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Novel H1N1 With D225N Raises Pandemic Concerns

Recombinomics Commentary 13:05
April 7, 2011

The steady increase in severe and fatal cases in Chihuahua, Mexico raises concerns that a novel H1N1 sub-clade is spreading throughout the Americas and worldwide.  The increase in cases in Mexico at the end of the flu season has striking parallels with the 2009 outbreak.  The decline in H3N2 cases creates an opportunity for variants to arise and become dominant, which was supported by the recently released sequences from patients in Chihuahua.

Of greatest concern was the presence of D225N in the H1N1 sequence from the fatal case (36M),
A/Mexico/InDRE1945/2011, from the traffic department.  The index case for the cluster was the partner of the above case and was diagnosed as a fatal atypical pneumonia.  The failure to identify influenza A or H1N1 increased concerns that the sub-clade was generating false negatives.  Reports indicate at least one additional co-worker was in critical condition, signaling transmission of a deadly sub-clade.  This was supported by the presence of D225N in the sample which was from the upper respiratory tract (nasopharyngeal swab).

The other two HA sequences
(A/Mexico/InDRE1946/2011 and A/Mexico/InDRE1947/2011) lacked D225N, but were otherwise identical to the above sequence at the protein level.  The sequence had A189T, a receptor binding domain change that may be linked to immunological escape.  Similar changes were seen in the 2008 seasonal H1N1 sequences evolving away from the immunological response to Brisbane/59/2007, which raises concerns that the aggressive vaccine campaign initiated in Mexico and Venezuela will have limited effect.  The current H1N1 target is California/7/2009, and a number of studies indicated the current H1N1 has evolved away from that sequence.

Anecdotal reports cite additional examples of D225N in severe and fatal cases, raising concerns that this sub-clade transmits.  The emergence of the current H3N2 sub-clade involved the acquisition of two similar changes, S189F and D225N.  Thus, D225N on the appropriate influenza genetic background readily transmits in humans, and the novel sub-clade in Chihuahua has A189T coupled withD225N in the fatal case.

The 2011 H1N1 from the United States has been withheld by the CDC.  A small series released by the Air Force indicated the novel sub-clade was widespread in the United States, although the 2011 sequences lacked D225N.  However, a closely related 2010 sequence from Pennsylvania, A/Pennsylvania/07/2010, had D225G, which has been linked to severe and fatal H1N1 cases.

Release of 2011 H1N1 sequences from the United States, including Texas and New Mexico, is long overdue.

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