China shares its bird flu questions

We've written here about China's failure to share viral isolates, but we hope we've also made clear that many Chinese scientists have been forthcoming in sharing much other scientific information with colleagues in other countries about their experience with bird flu. A good example of interesting and valuable information has just appeared (published Ahead of Print in CDC's journal Emerging Infectious Diseases). The paper has details on six H5N1 cases that occurred in China between October 2005 and October 2006. The cases were all in urban areas and had no known exposure to sick poultry or poultry that died from illness. They were among a total of 20 H5N1 cases in China reported in that period.

The Chinese investigators, with the collaboration of a scientist from the US CDC, interviewed patients and/or their relatives, reviewed medical records examined households and venues visited by patients in the two weeks prior to the onset of their illnesses (all but one of the cases died). A standardized survey instrument was used to collect the data from the patients or next or families:

Particular attention was paid to potential exposures such as contact with well-appearing, sick, or dead poultry; visits to poultry markets; or contact with persons with febrile respiratory symptoms in the 2 weeks before onset. A rural case was 1 that occurred in a village resident; an urban case was 1 that occurred in a city resident. (Yu et al., Emerging Infectious Diseases)

A Chinese city is considerably more populous than the average European or American city. The patients came from 6 different cities in 5 different provinces and the average population of the 6 was 8.3 million people. All patients were adults, ranging in age from 21 to 41, median 30 years old. None of the patients had contact with anyone with fever and respiratory disease. 136 close contacts of the patients, 389 healthcare workers and 115 people working in the poultry markets visited by the patients were under medical observation for 2 weeks. Five febrile illnesses developed in contacts but none were serious and none had evidence of H5N1 infection by RT-PCR of respiratory secretions or paired acute and convalescent serum samples. And 5 of the 6 had no direct contact with poultry. But there was some poultry association with all of them:

One patient prepared freshly slaughtered chicken that she purchased for cooking at a live (wet) poultry market. No patients kept poultry or other animals at home, and no poultry or poultry outbreaks were identified in their neighborhoods. Five patients had visited wet poultry markets within a week of illness onset, and all had visited a wet market during the 2 weeks before their illness. Three patients visited wet markets at least once a day before illness onset. Only 1 patient (case-patient 5) had any travel history in the 2 weeks before illness onset. That patient had visited his parents' home in a rural area, where healthy backyard poultry were kept outside the house, and he had visited a wet market in the same area 2 weeks before illness onset.

The data suggest visits to wet poultry markets are a risk factor for urban cases in China, although not the only one:

None of the 6 case-patients had known direct contact with poultry that were sick or died of illness. Two patients (case-patients 1 and 3) had no identified potential exposures except for visiting a wet poultry market during the week before illness onset. Four other case-patients visited wet markets, although other exposures could have potentially led to virus transmission. Case-patient 2 was an egg seller and could have also been infected by contact with fecally contaminated eggs. In 2005, influenza A (H5N1) virus was isolated from eggs brought to China by travelers from Vietnam (11). Case-patient 4 could potentially have been exposed to the virus through preparation of freshly slaughtered chickens purchased at a wet market. Case-patient 5 could have been exposed to the virus by visiting his parents' home, which had healthy backyard poultry outside, or by transporting eggs. Case-patient 6 could have been exposed to the virus at home, when his wife prepared a freshly slaughtered chicken purchased from a wet market. No epidemiologic evidence suggested human-to-human transmission of influenza A (H5N1) associated with the urban patients.

This isn't a large sample and we don't know is how many other people, of the same age and sex, selected at random in these cities, would have given similar histories (making this comparison is called case-control design in epidemiology). Clearly more needs to be done and these observations raise many other questions.

But the big one for us is this: if wet poultry markets is the true risk factor (and it may be), then of all the people visiting or working in wet markets, why these people?