The childrens' deaths were a mystery until the researchers went back and checked samples from the boy and found avian influenza virus.

"These cases suggest that the clinical spectrum of influenza H5N1 is wider than previously thought, and therefore they have important implications for the clinical and public health responses to avian influenza," the researchers wrote in the New England Journal of Medicine.

"The finding came in late 2004 after we tested several hundred samples," Dr. Tran Tinh Hien, the deputy head of the Ho Chi Minh City Hospital for Tropical Diseases and one of the study's authors, told Reuters.

The finding was part of a research programme between Britain's Oxford University and several hospitals in Vietnam to look into serious tropical diseases there, including the cause of encephalitis in the south, he said.

Hien noted that influenza viruses in general were known to cause encephalitis and can damage the respiratory, nervous and digestive systems as well as the heart, kidney and liver.

"But we have not found encephalitis among the patients who died recently from bird flu in Vietnam," Hien told Reuters.

MYSTERY INFECTION

It is not clear how the children became infected.

"At the time of the children's illnesses, the family owned apparently healthy fighting cocks. Many chickens and ducks were present in the hamlet and canal during early 2004, but none were ill," the researchers wrote.

"Only if the incubation period was unusually long could sister-to-brother transmission be implicated," they wrote.

"Nevertheless, the isolation of virus from a rectal specimen is a major source of concern, since it highlights a potential route of human-to-human transmission, especially in combination with crowded living conditions and diarrhoea."

What the World Health Organization fears most is that the virus could mingle with either human or pig influenza viruses, for instance by infecting a person who also had human flu, and acquire the ability to pass easily between people.

Such a new strain could kill tens of millions of people.

Given the researchers' finding on the 4-year-old boy, Asia's toll from the H5N1 virus is now 46 -- 33 Vietnamese, 12 Thais and one Cambodian. It has killed 80 percent of people diagnosed with the infection.

Flu experts say some people may not become fatally ill, so it is difficult to calculate a true mortality rate.

State media on Friday said Vietnamese scientists would conduct human tests of a new vaccine against the deadly bird flu virus, after successful results from initial tests on chicken and mice, which produced antibodies.

Vietnam said it may slaughter poultry in its big cities in another tough action in the war against the poultry virus that has spread to more than half its 64 provinces and cities since re-emerging in December and killed 13 people in recent weeks.

However, the virus had caused no new infections in poultry in nine of the affected provinces over the last three weeks, officials said.