Back in 2005, our government decided to buy a bunch of anti-virals just in case Bird Flu (avian influenza) made it to our shore. At the time, administration critics noted that Donald Rumsfeld owned a lot of stock in Gilead Sciences which shared the rights to the Tamiflu (oseltamivir) patent. Rummie’s stock in Gilead soared in price thanks to the huge sale to our government and the massive publicity that caused people to stockpile the drug. What few people outside the medical profession noticed was that scientists in Asia had discovered that influenza strains were showing resistance to Tamiflu
as had been predicted all along based upon its mechanism of action. Its competitor, Relenza (zanamivir) was not showing any sign of resistance. So, why did the administration decide to throw all of its money eggs into Rummie’s basket?
Here is the evidence. Keep in mind that Roche, the manufacturers of Tamiflu would have received reports of these studies long before they were published in scientific journals or released to the press, and the U.S. Each time a patient died of influenza on Tamiflu, Roche (and Rummie) would have known about it. The CDC also would have known about most of these results in advance.
http://www.scidev.net/en/news/tamifluresistant-bird-flu-found-in-vietnam.htmlStory from Oct. 2005 about how Tamiflu resistant bird flu had been found in Vietnam. A 14 year old with H5N1 was found to have a single mutation in one of the virus’s 8 proteins in most of the strains isolated from her blood. The article refers to a
Lancet article from August 2005 which also discussed the issue of Tamiflu resistance. Both articles question the practice of stockpiling only Tamiflu and recommend a combination of Tamiflu and Relenza. I referenced this article in a entry in Democratic Underground (just to prove that the topic was in the lay press) here:
http://www.democraticunderground.com/discuss/duboard.php?az=view_all&address=104x5249363In December, 2005, the New England Journal of Medicine (NEJM) had this article about a case history from
January 2005 .
http://content.nejm.org/cgi/content/full/353/25/2667They describe two pediatric patients who initially had Tamiflu suspectible influenza A H5N1 type. In both cases, the virus mutated and became resistant several days after high dose Tamiflu was started, even though the patients were improving, their viral count was going down, and treatment had been started early. The patients ended up dying. The authors conclude that pediatric patients who have no prior immunity to influenza are more likely to have prolonged infection and higher viral levels and this increases the chance that their virus will mutate.
In adults with influenza A (H1N1) or (H3N2) virus infection, the development of resistance to oseltamivir is rare, but resistant viral variants have been detected in up to 18 percent of children who receive oseltamivir
Snip
Strategies aimed at improving antiviral efficacy (e.g., the use of higher doses, longer durations of therapy, or combination therapy) may deserve further evaluation. In addition, antiviral agents to which oseltamivir-resistant influenza viruses remain susceptible should be included in treatment arsenals for influenza A (H5N1) virus infections.
In other words, they were recommending treatment with alternative medication such as Relenza.
And yet, the Bush administration chose to respond to the bird flu epidemic in Asia by buying up all the Tamiflu it could get its hands on, precipitating a run on the Tamiflu market and making Rummie a tidy profit.
There is more.
Also from December, 2005, NEJM
http://content.nejm.org/cgi/content/full/353/25/2633 Why is resistance developing to oseltamivir? Several years ago,structural analysis3 predicted that aspects of the chemical structure of oseltamivir (not present in zanamivir) could facilitate the development of resistance mutations that would permit neuraminidase to function, allowing drug-resistant virus to survive and propagate. This prediction is now being validated by clinical data.
Oops.
And then, there is the conclusion , which is much more alarming:
Like any successful infectious agent, influenza virus will most likely evolve to evade any single drug. By targeting several points in the viral life cycle simultaneously with different drugs, we are more likely to discourage the emergence of viruses that can resist all drugs at once. But we currently rely solely on the neuraminidase inhibitors — and solely on oseltamivir in many situations, such as in patients who cannot use inhaled medication or in patients infected with H5N1 virus, in whom systemic drug levels may be important. We must not abrogate the usefulness of these drugs by exposing circulating influenza to them in such a way as to facilitate the selection of resistant viruses. The study by de Jong et al. confirms that oseltamivir-resistant H5N1 virus is now a reality. The need to learn more about how and when resistance to the neuraminidase inhibitors develops, while we focus on the development of new antiviral drugs, is pressing. This frightening report should inspire us to devise pandemic strategies that do not favor the development of oseltamivir-resistant strains. Improper use of personal stockpiles of oseltamivir may promote resistance, thereby lessening the usefulness of our frontline defense against influenza, and should be strongly discouraged.
In other words, the authors predicted that if people were encouraged to stockpile---and overuse—Tamiflu, they would encourage the selection of resistant strains of influenza. And yet, that is exactly what the Bush administration did when they loudly purchased $1.4 billion of the drug, publicly proclaiming that it would save the lucky few from bird flu.
http://content.nejm.org/cgi/content/full/353/25/2636From the same Dec. 2005 issue:
"Doctor, I need a prescription for that bird flu drug." If recent newspaper headlines are any indication,1 this request has been repeated tens of thousands of times around the country this fall. So much oseltamivir (Tamiflu) has been prescribed — presumably for personal stockpiling in case of an avian influenza pandemic, given that the human influenza season has not yet begun — that at the end of October, the drug's manufacturer stopped shipping it to the United States.
