Saturday, April 23, 2005

Pandemic in slow motion?

It seems to be dawning on Vietnamese and WHO officials that the bird flu pandemic might already be on us. In today's Washington Post we read about the good news/bad news picture of a disease, influenza A/H5N1, becoming less lethal while at the same time perhaps becoming more widespread and easily transmissible. We raised this scenario here, here and here, and Henry Niman at Recombinomics has been hinting at the same thing, pointing out the larger clusters and reduced mortality of the northern Vietnamese cases compared to the southern ones. Now WaPo is catching up:
"The virus could be adapting to humans," said Peter Horby, an epidemiologist with the World Health Organization in Hanoi, the Vietnamese capital. "There's a number of indications it could be moving toward a more dangerous virus."

The mortality rate for bird flu in Vietnam this year is about 35 percent, almost exactly half that of last year, according to Health Ministry statistics. The mortality rate of the 1918 Spanish flu pandemic, by comparison, was less than 5 percent, but the outbreak killed an estimated 40 million people worldwide.

Officials said the drop in the bird flu mortality rate was more marked in northern Vietnam than in the south. While the virus in southern Vietnam is still killing at the same pace as last year, the rate in the area around Hanoi and elsewhere in the north has dropped from that level to as low as 20 percent. Vietnamese health experts said their suspicion that the disease is shifting is further supported by preliminary research showing a genetic change in the virus in the north resulting in the production of a protein with one less amino acid than in the south.
To our knowledge this is the first mention of a genetic difference between northern Vietnam H5N1 and southern Vietnam H5N1. Reading between the lines, it suggests the polybasic cleavage site seen in highly pathogenic avian influenza is shorter in the northern variant. To be infective, the HA (hemagglutinin protein spike) on the virus must be cleaved by the host into two pieces, HA1 and HA2. The enzymes that can fit into the narrow cleavage site of low virulence viruses are found in the respiratory tract in humans or intestinal tract of fowls, but if the cleavage site is "opened up" by some extra amino acids, more tissues can accomplish this and hence become vulnerable to infection, leading to pantropism, that is, infection of many organ systems besides the lung. Thus the nervous system, kidneys and other organs also start to fail rapidly in human infections with H5N1. If this is the nature of the genetic differences, it might mean that the northern variant is less prone to involve other organ systems.

But lower virulence H5N1 is not avirulent H5N1. In addition, much is not known of the specific virulence factors. Moreover, some flu experts think that the virus adapts further once it takes hold in the human population, with the second wave of a pandemic more severe than the first, as happened in 1918 - 1919. Even if the mortality is as low as 5% (probably the upper limit for mortality in 1918 flu), since there is essentially little natural immunity to H5N1 (except an unknown amount against the N1 component), a pandemic could infect 20% to 30% of the world's population, or 1.5 billion people. If only half of those became clinically ill and 5% of those died, it would amount to 40 million deaths, worldwide, roughly 130 Indian Ocean tsunamis.

The early signs of most pandemics are visible if you are watching closely. If you aren't, they seem to burst on the scene with scores, hundreds and then thousands of cases. Maybe CDC and WHO are watching closely. But they have waited so long to turn the wheel, now it is a bit like an auto accident that seems to be happening in slow motion without any ability to do anything but brace ourselves to spin out of control.