Bird flu studies may undermine credibility

Mar. 9, 2012, Toronto, ON – As influenza scientists and biosecurity experts continue to do battle over controversial bird flu studies, some in the flu world worry arguments being used to push for full publication of the studies may be eroding the credibility of the field.

This concern is not about whether the studies, which show how H5N1 flu viruses can be made to transmit easily among mammals (in this case ferrets), should be published. Many, though not all, flu scientists believe the papers should be published in full to further study of a virus that has alarmed them for years.

But some are uneasy about the way a number of proponents of publication are pursuing that end, at times taking positions that contradict long-held claims flu researchers have made about the importance of H5N1 work. Central to that concern is the assertion being made by a small group of flu scientists that the virus isn’t
as deadly as people have been led to believe, an argument critics see as a double-edged sword.

For years, flu researchers have privately suggested the official estimate of the percentage of human cases that are fatal, hovering just under 60 per cent, is likely off to some degree. But no one knows by how much and few believe the difference is big enough to substantially change thinking about the risk H5N1 poses. Most flu researchers see this virus in a class of its own.

But in this debate, a few scientists following the lead of veteran flu virologist Dr. Peter Palese of Mount Sinai School of
Medicine in New York City have been arguing the death rate attributed to H5N1 is likely “orders of magnitude” too high.

(To make an order of magnitude change, you have to move the decimal point one position to the left. So if this argument is correct, and there isn’t hard data to prove it is, a rate of 60 dead out of every 100 infected might become six out of 100 or six out of 1,000 or six out of 10,000. To put that in context, the Spanish Flu pandemic of 1918 is estimated to have killed two of every 100 people infected but seasonal flu kills fewer than one in 1,000 people infected.)

Claiming H5N1 isn’t dangerous is wielding a weapon that can as easily inflict an unintended wound on influenza research as score a victory in the battle to get the flu papers published, some in the flu world say.

Dr. John Treanor, an expert on influenza vaccines at the University of Rochester in northern New York State, explains the problem with the logic: “If you really believe that the intrinsic lethality of the H5 viruses has been overestimated to such a degree that actually H5 infections are no more serious than regular flu … why are you spending all this money studying it?”

Dr. Ilaria Capua, a prominent avian influenza researcher from Italy, agrees. “I don’t know if the scientists are aware that this could really negatively impact our funding. I don’t think that they really can see this.”

Pressing the claim is also potentially fuelling distrust at a time when the public may be receptive to the notion that flu and pandemics have been vastly overhyped.

After years of warnings that a catastrophic H5N1 pandemic might emerge, what materialized in its stead was the 2009 H1N1 pandemic. It is nearly three years since it started and the allegations that the flu world had been crying wolf for years are only starting to die down.

Researchers who assessed the H1N1 pandemic’s impact in terms of years of life lost argue its toll was greater than the public realizes. But to many, it seemed like a non-event. In Europe, the World Health Organization was pilloried for categorizing the outbreak as a pandemic and faced allegations it did so to help pharmaceutical companies sell vaccine and antiviral drugs.

Dr. Nancy Cox, head of the influenza division at the U.S. Centers for Disease Control, sees the danger. “There is fertile ground for the sort of belief that there’s been hype of H5N1’s severity and the potential for a severe pandemic to occur.”

“And I think that when one really steps back and looks at what we have learned from the patients who have been infected (with H5N1) since 1997 and the seroprevalence studies that have been done carefully and the laboratory work that’s gone on for many, many years, I see an H5N1 virus that really does pose a pandemic threat,” she says.

“Add potentially the pandemic could be worse by quite a bit than the 1918 pandemic, which was a very bad pandemic.”

(A seroprevalence study searches for missed cases by looking for antibodies in the blood of people exposed to a pathogen, in this case H5N1. A person who has antibodies, who survived infection, is said to have seroconverted.)

Capua also sees the public relations risk here.

“I think this to and fro, ‘It’s really dangerous’ and ‘No, maybe it’s not’ and ‘Palese is saying there are many more people who seroconverted,’ oh but ‘No, then, we’re not sure,’ it really does … make people believe this is like a big hoax,” Capua says from Padua, where she runs an avian flu reference laboratory for the World Organization for Animal Health.

“H1N1 backfired on influenza in general, and particularly on our research work. Because … everyone was saying the next pandemic was going to kill us all, and what happened? Not nothing, but something that wasn’t even comparable to what was being suggested or what the scientists were concerned about.”

Treanor sees inconsistencies too in arguments being made about how much risk the lab-made viruses might pose to humans based on studies in ferrets. Since the U.S. National Science Advisory Board for Biosecurity urged that details of how the work was done be withheld to prevent others from repeating it, a number of proponents of publication have downplayed the ferret model, even though it is widely used and accepted as the best animal model for flu.

Treanor says flu scientists can’t have it both ways. If the studies were worth undertaking, and worth publishing, the flu community must believe ferrets tell them something important about flu in people. “Why would you even do it if you don’t believe that the ferret is going to tell you something about transmission in humans?” he asks.

“If you believe the ferret data is worth having, if it’s a study that was worth doing in the first place, you also have to believe that those viruses are potentially quite dangerous. I don’t see any way of escaping that conclusion,” Treanor says.

Capua is also concerned about the shifting nature of the claims about what at least one of the studies found. Last week lead author Ron Fouchier, a flu virologist from Erasmus Medical Centre in Rotterdam, the Netherlands, gave a talk in which he “clarified” points that have been made public about his unpublished findings.

But some of his clarifications contradicted statements he was earlier quoted as making. For example, last fall Fouchier said the lab-made virus spread among the ferrets as easily as seasonal flu, but last week he said it transmitted poorly among the animals.

“I am completely confused,” Capua admitted about the new information. “Because it’s pulling in too many directions. And people will really think that there’s something else behind it.”