THE SEARCH FOR SARS'S PAST MAY HELP PREDICT ITS FUTURE
20 May 2003
Source: New York Times, May 20, 2003
The Search for SARS's Past May Help Predict Its Future
By LAWRENCE K. ALTMAN, M.D.
Even though SARS is contained or waning in many countries, scientists are still racing to discover its source. The virus that causes severe acute respiratory syndrome is a newly discovered member of the coronavirus family. Other family members cause mild infections like the common cold in humans and much more serious diseases among animals.
Did the SARS virus jump species from an exotic animal in a food market in China to infect a human and start a chain of transmission that has gone on for seven months? If SARS is an animal virus, did it mutate to cause a new human virus?
Or did the virus go undetected in animal species until now? If so, will SARS become another of the so-called zoonotic diseases like rabies that primarily affect animals and only occasionally infect humans and that often die out in humans on their own?
Or did the virus somehow come from another human coronavirus, perhaps mutating into a more deadly form?
These are among the questions that scientists are trying to answer, in part to help determine whether SARS might disappear on its own or become one more on the long list of endemic diseases that are permanent fixtures in many regions of the world.
In certain ways, the need to determine whether a new disease will become firmly established in a particular area is a new question, because most diseases have been present for centuries, if not longer. Relatively few new diseases have been detected in recent years, and most "new diseases" have turned out to be newly discovered old diseases after further scientific investigation.
Yesterday, the World Health Organization reported more than 7,864 cases, including 643 deaths in 30 countries, plus Hong Kong. The agency has said that Toronto and Hanoi have stopped the spread of SARS and that the disease is waning in Hong Kong and Singapore. But the W.H.O. has also warned that the raging epidemics in China and Taiwan remain a major challenge to containment.
Over the weekend, the W.H.O. brought together epidemiologists from many countries to review the data on SARS. They said that too little was known to predict accurately what the future would hold. Although they said the virus had been found on the feet of a cockroach and in a transitory case in a cat, a participant, Dr. Arlene King of Health Canada, told reporters that her group had found no evidence that animals or insects were spreading SARS.
Finding the virus in an animal species would most likely deal a major blow to the cautious optimism expressed by the W.H.O. officials who have pressed for a world attack on the disease in hopes of driving the disease back to wherever it came from in nature. That may still occur, even if the virus is found in one or more species of animals collected in the food stalls or elsewhere.
But knowledge that a SARS virus lurks in nature will most likely mean that SARS is here to stay, ready to be exported from an affected area elsewhere at any time. Finding an animal reservoir for the virus could also mean that it might disappear for periods and could then be reintroduced to infect humans periodically, making it difficult to control and impossible to eradicate.
The scientific search into the origins of SARS is mainly focused on the wild game and other food markets in Guangdong Province in China, where the world's first known case of SARS occurred in November. Guangdong is an area where merchants commonly sit on stacked cages of exotic animals in food stalls, a setting that could easily allow for the transfer of a virus from animals to humans.
No one knows for certain which person was first infected. A team of experts from the W.H.O. that examined information on the earliest case found an unusual preponderance of food handlers, caterers and chefs, about 5 percent of the first 900 patients, compared with less than 1 percent among patients with normal pneumonia.
Those clues and the Chinese practice of putting exotic species of animals on the dinner plate have led many scientists to theorize that SARS may have originated from handling or eating wild game.
So scientists have collected animals from among the thousands of cramped food stalls in China that sell snakes, chickens, cats, turtles, badgers, frogs and, sometimes, rats.
Immediately after the W.H.O. issued a global alert about the SARS threat on March 12, the United Nations agency assembled teams of laboratory scientists, clinicians and epidemiologists. They have shown an extraordinary degree of collaboration for usually highly competitive scientists.
A month later, the network found that the new coronavirus caused SARS, and on April 13, scientists in Canada announced that they had sequenced the genome of the SARS virus.
