OPTIONS VI: No Evidence For Mild Avian Flu

TORONTO, June 18 -- Highly pathogenic avian flu is rarely transmitted to people and apparently never in a mild or asymptomatic form, a Thai researcher said here.

A study of 901 people who lived near confirmed victims of the H5N1 avian flu strain showed no serological evidence that they had been infected and fought off the disease, Rapeepan Dejpichai, M.D., of the Thai Ministry of Health told attendees at the Options for Influenza Control meeting.

Even those who were in close contact with both infected birds and infected people showed no sign of ever having been infected, Dr. Dejpichai and colleagues found.

The study is consistent with findings in Hong Kong, China, and Cambodia, which showed viral seroprevalence of no more than 10% among poultry workers and people living in villages where H5N1 outbreaks occurred, she said.

But it contradicts a population-based study in Vietnam, published last year, that concluded that mild cases of the virus were likely to be common. (see Mild Avian Flu Transmission May Be Common)

From 2004 through 2006, Thailand had 25 confirmed cases of avian flu in humans, and 17 deaths. Dr. Dejpichai and colleagues interviewed 901 residents of four Thai villages where there had been at least one confirmed human case of H5N1 and an outbreak among poultry.

The participants were mostly male, with a median age of 40; 85.5% were selected by convenience sampling, the rest by random sampling.

Study participants were asked about respiratory illnesses and risk factors, such as exposure to infected birds or the human patients.

The researchers also took blood samples, which were tested for antibodies to the H5N1 virus, using the so-called microneutralization assay and confirmed by ELISA. An antibody titer of greater than 1:40 was considered positive.

The researchers found:

• There were no significant differences between the random and convenience samples.
• 68.1% reported contact with backyard poultry.
• 33.3% reported contact with sick or dead chickens without use of any protective equipment.
• 7.1% reported contact with the infected humans.
• All participants tested negative for H5N1 neutralizing antibodies.

During the time that the human victims were developing the disease, 118 study participants recalled having their own acute respiratory symptoms, Dr. Dejpichai said. Of those, 33% had had contact with sick birds but all had antibody titers less than 1:40 and were considered seronegative for H5N1 infection.

The results suggest that "H5N1 viruses circulating in Thailand during 2004-05 were transmitted inefficiently to humans," Dr. Dejpichai said.

She noted that the study is limited by the large convenience sample, and added that, although microneutralization is the gold standard for flu detection, it is possible that some cases were not detected.

The evidence, including Dr. Dejchipai's study, is mounting that mild or asymptomatic cases of H5N1 don't exist, said Joseph Bresee, M.D., of the CDC, who moderated the session and was not involved in the research.

Some investigators had "the suspicion that the high case fatality rate was because we were missing part of the pyramid," he said. "There were asymptomatic or mild cases that weren't presenting to care, for various reasons."

"More and more people are comfortable with the idea," he said, "that that simply isn't true - that the pyramid is an obelisk or something like that."

The finding is very important for surveillance, he said, because it means public health authorities can focus on places where very sick people are likely to come for treatment - hospitals and clinics.