Survey suggests avian flu cases may be going unnoticed

Jan 10, 2006 (CIDRAP News) – A survey conducted in Vietnam in 2004 suggests that human cases of avian influenza may be much more common but less severe than indicated by the numbers of confirmed cases, although the findings are not backed by laboratory testing.

In the questionnaire survey of more than 45,000 people in a rural area hit by avian flu in poultry, about 18% reported having had a recent flu-like illness, according to the report in Archives of Internal Medicine.

People who had had direct contact with sick or dead poultry had a significantly higher rate of flu-like illness, defined as cough and fever, than those without such contact. The authors—Anna Thorson, MD, PhD, of the Karolinska Institutet in Stockholm and several colleagues—estimate that 650 to 750 cases were attributable to contact with sick or dead poultry.

The findings "are consistent with a higher incidence of HPAI [highly pathogenic avian influenza] among humans than has been recognized previously," the report says. "The results suggest that the symptoms most often are relatively mild and that close contact is needed for transmission to humans."

The World Health Organization has logged 147 confirmed human cases of H5N1 avian flu, including 78 deaths, since late 2003. Disease experts have often speculated that the true number of cases could be significantly higher because of mild or asymptomatic cases going undetected.

As the authors acknowledge, however, the new study is only suggestive, because it involved no blood testing to verify H5N1 infection in the survey participants.

Capitalizing on a regular demographic survey conducted in a rural area of Ha Tay province of Vietnam, the authors added questions about flu-like illness and contact with poultry. The survey was conducted in the spring of 2004. Participants were asked if they had been sick with a cough and either fever or dyspnea in the previous 6 months and if they'd had any contact with poultry in that time.

About 84% of the 45,476 people surveyed lived in households with poultry, and about 26% (11,755) lived in households that reported sick or dead poultry, the article says.

Just having poultry in the household was not a significant risk factor for self-reported flu-like illness, but having sick or dead poultry in the household was (odds ratio, 1.14; 95% confidence interval [CI] 1.06 to 1.23). Contact with sick or dead poultry was even more significant, increasing the risk by 73% (odds ratio, 1.73; 95% CI, 1.58 to 1.89).

The researchers say the "convincingly higher" risk in people who had direct contact with sick or dead poultry demonstrates that "the flulike illness in our study was not easily transmitted from birds to humans."

The link between illness and contact with sick or dead poultry varied across different age-groups. There was no link at all in children younger than 7, while the association was strongest in adults between the ages of 19 and 45 (odds ratio, 2.36; 95% CI, 2.13 to 2.62).

People who had been sick after contact with sick or dead poultry also were more likely to have missed work or school than those who had been sick without such exposure, the report says.

The authors state, "In the absence of serological data, we cannot state the cause of disease." They say the findings could reflect other illnesses that strike both poultry and humans, such as psittacosis, but in the circumstances, avian flu was the most likely cause of the illness linked to contact with sick or dead poultry.

The data need to be confirmed by population-based serologic studies and by virologic testing in patients with mild infection, the researchers add.

Other disease experts varied in their reactions to the study.

Dr. Frederick Hayden, an avian flu specialist at the University of Virginia, said the study was evidence of the need for widespread blood testing in Asia to learn the true incidence of human cases, according to an Associated Press (AP) report today.

Dr. Gregory Poland, a flu expert at the Mayo Clinic in Rochester, Minn., took the findings seriously. "I would call this the smoking gun," he told the AP. "All of us have been concerned and have guessed that the data we have so far has been the tip of the iceberg."

Poland said the findings suggest that the prevalence of mild human cases in rural areas is "pretty high."

But Michael T. Osterholm, PhD, MPH, was skeptical of the authors' conclusions, given the lack of proof that the survey respondents had avian flu. He is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of this site.

"I don’t believe the study really adds much to our understanding of the possible relationship between H5N1 infection and mild illness," he said. "There is no serologic data demonstrating that the people even had H5N1 infection. Several recent efforts in Southeast Asia show that very few asymptomatic or mild infections occur in settings where we know H5N1 transmission has occurred."

In addition, the connection between reported illness history and the presence of sick or dead birds could be a result of "recall bias, a common problem in similar retrospective studies," he said.

Thorson A, Petzold M, Chuc NTK, et al. Is exposure to sick or dead poultry associated with flulike illness? Arch Intern Med 2005 Jan 9;166(1):119-23 [Abstract]

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