Study says new H5N1 strain pervades southern China

Nov 3, 2006 (CIDRAP News) – A new subtype of H5N1 avian influenza virus has become predominant in southern China over the past year, possibly through its resistance to vaccines used in poultry, and has been found in human H5N1 cases in China, according to researchers from Hong Kong and the United States.

The rise of the "Fujian-like" strain seems to be the cause of increased poultry outbreaks and recent human cases in China, according to the team from the University of Hong Kong and St. Jude's Children's Research Hospital in Memphis. The researchers also found an overall increase of H5N1 infection in live-poultry markets in southern China.

"The predominance of this [Fujian-like] virus appears to be responsible for the increased prevalence of H5N1 in poultry since October 2005 and recent human infection cases in China," says the report, published this week in the Proceedings of the National Academy of Sciences.

But other disease experts said they could see no evidence that the new strain increases the risk of a human influenza pandemic or is more virulent than other H5N1 strains. Meanwhile, Chinese authorities rejected the report, while a World Health Organization official in China renewed previous complaints that the Chinese have been stingy with information about H5N1 in poultry.

Infection rate in market poultry rises
The research team, including Yi Guan of the University of Hong Kong and Robert Webster of St. Jude's, tested more than 53,000 birds from live-poultry markets in six southern Chinese provinces from July 2005 through June 2006. About 2.4% of the birds (1,294 of 53,220) tested positive for the H5N1 virus, more than double the 0.9% positive rate in the preceding 12 months, according to the report.

The researchers analyzed the genomes of 390 (30%) of the 1,294 virus isolates and found that 68% (266 of 390) of them were in the new Fujian-like lineage. The prototype of this lineage was detected in March 2005, and few viruses like it were found in the ensuing few months. But the prevalence of the strain increased dramatically starting in October 2005, until it constituted 103 of 108 isolates tested from April through June of this year.

The team also determined that the hemagglutinin genes of five recent human H5N1 viruses from different Chinese provinces belong to the new strain. In addition, 16 poultry and wild-bird viruses from Hong Kong and two poultry isolates from Laos and Malaysia were of the same type.

To assess the effects of China's poultry vaccination program, the scientists tested serum samples collected from 1,113 market poultry in two provinces between November 2005 and April 2006. Hemagglutination inhibition testing showed that 16% (180) of the samples had antibodies against a 2002 strain of H5N1.

A subset of 76 of the 180 positive samples was then tested for neutralizing antibodies against the Fujian-like strain and two other recent H5N1 strains. Most of the samples had low levels of antibodies against the Fujian-like strain, though they had relatively high levels for the other two strains. The findings suggest that chickens in southern China "are poorly immunized against [Fujian-like viruses in comparison with other sublineages," the report states.

All the analyzed Fujian-like viruses had molecular characteristics that indicated sensitivity to oseltamivir, the first-choice antiviral drug for H5N1 infection. In addition, only six of the viruses had a mutation that confers resistance to amantadine, an older antiviral drug used to treat flu.

The authors contend that their findings show that the spread of the Fujian-like strain "has initiated a new transmission wave in Southeast Asia," comparable with the first wave in the region in early 2004 and the spread of H5N1 to Europe and Africa following China's Qinghai Lake outbreak in the spring of 2005. They say it is to blame for recent poultry outbreaks in Laos, Malaysia, and Thailand and for recent human cases in Thailand.

They also argue that poor results in China's poultry immunization program might have contributed to the rise of the new strain. "Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage," they write.

"The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures," the authors conclude.

Experts see no effect on pandemic risk
But the new findings do not signal an increase in the already serious risk of a human flu pandemic, according to Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.

"The key piece to the situation documented in this paper is that while there is a new strain, there's no evidence that it's more pathogenic or virulent than other existing strains, and there's no evidence that somehow we've selected out for a strain that is more likely to be transmitted to and by birds," Osterholm said.

"At this point, I see no data that support that this will contribute to increasing the risk of a human pandemic or worsening the situation with wild birds and domestic poultry in Asia," he added.

Michael Purdue of the World Health Organization's global influenza program expressed similar views, according to an Oct 30 Bloomberg News report. "We know that strains of flu supplant and replace other subtypes over time," he told Bloomberg. "In terms of human risk, there's nothing to suggest that there's more or less risk than there was before."

Joseph Domenech, chief veterinary officer for the United Nations Food and Agriculture Organization (FAO), said the FAO is checking whether vaccines in China are effective against the Fujian-like strain, according to the Bloomberg story.

Chinese officials reject study
Chinese officials rejected the study this week. The nation's Agriculture Ministry called the researchers' claims "totally different from the real situation," according to a report yesterday by China Daily.

"Gene sequence analysis shows that all the variants of the virus found in southern China share high uniformity, meaning they all belong to the same gene type," the ministry said. "No distinctive change was found in their biological characteristics."

The research report prompted Julie Hall, a WHO official in Beijing, to complain that China has been too reluctant to share H5N1 virus information and samples from poultry, according to news services.

"There's a stark contrast between what we're hearing from the researchers and what the Ministry of Agriculture says," Hall told the Associated Press. "Unless the ministry tells us what's going on and shares viruses on a regular basis, we will be doing diagnostics on strains that are old."

The Agriculture Ministry, in the statement quoted in China Daily, insisted it has been freely sharing virus information and related developments with the world.

Smith GD, Fan XH, Wang J, et al. Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci 2006 (published online Oct 30) [Abstract]

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