Why is the world so poorly prepared for a pandemic of hypervirulent avian influenza?

Abstract

The world is now extremely poorly prepared to counter a possible pandemic of hypervirulent H5N1 influenza. Most countries are planning for nothing worse than the Spanish flu pandemic. It may be possible that this can in large measure be explained as a consequence of an epidemic of wishful thinking, which may already have infected the health authorities (and parts of the scientific community as well) in most countries in the world. However, it may also be possible that it can have happened as a consequence of too little contact between medical scientists and more general biologists (natural scientists) from disciplines such as ornithology, ecology and evolutionary biology. This may have led to a lack of proper understanding among medical scientists (and health bureaucrats) of the nature of evolutionary processes affecting influenza viruses, as regards the evolution of host species adaptation, infectivity and virulence properties, and also a lack of appreciation of the ways in which such forms of evolutionary adaptation depend on ecological boundary conditions that have radically changed, comparing the world in 2006 to the world in 1918. While the Spanish flu virus possibly might be compared to a one-headed monster, it may be possible that highly virulent varieties of H5N1 virus might better be compared to a three-headed one because there is evidence of at least three independent virulence factors connected with three different genes. It is highly unlikely that all of the high-virulence alleles will simultaneously mutate and disappear if and when the haemagglutinin gene changes so as to make the haemagglutinin molecule better adapted for the human-type (alpha-2,6-linked) receptor (which is a necessary prerequisite in order that a pandemic with H5N1 virus may start). It is more probable that evolutionary adaptation of the haemagglutinin of H5N1 viruses to the human-type receptor will happen without any simultaneous change in those other genetic properties that now are important for explaining the exceptionally high virulence of certain strains of avian-adapted H5N1 influenza virus. The change of the haemagglutinin molecule from avian adaptation to human adaptation must be expected to act as an additional virulence factor because it will enhance the total number of cells that can be infected (per host organism), increase the total rate of virus replication and potentiate the effects of the other virulence factors already present. The monster will then have four heads, not three, and case fatality rates must be expected to become even higher than they have been until now, perhaps reaching as high as 98-99% (at least in poor countries with less than optimal nutrition). Key words: avian influenza, virulence factors, virulence evolution, risk estimates, emergency preparedness