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H1N1 Update

H1N1 Update:  Watching and Waiting  

by Ilene with guest expert Dr. Henry Niman at Recombinomics

EM of swine influenza (H1N1) virus particles (virions), determined to be the cause of the

Watching and Waiting

Although the numbers of new cases of swine flu have been declining in many regions, including the United States, it is too early to know whether or not there will be subsequent waves of disease.

"Based on my experience with new diseases and the lessons learned from past pandemics, I think we should remain cautious and observe the evolution of the pandemic over the next six to 12 months before declaring victory," World Health Organization Director General Margaret Chan tells Swiss newspaper Le Temps. (World Health Official Says Swine Flu Still a Threat)

Although the WHO is taking a cautious approach, changes in the virus’s genome that increase its virulence and resistance to Tamiflu are becoming more common.  Dr. Henry Niman, expert in flu virus evolution, believes another wave of flu illnesses will occur in early 2010.  In addition, he believes resistance to Tamiflu will become "fixed," similarly to how this genetic change evolved in the seasonal H1N1 virus.  (See Flu Update: Tamiflu resistance and Ukraine update, and Efficacy of Roche’s Flu Drug Tamiflu In Doubt, by David Phillips.)

WHO: H1N1 swine flu pandemic will stick around for another year

The World Health Organization warned government health authorities to remain vigilant on the H1N1 swine flu pandemic, saying the virus could mutate before vaccines can help it dissipate.

The World Health Organization is confident that the H1N1 swine flu pandemic will be under control in a year’s time – however, WHO officials warned global governments to remain vigilant for any mutations in the troublesome bug.

Dr. Niman believes this wave will be more severe than the previous two--but not due to random mutations. Rather, this will result from the process of recombination. Due to recombination, increasingly greater transmission of aggressive variants (D225G, D225E and D225N) and Tamiflu-resistant viruses will occur.


I’ve reprinted two recent articles at Recombinomics, with my comments in blue.

The WHO Surprise on D225G / D225N H1N1 Fatalities, Recombinomics Commentary

After considering the current available virological, epidemiological and clinical findings and following discussions on an earlier draft with WHO and its European-based Collaborating Centre ECDC has come to a preliminary formulation namely that the G222D/N variants exist in a small proportion of sporadic severe, as well as mild cases of 2009 pandemic influenza A(H1N1) infection and that these represents natural variation of the virus with no special association with severity of the disease course. As such and while they do not transmit they should have a minimal impact on public health and pandemic response. Current data suggests that the cases involving variant viruses in different parts of the world are unrelated and the underlying mutation events probably occurred independently from each other in the infected individuals as a consequence of the natural variability of influenza viruses and their inability to correct random coding errors. However because of that inherent variability and ability to surprise the 2009 A(H1N1) will need on-going combined virological, epidemiological and clinical surveillance and study.

The above comments in the latest ECDC report confirm attempts by WHO consultants to explain the strong association of D225G and D225N (aka D222G and D222N) with fatal and severe H1N1 cases as "random coding errors" even though the WHO regional lab in Mill Hill found D225G in four of four fatal cases, while the WHO region lab in Atlanta (CDC) found D225N in two of two additional cases, which were almost certain fatal cases also. 

D225G and D225N are rare and have been reported in about 1% of H1N1 HA sequences, yet they have a 100% case fatality rate in sequences from Ukraine… 

My comment:  Dr. Niman means that fatal cases in Ukraine, for which genetic analysis has been performed, have shown non-wild type variations at codon 225, e.g. D225G or D225N. He is not saying that all cases in which D225G or D225N is found are fatal. The proportions of all cases and non-fatal cases with the D225G and/or D225N markers are not known. 

Although there were a few mild cases with D225G in the US at the start of the pandemic last spring, including the vaccine target California/7, mild cases are common at the start of a pandemic because there is little immunity in the target population, and infections and symptoms can be caused by low viral loads which are effectively contained by a weak host response.  The association of D225G and D225N in severe and fatal cases since the summer has been remarkable, especially since the vast majority of pandemic H1N1 infections are mild and resolve without treatment.  In contrast, nearly 100% of recent cases with D225G, D225N, or both have been fatal or severe…

I think this is confusing and that Dr. Niman means the reverse--fatal and severe cases are consistently showing variations in the D225 position (either or both D225G and D225N).  However, the percent of all and mild cases with D225G and/or D225N markers is not known. In other words, not all cases with D225G or D225N are fatal or severe, and the statistics that would be helpful to know are unknown. 

