Recombinomics Commentary 14:15
November 25, 2009
The same mutation has been found in both fatal and mild cases elsewhere, including in Brazil, Japan, Mexico, Ukraine, and the United States, said the WHO.
WHO's spokeswoman in Beijing, Vivian Tan, said the agency is aware of three such cases in China that occurred in June and July that were similar to the cases being investigated in Norway. Tan said WHO had no information on the cases mentioned in the Xinhua report Wednesday.
There is no evidence the mutated swine flu virus is circulating widely in the world, Tan said, but since it has been linked to deaths in Norway and elsewhere, investigators are focusing on whether this mutation could be a marker for more severe disease.
The above comments are associated with a report of eight D225G isolates with in China. Genbank has three of the sequences, as noted earlier. The increase in examples to eight is not surprising since D225G was in four of four fatal cases in Ukraine and reports from Norway cited detection in three isolates, 2 fatal and 1 severe case who had recovered.
However, 25 HA sequences deposited at Genbank had an HA sequence that contained D225G, A/Norway/2924/2009, but also had the wild type sequence, raising concerns that D225G was circulating as a mixture that was most easily detected in lung samples, because the D225G was more than a "marker". It is a polymorphisms that was found in 1918 and 1919 samples which were well characterized for receptor binding properties, which indicated the change conferred increased binding to gal 2,3 receptors which are present in lung.
Concerns that this receptor binding domain change was widely circulating were increased because an HA marker on the Norway isolate with D225G was found on additional isolates in Norway, and worldwide (see list here). This marker was also in the HA sequences from the fatal cases in Ukraine. Full sequences from one of the Norway isolates, A/Norway/3364-2/2009, were deposited, and a marker on the NA sequence matched isolates with the HA marker, linking this broader set of isolate from Norway with the Ukraine sequences, which also had the NA marker, as did multiple other isolates (see list here).
These associations link Ukraine to Norway, but the D225G polymorphism has jumped onto multiple genetic backgrounds, which are widespread, increasing concerns the D225G is circulating undetected because it is concentrated in lung tissues and is poorly represented in nasopharyngeal swabs. Release of full sequences from China, as well as Norway, would be useful.
Ukraine Dead Approach 400 - D225G Spreads
Recombinomics Commentary 23:30
November 24, 2009
1,679,237 Influenza/ARI
99,661 Hospitalized
397 Dead
The above figures from the latest daily update from the Ukraine Ministry of Health support a decline in the rate of increases of cases and deaths, but the total is now almost 400 fatalities (see map). The spread was likely slowed by the country-wide closing of schools along with warmer weather. However, it is likely that the virus will return as temperatures drop and the traditional flu season begins, although it is unclear if seasonal flu will be in circulation in 2010.
The receptor binding domain change, D225G, was in four of four sequence from fatal cases, raising concerns that the 2,3 alpha specificity of D225G drove the H1N1 to the lungs and the total destruction. Three patients in Norway were said to also have D225G, and two of the three died while the third had been in serious condition. 25 HA sequences from Norway were deposited at Genbank, but only one had D225G, and it was a mixture. In Brazil both patients with D225G in lung samples had died, and the case in China had been in serious condition.
However, the severity of the infection may be related to the ratio of sequences with and without D255G, as well as viral load, because milder cases involving D225G have also been reported in the United States and Hong Kong.
More detail on additional cases, including sequences from upper and lower respiratory tract from the same patient would be useful.
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