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WHO Weather Report on Ukraine H1N1 D225G Required
Recombinomics Commentary 17:13
November 28, 2009

The question is whether this mutation again suggests that there is a fundamental change going on in viruses out there or whether there is a turn for the worse in terms of the severity.  I think that the answer right now is that we are not sure.  I want to answer why we are not sure in a way which explains why more investigations are needed. As you know these influenza viruses change frequently.  Their gene properties change because these are viruses which frequently undergo mutations and so mutations in and of themselves are not necessarily important and in fact, if every mutation was reported out there, it would be like reporting changes in the weather -

The above comments from Keiji Fukuda at Thursday's virtual press conference are in context, which highlights the need for additional data on D225G.  However there is a large body of evidence on this change and the Ukraine data is the most current and quite compelling.  Ten samples were collected from ten patients and nine represented the same sub-clade. However, only four were from tissues from fatal cases, but all four had D225G.   In contrast, nasopharyngeal washes were collected from the five surviving patients in western Ukraine and all sequences were the same sub-clade, but did not have D225G.  The finding of D225G in 100% of the fatal cases raises concerns, but the number of such cases is small.  However, well over 400 people have died in Ukraine, so additional samples from fatal cases should not be a problem, and collection of samples from both upper and respiratory tracts in the same patient would be useful.

An aggressive campaign on this change is warranted because the only reported tested sample for antigenicity was found to be a low reactor, and the only amino acid change in the HA sequence was D225G.  Since the same sub-clade was found in earlier collections in Norway, and the cases positive forD225G were fatal or severe, more interest in the change has been generated, but media reports state that the vaccine is effective against D225G, when the data presented on the Mill Hill characterization sheet at GISAID cites the antigenicity as being "low reactor", signaling a need for a new vaccine.

It has now been a month since the reported Ukraine samples were collected and hundreds have since died, so additional sequence data on fatal cases, including upper and lower respiratory tract origins from the same patient, should be available at this time.

Therefore, release of these sequences and a statement on the initial results, including the vaccine low reactor status of isolates from fatal cases in Ukraine, would be useful. 

Finding a receptor binding domain change which alters specificity in 100% of fatal cases is cause for concern, and release of additional sequence data is overdue, since some still need a weatherman to know which way the wind is blowing.

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