Spike in H1N1 D225G Cases in Spain Raises Concerns Recombinomics Commentary 23:34 January 16, 2010
As for the mutations detected by the National Epidemiological Surveillance Network in the last week have reported five new cases of mutation 'D222', three of them in two in the Basque Country and Andalusia.
Also, there is an increase in the number of viruses detected in cases from different regions who have the mutation 'D222E', with six patients in addition to the 34 already identified by the National Center for Microbiology.
So far Spain have been detected in ten cases with the D222G mutation. Three of them have occurred in Andalusia, three in the Basque Country, two in Catalonia, one in Castilla La Mancha and one in Galicia.
The above translation describes the doubling of D225G cases in Spain from 5 to 10 in one week. Moreover, 9 of the 10 were reported this month. In contrast, D225E, which is reported in Spain at a much higher frequency, rose from 34 to 40 reported cases. These data suggest D225G is increasing more quickly than D225E, even though D225E is much more prevalent. In public sequences from Catalonia, 60 sequences had the nucleotide change for D225E. Two also have the change for D225G, and two sequences have D225G without the D225E change. Both of these datasets suggest the ratio of D225G to D225E or wild type D225 is on the rise, even as cases decline.
This change in ratio is cause for concern. Mill Hill characterized a Ukraine isolate with D225G as a "low reactor" raising concerns that vaccinations, as well as natural immune responses to H1N1 infections will select for D225G and change ratios, as noted above.
At the time of the above report from Spain, WHO issued a report on D225G (called D222G using H1 numbering). The report noted that D225G have been identified in 52 patients, of which 26 were fatal. The report did not characterize the surviving patients, some of which are known to have been severe and some of which may still be hospitalized.
WHO characterized the cases as sporadic and spontaneous and lacking a geographic or temporal pattern and also warned of some examples which were positive when isolated in culture, but were not confirmed in original tissues.
However, most of the well known examples were from tissues that were necropsy or autopsy samples, and it was D225G or D225N in these tissue samples that raised alarms. The association with fatal cases was highest in samples collected during the traditional flu season, such as D225G in two lung samples or D225N in lung or throat samples tested at necropsy from July/August patients in Sao Paulo.
The movement of these markers from one genetic background to another, as well as fatal lung infections led to the prediction that D225G would be identified in fatal lung infections in Ukraine. Mill Hill confirmed this prediction when it released HA sequences from 10 patients. Nine were in western Ukraine and included lung samples from four fatal cases. All four samples were positive for D225G. Similarly, the CDC released sequences on two additional patients, which were almost certainly fatal and both samples had D225G. Later collections from lung samples in Kyiv and Chernihiv had D225G and D225N. The Kyiv sample also had D225A. In addition to the cases in Ukraine, patients with D225G and D225N have been reported in the United States, Mexico, Sweden, and Moldova all of which appear to be fatal or severe.
Similarly, the same sub-clade as seen in Ukraine and Moldova has been reported in fatal cases in Russia, supporting temporal and geographic clustering as well as transmission. Moreover, a fatal cluster in Romania also appears to involve D225G.
Thus, the association of D225G with a cases fatality rate in some countries of 100% and increases in reports and rations, such as the above report from Spain continue to increase concerns that the next H1N1 wave will have D225G/N at higher frequencies leading to more severe cases and fatalities.
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