Chinese man died three years ago of avian flu, not SARS

Chinese man died three years ago of avian flu, not SARS

Hong Kong

Jane Parry

Chinese scientists have said that a man who died of suspected severe acute respiratory syndrome (SARS) in November 2003 in fact died of the H5N1 strain of avian flu. The information came to light in a letter published on 22 June in the New England Journal of Medicine (2006;354:2731-2).

The letter is the first documented evidence that H5N1 bird flu was circulating in China long before the authorities there confirmed the first human case in the country in 2005. Furthermore, the case it describes precedes the fatal cases of H5N1 bird flu in humans in Vietnam and Thailand. The information in the letter is important because it raises concerns about the degree of openness of the authorities in China in disseminating information about H5N1 bird flu infections and also has implications for the development of a vaccine.

"There have been rumours circulating since 1996 about cases detected and not revealed, but we really don’t know what’s happening in China," said one microbiologist working in the field of H5N1. "Transparency has improved since SARS, but [because of] the way the government is run, with national, provincial, and local levels, we don’t know who has been hiding information such as this."

China’s Ministry of Health also seems to have been kept in the dark about the case and has so far refused to confirm that this was a case of H5N1 bird flu. It says that the results were from a single laboratory and that, in keeping with China’s diagnostic standards, there is a need to conduct parallel tests, which the ministry says are currently under way.

After the letter was published the World Health Organization immediately sent a formal letter to the ministry asking for clarification of what happened and when the tests were carried out. "Through informal contacts we’ve been told that this was the first time the Ministry of Health has heard of it too," said Roy Wadia, WHO’s spokesman in Beijing.

"We want to know all the particulars: what prompted them to test for H5N1 [and] the background and context to the case. It’s a significant case, because it would change the chronology of H5N1 on the mainland. It would put this case at the top of the list, ahead of the cases reported in Vietnam and Thailand not long afterwards. It raises all kinds of practical, academic, and ethical questions," said Mr Wadia.

WHO has had an initial response from the health ministry, giving the name of the man and a few details, Mr Wadia said. "He was described as a People’s Liberation Army (PLA) man. He fell ill on 25 November 2003. Medicine prescribed by the local doctor at the army clinic did not help. He was hospitalised on 29 November 2003 at the PLA 309th Hospital. His situation deteriorated rapidly, and he died on 3 December 2003. SARS tests came back negative. Tests were carried out retrospectively over a period of two years. The virus which was isolated and the gene sequencing strongly suggested H5N1, which was further supported when samples were compared with other samples of H5N1 from Vietnam and other countries."

The new information contained in the letter has a bearing on the development of a vaccine, its authors say. The virus bore a genetic resemblance to other bird flu samples from poultry outbreaks in China as well as Japan in 2004. "These findings suggest that influenza A/Beijing/01/2003 may be a mixed virus," the authors wrote. "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."

However, the letter falls short of providing sufficiently detailed information on the virus to be of direct use to scientists in developing a vaccine. One renowned expert in the field, who spoke on condition of anonymity, said, "The paper includes the phytogenic tree, and that is interesting to know, but it doesn’t provide the antigenic analysis required to prepare a vaccine strain, and so it’s not clear whether or not this strain is so fundamentally different."

* The letter concerns a 24 year old man who was admitted to hospital with pneumonia and respiratory distress in November 2003 and who died four days later. He tested negative for SARS. Lung tissue samples were subsequently cultured for other viruses, and these showed that he had been infected with H5N1 bird flu. The paper does not specify when the virus was isolated from the man’s tissue samples, and it is unclear whether this information has just come to light or whether the tests were done some time since November 2003 and the information has not been disseminated.

Experts working in the field say that the new information is interesting but not surprising. "Those of us working on H5N1 assumed with good reason that the virus has been circulating in China since 1996 and that there would have been human cases before," the expert source said.

The first documented deaths among humans from bird flu occurred in 1997 in Hong Kong, when an outbreak among poultry infected 18 people, killing six, and resulted in the slaughter of over one million birds in late 1997 and early 1998, successfully eradicating the disease in Hong Kong. In February 2003 a 33 year old Hong Kong man died of H5N1 bird flu. His 8 year old son was infected but recovered. The two had recently visited Fujian province in southern China, and during the trip the man’s 6 year old daughter died in Fujian of respiratory illness of unknown causes.

"At the time the authorities said that they must have contracted H5N1 avian flu somewhere else, because they did not have any outbreaks of the disease among poultry," the microbiologist said.

The paper does not specify where the man was treated, but one of the eight authors of the letter, Wei Wang, is from the 309th Hospital of the People’s Liberation Army. China’s army hospitals admit private civilian patients, but information about patients is not automatically shared with the civilian health authorities. "We know that during SARS there was a communication gap between the military hospitals and the Ministry of Health," Mr Wadia said.

On 21 June the journal received several email messages purporting to be on behalf of all the authors and from one of the letter’s authors, Cao Wuchun of the State Key Laboratory of Pathogens and Biosecurity in Beijing, asking for the letter to be withdrawn. As it had already been distributed in print form, and no reason for the request to withdraw was provided, the letter remained on the journal’s website while the journal’s editors investigated.

Two days later the journal’s editor, Jeffrey Drazen, issued a statement saying that Dr Cao had subsequently called and faxed the journal to deny that he had sent the emails. "He has not requested withdrawal of the report, and so it stands as published," the statement said. At the time the BMJ went to press the journal was in the process of securing similar written confirmation from the other seven authors of the letter.