CDC In Denial On H1N1 D225G/N Significance Recombinomics Commentary 23:16 March 7, 2010
"However, Dr. Nancy Cox, director of the Influenza Division at the US Centers for Disease Control and Prevention (CDC), said global H1N1 data so far do not show a clear association between the mutation and severe illness."
The above comments are by an agency in denial. The association between D225G and D225N with severe and fatal H1N1 infections is overwhelming. The recent report from Norway indicated that 9/27 (33%) of fatal cases in Norway had D225G or D225N. However, in Ukraine 27/37 (73%) of autopsy lung samples have D225G and/or D225N (11 have both). Similarly, D225G was in 40% of the fatal lung samples from 1918/1919. The data from Ukraine and 1918 are from direct sequencing.
The CDC has tried to limit the number of positives by excluding samples that are positive in culture but negative in the original sample. However, there is little evidence to support CDCs position that the negative data is true, while the positive data is false. Direct sequencing lacks sensitivity, and both D225G and D225N are frequently detected as mixtures, either with wild type or each other. The failure to find such mixtures is not unexpected, especially if one polymorphism (D225G) is at low levels, as would be expected in mild cases. The low level of D225G would provide a mechanism for transmission, instead of the WHO position that D225G is not transmitted and spontaneously appears again and again.
The Ukraine data does not support repeated spontaneous mutations. D225G and D225N are found in 81% of fatal cases that occurred over a short time frame. A sudden increase in spontaneous errors at the same time at two positions has no scientific basis. The proposals are little more than ad hoc arguments that are not supported by the data.
Similarly, the sudden appearance of the same change on multiple genetic backgrounds is not supported by a random mutation model, which is WHOs working hypothesis. These models are destroyed by the actual data, which is why the significance of D225G and D225N are downplayed and putative lab artifacts are introduced in attempts to discount and discredit the actual data, even when generated by the CDC itself.
The random mutation model is further discounted by the presence of two changes linked to the same codon, as well as the widespread detection of another polymorphism, D225E, at the same codon, which is associated with milder disease in several countries in western Europe, including UK, Spain, and Italy, where frequencies from 20-50% have been reported.
The RBD changes are clearly transmitted and clustered in time and space. The lack of data supporting random mutations, and the clustering of data which clearly refutes the model, have created an agency in denial of the overwhelming data linking D225G and D225N to severe and fatal cases, as well as the movement of these changes from one genetic background to another via recombination.
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