Because the molecular structure of the SARS virus does not resemble that of any known coronavirus, scientists theorize that it may have come from wild animals that had never been extensively studied.
As is standard in investigating a new disease, scientists deliberately infected animals with the SARS virus in one avenue of research. Experiments performed on primates in Rotterdam, the Netherlands, helped convince scientists that the new coronavirus was the cause of SARS. And experiments by scientists in Canada have shown that pigs and chickens are not vulnerable to SARS.
Another avenue of research has focused on finding the SARS virus in nature. So scientists have looked in the most logical place in the environment, the food markets in Guangdong. No findings have been reported.
Determining what gives rise to a new infectious disease is different from determining what perpetuates it.
For example, many scientists say they believe that the AIDS pandemic dates from an unknown point in decades past when a primate infected with the ancestor of H.I.V. bit a person or passed the virus through a wound in someone's skin. Then the AIDS virus was transmitted over time through sexual intercourse, intravenous drug use, from mother-to-child and contaminated blood transfusions to cause one of the worst pandemics in history.
Finding the SARS virus in an animal would still not tell scientists how the first person became infected with SARS, and health officials would have to determine whether the virus from animals was continuing to fuel the human epidemic. So far, the W.H.O. says, human coughs have clearly been the principal means that humans have spread SARS around the world.
Whether SARS will lead to a pandemic like AIDS cannot be predicted.
Dr. Julie L. Gerberding, the director of the Centers for Disease Control and Prevention, has said that health officials will need to remain vigilant against the danger that one case may cause an explosion at any time. So if SARS is here to stay, fire brigades of health workers will be needed to squelch brush fires every time a case is imported into a country.
Dr. David L. Heymann, the executive director of communicable diseases at the W.H.O., has repeatedly urged health officials to mount the strongest attack they can against SARS now, because they may never have another opportunity to contain it and prevent constant seeding from endemic countries to start outbreaks elsewhere throughout the world.
While Dr. Heymann has expressed optimism from the start about the ability to contain SARS, he has also been realistic, saying that finding an animal reservoir may make it impossible to contain SARS. Dr. Heymann said he expected the crucial information to come from Guangdong, where the disease has spread the longest. China now says there have been fewer than five new cases each day in recent days in Guangdong, an encouraging sign, even if an animal reservoir is found there.
But many epidemiologists are skeptical about the figures, because China has not given the W.H.O. full information about SARS in Guangdong and it has lied for months about the extent of the disease there.
The battle may not succeed in eradicating the disease, said Dr. Michael T. Osterholm, a professor of epidemiology at the University of Minnesota. But it will buy time while scientists try to develop a vaccine to protect against SARS and antivirals to treat it.
Dr. Osterholm expressed doubt that the virus would weaken as it spread in new waves among humans, saying:
"There is no evidence in infectious disease history that that type of mutation, or attenuation, occurs in the short term. It takes centuries."
People said in the early 1980's "that AIDS could be attenuated," Dr. Osterholm said.
"We have not seen any evidence of major attenuation in H.I.V. in the last 20 years," he said, "and look how many millions of people have been infected."
When an accurate diagnostic test becomes available, scientists will need to test large numbers of animals in the wild to determine the extent of SARS there. But even that information would probably not explain why the virus jumped species at this particular time.
Still another question is whether SARS will become more common at certain times of the year and then virtually disappear like influenza, which tends to cause most outbreaks during the winter in the Northern Hemisphere and the summer in Southern Hemisphere.
The fact that SARS is a respiratory illness reduces the chance of its eradication. Although people can protect themselves against contracting AIDS through sex, there is virtually no way to avoid being in the path of a virus dispersed in a cough at home or in an office. Wearing masks may be popular, but that is no guarantee against becoming infected with SARS.
Dr. Margaret Chan, the health director of Hong Kong, said most experts at the meeting believed that it would take at least a year to determine whether SARS was an endemic disease, and she has "committed to maintain the basket of public health measures for at least a year."