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Virus Hunting on the Web

Chlorea in Pakistan, Rift Valley fever in Kenya. news of epidemics spreas through the online “CNN of outbreaks.”

Despite its unsavory reputation as one of the legendary scourges of mankind, yellow fever is primarily a disease of animals-monkeys, in particular. In South America, the virus moves through the canopies of tropical rain forests in enormous waves. Carried by mosquitoes, its primary victims are howler monkeys, which are chimp-sized and notorious for being heard rather than seen. Researchers who study this jungle cycle of yellow fever say that they can tell when the waves of virus are rolling by because dead howlers start dropping out of trees. While the virus periodically finds its way into humans working in the rain forest, there hasn’t been an urban epidemic in this hemisphere since 1942, a situation that has epidemiologists and public health experts holding their breath.

In their worst-case nightmares, a traveler or tourist contracts yellow fever in the Amazon, gets on a plane before symptoms appear and gets off 3,000 miles away, where he or she can be bitten by the local mosquitoes before the disease has been discovered or diagnosed, and the victim effectively quarantined. That such nightmares are not solely the stuff of imagination was demonstrated on the night of June 28, 1996, when a Swiss physician posted a case report on a Web site known as ProMED-Mail. The report was short and pithy: the story of a single unfortunate, unvaccinated tourist, who contracted yellow fever on a boat trip through the Amazon on April 5, and died 10 days later in a hospital in Basel. The fact that such episodes have not yet sparked a new wave of urban epidemics of yellow fever, according to New York State Health Department epidemiologist Jack Woodall, founder of ProMED-Mail, can be attributed to a single factor: “pure luck.”

Welcome to the global village of emerging infectious pathogens, where the bubonic plague can erupt in India, ebola in Zaire, or avian flu in Hong Kong, and any or all could make it to Boston in 12 hours; where a traveler returning home can spread a disease to his family, friends and co-workers before making it to the hospital, perhaps infecting everyone he comes into contact with.

To fight the threat-popularized in such books as Richard Preston’s The Hot Zone and Laurie Garrett’s The Coming Plague-epidemiologists and public health experts have been trying to come up with methods of monitoring diseases that match the electronic rapidity of modern times. Yet because many repressive governments are loath to publicize their health problems, the job of disease reporting has fallen to non-governmental organizations, traditionally the World Health Organization (WHO). But the WHO will not release information on a potential epidemic until it has been reliably confirmed, which can take months. Public health experts who want their news now and not later have learned to rely on Woodall’s ProMED-Mail.

ProMED-Mail (the name represents Program for Monitoring Emerging Diseases) is an Internet, e-mail based system connected by satellite to ground stations and Internet nodes throughout the world. It can be found at www.healthnet.org and anyone can subscribe. Fill in your e-mail address and a dozen postings a day will appear in your in-box-cholera in Pakistan, Rift Valley fever in Kenya, tick-borne encephalitis in Russia, E. coli infections in Wyoming. In the four years since it went online, ProMED-Mail has grown from 40 subscribers in seven countries to 15,000 in 150 and is now considered by experts to be an indispensable, although not wholly reliable, medium for transmitting news of outbreaks and connecting health experts to the far corners of the globe. Meanwhile, the WHO has joined with Health Canada to produce what they call the “Cadillac of ProMEDs,” which was launched in early June.

The ultimate goal of these electronic efforts is what Woodall calls “global transparency” of disease reporting. Ideally, within days of an outbreak, public health officials worldwide will know where and what has happened and be able to mobilize immediately, sending teams to help contain the outbreak at its source or warning local hospitals and ports of entry to watch for travelers who might have to be quarantined. While the Internet is assuredly the way to do it, says Duane Gubler, director of the division of vector-borne infectious diseases at the Centers for Disease Control and Prevention, no one is quite sure yet what form the ultimate monitoring system will take, or who will run it. “This is the wave of the future as far as disease surveillance is concerned,” says Gubler. “Our challenge is how do we assure the quality of the reporting. If we can accomplish that and harness the thing properly, it’s going to be the best thing that ever happened to disease surveillance.”

To initiate a surveillance network that intends to cover the entire world, not to mention the entire spectrum of infectious disease epidemiology, it helps to have wide experience in the field, which is definitely the case with Woodall. He was raised in China by English parents and schooled in mosquito-borne diseases at the London School of Hygiene and Tropical Medicine. He has worked on yellow fever in Uganda and hemorrhagic fever in Bolivia, done lab work in the old Rockefeller Foundation labs in Manhattan and at Yale University in New Haven, and has run virus labs in the Amazon rain forest and in Puerto Rico. Before moving to Albany to take up his post with the New York State Health Department, he spent 13 years as an international health expert working for the WHO in Geneva. “Although I wasn’t just in Geneva,” he says. “I traveled all over the world-China, Africa, all over. Because I was the only virologist in Geneva who spoke Portuguese, I ended up setting up the first AIDS programs in the Portuguese-speaking countries of Africa. I did all kinds of things. I was a jack-of-all-trades.”

