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PCR pdmInfA Negative = No H3N2v Community Transmission?
Recombinomics Commentary 15:30
September 7, 2012

Specimens from humans infected with A(H3N2)v will be positive for InfA, H3, and pdmInfA markers and negative for H1 and pdmH1 markers.

The above comment is from the August 6, 2012 CDC document entitled “Data Interpretation Update to the CDC Flu rRT-PCR Dx Panel” which describes the marker pattern for H3N2v positives and allows states to classify samples with this pattern  as an H3N2v “presumptive positive”.  This update was due to the explosion of H3N2v cases and potential delays due to a CDC backlog in sequence verification.  Indeed the CDC has released full or partial sequences on 43 H3N2v cases (as well as one H1N2v) from samples collected in July and August.

However, the pattern for seasonal H3N2 differs from H3N2v in the pdmInfA (NP) marker, which is negative for seasonal H3N2, but also gives a false negative in samples with low RNA levels, leading to a misdiagnosis.  The samples can be definitively classified via sequence data, but sequencing priority has been give for H3N2v cases (48 of the 50 sequences from H3 positive samples collected after July 11, 2012 have been H3N2v).

The large number of H3N2v cases and sequences are linked to the CDC program of targeting swine exposure cases during the off season, which is due in part to the low levels of seasonal influenza.  In weeks 30-33 in the 2010-2011 flu season there were 6 confirmed seasonal H3 cases, and in the current 2011-2012 season the CDC identified 190 H3N2v cases in weeks 30-33.  However, as reported in the week 34 FluView, the CDC reported 233 seasonal H3 cases in weeks 30-33 this season, raising concerns the more than 38 fold increase in seasonal H3 cases is due to false negatives on the pdmInfA target.

The number of such cases confirmed by sequencing is unclear because only one seasonal H3N2 sequence (A/Wisconsin/20/2012 – 52M collected on July 24) has been made public, strongly suggesting that the vast majority of the 233 seasonal H3 cases reported for weeks 30-33 have not been sequence confirmed.

Thus, the CDC claim of no reported community transmission of H3N2v is largely based on a negative result for pdmInfA, which has been a false negative for prior H3N2v cases, such as A/Maine/06/2011, A/Maine/07/2011 and A/West Virginia/07/2011.

Release of sequences from the 233 “seasonal” H3 cases reported for weeks 30-33 would be useful.

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