A large cluster of human cases of H5N1 avian flu in Indonesia is raising questions about whether genetic susceptibility explains why some people exposed to the dangerous virus become infected while many more do not.

Scientists have been puzzled by why H5N1 doesn't jump to humans from birds more often, given the vast numbers of exposures people have had to infected poultry in affected countries.

News that six members of one family have been confirmed to have contracted the virus (another likely had it but died without being tested) inevitably points suspicion to some genetic feature of this family's make-up that rendered its members more vulnerable than others in their village in the Karo district of North Sumatra.

"It makes perfect sense. It would not surprise us at all," said Dr. Richard Webby, an influenza virologist at St. Jude Children's Hospital in Memphis, Tenn.

"There's plenty of evidence, not necessarily in influenza, but there are other . . . viruses where there are certainly host factors that predispose someone to more severe disease."

The World Health Organization confirmed details of the cluster Thursday.

A 37-year-old woman from the village of Kubu Sembelang fell ill on April 27 and died on May 4. No samples were taken during her illness or before her burial and it's unlikely the cause of death will ever be confirmed.

Since then, six of her blood relatives have fallen ill - two sons, a brother, a sister, a nephew and a niece. All have tested positive for the virus and five have died. Just how the family contracted the virus is not yet clear.

Clusters of cases are worrisome as they could signal that the virus is transmitting from person to person. But people who live in close proximity often share experiences and exposures. That makes it difficult to interpret whether a cluster is simply a series of bird-to-human cases or something more.

The Indonesian family cluster is the largest seen to date, but a number of groupings of cases among family members have occurred, most recently in Turkey and Azerbaijan.

And a WHO scientist who was involved in the investigations of those clusters said the latter, at least, should serve as a warning for those who want to jump to conclusions about genetic susceptibility.

The emergence of seven cases - some members of a family, some neighbours - in the tiny settlement of Daikyand in April rang alarm bells. While the source of that outbreak hasn't been officially declared, investigators believe the victims were involved in defeathering swans - an illegal activity which survivors of the victims tried to hide from authorities.

If the theory is correct, it was likely exposure, not genetics, that led to that cluster, said Dr. Guenael Rodier, special adviser for communicable diseases to the regional director of the WHO's European office.

"Of course you can imagine that some human beings offer more binding opportunity for the virus than others," Rodier said from Copenhagen.

"It's perfectly legitimate to think about it. But . . . we don't have enough cases today and pathology results to be able to document that."

"We can always explore a hypothesis. But my experience from the field is that often we have simple answers."

Trying to deconstruct family clusters looking for evidence of genetic susceptibility poses unique challenges for disease investigators.

"When you have clusters occur in families, sure, it's telling you something," said Dr. Keiji Fukuda, acting head of the global influenza program at the WHO's headquarters in Geneva.

"It's telling you that there is something different about that family as opposed to other people in the general community.

"But what it doesn't tell you again is whether there are shared exposures, shared conditions, shared behaviours, shared genetic backgrounds, shared local environment which is just different enough from their neighbours to make it so that they get infected as opposed to other people."

Even if scientists started to feel confident that genetic susceptibility may be playing a role, there is little that information can offer public health officials trying to quell outbreaks or lower the pandemic risk posed by the virus.

"When you're dealing with an urgent situation, you're really looking to find what you can change and make it a non-urgent situation," Fukuda said.

"And genetic background is just something that we can't modify."

It also doesn't necessarily say much about what the virus would be like if it mutated and became a pandemic strain, said Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

"We have to understand what is currently happening doesn't necessarily dictate the future," Osterholm said.

Osterholm said he worries people who are drawn to the genetic susceptibility theory may believe that if only a portion of the global population is vulnerable to the virus now, that will protect against it becoming a pandemic strain. But given that influenza viruses mutate constantly, this cannot be assumed to be a static situation, he said.