E627K from July Discovered Retrospectively, Tied to Vacation Island off the Netherlands in Diabetic Patient and Adolescent Female

Though the sequences have not been released, the team at Erasmus MC in Rotterdam has done us all a great service by providing an early report of 627K in the Netherlands. 

The multiple cases all vector from visits to a popular vacation island between July 13 and August 9.  Two of the cases do not appear to be related via direct contact, potentially indicating an endemic and silent spread of a minor PF11 population carrying the human-fit virulence factor 627K in a sub-clade that may match the major circulating sub-clade there but for the Lysine recombination.  Ten of twelve (83%) sample specimens from this geography fall into this sub-clade indicating the potential for dominant circulation in that area.

As this release of information via Promed is very limited, additional evalution and insight will require amendment and revision to this article as the matter is clarified on several accounts, including specification of the E627K sequence count and the various ratios confirming the certain Hydra Effect demonstrated in the study population.

In our reading, 4 distinct cases are discussed in the Osterhaus release. Which two of the four are described as having the E627K is questionable and will determine the H2H transmission assumptions.  The researchers may have mentioned “two patients” because the family contact and the younger sister may have been directly evaluated by them in a clinical setting?

• Male Diabetic who may have shared activities with ill female camper, onset 2009-08-09
• Female camper, onset after returning home 2009-07-20 
• Female family contact of ill camper, onset after camper returned on 2009-07-20
• Younger sister of female family contact, onset 2009-07-23

This highly interpretive post is preliminary based on inconclusive language in the press release.
No mention is made of the correlating PB2 virulence of aa701N and aa703K at this time in the information released.  We suspect these to be absent due to the non-fatal clinical outcomes; however, confirmation would be useful.

As the samples were examined retrospectively, little new observational evidence will be forthcoming.  Rational projections due to this 627K mid-Summer emergence in the Netherlands and the late May emergence in Shanghai71T could cause us to expect a geographically-dispersed, wild-type sub-population carrying this virulence factor.

Tenacious sub-clonal evaluation of current sequences in the United States will likely indicate mixed peaks at the PB2 residue coding for the Lysine at 627.



For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.

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

How Long Will the Pandemic Last?

The Road to Post-Omega PF11

How long will the Pandemic last?

Process: Predictions involving the outcomes of unprecedented or entirely new events must utilise theory.  Very few outside the scientific community revel in the joys of Theory, but today you may come to appreciate the practical value of theoretical reasoning.  Theory, the primary tool to explore anything unknown, generally begins with new tags or agreed definitions so that the discussion may embark.  The present framework of discussion, of theory, around PF11 appears to be lacking several important terms, specificity, control variables, causality determination and scientific rigour. 

So let's make an attempt to plant some markers and comport a discussion on one simple and important area of measurement, PF11 Timing.  Let's call today's virus, PF11_β, and a future tipping point, PF11_Ω, for ease of discussion.  Let's agree that we must progress beyond that future event of PF11_Ω before the Pandemic will dissipate.  (Glossary)

The distance between PF11_β and PF11_Ω is unknown.

And that delta, that difference, will remain unknown until some point in the distant future when we can retrospectively measure the closing event. Today, we'll talk about the road that everyone will travel from this moment until that closing event.

The journey between the two points will be progressively inundated with higher levels of impediment to the traveler. The traveler may not declare an optional routing. Due to decisions made by others, the traveler’s only available option is to agree and undertake the journey as given.

We all are driving the only highway (ΣPF11) between this small town of Bad (PF11_β) and the metropolis of Worst (PF11_Ω).  We know that no one knows the rate of speed we are traveling because no speedometer may be calibrated for a non-uniform progression.  Measurement is incomplete for all practical purposes. Fits and starts will be the norm.  We also know that each family will be affected by various types of collisions along the way.  In the veritable infinity of infectious vectors, few will emerge without themselves, their family or some important person in their lives being impacted.  Density, proximity and movement guarantee collision in any bounded system and this system is distinctly bounded.

As the traveler succeeds in passing each mile with the almost certain collisions and if they are able to survive the increasing number of attack vehicles (recombinants from the Influenza Flux), the lost segments of road (poorly chosen mediation measures) and the dwindling availability of fueling stations, eventually they will arrive at a better place. Though PF11_>Ω, this first city on the other side of Worst, is not the ultimate destination, any relief after that pandemic journey will be appreciated and any glimmer of light will be a sight for sore eyes.

Eventual arrival is the key concept. How long will this journey last and what must you do to eventually arrive are the important questions.

Someday long hence, you may rate this trip as “Somewhat Unpleasant” or “Utterly Devastating” depending on how well you’ve equipped your individual journey with actionable Knowledge and viable provisions. Though a fully intact arrival might be your goal, the most capable and well-Led travelers will realise that completion of this journey with only minor impact is a deep blessing because you’re going to need to see around corners to get there at all. While others planned your route straight through renegade territory, the responsibility now falls on you to cross this expanse of impediments and the ostensible rest areas are unprotected.

Renegades abide no law and a virus abides no social messaging campaign. A virus does not care and a virus does not feel. A virus just makes copies and reacts to the environment by acquiring new genetics. A virus escapes and evades. You are now being forced to drive your family directly into a hundred-mile wide, bone-dry forest in a three-year drought that has been primed by summer heat. From the moment you enter the expanse, you can feel the dryness of the stick wood and you know the logical outcome, but your route planners have given you no exit from this road. You can’t race this virus. One stray spark and everything changes.

On what type of journey do you wish to lead your family? Where on the scale between “Somewhat Unpleasant” and “Utterly Devastating” do you wish for your future rating to stand? Your actions today select your rating for tomorrow. This article provides you the initiative you need to act.

The route has been decided by our lack of determination, by our abdication of responsibility to untrustworthy people. Continue to Follow or Start to Lead, but be certain to load your vehicle well because your journey is beginning.

Glossary

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.

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

TamiFlu Shortage in Prime Risk Group Occurs Only 4 Weeks After School Starts

Children congregating in schools and universities appear to be the highest risk group for PF11 infection.  School has been in session for approximately 4 weeks.  Very little cold weather has occurred in the United States at this time.

Roche announced today that a shortage exists in their production of TamiFlu for children (liquid form).  The company advised pharmacists to grind the adult pill-based drug and adjust the dosage for children. 

Health officials say that priority will be given to those hospitalised.  If TamiFlu is effective only if used within 48 hours of symptoms and more than half of some populations do not present with the official case definition of fever, then few who are hospitalised will be within that 48 hour window.  Hospitalisation will primarily occur after significant viral replication time has passed (>48 hours) and the patient presents with incapacitating signals.  This prioritisation appears to be misguided given the Facts.

• TamiFlu resistance is geographically widespread in PF11 as demonstrated in the sequence databases.
• PF11 has not yet begun to peak. 
• Public health officials expect cold weather combined with the school gatherings to spur the case count substantially.

These three material impacts on the pandemic combined with the early shortage of the primary mediation measure espoused by public health officials leaves the public with very few, publicly-messaged, viable options.

Please review our research section discussing proposed mediation measures for further information.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.

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

TamiFlu Resistance Database Expands, But Remains Incomplete. Two Year Pandemic Predicted.

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.

We would like to thank those teams who have placed their sequences on deposit at GenBank and GISAID for the scientific community to evaluate.  The NA and HA for TamiFlu Resistant A/Singapore/57 from 2009-05-30 are again downloadable from the European EpiFlu database as GISAID has thankfully been able to re-establish access to their data.

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 at GenBank, 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.

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.


For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.

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