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WINTER 2007
Averting the Next Pandemic
by Sam Fahmy

By studying avian influenza through a range of collaborative inquiries, UGA researchers and their cooperators near and far are seeking to defeat a wily and potentially deadly enemy.

David Stallknecht recalls the first time he saw what avian influenza could do, and it was well before “bird flu”—a term so vague that scientists scoff at it—became the stuff of newspaper headlines and made-for-TV movies.

The year was 1983, and Stallknecht was a field technician working for the Southeastern Cooperative Wildlife Disease Study (SCWDS), a program based at the University of Georgia. He had been sent to Pennsylvania to investigate whether wild birds were involved in an outbreak of highly pathogenic avian influenza in domestic poultry.

On a cold November day, Stallknecht, normally a jeans and T-shirt kind of guy, stepped out of his truck and onto a farm wearing a bright white HazMat-style jumpsuit and a face mask.

“I remember seeing a flock of domestic guinea fowl with a mortality rate of 90-plus percent,” said Stallknecht. “And although that seems like just a number, when you actually see 90 percent of 12,000 birds lying on the ground it makes an impression. It absolutely makes an impression.”

Stallknecht is now an associate professor in UGA’s College of Veterinary Medicine and a scientist at SCWDS, one of the nation’s leading wildlife research groups. In its 50-year history, researchers from SCWDS—or “squidis” as they call it—have investigated cases of sick or dying wildlife in more than 200 species, ranging from white-tailed deer and shorebirds to black bears and bald eagles.

Dr. David Swayne came to avian influenza research in a less dramatic though no less significant way. He had initially wanted to study Marek’s disease, which was deadly to chickens and costly to the poultry industry until 1970, when a vaccine was introduced.

His mentor at Ohio State University, Richard Slemons, suggested that he change his research focus and study avian influenza. “He said, ‘You ought to get away from this Marek’s disease and work on a disease that will last you a lifetime,’” Swayne recalled.

Now, Swayne directs the Southeast Poultry Research Laboratory (“Southeast Poultry”), an internationally recognized facility, based in Athens, Georgia, of the U.S. Department of Agriculture’s Agricultural Research Service. For the poultry industry, Southeast Poultry is the equivalent of the Centers for Disease Control and Prevention.

Working just a few miles apart and often in close collaboration, the two men now find themselves at the forefront of one of society’s most pressing efforts: to understand and ultimately minimize the risks caused by avian influenza viruses, which could threaten wild birds, the state’s $13.5 billion poultry industry and human health.

Together and individually, they’ve racked up a long list of research accomplishments in this field. Still, they realize that plenty more remains to be done.

“You cannot know enough about how these viruses function in nature,” said Stallknecht. “If you do know something about the natural system, when something like [highly pathogenic Asian] H5N1 avian influenza comes down the pike you have an indication of where to look for it, how to look for it, what species to look in, and the probability of it getting here.”

While the average person may think of avian influenza as a single virus—and a scary one at that—the truth is that the term refers to a spectrum of viruses distinguished by certain proteins on their surfaces. The “H” refers to hemagglutinin and the “N” to neuraminidase, both of which are major contributors to the virus’ ability to spread in the body. There are 16 H subtypes and 9 N subtypes, with various combinations possible. Some examples include H1N1, H1N2, H3N2 and, of course, the feared H5N1. When an avian influenza virus causes only mild symptoms in chickens, it is referred to as a low-pathogenicity strain. If it’s capable of causing hemorrhaging and death, the strain of the virus is clearly high-pathogenicity—or “high-path.”

Only viruses of the H5 and H7 subtypes have been high path—the devastating Pennsylvania outbreak that initiated Stallknecht was caused by the H5N2 subtype—though H5 and H7 viruses aren’t necessarily high path. Most produce relatively mild symptoms, such as lethargy or ruffled feathers, in birds.

Still, high-path Asian H5N1 is the virus that most media reports focus on, and with good reason. In 1997, it began infecting humans in Hong Kong. Eighteen people were hospitalized with severe infections, and six of them died. Hong Kong’s entire poultry population of 1.5 million birds was culled in three days, a move that many believe averted a human catastrophe.

In 2003, the virus again began causing outbreaks in poultry in Asia. This time, it went undetected and unreported, possibly for months. In December 2003, the virus was confirmed in South Korea. In early 2004, it was confirmed in Vietnam, Thailand, Cambodia, China and Japan. The first human cases of this wave occurred in Vietnam, and by 2006 the virus had killed more than 150 people in 10 countries.

Epidemiologic investigations by agencies such as the World Health Organization and the CDC revealed that the deaths were mostly limited to people who had had close contact with poultry—nothing to ignore, but not a global threat, as most people do not have such contact. The concern, however, is that the virus might mutate into a form that is easily transmissible from person to person, potentially triggering something on the scale of the 1918 flu pandemic, which killed an estimated 20 to 40 million people worldwide.

