Cambodian study suggests mild H5N1 cases are rare

Sep 7, 2006 (CIDRAP News) – Researchers who tested 351 Cambodian villagers after they had extensive contact with avian influenza–infected poultry in 2005 found that none had antibodies to the H5N1 virus, suggesting that it doesn't easily spread to humans and that mild cases are rare.

"Our findings suggest that asymptomatic and mild H5N1 virus infections had not occurred in the population we investigated," says the report, published by Emerging Infectious Diseases. The study was done by an international team of scientists, with Sirenda Vong of the Institute Pasteur in Phnom Penh, Cambodia, as first author. Preliminary results were reported at a conference last March.

Some experts have speculated that the current case-fatality rate for H5N1 avian flu, about 59%, could be inaccurate because mild or asymptomatic cases have gone undetected. Few such cases have been found in the limited number of studies on the topic so far.

The village involved in the new study was the home of a 28-year-old man who had Cambodia's second confirmed H5N1 case. The man, from Banteay Meas district in southeastern Cambodia, died in March 2005.

After his death, Cambodian health officials launched an investigation to find additional cases and identify how the patient was exposed. The researchers said the rural village setting allowed them to study the epidemiologic features of the H5N1 virus in poultry and humans. Focusing on a 1-kilometer radius around the patient's house, the researchers conducted a retrospective survey of poultry deaths immediately after the patient's H5N1 infection was confirmed. Two months later they conducted a serologic investigation of members of 93 households.

Villagers were questioned about recent illnesses in their chickens, and researchers collected samples from sick, dead, and randomly selected healthy chickens. The investigators also interviewed villagers about their exposure to animals and the environment during the previous 12 months and took blood specimens from each of them.

The poultry survey revealed that 42 households were likely to have had an outbreak of H5N1 in poultry, reflecting an overall attack rate of 27% among households with chickens. Only two households reported the simultaneous deaths of ducks, and raising ducks with chickens was not associated with deaths in chickens.

Cloacal specimens from two sick chickens tested positive for the H5N1 virus. The owner of the chickens reported that the man who died of avian flu had spent daylight hours in his compound.

In the serologic survey, investigators found that substantial numbers of villagers had had regular, close contact with poultry or pigs over the previous 12 months. Despite this, none of the villagers reported having had a febrile or respiratory illness during the same period, and none of the residents had antibodies that suggested they had been infected with the H5N1 virus.

The researchers said their finding of little H5N1 transmission between infected poultry and humans is consistent with recent studies among healthcare workers and household contacts of patients. The findings also suggest that none of the villages had an asymptomatic or mild H5N1 infection, they added.

The authors said they couldn't explain why only one person became infected when so many others had similar exposure and did not have evidence of infection. "H5N1 virus transmission in humans may be rare because it only occurs in exposed persons with unique host susceptibilities and a predisposition to an abnormal inflammatory response that results in severe and fatal outcomes, rather than causing a broad spectrum of illness with mild disease and subclinical infections," the article states.

The scientists found that some poultry-keeping practices appeared to affect a flock's chance of contracting the H5N1 virus. Handling poultry, cleaning their stalls and cages, and collecting feathers seemed to reduce infections, while purchasing live poultry seemed to increase the risk.

Though the H5N1 virus does not spread easily to humans, the researchers cautioned that that could change as the virus continues to circulate and evolve, and they called for routine, extensive investigations of all H5N1 outbreaks among humans and animals.

Vong S, Coghlan B, Mardy S, et al. Low frequency of poultry-to-human H5N1 virus transmission, southern Cambodia, 2005. Emerg Infect Dis 2006;12(10) [Full text]

See also:

Mar 27, 2006, CIDRAP News story "Mild H5N1 cases weren't missed in Cambodian outbreak"

Mar 29, 2005, WHO statement on second Cambodian case
http://www.who.int/csr/don/2005_03_29b/en/index.html

Sep 29, 2005, New England Journal of Medicine article "Avian influenza A(H5N1) infection in humans" (see table 2 for results of serologic testing of patient contacts) [Full text]

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