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Paradigm Shift Intervention Monitoring
2011 H3N2pdm11 Pandemic By Accident
The above comments from the latest CDC “Have You Heard?” confirmed the lack of an aggressive surveillance program in children under 10, which have been running at a rate of 100% novel influenza for the seven most recent sequences, as well as significant issues in the detection of novel influenza by state labs.
The detection issues are related to the targets in the PCR test, which is directed at seasonal H3N2 and H1N1pdm09. Although the novel influenza will be influenza A positive, further characterization may give anomalous results, as was seen for the first confirmed novel case this season, A/Pennsylvania/40/2010 which was confirmed five months after infection because it initially was mis-diagnosed as seasonal H3N2 (positive for H3 but negative for NP). The same result was obtained for the second case in Maine, A/Maine/07/2011. However, both cases had a “swine exposure” and were sent to the CDC for further testing, where sequencing confirmed they were novel trH3N2 cases.
Since all of the recent novel cases (H3N2pdm11, trH3N2, trH1N2) have the same NP, all have the potential for generating a false negative for the NP gene. The trH3N2 may register as a positive for H3 leading to a mis-diagnosis as a seasonal H3N2, while the trH1N2 would generate an anomalous result, because there is no routine testing for seasonal H1.
Thus, an accurate result required more sophisticated testing by the CDC. This testing focused on “swine exposure” samples in the off season, leading to the linkage to swine exposure, even though the role of the exposure was to get the CDC to test the sample, and had nothing to do with the true origin of the virus (which was from humans).
Now the CDC is accidentally identifying novel cases because they have requested initial samples from the various states. However, they should be requesting many more than one sample per state, and should focus on those under 10, because they are most vulnerable to the various novel cases identified in recent sequences.
All of the novel H3 cases have an H from seasonal H3N2 circulating the the mid-nineties, while all N2 genes are from human H3N2 cases circulating around 2003 (although the recent human cases have N2 that represent 3 different lineages circulating in swine (one from trH1N2, and two from trH3N2). As a result, older adolescents and adults may have some immunity due to prior exposures to seasonal H3N2 in the 1990’s or 2003, leading to milder cases which do not seek medical attention, or low RNA cases which are misdiagnosed as seasonal H3N2. Similarly, detection of trH1N2 may be limited to those with high RNA levels, since seasonal H1 is no longer included in routine tests (including the newly approved PCR kit).
Consequently, the CDC should be requesting larger numbers of influenza A positive samples for sequence analysis, to get a true picture of the number of different constellations circulating in children as a primary effort, supplemented by sequencing of adult cases, especially those that are weak positives.
Instead, the CDC continues to focus on samples with “swine exposure” which continues to be hazardous to the world’s health.