When a global outbreak becomes local

For the shoe-leather work of public health, Connecticut officials seek help from Yale’s disease detectives.

By Jennifer Kaylin

James L. Hadler, M.D., M.P.H. ’82, like public health officials around the country, spent last winter reading with only mild concern about an atypical pneumonia outbreak in south China. But then something happened to catapult the illness from “something that bears watching” to an urgent priority.

A student from the University of Connecticut had flown to Germany in March on an airplane with a doctor from Singapore who had been diagnosed with the potentially lethal new illness called Severe Acute Respiratory Syndrome (SARS). Even more alarming, the student was running a fever but continued to attend classes.

“We were facing the possibility of a SARS outbreak on the largest campus in Connecticut,” says Hadler, chief epidemiologist for the state Department of Public Health and associate clinical professor of epidemiology at Yale. “And we had two prominent basketball teams playing in national tournaments. If those players had been exposed, they could have spread the disease across the country.”

Working with UConn officials, Hadler and his staff immediately went to work identifying everyone who attended classes or had contact with the potentially infected student. Classmates and professors were notified and examined if they developed symptoms of fever or cough. Blood samples from the student went to the Centers for Disease Control and Prevention (CDC) for testing. Miraculously, nobody developed a SARS-like illness. The blood test results for the student on the plane returned negative for the SARS-related coronavirus.

While the outcome could not have been brighter for Connecticut, the incident raised questions in the minds of researchers at the CDC who were working frantically to unravel the SARS mystery. If the student had direct exposure to someone with the illness, why didn’t he get infected? And if SARS isn’t transmitted through face-to-face contact, then how is it spread? The CDC researchers decided to look more closely at how the infection might or might not spread on an airplane, and because Connecticut was the first state to deal with a large-exposure scare and had several persons who had shared a flight with someone with SARS, they decided that was one place to start.

The monumental task of getting airplane manifests and contacting every Connecticut resident who had been on a flight with a confirmed SARS sufferer was too much for a state health department already overburdened with other public health emergencies, most notably bioterrorism preparedness, administering smallpox vaccines and dealing with suspected SARS cases—not to mention the more prosaic task of tracking less novel diseases that cause significant mortality and morbidity. So Hadler turned to the Connecticut Emerging Infections Program (EIP) at Yale for help.

The federally funded program is housed in a suite of offices in downtown New Haven and staffed by the Department of Epidemiology and Public Health. A joint program of the state health department and the CDC, it was created in 1995 in response to an Institute of Medicine report that found that the nation was not equipped to deal with infectious disease outbreaks, partly because the infrastructure that had once been in place had been decimated by budget cuts and eroded by complacency.

“There was a degree of hubris involved,” says James I. Meek, M.P.H., associate director of the EIP at Yale. “The attitude was ‘We have antibiotics now, so everything is under control.’ Then, of course, aids burst our bubble.” Add to that a resurgence of tuberculosis, antibiotic-resistant bacterial infections, changing habitats, a global food supply and worldwide travel, and Meek says it’s safe to say that “infectious diseases are going to be a continuing threat to us.”

Connecticut’s EIP is one of 10 such programs around the country. They are run by state health departments, but some, like Connecticut’s, have links to academic institutions. The Yale staff works with the state health department to conduct population-based surveillance and research. “We’re basically disease detectives doing shoe-leather epidemiology,” Meek says.

When the Yale researchers were contacted by the state to help with the SARS outbreak, they began working with the CDC. The CDC had by then secured the cooperation of the airlines and reviewed its lab results to identify which flights had confirmed SARS cases. It took two months before they actually started contacting passengers, so Meek says nobody was too alarmed when a health worker phoned to discuss their potential exposure to SARS. “Once we explained to them that if they were going to get sick they’d already be sick, everyone was very cooperative and happy to help.”