The virus has already demonstrated, however, one other troubling characteristic. Avian influenza viruses typically originate in wild birds and then begin infecting poultry, but this strain has shown the ability to move back into wild birds. This phenomenon potentially provides a way for migratory birds to spread the virus across continents.

Swayne, Stallknecht and their colleagues at Southeast Poultry and SCWDS have long been working to better understand avian influenza and its role in the environment—way before it became the disease du jour.

Since coming to Southeast Poultry in 1994, Swayne has helped to nearly triple the amount of federal support that the facility receives—from $2.7 million to more than $7 million in USDA funding—a good fraction of which is devoted to avian influenza. Among other notable accomplishments, research conducted by Swayne and his staff led to the licensing in 1998 of the first H5 vaccine—to international veterinary-vaccine manufacturer Merial Ltd.—which has since sold more than one billion doses. The researchers are currently working to develop vaccines for other avian influenza types and learn the most effective ways to administer the vaccines.

In 2002, Southeast Poultry staff led by David Suarez devised a new diagnostic test for avian influenza that has substantially reduced the time it takes to identify the virus—from one or two weeks to just three hours. Southeast Poultry researchers also identify and, often, further study avian influenza viruses that are sent to their lab from around the world. If the high-path Asian strain of H5N1 ever makes its way to North America, researchers at Southeast Poultry will likely be the ones to identify it.

In Southeast Poultry’s work with SCWDS, one of the most enduring collaborations between the two labs is their eight-year-old effort to monitor migratory birds for avian influenza viruses. Slemons at Ohio State and Kevin Winker at the University of Alaska-Fairbanks also contribute to the effort, which allows scientists to track how the dominant viral species change through time and move through populations. So far the researchers have sampled over 12,000 birds and cataloged more than 1,000 viruses.

Researchers from Swayne’s and Stallknecht’s facilities also collaborated on a study published last fall that identified two species—the common wood duck and laughing gull—that are very susceptible to high-path Asian H5N1 avian influenza viruses and have the potential to transmit them. The scientists also found that other birds known to be important avian influenza virus reservoirs, such as mallards, Northern pintails and blue-winged teal, are not highly susceptible and probably not likely to transmit H5N1.

In low-path avian influenza, most of the virus is shed in the birds’ feces. The virus then spreads as other birds drink from contaminated water. The researchers found that in high-path Asian H5N1 avian influenza, however, the birds shed most of the virus through their respiratory tracts. Knowing more about which birds to look for and the best way to collect samples, researchers are in a better position to quickly detect H5N1 if it were to arrive in North America.

Stallknecht has just begun work on a planned three-year grant, totaling $2.6 million, from the CDC to investigate the possibility of human contact with avian influenza viruses. He will draw on the expertise of researchers across campus, at Southeast Poultry and at other federal and state agencies.

In the first part of the study, Stallknecht, doctoral student Dr. Justin Brown, and colleagues at Southeast Poultry will examine how long avian influenza viruses remain infectious in water. With the help of Lisa Stewart at the U.S. Geological Survey’s Water Science Center, the researchers will explore how factors such as temperature, pH and salt concentration influence viral persistence.

Next, Dana Cole at the Georgia Department of Public Health, Steve Valeika at the UGA College of Public Health and Pej Rohani at the Institute of Ecology will work with the researchers to assess the probability of human contact with the viruses. For example, are duck hunters at risk? How about swimmers?

Erin Lipp at UGA’s Department of Environmental Health Science will examine whether filter feeders such as clams and mussels have the potential to concentrate the viruses and sicken those who eat them. On the other hand, it’s possible that the filter feeders may reduce the likelihood of transmission by removing the viruses from the water. Maricarmen Garcia and Mark Jackwood at the UGA Poultry and Diagnostic Research Center will examine the risk to poultry workers and the persistence of the viruses on surfaces such as poultry litter.

Finally, the team will collaborate with Mark Tompkins at UGA’s Department of Infectious Diseases and Elizabeth Howerth at the Department of Pathology (both in UGA’s College of Veterinary Medicine) to assess the ability of low-pathogenic avian influenza viruses to infect mammals. In that way, the potential risk to humans may be better understood.

“To prevent the next pandemic, we really need to understand how these viruses operate,” Stallknecht said. “So it really calls for a broad perspective.”

The 1983 outbreak that gave him his start in avian influenza research cost the federal government $63 million, and consumers paid an extra $350 million in higher poultry prices. Seventeen million birds died or were culled as a result of the outbreak. Still, Stallknecht points out that the virus responsible for the outbreak was effectively eradicated in two years.

Worldwide, the Asian H5N1 strain has already caused more damage and persisted longer than the virus that caused the Pennsylvania outbreak. But the researchers hope that their work will uncover simple preventive measures that can keep poultry, wild birds and people healthy.

“By studying these viruses and by looking at the interface between wildlife, domestic poultry and agriculture, we can hope to prevent what’s happened in Asia from happening here,” Swayne said.

For more information contact David Stallknecht at dstall@vet.uga.edu or David Swayne at dswayne@seprl.usda.gov.