A new study of human cases of H5N1 avian influenza in Thailand suggests that a number of cases might have gone undetected and that the disease may prey on children disproportionately.

Thai investigators reviewed 610 illness cases that occurred from January through March of 2004 and had features suggesting possible H5N1 infection. Twelve of those were confirmed as H5N1, and 7 of the 12 patients were children younger than 14 years, according to the report, published online by Emerging Infectious Diseases.

Because up to 61% of rural residents in Thailand have regular contact with backyard poultry flocks, "The 12 cases we report likely represent the end result of hundreds of thousands of potential exposures and an unknown number of human cases," the report states. It was written by Tawee Chotpitayasunondh, a pediatric infectious disease specialist at Queen Sirikit National Institute of Child Health in Bangkok, and colleagues.

They suggest that H5N1 cases are not easily detected because the disease has few distinctive clinical features and specific diagnostic tests are not widely available. The illness typically involves pneumonia, but pneumonia due to other causes is fairly common in rural Asia.

"Human infections with highly pathogenic avian influenza may be easy to miss in the context of the regular incidence of pneumonia in much of rural Asia, where the capacity to make specific etiologic diagnoses remains limited," the report says. The authors suggest that these circumstances may explain why "human cases have been few and have been reported only from Vietnam and Thailand."

The World Health Organization (WHO) has recognized 44 human cases of H5N1 avian flu in the past year, including 27 in Vietnam and 17 in Thailand. Twenty cases in Vietnam and 12 in Thailand have been fatal. The official WHO count does not include two cases reported in Vietnam in the past week. A case in a 16-year-old girl was reported last week, and news services today reported a fatal case in a 9-year-old boy. If confirmed, those two cases will bring Vietnam´s total to 46, including 21 deaths.

Disease experts fear that the H5N1 virus may spark a human flu pandemic if it finds a way to spread easily from person to person. Only one possible case of person-to-person transmission has been recorded so far.

The Thai investigators examined all cases in the first 3 months of 2004 in which patients were hospitalized with pneumonia or influenza after exposure to sick poultry. They classified cases with laboratory evidence of H5N1 infection as confirmed. Cases in which patients had been exposed to sick poultry and had either severe pneumonia or laboratory evidence of influenza A, but without confirmation of H5N1, were defined as suspected.

The researchers found 12 confirmed and 21 suspected H5N1 cases among the 610 potential cases reported from 67 of Thailand´s 76 provinces. Eight of the 12 confirmed case-patients died. The median age of the confirmed patients was 12 years (range, 2 to 58) and that of the suspected patients was 33 (range, 1-67).

All the confirmed patients came from villages where abnormal chicken deaths had occurred, and nine lived in houses where backyard chickens had died unexpectedly, the article says. Eight patients had had direct contact with dead chickens.

All the case-patients had fever, cough, and dyspnea when they were hospitalized, and 5 of the 12 had myalgia and diarrhea. Chest radiographs were abnormal in all the cases. In the late stages of the illness, nine patients suffered respiratory failure and five had cardiac failure. The patients who died had a significantly lower lymphocyte count at hospital admission than those who survived.

The 12 patients were all treated with broad-spectrum antimicrobials, and seven were also treated with the antiviral drug oseltamivir. Two of the patients who received oseltamivir survived the illness. The survivors started oseltamivir treatment a median of 4.5 days after the onset of symptoms, versus 9 days for those who died despite treatment with the drug.

"We advocate using this agent in the early treatment of case-patients with suspected H5N1 influenza, in agreement with the recommendations of WHO," the authors say.

The investigators advocate specific testing for H5 influenza when a patient has a history of contact with sick poultry, young age, pneumonia and lymphopenia, and progression to acute respiratory distress syndrome.

The researchers suggest that recent H5N1 cases have been more severe than the 18 H5N1 cases that occurred in Hong Kong in 1997. Six, or 33%, of the Hong Kong patients died, as compared with 68% of patients reported in 2004 at the time the report was written. "Several lines of evidence indicate that the H5N1 viruses have evolved to more virulent forms since 1997, with different antigenic structure, internal gene constellations, and an expanded host range," the report states. "This virologic evolution may be a factor in the persistence of H5N1 viruses in the avian populations."

Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, et al. Human disease from influenza (H5N1), Thailand, 2004. Emerg Infect Dis 2005 Feb;11(2) [Full text]