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446 Dead in Ukraine -
D225G and Deaths Spread
The above numbers represent the latest update from the Ukraine Ministry of Health. As the number of cases approach 2 million, the rate of increase has slowed and shifted to the east. The largest daily update was in Donetsk, which rose by 5892 cases to 127,584 (see map). However. Increases in deaths are being report across the eastern border in Russia, were there have been 30 deaths reported in Saratov. Similarly, almost 200 deaths have been reported in Turkey, raising concerns of D225G spread.
The initial data showed strong association of D225G with fatal cases. Of the 9 samples from western Ukraine, all four fatal cases had D225G. In contrast nasal washes from surviving cases were positive for the same sub-clade, but were wild type at position 225, suggesting that infections were mixtures and virus with D225G targeted the lung, while wild type remained in the upper respiratory tract.
This tissue tropism poses surveillance problems, because most sequences come from nasal pharyngeal swabs, which may not reflect D228G in the lung. Currently, only 1% of HA sequences have D225G, although it was present in April in the vaccine target, A/California/7/2009, as a mixture. The version with D225G was selected for the target in the attenuated carrier distributed as a flu mist. In contrast, the killed infected vaccine has the HA version of California/7 with wild type D at position 225, raising concerns that killed vaccine or natural immunity will select for D225G. This concern was increased when Mill Hill labeled Ukraine H1N1 with D225G a low reactor.
The reporting of D225G in all fatal cases in Ukraine should be followed up with additional sequence data on more of the 400+ fatalities. Collections from the upper and lower respiratory tract in fatal cases would help define the significance of D225G in fatal lung cases, and also determine the ratio of components of mixtures with and without D225G.
An increase in the D225G ratio would be cause for concern.