November 25, 2011
CDC Hopes and Dreams On 2011 trH3N2 Evolution
Posted by: admin : Category: Flu vaccine
The sequence data provides compelling evidence for human transmission, and the evidence was initially made public in November, 2010 when the CDC released the sequence data on trH3N2 cases. The sequences were released just after the WHO issued a pager alter on two trH3N2 patients and the sequences (A/Wisconsin/12/2010 and A/Pennsylvania/14/2010) raised concerns. Many of the internal genes from cases were clustering phylogenetically, signaling adaptation to humans. But, the CDC place out its first “Have You Heard” on trH3N2, which suggested the two cases did not represent human transmission because of differences between the two sets of sequences.
The acquisition of the M gene likely occurred as a result of swine being co–infected with the swine influenza A (H3N2) virus and the human 2009 H1N1 virus. While we know the M gene plays a role in influenza virus infection, assembly and replication, the significance of this change in these swine–origin influenza A (H3N2) viruses is unknown at this time. CDC continues to investigate the implications of this genetic change.
The closest demographic match from WHO reported cases is a fatal case (2M) in Depok City, West Java who developed symptoms on February 3, 2011 and died February 6 (an unusually small time frame).
The sequences had a series of receptor binding domain changes flanking position 190 (D187N, A188G, R193M). This series is remarkable similar to changes associated with the fixing of oseltamivir resistance in seasonal H1N1 (all HA sequences changed position 193 (A193T) with a variety of combinations at positions 187, 189, and 196).
The similarities between seasonal H1N1 and pandemic H5N1 are striking. In late 2007 / early 2008 oseltamivir resistance started appearing in multiple countries in the northern hemisphere in patients who had not been treated with oseltamivir (Tamiflu). All sequences were from clade 2B (Brisbane/59) and the frequencies varied (highest in northern Europe, including Norway where initial cases were reported). A subset of those cases had A193T. In the 2008 southern hemisphere flu season, the frequency of H274Y rose to 100% in South Africa and A193T was in the dominant sub-clade. Similar sequences were found in Australia, and in late 2008 the 100% frequency for H274Y spread throughout the northern hemisphere. Virtually all sequences had A193T as well as changes at two or more flanking positions (187, 189, 196). These combinations likely facilitated immunological escape, from responses to prior infections or vaccinations.
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Similarly, the first reported case with an M gene from H1N1 was from an infection in late July, so the 2011 cases were reported over a 2 month time period prior to the report, and there were 3 more October cases, bring the total number of reported cases to seven over a three month period. Moreover, the first 2011 case had no swine exposure. The CDC speculated that the case was infected by his caretaker, who had swine exposure, but neither the caretaker nor associated swine had symptoms, and no SOIV has been reported in either.
As seen above, like the WHO update on pandemic vaccine target, the 15 trH3N2 confirmed cases are reports as beginning in 2005, although the first US case was reported in August. 2009. Thus, the concentration of cases is far higher than indicated on the WHO website designed for submission and reporting of a variety of cases including those infected by a novel influenza, such as trH3N2.
