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The virus responsible for recent bird flu outbreaks — including those that resulted in human fatalities — has become widespread among poultry in Asia, posing a serious threat to animal and human health in the region and becoming difficult to eradicate, according to the findings of a five-year study published in Nature this week.

As a result, write the authors of the study, recent developments "pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required".

The news comes in the same week as new bird flu outbreaks have been confirmed in China and Thailand. Bird flu has also been reported Cambodia and Vietnam in recent weeks.

The researchers, from China, Thailand, the United States and Vietnam, studied the evolution of the bird flu virus, and showed that a single dominant form emerged in 2002. This form was responsible for the 2003–2004 outbreaks in China and seven other Asian countries.

Their study "is a huge stepping stone," says John Oxford, professor of virology at the Queen Mary School of Medicine, London, who told SciDev.Net that he has never previously "known a virus to be traced so cunningly and accurately".

The now-dominant form of the virus is called 'Z' by the researchers. Since its emergence, in both chickens and ducks, it has replaced the 15 other genetically-distinct types of the bird flu virus. This indicates that the virus's rapid evolution is increasing its ability to survive. The authors warn that the 'Z viruses' could continue to evolve "to achieve greater viral fitness."

Two mutations found by the team in most samples of Z virus could make bird flu increasingly difficult to control.

One mutation, found in all human and bird flu viruses in samples from Thailand and Vietnam, confers resistance to a group of antiviral drugs used to treat human influenza. The other could help it avoid the host's antibody response — an aspect of our immune response that helps kill an intruding virus.

Currently, bird flu does not transmit easily from poultry to humans, and there is no conclusive evidence of human-to-human transmission. But this may change, as extensive exposure of the virus to the human population increases the likelihood that it will mutate or combine with a human influenza virus to become more infectious and dangerous to humans.

Furthermore, the researchers say that the bird flu virus can combine its genes with those from a contemporary human influenza virus that is endemic in pigs in southern China. Pigs have been known to provide a 'melting pot' in which human and animal influenza viruses can combine their genetic material. There have been controversial reports of H5N1 in pigs this year, although the Food and Agriculture Organisation said in February that they were unjustified.

"It is imperative that outbreaks of [bird flu] in poultry in Asia are rapidly and sustainably controlled," say the researchers. "Governments in the region face an endemic and recurrent problem that presents a serious threat to human health."

The authors suggest that migratory birds may help the virus to travel quickly across Asia. Bird flu outbreaks have occurred almost simultaneously across the region, from China to Indonesia, and in areas that are not adjacent. The timing of outbreaks in China since 2001 has coincided with the general period of bird migration into southern China, and the Z form of the bird flu virus has been found in five species of migratory birds.

"The potential role of wild birds in the maintenance and spread of [bird flu] viruses must be considered in strategies for regional control," say the investigators.

As an example of effective control policy, the authors point to Hong Kong, where preventive measures have included slaughtering chicken, health checks, market patrols and daily door-to-door dead chicken collections. These, they say, have allowed Hong Kong to remain remarkably free of outbreaks in 2004.

Meanwhile, Hong Kong's secretary for health, welfare and food, Yeoh Eng-kiong, resigned this week in the fallout from the SARS epidemic (see Top Chinese scientists 'punished' over SARS outbreak). Cheuk Wing-hing, his deputy director of the Food and Environmental Hygiene Department, however, remains a member of the local government. Together, Yeong and Cheuk were responsible for much of the bird flu control measures enforced in Hong Kong.

Reference: Nature 430, 209 (2004)

Link to full paper by Li et al in Nature

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