Then, quietly, next year the CDC decided to add a little Relenza to its stockpile. Just 20%, without a lot of fanfare. Certainly not with the Tamiflu hype. I don’t remember people running to their doctors demanding prescriptions of Relenza “just in case.”
http://www.medicalnewstoday.com/articles/47960.phpBy February, 2008, the scientists’ predictions were born out. Tamiflu resistance was seen in the United States.
http://www.recombinomics.com/News/02160803/Tamiflu_Chicago.html The above comments on ten oseltamivir resistant cases in Chicago, including eight from one health care facility, suggest the incidence of Tamiflu resistance is on the rise in the United States. To date the US has reported 16 cases for the entire season, so if the 10 cited above are in the influenza surveillance network, the number of positives will be markedly higher in the near term. It is likely that the 10 will be H1N1 and resistant because of H274Y, which is true for all isolates reported this season in the United States.
The high concentration at one facility suggests the H274Y is evolutionarily fit, although there is a possibility that these patients were being treated with Tamiflu. However, reports from Europe, where Tamiflu resistance is high, indicate such cases were not treated with Tamiflu.
These cases could pose a serious health problem in at risk populations because Tamiflu is rendered useless by H274Y, and the recent H1N1 isolates in the US and Europe have been the Brisbane strain, which is not well recognized by the current trivalent vaccine. The match failures for H3N2 and influenza B, coupled with the poor match for Brisbane H1N1 has been associated with rapid spread of influenza in the United States, which has generated an MMWR report this week, and the second CDC news conference in a week.
This latest explosion in Tamiflu resistance suggests the frequency will continue to grow. The Tamiflu status of these 10 patients would be useful.
At the same time, doctors were detecting a significant level of Tamiflu resistance in the same strains of influenza in Europe.
http://www.medicalnewstoday.com/articles/95996.phpThis brings us to the 2009 season. As they predicted last year, this year Tamiflu resistance is everywhere.
http://www.nytimes.com/2009/01/09/health/09flu.html Virtually all the dominant strain of flu in the United States this season is resistant to the leading antiviral drug Tamiflu, and scientists and health officials are trying to figure out why.
The authors say it not because people have taken Tamiflu, but that just seems too silly for words. Charles Darwin would say that you select for one of two equal genetic variants only if one of them confers an advantage. Tamiflu resistance should confer an advantage only in the presence of Tamiflu. If a simple base pair change confers an advantage in
two situations, I would be very surprised. I mean, what are the odds?
Dr. Niman said he was worried about two aspects of the new resistance to Tamiflu. Preliminary data out of Norway, he said, suggested that the new strain was more likely to cause pneumonia.
The flu typically kills about 36,000 Americans a year, the C.D.C. estimates, most of them the elderly or the very young, or people with problems like asthma or heart disease; pneumonia is usually the fatal complication.
And while seasonal flu is relatively mild, the Tamiflu resistance could transfer onto the H5N1 bird flu circulating in Asia and Egypt, which has killed millions of birds and about 250 people since 2003. Although H5N1 has not turned into a pandemic strain, as many experts recently feared it would, it still could — and Tamiflu resistance in that case would be a disaster.
Post influenza pneumonia has become complicated in recent years by the increase prevalence of methicillin resistant staph aureus (MRSA), which can be fatal. This bacteria colonizes the nose and can cause bronchitis and then pneumonia in otherwise healthy people who have had influenza. Ordinary antibiotics of the kind that you take by mouth will not treat it. This complications has lead to a recommendation that all children 2-19 receive the flu vaccine. However, vaccines are not always effective. If anti-virals do not work, we may see an increase in hospitalizations and fatal pneumonia.
In 2005, the Bush administration and Donald Rumsfeld knew that Tamiflu had a resistance problem. The medical community predicted that if it was used as the single, staple therapy for influenza, resistance would become widespread. Doctors recommended that research be done to expand the number of available treatment options for influenza, and that care be taken not to overuse Tamiflu.
Rather than following the advice of the medical community, the Bush administration sought to increase the sale of Tamiflu, prop up its manufacturer’s stock----and make Rummie a tidy profit---by buying a huge stockpile of it, in essence telling the American public
We believe in Tamiflu. This is a cure all you can count on. This had the effect of accelerating the rate of drug resistance.
PS. Because I like to connect the dots, here are a couple of links to some other old journals. I included the Tamiflu federal tax dollar give away in my journal
Welcome to Life Aboard the B Ark last fall.
http://journals.democraticunderground.com/McCamy%20Taylor/307 And, in March, 2007, I noticed that the FDA was helping Glaxo-Smith-Kline make more money by doing something very unusual. The FDA decided to ban three time tested drugs, which allowed GSK to increase its sales of three of its expensive patent meds.
http://www.dailykos.com/story/2007/3/2/14243/36440 I mention this here, because GSK makes Relenza, and I have always wondered why the Bush administration did GSK such a big favor in 2007. Maybe they were paying them back for not raining on Rummie's parade in 2005-6. Just a thought.
Oh, and here from Wiki, everything you never thought you would need to know about Tamiflu
http://en.wikipedia.org/wiki/Oseltamivir
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