This "random mutation" paradigm constantly produces "surprises", for which the above "experts" readily acknowledge on a very regular basis.  They were surprised and baffled by H274Y Tamiflu resistance in patients infected with seasonal H1N1, and will again be surprised and baffled by the same result in pandemic H1N1.

WHO’s reliance on consultants who try to use random mutation to explain these examples of 100% case fatality rates in multiple countries is cause for increasing concern.

Ukraine Fatalities Spike to 675 – Two Day Total 42, Recombinomics Commentary

3,669,751 Influenza / ARI

207,013 Hospitalized

675 Dead

The above figures are from the Ukraine Ministry of Health and represent a spike of 42 fatalities in the past 48 hours…

A preliminary report by WHO and ECDC has suggested that the presence of D225G and D225N in the fatal cases is due to random copy errors, even though the cases in Ukraine involve two different changes, which represent the only non-synonymous HA differences between the fatal and recovered cases, and recently patients with both changes have been identified in the United States (Utah), Sweden (Stockholm), and Mexico (San Luis Potosi)…

The recent surge in fatal cases should allow for additional sample collection over a two moth time frame to allow for more extensive analysis, which will highlight the failure of random mutations to explain the dangerous polymorphisms, D225G and D225N… 

My comment: the random mutation theory fails to account for the quickly spreading changes in the H1N1 virus as well as the recombination theory.  For example, see 

Flu viruses, including the H1N1 varieties, are known for quickly changing genetically. Recombination is the driver of rapid molecular evolution, a process whereby small bits of genetic information pass between viruses so a virus may quickly acquire a genetic variation that has previously evolved and already exists in the viral reservoir (the pool of viruses circulating in a population). Unlike sporadic mutations, recombination reflects the acquisition of genetic material that has withstood the Darwinian test of time. Compared to sporadic mutation, recombination is a quicker, non-random mechanism for genetic change.

Changes in the H1N1 viral genome are natural. The viral reservoir consists of wild-type viruses (the predominant viruses) and low levels of variants carrying a variety of different sequences called “polymorphisms.” While recombination is not the currently favored theory regarding how flu viruses evolve, Dr. Niman believes it is the correct theory. The theory of recombination as a mechanism for genetic change has led to accurate predictions about how the flu virus would evolve as infection rates increase. As the size of the viral reservoir continues to expand, viruses with genetic differences, “polymorphisms,” become more evident.


According to the WSJ, Retailers Jockey to Market Swine-Flu Shots:  

Pharmacies, supermarkets and other retailers are jockeying to become the go-to provider for swine-flu vaccinations, in a bid to attract more customers and, in many cases, promote their in-store health clinics.

With the vaccine becoming more widely available, Rite Aid Corp. is placing signs that read, "Protect Yourself: H1N1 Vaccinations Are Available," on the front doors of its drugstores and hanging similar banners inside. Kroger Co. is promoting its H1N1 flu shots on the cover of the grocery chain’s weekly ad circulars. Starting next year, Walgreen Co. plans to advertise its supply of the vaccine in television spots and on its Web site…

An uptick in swine-flu shots could help generate traffic for retailers at a time when consumer spending has been weak. While drugstores’ prescription sales have been rising, front-of-the-store sales of nearly everything from potato chips to batteries to deodorant have slowed. Over the past year, major grocers have been reporting declining same-store sales, a key indicator of a retailer’s strength.

"We clearly see potential opportunity" in the vaccinations, says Brian Dowling, a spokesman for grocer Safeway Inc., which runs Dominick’s, Von’s and Tom Thumb stores. "The vast majority of our pharmacy customers shop the rest of the store."

Indeed, retailers are hoping the H1N1 shots will spark a jump in sales of other flu-prevention products, such as hand sanitizer. 

While swine flu vaccines would remain effective against Tamiflu-resistant variants, there is evidence that the injectible vaccines would not afford sufficient protection against D225G variants, making these vaccines less effective against particularly aggressive sub-types of viruses. In contrast, the Flu Mist vaccine was developed against viruses with the D225G marker, so it is likely to be more effective against viruses with this worrisome genetic variation.


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