Woodall eventually ended up in the WHO branch of epidemiology, surveillance and health statistics, which is where he was when he started down the path that led to ProMED-Mail. After co-authoring a paper on biological weapons disarmament, as Woodall tells it, he ended up on the Iraq desk of the WHO during the Gulf War. In 1993, that assignment brought him into contact with the Federation of American Scientists, which was co-sponsoring a meeting in Geneva with the WHO on a program to set up ProMED centers around the world that could monitor outbreaks of emerging pathogens as well as the kind of disease activity that might signify biological warfare and bioterrorist activities. Woodall was in charge of the task force on communication, whose goal was to determine how best to connect the centers.

While the centers have yet to be funded, Woodall took his part of the project and developed it into ProMED-Mail, with the crucial help of SatelLife, a Boston-based organization founded in 1989 by Bernard Lown. Lown is a cardiologist and inventor-of the defibrillator, most famously-and founder of the International Physicians for the Prevention of Nuclear War, an association that won the Nobel Peace Prize in 1985. After winning the prize, Lown set out to establish a network that would bridge the gap between medicine in the developed and underdeveloped worlds.

Lown decided that the technology needed to accomplish that task was a communications satellite dedicated to the purpose. In 1989, SatelLife became the first nonprofit organization in the world to launch its own communications satellite, HealthSat 1, which was supplanted in 1993 by HealthSat 2. The satellite, roughly the size of a television set, circles the globe every 100 minutes in a “low-Earth” orbit at an altitude of 550 miles. It passes over ground stations anywhere from four to 14 times a day, at which times the ground stations can upload or download messages. When the satellite is over Boston it downloads incoming messages to the SatelLife offices and takes on outgoing mail. The ground stations themselves are simple: desktop computers with a small radio and an omnidirectional antenna. “Uploading and downloading e-mail four times a day doesn’t sound like much today,” says Woodall, “but even today in countries like Zaire with no telephone and no e-mail provider, four times a day is a hell of a lot better than nothing at all.”

In 1994 Woodall was introduced to SatelLife executives, who offered to host ProMED-Mail for free until funding could be obtained. ProMED-Mail officially went online that August with a $50,000 startup grant from the Rockefeller Foundation, $1,000 a month for expenses from the Federation of American Sciences, and SatelLife subsidizing the rest. Woodall enlisted half a dozen chronically overworked and unpaid moderators to serve as editors and to oversee the correspondence and weed out the more obvious rumor-mongering.

After four years, Woodall calls ProMED-mail the “CNN of outbreaks,” a description few epidemiologists dispute. “We have more subscribers from the CDC alone then we have from any other entire country in the world except Australia,” says Woodall. “We have subscribers from NIH, FDA, you name it; they know we’re the place to get breaking news on outbreaks.”

ProMED has proven over the years that if an epidemic breaks out anywhere in the world, you’re likely to hear about it first there, from dengue in Malaysia to a 1996 ebola outbreak in Gabon. If the information does not come from government health agencies, it is likely to come from a physician or missionary working in the middle of nowhere, which was the case with the Gabon ebola outbreak. “We had information from the Central African Republic before anybody else had it,” says Charlie Callisher, a ProMED moderator at Colorado State University. “Not that we go out necessarily looking for it, but there are missionaries out there who read ProMED. They’re thrilled they have it. It keeps them in touch with the outside world, and if they see something funny, they tell us first.”

The story of the Swiss tourist who succumbed to yellow fever is a classic case of ProMED’s impact. The Swiss physician who reported the case got to ProMED only after Woodall noticed a submission the doctor had made to a Web site known as Outbreak (see sidebar: “Epidemiology at the Web Cafe”), for which Woodall serves as chief of the scientific review team. When the physician mentioned he had seen a case of yellow fever, Woodall promptly asked him to post a case report on ProMED, which led to the WHO and Pan American Health Organizations (PAHO) learning of the situation. PAHO informed the Brazilian government, which initiated a vaccination campaign in Manaus to avoid a possible outbreak. “It’s a damn good thing they did,” says Woodall. “Six months later the same thing happened to an American tourist. He had been told to get vaccinated, but couldn’t be bothered. He went to the same area, went fishing on the Amazon, got sick, went through Manaus, waited overnight for a plane, and got back to Tennessee to die.”

