Tamiflu Resistance and The Fall of H1N1 Drug Companies
by ilene - December 15th, 2009 10:25 am
The Shocked Investor picked up my latest article on swine flu and the emergence of tamiflu resistance, and connected the development with moves in "flu stocks." I’ll note that the current H1N1 vaccines should still be effective against tamiflu resistant viruses, but the injectible vaccines may not be very effective against viruses with receptor binding domain changes, represented by the D225G marker, or other changes in the 225 position. On another note, Dr. Henry Niman is predicting another wave of infections sometime this winter. Read more here. – Ilene
Tamiflu Resistance and The Fall of H1N1 Drug Companies
Courtesy of The Shocked Investor
We track all H1N1 companies live here. These companies had been up hundreds of percent earlier this year and have taken a beating recently, as we expected (and wrote about). This was the situation in October:
And this is the status today:
(CHIP was sold.) Note the declines since October.
You may receive technical analysis and alerts of these companies sent automatically to you, by entering the symbols in the Technical Trend Analysis Tool. Here is the current ROI:
Coincidentally with the drop of these H1N1 companies has been the news of Tamiflu resistance. Ilene, from Phil’s Stock World, has an update on H1N1, again speaking to Dr. Henry Niman. She discusses several timely topics which directly affect a couple of the companies above.
The Emergence of Tamiflu Resistance
The swine flu virus has been increasing showing changes leading to greater incidences of Tamiflu resistance, but this being downplayed by the CDC and WHO. The CDC recently issued this CDC report:
A total of 29 cases of oseltamivir resistant 2009 influenza A (H1N1) viruses have been identified in the United States since April 2009. In specimens collected since September 1, 2009, 19 cases have been identified in the United States, including three newly identified cases since last week. The proportion of oseltamivir-resistant 2009 H1N1 viruses does not represent the prevalence of oseltamivir-resistant 2009 H1N1 in the U.S. Most cases were tested because drug resistance was suspected. All tested viruses retain their sensitivity to the neuraminidase inhibitor zanamivir. Of the 29 total cases identified, 19 patients had documented exposure to oseltamivir through either treatment or chemoprophylaxis, eight patients are under investigation to determine exposure to oseltamivir, and two patients had no
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Swine Flu Virus: Changes and Consequences
by ilene - December 14th, 2009 12:52 pm
Swine Flu Virus: Changes and Consequences
By Ilene with guest expert Dr. Henry Niman
Background
Dr. Henry Niman heads the research company Recombinomics Inc. Recombinomics has a small group of researchers who analyze the sequence data from viral samples isolated from patients diagnosed with swine flu. Its website is a terrific place to find the newest information available.
Dr. Niman has kindly been answering my questions regarding the H1N1 virus, its evolution, and the implications regarding the spread of disease. Because the terminology may be unfamiliar, a brief introduction may be helpful towards better understanding both the H1N1 virus and the swine flu disease.
Recombination
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.
Ukraine Outbreak
The outbreak in Ukraine was initially described in many media reports as a new lung-blackening “mystery disease,” leading to many false and misleading Internet stories. According to Dr. Niman, it was clear from the start that H1N1 was killing an unusually high number of previously healthy young adults… (See Flu News: D225G Follow-up)
Dr. Niman wrote a number of commentaries on the rising death toll and the need to make the sequences public. He predicted the deaths would be associated with a receptor binding domain change in the wild-type H1N1 virus (the predominant virus) to…
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What’s new with the flu?
by ilene - December 5th, 2009 1:26 pm
What’s new with the flu?
By Ilene with guest expert Dr. Henry Niman
Tamiflu resistant swine flu virus strains, circulating along with the wild-type (more prevalent, Tamiflu sensitive) viruses, are increasing in numbers, as the pool of viruses continues to expand. This is not due to sporadic point mutations, nor is it to do a nefarious government plot. This is how nature works, and knowledge of viral evolution leads Dr. Niman to predict that the number of Tamiflu-resistant cases will continue to increase.
