Today it was announced that a new human trial of Tamiflu dosage was going to be conducted. The participants in the test will be human victims of H5N1 as well as severe seasonal flu.
Doctors test double Tamiflu dose to cut H5N1 deaths
Wed Mar 28, 2007 1:52PM BST
HONG KONG (Reuters) - Doctors in Asia and the United States will give double doses of Tamiflu to patients suffering bird flu and severe seasonal human flu from May in a trial aimed at cutting high death rates from avian flu.
People infected with the H5N1 bird flu virus are now prescribed the standard dose of Tamiflu, which is one capsule twice daily for five days.
But less than half the patients survive.
"In animal studies, higher doses of Tamiflu have resulted in higher cure rates for H5N1. The death rate from H5N1 is 60 percent, we want to see if we can solve this problem," said Tawee Chotpitayasunondh, senior medical officer at Thailand's Ministry of Public Health.
The Cyber Flu Community has been discussing the Tamiflu dosage regimen since the middle of 2005 when information on a mouse study came to our attention. The published findings of this study may be found here, and a more "user friendly explanation of the study's findings may be found here, from the National Institute of Allergy and Infectious Diseases.
While we are not privy to treatment protocols, I do wonder if there are primary treatment doctors in areas experiencing human H5N1 infection that have already "tweaked" the Tamiflu dosage and that may be why we are seeing a reduction in CFR (Case Fatality Ratio). Helen Branswell did an excellent piece on the recent meeting in Turkey of over 100 physicians with experience treating human H5N1 infections.
Doctors who have treated bird flu cases meet to share treatment info
HELEN BRANSWELL
Doctors who have treated H5N1 avian flu patients are meeting in a Turkish seaside town to try to find answers to the myriad mysteries that remain about what the brutal virus does to its human victims and how dismal survival rates might be improved.
The World Health Organization hopes that by pooling patient data, the meeting will answer critical questions such as whether all lineages of the H5N1 virus cause the same severity of disease and how best to treat pregnant women who become infected.
Based on what it learns at this meeting, the WHO will update H5N1 treatment guidelines, so that doctors who face cases in the future can benefit from the successes - and missteps - of those who have treated patients in the past.
"There's a real deficit there," says Dr. Frederick Hayden, a WHO influenza expert and a key organizer of the meeting.
"We don't have basic information at hand to try to give the best advice. We're going to address that gap."
The meeting will also seek buy-in from doctors for a new patient data collection system the WHO hopes to get up and running.
Doctors treating H5N1 patients - past, present and future - would be asked to submit a couple of pages of standardized clinical and treatment information so that the global health body can track patterns of disease and treatment efficacy on an ongoing basis.
"This will give us, I think, the best available opportunity under the current circumstances to make sense out of what's happening," Hayden said.
The 100 or so doctors and other experts are meeting in Antalya, in southern Turkey. The meeting, which is being held Monday through Wednesday, is being hosted by the Turkish government.
It is a follow-up to a conference that was held in Hanoi in May 2005. At that point three countries - Thailand, Vietnam and Cambodia - had reported human cases of H5N1; there were 89 confirmed cases and 52 deaths.
Since then nine more countries - Azerbaijan, Iraq, Indonesia, Laos, Egypt, Nigeria, Djibouti, Turkey and China - have reported human cases. As of Sunday, the WHO had confirmed 279 cases since November 2003; 169 of those people died.
In the intervening months, small collections of case data have been published in medical journals. An account of the treatment of eight patients in Turkey. A paper describing a similar number in Indonesia. A report that revealed how patients responded - or didn't - to treatment with the antiviral drug oseltamivir (Tamiflu) in southern Vietnam.
But in the main, the details of the symptoms and disease progression of the vast majority of H5N1 patients, the steps their doctors took to try to save them and the outcome of those treatment choices remain locked up in the files of doctors who cared for them.
"There is a huge number of unanswered questions about human infections with highly pathogenic H5N1 viruses," says Dr. Tim Uyeki, an influenza expert from the U.S. Centers for Disease Control in Atlanta, who is attending the meeting.
"I think it's so important to share information so others can benefit from the experiences of those who have dealt with this."
Pooling data should allow patterns to come into focus in a way that is impossible when two or three doctors are looking at a handful of cases.
The meeting is taking place behind closed doors to encourage doctors who may be working on scientific articles to share their findings before publication. Hayden says he's been told some large, unpublished sets of patient data will be presented in Antalya.
This bit is continually railed against in the Cyber Flu Community. Instead of the free exchange of information that can be used to save people's lives it is being hoarded all in the name of being able to publish a paper. Selfish and ego driven concerns outweigh the potential life saving addition to the general knowledge base.
"They'll tell us what's been done and what's happened. That may allow one to say: 'This does not work and we shouldn't be doing this.' That's sometimes just as important as saying: 'This does work,"' Hayden notes.
In addition to learning about past cases, gathering together the physicians who have treated H5N1 cases in 12 countries should enhance research collaborations - including planned clinical trials of intravenous forms of two antiviral drugs - zanamivir (sold as Relenza) and peramivir, a drug still in development.
(GlaxoSmithKline, which makes Relenza, has shelved plans to test an intravenous form of the drug in the United States, but is in discussions with a WHO-organized treatment network in Southeast Asia to test the new formulation there.)
Dr. Menno de Jong believes opportunities for additional research are inevitable when some many clinicians from so many countries are brought together.
"If we can make a list - What are the questions of highest priority and what needs to be done to answers those questions? - I think that already will be a big gain for a meeting like this," says de Jong, a virologist at the Tropical Medicine Hospital in Ho Chi Minh City, Vietnam, where some of the first H5N1 patients were treated.
Still, some mysteries won't be solved until more autopsies are done on H5N1 cases, de Jong insists.
It's believed there have only been about a handful of autopsies on people who succumbed to the assault of this vicious virus. To date cases have occurred in countries where, for cultural or religious reasons, autopsies are not done.
De Jong says pleas for more autopsies are made at every scientific meeting on H5N1, but they haven't produced results. He suggests a way around the autopsy barrier would be to encourage hospitals treating H5N1 cases to do post-mortem biopsies - using special biopsy needles to take bits of key organs for study.
Since the Cyber Flu Community has been aware of higher dose Tamiflu treatment for almost two years now, and many plan to utilize the increased dosage levels, why is it only now that the experts are getting their heads together and planning to put this protocol to the test?
It is widely believed that an H5N1 infection treated with Tamiflu runs the risk of creating Tamiflu resistant strain(s), and we have already seen a few instances of this. If the current recommendations of 2 capsules a day for 5 days is inadequate to kill the virus, but only to blunt it, the danger of resistance is magnitudes greater. This doesn't address the issue of life saving dosage, a separate issue, and one of no less importance.
As Tamiflu is in such limited supply it would be much more efficacious if the supplies we did have were used to the maximum benefit, even though that means treating 2/3 fewer. Whether that is for treatment of the ill or as a prophylactic for HCWs and other Essential Service persons can be argued separately, but if it is used as treatment we owe it to all those that will not receive any, to use what we have to gain the best possible outcome. Of course, that means reducing our "courses of treatment" stockpile by two-thirds, assuming 32 capsules vs 10 for an effective course.
But this points out how far ahead of the curve the knowledgeable and dedicated Flubies are.... we had this information twenty-one months ago. It also points out how important information is, if we have it, we can act upon it, if not, it could have dire consequences.
Comments