Bird flu study shows virus evolution in action
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Bird flu study shows virus evolution in action
Wed Dec 21, 2005 5:13 PM ET
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - At first it looked like the 13-year-old girl was lucky. She only had a little pneumonia in one lung and doctors had treated her early with Tamiflu, a drug known to be effective against avian influenza.
She "presented to a hospital in Dong Thap Province on January 22, 2005, with a one-day history of fever and cough," wrote Dr. Menno de Jong of the Hospital for Tropical Diseases in Ho Chi Minh city and colleagues.
And for several days, the drug seemed to be working. But then the girl began struggling to breathe and needed more and more oxygen.
The pneumonia worsened and she died six days after being admitted.
Tests done in Hong Kong showed the virus infecting her had mutated in a way known to make it immune to Tamiflu. She had a "H274Y substitution in the neuraminidase gene, which confers high-level resistance to oseltamivir (Tamiflu)," the researchers wrote in a report published in the New England Journal of Medicine.
The same thing happened with another patient treated by the same group. And four of eight patients they treated with Tamiflu, made by Roche AG under the generic name oseltamivir, died despite treatment with the drug.
No one is surprised -- viruses often develop resistance to drugs. For this reason, AIDS infections are treated with a cocktail of drugs.
"The best prevention of resistance is to suppress replication as completely and as early in the infection as possible. The paradigm 'Hit hard and Hit early' which has been used in the past for HIV/AIDS therapy is most likely true for influenza and undoubtedly many other viral infections," De Jong said in a statement.
NATURAL SELECTION IN ACTION
"Anything that you throw at a virus, a virus can evolve to evade it," said Dr. Anne Moscona, an expert in pediatric viral diseases at Weill Medical College of Cornell University, New York, in a telephone interview. "You can't attack a virus with just one compound."
Tamiflu is one of two influenza drugs in a class called neuraminidase inhibitors. These drugs target a protein on the surface of cells called sialic acid. Influenza viruses use an enzyme called neuraminidase -- the "N" in H5N1 -- to attach to the cells it infects.
Tamiflu and the other neuraminidase inhibitor, Relenza, block the neuraminidase enzyme used by the virus and keep the virus from hooking onto the sialic acid "doorway" on the cell.
But influenza viruses are mistake-prone -- they constantly evolve and change, and the neuraminidase structure can change, too.
Tamiflu does not block neuraminidase perfectly and has to make it stretch a little, Moscona said. "The structure of Tamiflu is such that several mutations are possible that allow for the neuraminidase molecule to still work and the virus to remain viable," Moscona said.
"The structure of Relenza is somewhat different, so that it seems to be somewhat less likely to allow for the development of resistance."
But Relenza, known generically as zanamivir, has its own drawbacks -- it must be inhaled, making it inappropriate for some patients, and it may only treat the lungs, while H5N1 attacks other organs, too. Maker GlaxoSmithKline is working on an injectable version.
Moscona said the report clearly illustrates why governments but not individuals should stockpile Tamiflu.
"One thing about stockpiling -- people are going to tend to share. They'll try to make a small amount go farther because there is a shortage," she said.
That will make resistance evolve even more quickly.
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Even Tamiflu is useless.
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REALLY!?
Then something like the movie "Aeon flux" will happened?
A virus that kill off 99% of the earth's population? -
More evidence bird flu can evade drug: report
Wed Dec 21, 2005 6:21 PM ET
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - Doctors in Vietnam reported on Wednesday they had found more evidence that the H5N1 bird flu virus can quickly mutate into a form that resists the effect of Roche AG's frontline drug Tamiflu.
Four of eight patients treated in Vietnam for bird flu infections died despite the use of Tamiflu, Dr. Menno de Jong of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City and colleagues wrote in the New England Journal of Medicine.
Tests showed that in two of the patients, the virus had become resistant to Tamiflu. And in one patient, the drug was used very early on, as is recommended.
"It is becoming clear that to treat avian flu with neuraminidase inhibitors (such as Tamiflu) we are going to need higher doses and longer course of treatment for it to work," said Dr. Anne Moscona, an expert in pediatric viral diseases at Weill Medical College of Cornell University, New York.
She and other experts said the findings showed that such drugs must be preserved carefully and used properly.
The H5N1 influenza virus has killed 71 people in Indonesia, Thailand, Vietnam, China and Cambodia since 2003.
The H5N1 strain is difficult for people to catch. However, experts fear it could evolve into a form that could pass easily from human to human, causing a pandemic that could kill millions.
The researchers and outside experts said the report concerned only a few people and stressed that more study is needed. Of the 138 people known to have been infected with H5N1, 31 have been treated with Tamiflu, Roche says.
"This currently is not a pandemic strain," Dr. David Reddy, Influenza Pandemic Taskforce Leader for Roche, told reporters in a telephone briefing.
A MUTATING VIRUS
"As it becomes a human pandemic it must change. It must shift. That may lead to a loss of virulence. However, we are dealing with a worst-case scenario today and we have to learn how to best manage it," Reddy added.
The findings add to a report published in October about a 14-year-old Vietnamese girl who survived an H5N1 infection after being treated with Tamiflu, but who had a drug-resistant virus strain in her body.
Four drugs treat influenza, but H5N1 already resists two older drugs, amantadine and rimantadine.
Countries have been stockpiling the newer drugs, known as neuraminidase inhibitors -- Roche and Gilead Science's Tamiflu, known generically as oseltamivir, and GlaxoSmithKline and Biota's Relenza, known generically as zanamivir.
De Jong and Moscona agreed that Relenza is a good alternative to Tamiflu.
"Furthermore, Relenza is active against Tamiflu-resistant virus," De Jong said in an e-mail.
But Relenza currently must be inhaled and may not be useful in patients with respiratory conditions such as asthma, and it might not spread past the lungs to protect other organs.
There is not enough of either drug to treat more than a fraction of patients should a bird flu pandemic erupt this year. Roche is trying to license a generic process and step up its own production to 600 million treatment courses by 2007.
There is an H5N1 vaccine but it is experimental and is unlikely to work well against whatever pandemic strain may eventually emerge.
De Jong said Tamiflu must be used early on in infection to do any good against any type of influenza. As with AIDS, a cocktail approach may be needed.
There are few options now. De Jong said one possibility to add to a cocktail is an antiviral used against hepatitis called ribavirin. BioCryst Pharmaceuticals, Inc. has a new neuraminidase inhibitor in the works called peramivir, which "may be an option in the future", De Jong said. -
I know in the past there are some virus (maybe 'Black Death') more serious than the now bird flu. But if bird flu mutate further, hmm... it can kill lots more, as people are globally linked...Originally posted by maggot:REALLY!?
Then something like the movie "Aeon flux" will happened?
A virus that kill off 99% of the earth's population? -
I can't exactly remember the name of this disease, but the newspapers reported that this diseases genetic composition is about the same as bird flu. If it can kill so many people that time, this time could be worse if we don't find a cure fast enough.Originally posted by News:I know in the past there are some virus (maybe 'Black Death') more serious than the now bird flu. But if bird flu mutate further, hmm... it can kill lots more, as people are globally linked...