Monday, May 02, 2005

H5N1 worry steps up a notch

Both The Independent (UK) and The Globe and Mail (Canada) are carrying stories warning that H5N1 is mutating into a form more likely to cause pandemic disease. The essential facts have been frequently reported on this site (e.g., here and here) and on Henry Niman's Recombinomics site (example) , so they are not "new" developments. The main facts are the drop in lethality in north Vietnam, the change in cluster number and size, and some evidence of genetic change in the HA protein of the virus (loss of an amino acid, presumably in the polybasic cleavage site). What is new is the tone of worry seeping into WHO's and CDC's public pronouncements. Prior to this both agencies have been hesitant to suggest something was actually happening, as opposed to a theoretical possibility it might happen.

Some examples:
“Both of those observations [lethality and cluster number], if they're true, might indicate that the virus is evolving to be a more efficient human pathogen. A more effective human pathogen,” says Dr. Scott Dowell, the senior official in Southeast Asia for the U.S. Centers for Disease Control.

“We've been following that very, very closely and continue to be quite concerned that that may be the case.... (But) there is frank scientific uncertainty about what it really means.”

Dr. Dowell is director of the CDC's international emerging infections program based in Thailand.


Dr. Dowell, a man who measures his words with care, admits he is more concerned about the threat posed by H5N1 now than he was six months or a year ago.

The apparent changes to the pattern of human infections and an observed change in the molecular makeup of the few virus samples that have emerged from Vietnam this year account for his rising concern.

“The little (molecular) information that we have — and it's from a handful of isolates that have come out of Vietnam — is also concerning,” Dr. Dowell said in an interview from Bangkok.

“What I'm hearing is concern that's paralleling the concern about the change in (disease) epidemiology.” [Helen Branswell in The Globe and Mail]
Here, from The Independent:
'Suddenly it's a very different virus that might suddenly become extremely transmissible,' said Peter Horby, of the WHO office in Hanoi.

He said that it is impossible to predict when that might happen, but there were 'a number of indications' that the virus was already becoming more dangerous.


A second ominous indication is that the flu has been widening its targets in northern Vietnam. Previously it mainly attacked children and young adults, but now it is affecting all age groups.

Then, while almost all previous victims have been infected directly by chickens or ducks, there is a steadily increasing number of clusters of disease, where it appears to have spread between people. There are now at least seven of these, almost all in the northern province of Haiphong. WHO officials say this is unprecedented.

Finally, the virus itself seems to have changed physically. Vietnamese health experts say that it has evolved in the north of the country by dropping an amino acid.

The US Government's Centers for Disease Control and Prevention, which has analysed many of specimens of the virus from Vietnam, adds that new strains of it 'are becoming more capable of causing disease for mammals'.
At the same time, both articles "balance" these unsettling predictions with qualifications that tend to vitiate their force, namely that we know little about what makes for virulence. Niman has taken a dim view of these hedges, insisting quite forcefully that current flu prognosticators are ignoring the evidence that recombination rather than reassortment or random mutation is what is driving genetic variation at this point. This is a controversial position in some quarters, but Niman makes a strong case for it.

What is not clear to me is how this difference of opinion could or should alter preparations or responses. We invite Dr. Niman to lay this out for us.