EIP epidemiologists contacted 15 Connecticut residents who were on a flight with a confirmed SARS case and interviewed them about their seat location and movements on the plane as well as their post-travel health. They also obtained blood samples to see whether the passengers had developed antibodies to the SARS coronavirus, which would indicate that they’d been exposed and transmission had occurred. Meek says the goal is to learn more about the transmission dynamics of the virus and to gain a better understanding of how much asymptomatic illness may be present.

One obstacle to getting meaningful results is the accuracy of people’s memory. “Recall is always a problem with epidemiological research, and after two months it’s going to be very limited,” says Meek. “Still, it was a 14-hour flight, so we found their recall was pretty good.”

Robert Heimer, M.S. ’80, Ph.D. ’88, associate professor of epidemiology and pharmacology, is in charge of the program. “It’s not glamorous work, but it’s necessary work,” he says of the EIP, which has an annual budget of roughly $1.5 million and a staff of 12 to 14 full-time epidemiologists and lab technicians. Three physicians also work part time as clinical consultants and principal investigators for some studies. The researchers all have ongoing projects, such as studies of food- or tick-borne illnesses, but they can be temporarily reassigned if there’s an emergency.

In the case of SARS, for example, the airplane study was just one part of their mission. Researchers also had to turn their attention to the Yale campus to attend to another important facet of their jobs: education. With its population of international students and faculty, many of whom travel frequently to Asia, the Yale community was understandably jittery. “There was a good deal of anxiety and misunderstanding in the beginning,” says Michael H. Merson, M.D., dean of public health.

Working with university officials, Merson joined with other Yale physicians to hold three briefings around campus and post advisories on a website. “We did our best to keep people informed and to set sound policies,” such as recommending that graduation go forward and that guests from China be allowed to attend, he says.

As the program’s director, Heimer understands the fear and misunderstandings a new infection can generate. Occasionally a disease comes along with great destructive force, as happened after World War I when an influenza pandemic killed 25 million people worldwide. Heimer said that with SARS the initial fear was that it could be that kind of easily transmittable, upper-respiratory infection. But once that turned out not to be the case, he thinks the focus should have shifted from SARS, which has infected 8,500 people and cost an estimated $30 billion so far, to other public health threats, such as hiv, which infects 15,000 people a day.

“Once we knew what it was, that it wasn’t an influenza thing, and we knew how not to get infected, we should have stopped worrying, and the media and the public should have focused on more pressing issues,” Heimer says.

Meek and his colleagues agree. “All anyone at the soccer field wants to talk to me about is what’s going on with SARS,” says researcher Ruthanne E. Marcus, M.P.H., a lecturer in epidemiology. But the EIP also tracks many other illnesses that pose a far more immediate threat to most Connecticut residents. “Everyone thinks of the biggies, like AIDS, SARS and West Nile, but there are a lot of run-of-the-mill infectious diseases out there,” Marcus says. For example, she focuses on foodborne pathogens, such as E. coli and Salmonella, which are a growing concern because of the number of meals eaten in restaurants and America’s growing appetite for imported foods.

Chronic liver disease, tick-borne ailments and unexplained illnesses and death are other health issues EIP researchers monitor. They predict that as the population ages and as Connecticut residents choose to live in wooded environments that bring them into closer contact with ticks, rodents and other potential disease carriers, emerging infections will become an increasingly important health care specialty.

If SARS has served as a distraction, the even larger recent diversion of resources has been to bioterrorism. Far from seeing this as undermining their work to cope with less headline-grabbing health threats, though, epidemiologists see the focus on bioterrorism as a potential boon for the whole field of emerging infections. The recent anthrax scare and the ongoing fear of bioterrorism have contributed to a heightened awareness about infectious diseases in general, they say, and an understanding within the public health community of the importance of a well-supported public health infrastructure to deal with them. It will be another hurdle to get the public to focus on public health and not be sidetracked by the next new thing in emerging infections.

