Stephen Smith, GLOBE STAFF
1,534 words
29 April 2003
The Boston Globe
THIRD
C.1
English
Copyright (c) 2003 Bell & Howell Information and Learning Company. All rights
reserved.
It all started with the fruit bats, the ones with a weakness for mango and a reputation for nasty table manners.
It ended with 1.1 million pigs slaughtered, 105 humans dead, and the discovery of a new peril to mankind.
When the curtain rose on Nipah virus in 1998, it was a drama in three acts, spotlighting performances from bats, pigs, and humans in a story as old as the first microbes to spread disease and misery on Earth. Somehow the virus catapulted from one species to another and then a third, with profoundly varying health consequences.
Now, disease detectives hot on the trail of the coronavirus implicated in the outbreak of severe acute respiratory syndrome, or SARS, are increasingly suspicious that a similar phenomenon unfolded with that disease, which appeared out of nowhere one autumn day last year on the lower lip of China. They're looking at everything from primates to the exotic reptiles that wind up on dinner tables in southern China as potential routes of transmission for the virus to humans.
"It can't have emerged from the primordial ooze - it just doesn't happen like that," said Dr. Ken McIntosh, chief emeritus of infectious disease at Children's Hospital Boston and among the scientists who in the 1960s discovered coronaviruses that are blamed for up to one-third of all human colds.
Though it sounds like the plot line from a Robin Cook novel, in fact three out of every four newly emerging diseases striking humans originated in animals and somehow jumped from one species to another. Consider: Mosquitoes gave humans the West Nile virus, which killed 284 people in the United States last year. The rare but deadly hantavirus comes from deer mice. The AIDS epidemic began with chimpanzees.
"It seems bizarre, doesn't it? I mean, why should we come into contact with animal viruses?" said Peter Daszak, executive director of the Consortium for Conservation Medicine, an alliance incorporating the Wildlife Trust and departments at Harvard and Tufts universities. "We're massively involved with the animal ecosystem."
The result - viruses and bacteria that perform microscopic sleight-of-hand to adapt to new hosts whose immune systems are especially vulnerable to novel invaders.
The transfer of disease from animals to humans is known as zoonosis, a process fueled by the constantly evolving genetic profile of viruses and bacteria. Because these bugs reproduce so rapidly, they constantly spawn new generations that are slightly different than their forebears.
Most of the time, these variations make little difference, but every now and then a key protein or enzyme change will empower the virus to attack new targets.
"Viruses are fairly primitive organisms and their machinery to duplicate their genetic material is also primitive," said Dr. Gio Baracco, an infectious disease specialist at the University of Miami and the Miami Veterans Affairs Medical Center. "And that machinery makes mistakes. Usually, these mutations have some kind of handicap that doesn't allow them to survive.
"But sometimes, that mutation will increase the ability of a virus to resist a particular antibiotic or to survive in a particular environment or to affect some other species."
That sort of mutation lies at the heart, for example, of the influenza viruses that kill 36,000 people on average every year in the United States.
The genomic structure of a flu virus is like a necklace with a series of charms constituted of gene clusters: Replace one charm with another harvested from a different strain and, voila, a new form of the flu is spawned.
Pigs, it turns out, are remarkably efficient incubators for viruses to mutate into new forms. A pig can be exposed to a flu virus transmitted by a bird and then to a second virus spread by a human. Once both viruses set up shop inside the pig, they can begin swapping genetic secrets, with the result being a viral recombination - and a novel strain of the flu.
"In some cases, what can start off as a relatively isolated incidence of cross-species transmission can result in a significant outbreak, but it's very difficult to predict the course of these diseases at the outset," said Dr. Paul Johnson, an infectious disease specialist at Harvard Medical School. He argues that the real surprise is that animals don't transfer more diseases to humans.
In Malaysia in September 1998, humans were being felled by a mystery infection that arrived with high fever and muscle aches and, in the most dire cases, lethal brain swelling. The disease erupted in the northern part of the Malaysian peninsula, ultimately sweeping across the nation during a seven-month rampage that claimed 105 human lives.
As disease trackers hunted down the origins of the epidemic, they were drawn to a sprawling pig farm in the town of Ipoh, a plantation that came to be recognized as the epicenter of what was branded Nipah virus infection.
Although the definitive transmission route of the illness may never be established, the prevailing belief at the World Health Organization is that the virus originated with fruit bats. Daszak, of the Consortium for Conservation Medicine, has investigated the outbreak and believes the most probable explanation for the migration of the virus from bats to humans involves pigs.
According to this theory, the bats descended upon mango trees that bracketed the farm, leaving behind detritus from their meal. Pigs in their sties feasted on mango leftovers contaminated with bat saliva that carried Nipah virus. While that virus doesn't appear to make bats ill, it causes a respiratory ailment in pigs that manifests with a hacking cough.
Disease specialists found that the human victims contracted the same strain of the virus that had infected pigs.
But then the virus did something that viruses are typically loathe to do: It made people so sick that many died, taking the virus with them. Usually, viruses aim to strike a survival balance in the organisms they infect: They want a home, and they want to rule it, but they don't want to destroy it. In humans, Nipah caused encephalitis, killing half of the people who developed symptoms and infecting them in such a way that the virus was unable to jump from one human to another.
"For some reason, the Nipah virus didn't like the human host in the long term," said Dr. George Saperstein, chairman of the Department of Environmental and Population Health at the Tufts University School of Veterinary Medicine. "It didn't find a mechanism to survive along with the host or a reservoir to hide out between outbreaks."
The spread of Nipah across Malaysia provided potent evidence of the forces that conspire to spread illness.
Some scientists, such as Daszak, argue that viruses in the modern world are more prone to hurdle the species barrier because farming and industry have relentlessly breached ecological barriers that once kept diseases isolated.
And then there is the law of unintended consequences: The attempt to control the outbreak by slaughtering pigs wound up spreading it more quickly.
"If I have 20,000 pigs that are worth $100 a piece and if somebody's going to destroy them all because there's disease in them, and I have a chance to sell them somewhere else, greed becomes a factor," explained Thomas G. Ksiazek, chief of the special pathogens branch at the US Centers for Disease Control and Prevention.
Ksiazek, who studied the Nipah outbreak, is already immersed in unlocking the secrets of SARS. He was lead author of a New England Journal of Medicine article that identified a novel coronavirus as the likely cause of the respiratory illness.
But where, exactly, did that virus come from?
In coming months, he and other scientists will seek to answer that riddle. It is improbable, Ksiazek and other disease specialists said, that SARS derived from animal stocks that are widely traded - pigs or chickens, for example. If it had, it likely would have been identified before, because of the economic implications of such an infection to livestock trade.
So, they will perform old-fashioned gumshoe epidemiology, tracing where the first victims of SARS traveled - and what animals they came into contact with. The lessons from their search could lead to a better understanding of the virus and the methods for treating and controlling the disease.
And it will provide more information about why molecular bugs jump species to species, a process destined to persist regardless of man's interventions.
"It's like getting into the business of trying to stop asteroids heading for the Earth," McIntosh said. "This has been happening forever. There are plenty of other things to worry about - like just getting people to wear seat belts."
SIDEBAR: TWO DIFFERENT ROUTES TO INFECTION PLEASE REFER TO MICROFILM FOR CHART DATA. Stephen Smith can be contactedat stsmith@globe.com.
Caption: As an example of how people come in close contact with animals in some parts of the world, a man delivers a pig carcass to a market in Hong Kong. / AFP PHOTO