Battling Bird Flu

Now to improve bird flu drugs for humans. Still at Mahidol University’s faculty of tropical medicine, they analyze how the anti influenza drug oseltamivir and a similar medicine are received, digested and disposed by the human body. Bird flu is caused by the H5N1 virus. Infections in humans are extremely aggressive, and life threatening whether or not (!) medicated within hours after the outbreak. 
Better and more efficient drugs may mean more lives saved and that is what this research, pharmacokinetic analysis in science lingo, is all about.
“Look here,” says Niklas and shows some slides from Vietnam.
“This is a patient’s lungs when bird flu is diagnosed on day one. Here are the same lungs three days later. You can see how they have collapsed. It was a very fast process, only 72 hours from initial symptoms to death.”
Graphic, terrifying images. The transformation from nice white lungs to a blackened blur took a mere 72 hours. It becomes painfully obvious now why immediate treatment is of the highest importance to raise survival chances.
The first recorded H5N1 case in humans was reported from Hong Kong to the World Health Organization, WHO, already in 1997. That year six people in Hong Kong died from the disease. Early 2003 bird flu cases in humans happen again in China and the disease later spreads. As of 11 April 2007 have 291 human bird flu cases been reported to the WHO and 172 of these patients, almost 60 percent, died.
A vaccine against bird flu will require many more years of research and development, if it ever can be made. Meanwhile, the only instant treatment available is oseltamivir, commercially available as Tamiflu from the Swiss pharmaceutical giant Roche, and the not yet approved drug zanamivir (zanamavir is however approved for inhaled use).
Niklas, director of clinical research at the laboratory, and his six co-workers in the team will conduct several types of analyses of samples from healthy persons as well as from H5N1 infected patients. Their laboratory in Bangkok is the pharmacology hub in a research network called the South East Asian Influenza Clinical Research Network. It is a multilateral, collaborative network based on shared principles of respect and commitment to advancing treatment and control strategies for influenza through quality clinical research.
Its partners include hospitals and institutions in Indonesia, Thailand, Vietnam, US National Institute of Allergy and Infectious Diseases – NIAID, Oxford University, Wellcome Trust and WHO.
The main funders are NIAD and Wellcome Trust. The network does not accept direct financial support from pharmaceutical concerns or other for-profit entities.
Test persons will receive oseltamivir and zanamivir in different dosages, including some combinations of the medicines, over varying timeframes.
Hopefully this will yield valuable data how to fine tune the drugs, and what dosages work best in different circumstances, to become as efficient as possible against bird flu.
The first study began November 2006. It is a pharmacokinetic study of loading dose oseltamivir in healthy volunteers. It was conducted at the Faculty for Tropical Medicine, Mahidol University in Bangkok, where the laboratory is located. Some 2 500 samples are being analyzed with first results expected shortly.
“A drug’s efficiency peak is followed by a slowdown to a lower stage until a new dose is taken. In this study we want to find out with what loading doses we maintain the best longtime effect.’
Their second bird flu study will compare a standard to a two-fold higher dose regimen of oseltamivir treatment of both avian influenza and severe human influenza in hospitalized children and adults. This study will provide new knowledge about influenza diagnosis, pathogenesis, and responses to antiviral therapy. This study starts in the first quarter of 2007 and is conducted at 11 hospitals in South East Asia.
“Our third study is probably the most useful and detailed one. Healthy volunteers will receive oseltamivir as well as zanamivir,” says Niklas.
“We consider more studies, for example one which would look at intravenous medication on bird flu patients in Indonesia. But a decision about future studies has not yet been taken in our research network steering committee,”
It was the leading role in worldwide malaria research at Dalarna University, their home institution in Sweden, which brought the couple to Bangkok from a quiet Borlänge in the summer 2003. Both were hired for five years as analysts in a malaria drug measurement programme by the Wellcome Trust – Mahidol University – Oxford Tropical Medicine Research Programme at Mahidol University. They were successful at developing new assays for malaria drugs, and were asked to conduct the influenza drug measurement for the South East Asia Influenza Clinical Research Network.
“Nice propaganda for our laboratory to be invited for the influenza research project,” comments Niklas.
Niklas Lindegardh has a PhD in analytical chemistry from Uppsala University while his wife Anna Annerberg is an engineer in chemistry with emphasis on analysis.She is currently working on her doctoral thesis along with the daily duties at the new laboratory, which is in a connecting building next to where they did malaria research.
“This laboratory is larger and we have acquired more sophisticated analysis equipment,” explains Niklas.
“Totally we have spent around 6 MSEK on instruments and technology. And we have been audited and approved by an independent agency, which is reassuring for us and our partners.”
“I am often invited to give lectures when I make visits to Sweden. That is one way to spread the word what we do here. And I am also supervising two Swedish PhD students.”
“Another example of feedback at home is that a third Swedish colleague is due to arrive at the laboratory later this year.  Recently Niklas and Anna have received a new stamp of approval that their pharmacokinetic research is excellent. Plans are underway to create an international malaria research network with the Asian center here in Bangkok,”
“We are in discussions about that. This network would be supported by grants from the Bill & Melinda Gates Foundation and Wellcome Trust. The idea is to analyze one or a few drugs per laboratory which is a good idea as it is an efficient way to conduct studies,” concludes Niklas.
 It seems that the stay here can be long and fruitful for the Swedish couple as well for those who risk H5N1 infections and malaria parasites. The latter is the third after aids and tuberculosis measured as humanity’s worst killers. Between one and three million people die of malaria every year and 400 million people get the disease annually, children suffer worst and have the highest mortality rate among malaria sufferers.

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