At the Recombinomics website, today, additional support for Dr. Niman’s theory is presented. Growing numbers in the country of resistant viruses are showing up in clusters, for instance in the Maryland/Virginia area and in Pennsylvania. These clusters of Tamiflu-resistant cases most likely reflect a larger pool of resistant viruses circulating in the U.S. and other countries. "These repeated reports of H274Y [i.e., genetic change causing Tamiflu-resistance] in geographic clusters, as well as transmission clusters, suggest that H274Y has passed a tipping point, and reports of H274Y will increase in the upcoming weeks." H1N1 Tamiflu Resistant Cluster in Pennsylvania,
Separately, the ratio of D225G swine flu virus variant to wild-type variant may also be increasing. As this variant may cause a more severe disease by binding in the lungs, rather than just in the upper airways, this is cause for concern. The more aggressive course of disease apparently occurring in Ukraine may be the result of an increasing ratio of a more virulent D225G virus to the wild-type virus.
Further investigation is needed. Because the wild-type virus binds in the upper respiratory system while the D225G variant binds in the lungs, tissue samples from individual patients should be taken from both regions in order to see more accurately how the virus is evolving.
Here are two of Dr. Niman’s recent updates discussing these developments. For more, visit Dr. Niman at Recombinomics.
H1N1 Tamiflu Resistance Crosses Tipping Point
Recombinomics Commentary 03:07
December 4, 2009
Within the past two weeks, the number of documented cases of oseltamivir resistance in H1N1 viruses has risen from 57 to 96. Around one third of these cases occurred in patients whose immune systems were severely suppressed by haematological malignancy, aggressive chemotherapy for cancer, or post-transplant treatment. The clusters in the two hospital wards should be viewed in the context of
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Flu News: D225G Follow-up
by ilene - November 28th, 2009 2:56 pm
In case you missed my latest update on the flu, I’ve added to it here. – Ilene
Flu News: D225G Follow-up
By Ilene with guest expert Dr. Henry Niman
Dr. Henry Niman heads the research company Recombinomics Inc. Recombinomics has a small group of researchers who analyze the sequence data from viral samples isolated from patients diagnosed with swine flu.
I spoke with Dr. Niman last week about the evolution of the H1N1 virus as it circulates through the world’s population. These changes are natural—and Dr. Niman’s research on the subject allowed him to predict how the virus would change as infection rates increase and time goes on. The outbreak in Ukraine was initially described in many media reports as a new lung-blackening "mystery disease," leading to many false and misleading Internet stories. According to Dr. Niman, it was clear from the start that H1N1 was killing an unusually high number of previously healthy young adults.
H1N1 infection seemed to cause more severe illness in Ukraine, and Ukraine officials asked the WHO for assistance. The WHO interfaced with Ukraine labs in Kiev and sent groups into western Ukraine to survey the problem and gather information. As part of the investigation, the WHO sent samples to Mill Hill in London, one of several regional centers that performs genetic analysis for the WHO.
Subsequently, the WHO issued several non-informative reports but held the sequences at Mill Hill for analysis. Dr. Niman wrote a number of commentaries on the rising death toll and the need to make the sequences public. He predicted the deaths would be associated with a receptor binding domain change in the wild-type H1N1 virus (the predominant virus) to a variant form, characterized by the D225G genetic marker. Wild-type H1N1 has a D at position 225 of the viral protein Hemagglutinin (HA), and is referred to as D225. The variant protein, D225G, has a genetic change causing a change in position 225 of the protein. "D" is the symbol for the aspartic acid which is present at position 225 of the wild-type protein. Glycine, symbol G, replaces aspartic acid in D225G variants. Hemagglutinin is one of two surface proteins projecting out from the surface of the virus. The function of the HA protein is to bind viral particles to susceptible cells in the host animal.
The…
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Flu News: What is the significance of D225G?
by ilene - November 25th, 2009 4:28 pm
Swine Flu News: What is the significance of D225G?
