Report: China had human H5N1 case in late 2003

Jun 22, 2006 (CIDRAP News) – A 24-year-old Beijing man died of H5N1 avian influenza in November 2003, nearly two years before China reported any human H5N1 cases to the World Health Organization (WHO), according to Chinese scientists writing in today's New England Journal of Medicine.

The letter has renewed speculation about how many H5N1 cases might have been missed or not reported in China, especially before late 2005, according to news services.

And in an unusual twist, the New England Journal said the authors asked that the letter be withdrawn, but the issue had already been published. The authors did not explain why they wanted to withdraw the letter, but the journal was investigating, according to an editor's note on the journal's Web site.

News reports said the request to withdraw the article was sent in an e-mail message yesterday morning. Karen Pederson, a spokeswoman for the journal, could not speculate why the scientist made the request, according to the Associated Press (AP).

The letter says the man's illness originally was thought to be severe acute respiratory syndrome (SARS), which was emerging in China in late 2003. Also, the H5N1 strain identified in the case was found to share characteristics with H5N1 viruses from poultry in widely scattered parts of China and even in Japan.

The earliest human H5N1 case in mainland China included by the WHO in its current global case count occurred in October 2005. The WHO launched that count in early 2004, shortly after cases began cropping up frequently.

However, in February 2003, H5N1 infection was confirmed in two members of a Hong Kong family who had fallen ill while visiting mainland China (see link to CIDRAP News story below). The first known human H5N1 cases occurred in Hong Kong in 1997. The virus did not surface again in people until 2003.

Report surprises WHO
WHO officials were reported to be surprised by today's report, which came from eight scientists at four different Beijing medical facilities.

"We will formally request the Ministry of Health to clarify this" and why it has taken more than 2 years for the results to be announced, said Roy Wadia, WHO spokesman in China, as quoted in an AP story yesterday.

In a Canadian Press story yesterday, Wadia said, "We would certainly want much more information as to exactly what happened, who this case was, what the possible source of infection was, where he was infected, the treatment—all the standard questions."

"It raises questions as to how many other cases may not have been found at the time or may have been found retrospectively in testing," he told Bloomberg news in a story today.

A New England Journal editor, Lindsey R. Baden, MD, could not explain the delay in reporting this case but suspected it took the Chinese scientists time to realize they had a novel H5N1 strain and sequence the virus, the AP story said.

"It's to be praised that they are doing this kind of work and sharing it," he told the AP.

Case was suspected to be SARS
In the letter, the scientist wrote, "Because the clinical manifestations were consistent with those of the severe acute respiratory syndrome (SARS) and occurred when sporadic cases of SARS were described in southern China," samples from the patient were tested for the SARS coronavirus. All the tests were negative.

The authors cultured a virus from a sample of the patient's lung and identified it as an H5 avian flu virus. "The genomic sequence of the virus (A/Beijing/01/2003) was determined, and its eight segments were genetically related most closely to corresponding sequences of influenza A (H5N1) viruses that had been isolated from chickens in various regions in China in 2004," the letter states.

Specifically, the segments were most closely related to corresponding segments of H5N1 viruses from Guangdong province (in southeastern China), Jilin province (northeastern China), Hubei province (mideastern China), and Japan.

"These findings," the scientists write, "suggest that influenza A/Beijing/01/2003 may be a mixed virus."

The authors suggest that their findings have important implications for selecting viruses to use in an H5N1 vaccine. "The genetic distance between the isolate reported and the strain currently proposed for vaccine development (A/Vietnam/1203/2004) implies that viruses from different regions may need to be considered in the development of an effective vaccine against influenza A virus," they conclude.

A similar conclusion was reached by the authors of a massive phylogenetic analysis of H5N1 strains from Hong Kong and mainland China, reported earlier this year (see link to February CIDRAP News story below).

Commenting on the letter, the WHO's Wadia told Reuters, "It reinforces what we have known for a very long time, which is that the H5N1 virus has been in the environment of this part of the world for a while, and it's therefore not surprising that you would have these sort of cases."

He added, "In fact, WHO said in February 2004, when China was awash in poultry outbreaks at the time, that it would not be inconceivable that there could be sporadic human cases on the Chinese mainland that may not have been tracked or confirmed."

The eight authors of the letter work at the State Key Laboratory of Pathogens and Biosecurity, the Beijing Institute of Microbiology and Epidemiology, the 309th Hospital of the People's Liberation Army, and the Beijing Genomics Institute, all in Beijing.

Zhu Q-Y, Qin E-D, Wang W, et al. Fatal infection with influenza A (H5N1) virus in China (letter). N Engl J Med 2006 Jun 22;354(25):2731-2 [Full text]

See also:

Mar 13, 2003, CIDRAP News story: "WHO issues alert over atypical pneumonia outbreaks in Asia"
http://www.cidrap.umn.edu/cidrap/content/other/sars/news/atypneumo.html

Feb 10, 2005, CIDRAP News story: "Report depicts China as launching pad for avian flu"

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