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Commenting on the point genetic mutation seen in throat swabs of three patients who succumbed to the virus, Chadha said, "We didn't see any change in the genetic make-up of the virus after that." Of the three patients, two were from Pune and one from Nashik, added Chadha. The mutation was detected in the haemagglutinin (HA) region of the virus' gene, she added. The above comments describe a cluster of severe/fatal cases in a family in Bhatkal as well as a “point genetic mutation” in three fatal cases in Pune and Nashik. The “mutation” is almost certainly D225G, which has been reported in prior fatal cases in India in the Pune area. This polymorphism is most easily detected in lung samples because it is frequently transmitted as a mixture and is a minor component in throat swabs, but becomes the major component in lung samples because of the affinity for the 2.3 receptors found on the surface of human lung cells. Thus, the levels of D225G in the tested patients are likely to be markedly higher than the frequency detected in throat or nasopharyngeal samples. The clustering of severe /fatal cases in the siblings in Bhatkal may also signal the presence of D225G/N. Recent sequences from Singapore and Nanjing, China had D225G and the relatedness of the sequences between samples that clustered in time and space strongly suggests transmission of D225G, which would explain the clustering in the siblings. Clusters of severe/ fatal H1N1 cases remain a concern and the spike in H1N1 cases and deaths in India dictate more aggressive sequencing of lung samples from these patients. Media Links Recombinomics
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