TamiFlu Resistant Singapore57 Sequence Available at GISAID EpiFlu database; 106I, 248D, H275Y

The NA and HA for A/Singapore/57 from 2009-05-30 are again downloadable from the European EpiFlu database as GISAID has thankfully been able to re-establish scientific community access to their data.

The NA of Singapore57 is an exact nucleotide match with Denmark528. 

Furthermore, Singapore57 is a match at all positions (1409) but C823T (TamiFlu Resistance) with:

A/Wisconsin/629-D01445 (1Y, 2009-5-24)
A/Bethesda/SP508 (14F, mid June)
RhodeIsland07 (HA:296H)
Massachusetts08 (14M)
Michigan06 (14M)
NewYork (many sequences from young people)
WestVirginia01 (15M)
Texas39 (12F, late May)
Arizona05 (4F, late April)
Utah02 (8F)
Utah04 (9F, late May)
Utah11 (9M, mid June)
Nevada03 (2F, late April)
Montana06 (14M, early May)
Georgia08
Oregon20
Canada (several)
Thailand (several, mid June)
Taiwan (several)
Germany (2 including Bayern66)

The geographic range of this PF11 background is extensive, with exceptional breadth in the United States and the background correlates to young people.

TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism on Singapore57 coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:

106I, 248D, 275Y, 286S

The following permutations are now represented on the nine PF11 anti-viral resistant sequences:

106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57

Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 9 with 106V.

The addition of Singapore57 re-leverages position 248 to Aspartate (D) with 5 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.

Many TamiFlu Resistant cases have been reported that have not been sequenced and deposited in the United States and worldwide.  Dr. Jonathan McCullers of St. Jude Children's Research Hospital in Tennessee reported a TamiFlu Resistant case yesterday, along with 12 child ICU cases and one child death.  Dr. McCullers indicates "a tremendous rise in cases" which began approximately one week after school resumed, well within the 3-10 day incubation period that we predicted post-congregation.  Dr. McCullers maintains that we are in the beginning of a two year pandemic that will have multiple peaks.  We agree that a period of 13 to 24 months from March 2009 is well within the expected duration.  Considering PF11's current position in the inter-species Influenza Flux and the high genetic variance demonstrated by the Hydra Effect, the lower boundary of our estimate (13 months) is unlikely unless the Case Fatality Rate increases significantly because PF11 rapidly depletes the population of potential hosts.

23 clinical observations have been publically discussed as TamiFlu Resistant in recent weeks around the world and most are not yet sequenced and deposited.  These cases concur with many of the geographic regions having sequences on file that match current TamiFlu Resistant sequences but for the H275Y.  In other words, the genetic acquisitions were predictable and expected to occur upon a proximal donor with 275Y co-infecting a host in that region.  An opportunity to review the full diversity of the anti-viral resistant strains would allow determination if, in fact, a silent spread of human-fit and reasonably transmissible TamiFlu Resistant strains is underway at this time or if we are seeing the improbability of an extensive and accurate selection due to treatment that is currently being purported as an explanation.  Evidence exists tending toward a silent spread, including that a substantial list is described with very early sampling and detection of H275Y, prior to any acceptable period for de novo / selective revision.  A minor sub-population of 275Y may be incorporated widely into the PF11 reservoir at this time.

The two youth in early July attending the North Carolina summer camp either spread their PF11 version one to the other or were each infected from a common carrier with a parental PF11 275Y Neuraminidase as is evidenced by the co-factor SNP on the NA of their sequences coding for 223V, known to amplify the 275Y TamiFlu resistance in H3N2.

A more robust database of sequences would be useful to invigorate the scientific community and the public in navigating this distant journey.

An n higher than 9 may assist us to align.

Please visit GeneWurx.com for insight into the latest published studies.