HKU drug cocktail for bird flu ups survival rate fourfold in mice
A University of Hong Kong research team says it has found a possible new way of treating bird-flu infections in humans after a drug-cocktail trial on mice proved effective.
The team, led by the university's head of microbiology, Yuen Kwok-yung, and colleague Zheng Bojian, found that the use of three drugs in combination on mice infected with H5N1 virus raised their survival rate fourfold, compared to those treated with only one drug.
The findings, said by the team to be the first such breakthrough in 10 years, will be published tomorrow in US science journal the Proceedings of the National Academy of Sciences.
'In the last 10 years, no treatment regimen has worked in patients. Even in mice, no regimen has worked if the treatment is delayed beyond 48 hours,' Professor Yuen said.
'Tamiflu has been used on many patients but the mortality rate is still high at 50 to 80 per cent. This study suggests a new cocktail treatment is effective in mice.
'Hong Kong does not have any [bird flu] patients so we can't test it on humans, but experts elsewhere can consider using it in a human trial.'
The team injected 1,000 lethal doses of the H5N1 virus into each mouse. The dose normally kills 50 per cent of all infected mice within 14 days. It did not treat the mice until 48 hours after they were infected.
Three mice were given a cocktail of three drugs: an antiviral called zanamivir, or Relenza, and two anti-inflammatory agents - a Cox-2 inhibitor called celecoxib and another drug used to treat inflammation of the digestive tract called mesalazine.
The survival rate of the treated mice was 53.3 per cent, compared to 13.3 per cent for mice treated only with zanamivir.
The cocktail therapy is also helpful in controlling the 'cytokine storm', a severe immune response that can kill H5N1 patients and is triggered by the virus.
Professor Yuen said zanamivir alone only suppressed the viral load but did not suppress the cytokine storm. 'But with the combination, both the viral load and cytokine storm are suppressed and the survival rate increases. All three drugs have very few side effects if they are taken by patients for only 14 days. And they are readily available,' he said.
William Chui Chun-ming, education director of the Society of Hospital Pharmacists, said the study was a good start but human trials would be needed.
Mr Chui said the Cox-2 inhibitors could control the immune system and the effects of cytokine. The overproduction of cytokine, or the 'cytokine storm' kills patients by causing multiple organ failure.
The World Health Organisation recommends using Tamiflu to treat bird flu. But scientists are racing to find alternative treatments given the virus' growing resistance to the drug.
The Hong Kong government has 20.5 million doses of antiviral drugs - about 19 million doses of Tamiflu and 1.5 million doses of Relenza.
The H5N1 strain of bird flu first jumped the species barrier to humans in 1997 in Hong Kong, infecting 18 people, of whom six died. Some 1.4 million chickens, ducks and geese in the city were culled.
Since then it has killed 242 of 385 people infected, most of them in Asia.
Professor Yuen's study was conducted in HKU's new bio-safety laboratory, which became fully operational last year. It was built after the Sars outbreak to facilitate research into infectious diseases.
