Since a cluster of avian flu cases killed seven members of a rural Indonesian family, it appears likely that there have been many more human-to-human infections than authorities have previously acknowledged.
The numbers are relatively small, and they do not mean that the virus has mutated to pass easily between people - a change that could touch off a worldwide epidemic. All the clusters of cases have been among relatives or in nurses who were in long, close contact with patients.
But the clusters - in Indonesia, Thailand, Turkey, Azerbaijan, Iraq and Vietnam - paint a grimmer picture of the virus' potential to pass from human to human than is normally described by public health officials, who usually say such cases are rare.
Until recently, World Health Organization representatives have said there were two or three such cases. On May 24, Dr. Julie L. Gerberding, director of the U.S. Centers for Disease Control and Prevention in Atlanta, estimated that there had been "at least three." Then, on May 30, Maria Cheng, a WHO spokeswoman, said there were "probably about half a dozen." She added, "I don't think anybody's got a solid number."
Dr. Angus Nicoll, chief of flu activities at the European Center for Disease Prevention and Control, acknowledged that "we are probably underestimating the extent of person-to-person transmission."
The handful of cases usually cited, he said, are "just the open-and-shut ones," like the infections of nurses in the 1997 Hong Kong outbreak and of a Bangkok office worker who died in 2004 after tending her daughter who fell sick on an aunt's farm.
Most clusters are hard to investigate, he said, because they may not be noticed until a victim is hospitalized and are often in remote villages where people fear talking. Also, he said, by the time doctors from Geneva arrive to take samples, local authorities "have often killed all the chickens and covered everything with lime."
The WHO is generally conservative in its announcements and, as a U.N. agency, is sometimes limited by member states in what it is permitted to say about them.
Still, several scientists have noted that there are many clusters in which human-to-human infection may be a more logical explanation than the idea that relatives who fell sick days apart got the virus from the same dying bird.
In a letter published in November in Emerging Infectious Diseases analyzing 15 family clusters from 2003 through mid-2005 in Southeast Asia, scientists from the disease control centers, the WHO and several Asian health ministries noted that four clusters had gaps of more than seven days between the time family members got sick. They questioned conventional wisdom that only one, the Bangkok office worker, was "likely" human-to-human.
Dr. Henry L. Niman, a biochemist in Pittsburgh who has become a hero to many Internet flu watchers and a gadfly to public health authorities, has argued for weeks that there have been 20 to 30 human-to-human infections.
Niman says the authors of the Emerging Infectious Diseases article were too conservative: Even though the dates in it were fragmentary, it was possible to infer that in about 10 of the 15 cases there was a gap in onset dates of at least five days, which would fit with the flu's incubation time of two to five days.
And in a study published last month about a village in Azerbaijan, scientists from the WHO and the U.S. Navy said human-to-human transmission was possible. That conclusion essentially agreed with what Niman had been arguing since early March - that it was unlikely that infections among six relatives and a neighbor, with onset dates stretching from Feb. 15 to March 4, had all been picked up from dying wild swans that the family had plucked for feathers in a nearby swamp in early February.
While Niman is an irritant to public health officials, his digging sometimes pushes them to change conclusions, as it did in the recent Indonesia case. The WHO at first said an undercooked pig might have infected the family, but Niman discovered that the hostess was sick two days before the barbecue and the last relative was infected two weeks after it.
His prodding, picked up by journalists, eventually led the WHO to concede that the virus had probably jumped from human to human.
Niman contends that the largest human-to-human cluster so far was not in Indonesia, but in Dogubayazit, Turkey, in January. WHO updates recorded 12 infected in three clusters, and quoted the Turkish health ministry blaming chickens and ducks. Niman counted 30 hospitalized with symptoms and said that the three clusters were all cousins and that most fell sick after a family party Dec. 24 that was attended by a teenager who fell sick Dec. 18 and died Jan. 1.
Niman also said clusters were becoming more frequent, especially in Indonesia. On June 2, two more emerged there, one including a nurse whose infection has not yet been confirmed. With 36 deaths, Indonesia is expected to eclipse Vietnam soon as the world's worst-hit country.
Dr. David Nabarro, chief pandemic flu coordinator for the United Nations, said that even if some unexplained cases were human-to-human, it does not yet mean that the pandemic alert system, now at Level 3 ("No or very limited human-human transmission"), should be raised to Level 4 ("Increased human-human transmission").
Level 4 means the virus moves between some people who have been only in brief contact, as a cold does. Right now, Nabarro said, any human transmission is "very inefficient."
Level 6, meaning a pandemic has begun, is defined as "efficient and sustained" human transmission.