How much H5N1 infection in Vietnam?

A nagging question about H5N1 infection in Vietnam is whether there is considerably more mild, clinically undetected or inapparent infection than accounted for by only considering the most seriously ill cases admitted to the hospital. Since the most seriously ill are the tip of the iceberg in most human viral diseases this is a plausible concern. Its significance would be that there is more transmission of the virus either from poultry to humans or from human to human than has been conceded at present.

Equivocal evidence to suggest this has apparently been obtained by a joint Vietnamese-Canadian research team working in Hanoi. Using a method called a Western blot, the researchers tested hundreds of stored blood samples to see if they showed evidence of antibodies to H5N1. Rumors are that "scores of samples came back positive." As a consequence Vietnam asked for international assistance:

A team of international influenza experts is in Hanoi, at the invitation of the Vietnamese government, to investigate worrisome signs the avian flu virus known as H5N1 may be adapting in ways that may make it more likely to spark an influenza pandemic, the World Health Organization has confirmed.

The group of about a half-dozen virologists and epidemiologists from the United States, Britain, Japan and Hong Kong will be following up on concerns raised at a special WHO avian flu summit held last month in Manila, spokespersons for the organization said Thursday.

The team will also be analysing some potentially disturbing but hard-to-assess test results that could suggest a significant number of additional human infections have occurred but went undetected. (via Canadian Press)

That's what we know at this point, but it hasn't prevented the spin machine from going into action. Apparently the results aren't that hard to assess for WHO the spokesman:

"These are highly questionable results," said Dick Thompson, director of communications for the WHO's communicable diseases branch in Geneva.

The official explanation for this diffidence is the possibility the Western blot is not sufficiently specific to rule out it is detecting antibodies to other influenza strains than H5N1, although for other viruses "Westerns" are used as confirmatory tests because they are more specific than the usual ELISAs. Westerns are "antibodies against antibody" tests and are not especially easy to do, but are easier and less hazardous than the current gold standard, the neutralization test. Neutralization tests use live H5N1 virus and tissue culture cells. If the subject's serum contains antibodies to H5N1 it will block its infectivity. This is not only a technically demanding test but requires adequate biosafety measures, not available in Vietnamese laboratories. The Canadian team was trying to see if Westerns could substitute for neutralization tests, so this effort could properly be considered a research study.

However that doesn't mean it is of no significance. There is good reason to believe Westerns are both sensitive and specific and would make a good substitute for neutralization assays. The next step is to verify the Westerns with neutralization tests, which will necessitate sending the blood sera outside of Vietnam to a WHO reference laboratory. Without analyzing the results it is hard to understand how the WHO spinmeister is able to dismiss the results so blithely. Indeed the dispatch of a high level team--a half-dozen virologists and epidemiologists from the United States, Britain, Japan and Hong Kong--could hardly be justified if the results and the general situation seemed unproblematic. Once again, WHO is playing the part of the World Reassurance Organization.

Meanwhile a systematic seroprevalence survey in Vietnam and Thailand is long overdue, either with Westerns if prove reliable, or neutralization tests if need be. Let's get on with it.