Indonesia: probably H2H2H

WHO is now saying what could be inferred from their update yesterday: it is likely that for the first time H5N1 has spread from human to human to human -- three generations of cases, possibly four. This does not mean that a pandemic strain has started but it is another warning signal.

If we take the statement that there has been no change in the virus (let's see the sequences!), then there is another inference we might make. This is just the first time WHO has acknowledged this, not the first time it has happened. Since many cases in Vietnam, China and elsewhere lack solid evidence of close contact with poultry this may have happened many times over (see our post here). The index case here was a vegetable seller in a market where there were live animals, so she wasn't in contact with poultry as an occupation. She might well have contracted the disease from sick poultry at the market but she might also have contracted it from someone else at the market (or elsewhere).

As a result of this cogent evidence in Indonesia, WHO may convene a standing committee of experts to decide if the pandemic alert level should move from the current Phase 3 to a new Phase 4. Here is a description of Phase 3, Phase 4 and Phase 5 (see Flu Wiki for more details):

Phase 3: Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact.

Phase 4: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.

Phase 5: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans, but may not yet be fully transmissible (substantial pandemic risk).

Note: The distinction between phase 3, phase 4 and phase 5 is based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal strain), and/or other scientific parameters.

Many (including us) believe we have been in Phase 4 for some time, but WHO has been reluctant to make the call. It appears now they may do so. We shall see. WHO may still decide there is as yet no sufficient evidence the virus has changed and keep the level at 3. In an interview with Helen Branswell of Canadian Press, WHO spokesperson Maria Cheng said this:

"This is the first time we have seen cases that have gone beyond one generation of human-to-human spread,'' Cheng told The Canadian Press.

"It is an evolving situation and it is possible we would convene the task force if we saw evidence the virus was changing.''

[snip]

Cheng noted the pattern of infections in this cluster seems to point away from a substantial change in the transmissibility of the virus. So do the genetic sequences of two viruses retrieved from this group of people. A statement from the WHO said analysis of those viruses showed "no evidence of significant mutations.'' (Helen Branswell, Canadian Press)

Branswell also interviewed U.S. infectious disease expert D. A. Henderson who was not so sanguine. He points out that the disease spread beyond immediate caregivers to an 18 month old and a 10 year old.

"They all had contact, but it was not the kind of contact we've had described before, where the caregiver would be really heavily exposed,'' he noted.

"And from that standpoint, I find this worrisome. And I think there is an awful lot of information we need about those cases and the circumstances.''

"An awful lot of information" is not what we are getting, however. We do get much handwringing about the difficulty of getting cooperation from fearful and suspicious villagers whose relationship with the central government in Indonesia has been distant and hostile.

"We are still not getting the level of co-operation we would consider optimal,'' Cheng admitted.

Additional WHO personnel are being sent to the village. Included in the group is an expert on social mobilization -- the art of gaining local trust and co-operation in the high tension setting of an infectious disease outbreak.

While you're at it send some of those experts on social mobilization (and social responsibility) to Geneva, Atlanta, Weybridge, Hong Kong, Nashville, Los Alamos, New York. It is not just villagers that aren't cooperating. The genetic sequences need to be released, not just from this cluster but from many others WHO, CDC and individual researchers have not deposited in GenBank (discussion at Flu Wiki here). The lack of cooperation from knowledgeable international and national health officials and eminent scientists has been worse than that of the frightened villagers. It is inexcusable and irresponsible.

To my public health colleagues: Get your own house in order before blaming desperate villagers. Release the sequences and write your papers afterwards. These are not ordinary times. Your resumés are long enough.