case has been reported (in 2008).

The absence of clade 2.2.1 F in any human cases since 2008 raises concerns that clade 2.2.1 G is well adapted to human infections, and the linkage to poultry in the area is more closely related to testing requirements that sourcing of the infection.

Concerns of adaptation are also increased by recently released sequences from Egypt from 2010 poultry isolates, which have PB1 and PB2 recombined sequences with regions from H1N1pdm09 and seasonal H1N1.  Moreover, the Kawaoka paper on H5N1 transmisison used H5 on an H1N1pdm09 genetic background.

Sequences from internal genes from human cases in Egypt have been limited to those from 2006.  Sequences from internal genes of the human cases should be generated and released immediately.

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