By Ilene
With the current rush of news about the swine flu virus morphing into more aggressive lung-shredding and tamiflu-resistant mutants, there is some confusion as to why these changes are being seen in people in "hotspots" around the world, with no clear connection to each other. Officials at the WHO and CDC suggest that the same mutations are arising spontaneously in multiple locations but this doesn’t quite make sense. To better understand how changes in the swine flu virus may be occurring, I contacted Dr. Henry L. Niman, founder and president of Recombinomics. Dr. Niman has been an active researcher in the evolution of flu virus. His latest thoughts on the ongoing progression of the flu pandemic may be found at his website, Recombinomics.
For a little background, the D222G mutation or D225G mutation (same mutation, different numbering system) was found in three cases in Norway ("Norway" mutation), and in other countries, including Brazil, China, Japan, Mexico, Ukraine, the United States, and more recently Hong Kong. The change in a single nucleotide results in an amino acid change in the virus’s receptor binding protein. This has the effect of allowing the virus to bind receptors in the lung tissue, rather than the more usual binding to cells in the upper airways. Theoretically, this may confer greater virulence to the virus, potentially leading to more severe disease as the infection invades deeper in the respiratory tract. This change was also seen in the 1918 flu pandemic, in some (but not all) cases.
Recombinomics
The name of Dr. Niman’s company "Recombinomics" is taken from the word "recombine" or "recombination" – the driver of rapid molecular evolution and the emergence of infectious agents. Recombination* is a mechanism whereby small bits of genetic information pass between viruses so that a virus may quickly acquire a genetic change that evolved previously over the years in other viruses. Recombination is similar to reassortment, but with less genetic material being exchanged.
Sporadic mutations do not usually lead to successful adaptive changes – often they have no effect or prove to be non-adaptive, with the mutation failing to be further replicated. In contrast, recombination allows viruses to quickly alter their characteristics by acquiring genetic material that already exists in the viral reservoir (i.e., the pool of viruses circulating in a population). This…
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Swine Flu News
by ilene - November 20th, 2009 8:11 pm
Swine Flu News
By Ilene
The good news is that the number of new cases appears to be dropping off in most of the United States. More good news is that the swine flu vaccine appears to be reasonably safe, with no increases in serious events, including death, above the expected baseline rate. The not-so-good news is that a currently noted "peak," in flu language, is temporary. Additional waves of increasing illness are expected. Other bad news is that pediatric deaths from the swine flu are already considerably higher than in seasonal flues, and the numbers are expected to continue rising. In addition, viruses with specific mutations, D222G or D225G, and a mutation resulting in tamiflu resistance, are being isolated from cases in multiple locations.
Estimated Statistics:
Update from the CDC, Weekly 2009 H1N1 Flu Media Briefing, Anne Schuchat, director of vaccination and respiratory disease at the C.D.C:
these estimates will give a single number and then a range, a lower and upper estimate around each number…. So for April through October 17th, we estimate the 22 million people have become ill from pandemic influenza. We estimate 98,000 people have been hospitalized so far through October 17th. And the upper and lower estimates on hospitalizations are from 63,000 to 153,000. We estimate that 3,900 people have died so far in the first six months of the pandemic from this virus. And the estimates there are from 2,500 up through 6,100 people having died so far. We’ve been talking a lot about this pandemic being a younger person’s disease, that it’s disproportionately affecting children and young adults and relatively sparing the elderly, very different from seasonal flu… [In] children under 18, we estimate 8 million children have been ill with influenza, 36,000 hospitalized, and 540 children have died…
I do believe that the pediatric death toll from this pandemic will be extensive and much greater than what we see with seasonal flu…The numbers I’m giving are through the first six months through October. We have had a lot of disease since then and we’ll probably have a lot of disease going forward…
What does this look like compared to previous pandemics. The estimates I’m giving you are the first six months. This is April through the middle of October. We have a long flu season ahead of us. In typical seasonal flu we see disease from
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Philip R. Davis is a founder Phil's Stock World, a stock and options trading site that teaches the art of options trading to newcomers and devises advanced strategies for expert traders...
Ilene is editor and affiliate program
coordinator for PSW.