May 22 2005
Reports of disturbing changes to the H5N1 virus circulating in Asia is causing great concern and has prompted the World Health Organization (WHO) to urge countries to prepare for a influenza pandemic.
The latest report raises concerns that changes in the molecular and disease pattern could indicate the virus is becoming more adept at infecting people. It also appears that some strains of the H5N1 virus may be developing resistance to oseltamivir, a drug wealthier nations are desperately stockpiling as fears of a pandemic rise.
Dr. Keiji Fukuda, a flu specialist from the U.S. Centers for Disease Control (CDC), who is being seconded to WHO's global influenza program, says that the report signifies the rising concern and the level of anxiety regarding the virus has risen.
The report authors do however concede that they have limited scientific evidence on which to determine whether H5N1 is becoming an even graver risk to mankind, but according to Fukuda they are concerned that that is what might be happening.
These alarming changes are being observed in the northern part of Vietnam where Fukuda was part of a recent three-person WHO mission to the country.
One leading U.S. epidemiologist, Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, says the report contains no single smoking gun to suggest H5N1 is becoming a pandemic strain, but the combined evidence paints a compelling picture that cannot be ignored, and that H5N1 is "headed in the direction that none of us would like to see it go".
The report of a case where the virus was partially resistant to oseltamivir will worry public health officials around the world.
Oseltamivir, sold as Tamiflu, is one of only two antiviral drugs known to work against H5N1 and is the first choice for pandemic planners because it is easier to use than the alternative, zanamivir.
Dr. Frederick Hayden, an antiviral expert at the University of Virginia, insisted it wasn't necessarily disturbing to find limited resistance to the drug because it has also been documented in a small percentage of infections with human flu strains.
Although the finding raises the spectre of a resistant strain of the virus becoming dominant and spreading among people, creating a situation where the world has virtually no therapeutic weapons to combat pandemic flu in the months before a vaccine could be produced.
Hayden also says that human flu strains resistant to oseltamivir are generally less fit and don't transmit as well.
But Dr. Earl Brown, an influenza virologist at the University of Ottawa, said oseltamivir is too new a drug for anyone to assume that pattern will persist across all subtypes of influenza.
He says the indications from laboratory data shows that the virus is a weaker virus when it comes to resistance to the drug, and if that is the case, it is good. But he also says that given the limited experience with the drug, it is not possible to be categorical at this point.
The report also outlined the disturbing changes in infection patterns in northern Vietnam, where this spring there have been more clusters of cases, clusters that lasted for longer periods of time, and a greater age range among human cases.
The changing patterns suggest the virus has altered and among the possibilities is that the genetic mutations have allowed the virus to be transmitted more easily to people in the first place, or among them after a first case occurs.
The molecular analysis of the virus shows genetic changes near what's known as the "receptor binding site" - the point where the invading virus attaches to the cell walls of a host. As flu viruses made entirely of avian influenza genes don't tend to bind well to human receptor binding sites the changes could be a sign that ithe virus is evolving in order to be a better fit. As so little is known about flu, the implications of these changes are unpredictable.
Dr. Frank Plummer, scientific director of Canada's National Microbiology Laboratory in Winnipeg, which sent a team of three scientists to Hanoi says the information is 'pretty sketchy '.
The team, led by Dr. Yan Li, chief of the influenza laboratory, will help scientists at Vietnam's National Institute of Hygiene and Epidemiology analyse blood samples from contacts of H5N1 cases to determine if additional undetected infections have occurred.