Flu viruses described as sloppy, capricious, and promiscuous

There are some basic principles in assessing the threat of an influenza pandemic, according to Dr. Danuta Skowronski, a physician epidemiologist at the BC Centre for Disease Control. The first is that influenza viruses are "highly changeable".

"What may be true today of an influenza virus is not necessarily going to be true tomorrow," Skowronski told the Straight.

The Spanish flu of 1918 caused the worst pandemic of the past century, killing between 20 million and 40 million people around the world. Skowronski noted that pandemics occur when a new virus enters the human population and causes serious illness. This has already happened with the H5N1 subtype of avian influenza, which is spreading rapidly across Europe, Asia, and parts of Africa. Since it showed up first in 1996 and again in 2003, more than 100 people have died.

Pandemics also require easy human-to-human transmission, which hasn't happened with the H5N1 subtype. Skowronski noted, however, that all previous pandemics originated with avian-influenza viruses. She also said that wild waterfowl are a constant source of new viruses and suggested the risk increases whenever "intense outbreaks" occur near dense human populations.

"The WHO [World Health Organization] refers to influenza viruses as sloppy, capricious, and promiscuous," Skowronski said.

They are "sloppy" viruses because they often make "errors" in their replications. The viruses' capriciousness is demonstrated by their propensity for changing in unpredictable ways. They are also promiscuous because an infected bird or human produces hundreds of millions of progeny viruses. Skowronski described this process as "accelerated evolution".

She noted that the individual likelihood of a mutation causing a pandemic is extremely low. However, the risk of a random error increases the more often the virus replicates. And this virus, she said, is an "efficient replicator".

"The 1918 pandemic, which was possibly the worst medical holocaust on record, was due to direct adaptation-just a few minor changes again in that virus," Skowronski said. "That was an avian-influenza virus that somehow adapted to people. It had a very strange predilection for healthy young people."

She noted that people between the ages of 25 and 35 suffered the highest "case fatality rate", even though the virus attacked other age groups at higher rates in 1918. That contrasted with the pandemics of 1957 and 1968, in which the greatest mortality rates were among the elderly and the very young. Even during the worst outbreaks of 1918 and 1919, the fatality rate was still less than 10 percent, she said. More than 90 percent recovered without vaccines, antiviral medications, or antibiotics (for secondary bacterial infections).

"That's because it's all about numbers, numbers, numbers," she said. "Even a low risk of dying multiplied by the many millions that were infected translates into large numbers dead. But your individual risk is actually quite low."

Skowronski said pandemics have occurred irregularly every 10 to 40 years, dating back for centuries. She noted there have been 21 "high-path" avian-influenza outbreaks causing severe illness in birds since researchers began tracking them in 1959.

Only seven of these high-path outbreaks involved numerous poultry farms, she said, and only one spread to other countries. The H5N1 subtype, on the other hand, has been identified in more than 40 countries. Eight countries have recorded human cases. "And, again, in terms of human infections due to avian influenza, that's also previously been rare, with only 100 prior to H5N1 emerging," Skowronski said.

There are 16 "H" and nine "N" proteins ("hemagglutinin" and "neuraminidase") on an influenza virus, according to University of Ottawa virologist Dr. Earl Brown. Brown told the Straight that there appears to be a "fairly significant genetic barrier" preventing the H5N1 subtype from becoming a human-adapted virus.

Brown described himself as the only Canadian scientist who works on the molecular genetics for influenza viruses. He said it is "unlikely" on the balance of probabilities that the H5N1 subtype will cause a pandemic. "I've never seen H5s establish themselves in humans," he said. "If H5 did, it would be another thing we haven't seen historically. It doesn't mean it won't happen."

On March 22, scientists reported in the journal Nature that the avian-flu virus can only enter cells deep within the respiratory system, which have a welcoming receptor. The group, led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka, reported that this provided a "rational explanation why H5N1 viruses rarely infect and spread from human to human, although they can replicate efficiently in the lungs".

In a UW-Madison news release, Kawaoka said no one knows if the virus will evolve into a pandemic strain. He added that it would require "multiple mutations". Skowronski noted that true scientists avoid making "dogmatic statements", even though the media, governments, and perhaps even the public prefer more decisive comments.

"Much of what we're doing as scientists in observing what's going on with H5N1 is speculation," she said. "But what we're saying is listen-we're picking up some worrying signals."