After the 1995 ebola outbreak in Zaire, the WHO established Heymann’s EMC, which oversees the organization’s global surveillance networks. The network collects information from some 1,000 laboratory centers around the world, including more than 200 specializing in infectious diseases. “For arboviruses and hemorrhagic fevers,” explains Heymann, “we have 37 labs throughout the world constantly receiving specimens to look for ebola, dengue, and yellow fever. The results are given to WHO and to the country where the specimen originates. We then look to validate the results, and if it’s an outbreak situation, we look to get the necessary groups involved, to make sure the outbreak is addressed and contained.”

The WHO says it receives as many as five unconfirmed rumors a week of new infectious-disease outbreaks, by telephone, newspaper or e-mail. Each rumor is then investigated and a rumor/outbreak list is sent out electronically on a need-to-know basis to relevant personnel at the WHO, its collaborating centers and other public health authorities. These reports, however, are not intended for public consumption. The WHO will only post news of an outbreak on the EMC’s public Web page after confirmation. Because confirmation often requires sending specimens to a laboratory that may be outside the country of origin, the WHO system is notoriously slow at alerting the world at large to outbreaks.

To strengthen the system and accelerate its response time, the WHO has recently joined with Health Canada to create the Global Public Health Information Network (GPHIN), which Heymann says will “really be the system” because it will subsume ProMED within it. GPHIN will include all the reports from ProMED, but also incorporate information gathered from other sources.

GPHIN is the brainchild of Rudi Nowak, a Canadian physician and public health specialist and former director of Canadian quarantine operations. Nowak says that he realized the contemporary world had drastically changed the nature of his business and that the problem had to be addressed. “We’re not talking quarantine the way it used to be,” he says. “People boarded a ship in Europe, for instance, and it took them 11 or 12 days to come to North America, and some got sick and died, and those that were sick were put into quarantine when they arrived. Now people can get anywhere within hours, and they can get exposed to serious pathogens without even knowing it and get back home within the incubation period of the disease.” The way Nowak likes to put it is that quarantine has moved “from the seaport to the emergency room.”

GPHIN uses a search engine to scan the Web continuously for all information pertaining to infectious diseases, including specific sites such as ProMED. The search engine stores the findings under six headings: cholera, salmonella, hemorrhagic fevers, antibiotic resistance, encephalitis, and floods. The latter, says Nowak, “because if you have floods, cholera is just around the corner.”

GPHIN then further breaks the incoming information into three bins, depending on how urgently they have to be addressed: a “hot” bin, for the first report of outbreaks; a “standby” bin, for collateral information on existing situations; and a bin for rejected information, which can include worthless rumors and irrelevant information. GPHIN then extracts the relevant information from each report and places it in an “intelligence” report that can be scanned quickly. This step is currently carried out by humans, says Nowak, but only until commercial artificial intelligence technology is available.

When users enter the Web site, they’ll start with the latest intelligence reports, and if they want more detailed information they can go to the original reports from which the intelligence was gathered. “Initially they can simply come in and say, Let’s look at the cholera bin and see what’s happened around the world in the last 24 hours.’ They can then scan through reports as they come in.” GPHIN is also fully interactive and so, as with ProMED, anyone reading the page who has something important to add can do so.

Nowak and his collaborators officially launched GPHIN in early June, and the system began searching the Web in both French and English. Eventually, it will expand to all seven WHO official languages. What the system won’t do-unlike ProMED-is report to the public. The current system is designed for public health officials and no one else. “We cannot really be accused of being in the business of spreading rumors,” says Nowak. “The information sooner or later will be available to the general public, but it has to be verified. We don’t want to create unnecessary anxiety among the public.”

With a little luck, ProMED and GPHIN will both take care of what CDC arbovirus researcher Paul Reiter suggests has been the regrettable history of infectious disease fighting to date. To put it simply, he says, all the monitoring and surveillance has only served to mobilize the world’s resources to fight “ex-epidemics. Whenever we’ve been sent out to epidemics, we’ve always arrived when the epidemic was pretty much history.” He cites, for example, a 1993 yellow fever epidemic in Kenya, at which the medical cavalry arrived in time to see the last two cases. Or, going way back, a yellow fever epidemic in the Omo River Valley in Ethiopia between 1960 and 1962. “You had something like a million people susceptible to yellow fever,” says Reiter, “with 30,000 deaths”; no one outside Ethiopia, he says, “had the faintest idea until it was all over.” Now with the Internet the news should get out in time to make a difference. “We’re primed,” he says.

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