Still, for researchers in the EIP, tracking down the causes and transmission dynamics of elusive illnesses, whether new and emerging or old and resurgent, comes down to creative, grass-roots detective work and a mind open to the unexpected. As Meek says, “When most people hear the pounding of hooves, they look for horses. As epidemiologists, now we also have to look for zebras.” YM

Jennifer Kaylin is a freelance writer in New Haven.

A global prescription for a global outbreak

If the SARS outbreak has taught us anything, it is how interconnected the world is and how vital is the need for global cooperation on public health issues.

So says Ilona S. Kickbusch, Ph.D., head of the division of global health at the School of Public Health. “This isn’t just an issue for developing countries,” she says. A case in point is how, in a matter of weeks, travelers spread the disease from China’s Guangdong province throughout Asia, Europe and North America. “When the SARS outbreak spread to Canada we saw just how close to home it really was.”

Although it falls largely to the World Health Organization (WHO) to provide international public health oversight, prior to the emergence of SARS, Kickbusch says, the agency’s hands were tied economically and statutorily. The WHO budget has been stagnant at $800 million a year (less than it takes to run the average hospital in the United States) for the past 15 years. (It has another “voluntary budget” of about $800 million, but that money must be spent on projects identified by the contributing countries.)

What’s worse, if an outbreak occurred, the WHO had to get permission from the host country to investigate. “For political and economic reasons, some countries weren’t as compliant as one might wish,” she says. Also, countries only had to report named illnesses, not atypical syndromes, so a new illness like SARS could go unreported.

As a result of SARS, though, the World Health Assembly, WHO’s governing body, voted to give the WHO more latitude in responding to global health threats. A resolution adopted by the assembly in May requests that WHO consider information about epidemics from nongovernmental sources and conduct on-the-spot studies within affected countries to ensure that control measures are adequate to prevent international spread of the syndrome. Kickbusch says that’s a good start, but more must be done, including intensified global surveillance and laboratory work, funded in part by public/private initiatives.

Kickbusch would also like to see more well-trained public health professionals working at the ground level, and she says there need to be clearly stated consequences, such as economic sanctions, for those countries that withhold important public health information or fail to act as responsible global citizens.

“It’s a matter of global security in the widest sense,” she says.

—Jennifer Kaylin

SARS remains a moving target

The disease that emerged in Asia late last year, SARS, is a moving target, according to Vincent J. Quagliarello, M.D., HS ’81. “Every day,” he told an audience at this year’s medical school reunion, “there is something new reported in The New York Times from somewhere around the world.”

What is known about SARS, said Quagliarello, professor of medicine and clinical director of the Section of Infectious Diseases, is this: it is a previously unrecognized member of the well-known coronavirus family which causes about a third of the cases of the common cold. It was first reported last November in China and, in very short order, swept across three continents. Infections travel through close person-to-person contact, mostly among family members or health care workers. Symptoms include fever, headache, myalgias, a dry cough and shortness of breath. Although only about 8,500 people worldwide have been infected, SARS has a mortality rate of 9 percent and it has provoked fears around the world. The resulting economic impacts have been devastating for Asia and Toronto. China and South Korea have lost about $2 billion in tourism, retail sales and productivity. Hong Kong, Taiwan and Singapore estimate losses at $1 billion each.

Major league baseball players were advised to avoid crowds in Toronto, where thousands of people were quarantined. All over Asia people donned protective face masks. In Singapore, Quagliarello said, the Catholic Church suspended confessions and granted a general forgiveness.

SARS, he continued, is a sign of globalization. “Within weeks SARS has spread over three continents to cause a devastating impact on our societies,” he said, adding that there is a bright side. “At the same time, however, investigators from over 10 countries have collaborated to identify the virus, screen for potential antiviral therapies and initiate vaccine development.”

—John Curtis


			Originally published in Yale Medicine, Autumn 2003. Copyright © 2003 Yale University School of Medicine. All rights reserved.