Feature: Infectious Disease

We may see malaria, tuberculosis, pneumonia, and measles as illnesses of the past. But worldwide, more than 90 percent of deaths from infectious diseases are caused by only a handful of diseases, including these "old" threats. In developing countries they continue to kill at an alarming rate, striking mostly children and young adults. The World Health Organization estimates that every three seconds a young child dies-in most cases from an infectious disease.

We're not safe in the developed world either. Widespread outbreaks of emerging infectious diseases like SARS, West Nile virus, and most recently, avian influenza, loom large. Left unchecked, today's emerging infectious diseases can spread to become the pandemics of tomorrow. Think of this: 30 years ago HIV/AIDS was contained to a remote part of Africa. Today it is one of the world's top killers with 40 million people living with the disease and no end in sight.

School of Public Health faculty members have long understood that these diseases need to be addressed at the global level. They're working at home and around the world to confront infectious disease head-on and at all levels, from microbial surveillance to vaccinations and treatment to disaster response and public preparedness.

CIDRAP: Information to Action

The University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP) works to translate scientific information to real-world action. CIDRAP's director is SPH professor Michael Osterholm, one of the word's most renowned experts in infectious disease epidemiology. Through its Web site (www.cidrap.umn.edu) the center provides an Internet-based "living textbook" of the latest information on bioterrorism, food safety, and infectious diseases. In the past year, the CIDRAP Web site was credited with having the most accurate accounting of H5N1 avian flu cases-surpassing the accuracy of the World Health Organization's Web site.

CIDRAP staff work with University of Minnesota leadership and international, national, and state public health agencies to advise them on pandemic influenza preparedness. The center has led tabletop exercises and provided state and local health departments with a list of preparedness objectives. Recently, CIDRAP hosted an online teleconference to help other large universities best serve their communities in the face of an influenza outbreak. Twelve major universities participated, as well as CDC representatives. "CIDRAP has become an important resource to government and private industry, as they increasingly focus on the issue of a potential pandemic," says Jill DeBoer, CIDRAP associate director, who also heads the University's emergency preparedness program. "We're able to synthesize the latest information to help communities plan strategically."

HIV/AIDS

Epidemiology professor Alan Lifson is working with the government of Guyana and other collaborators to scale up that country's HIV/AIDS care and treatment. As one of the poorest countries in the Caribbean, Guyana has limited resources to fight HIV/AIDS, which has become the leading cause of death for 25 to 44-year-olds. Lifson is partnering with Guyana's Ministry of Health, the International Training and Education Center on HIV, the CDC, and other partners to train health care workers on the most effective way to treat the disease. He's also partnering with medical and other professional schools in Guyana to develop curricula on the subject.

Lifson says one of the biggest challenges to health care workers is the complicated and ever-changing nature of HIV/AIDS treatment. Training is needed to address effective ways of treatment, so the most useful drugs are used, side effects are minimized, and patients don't develop resistance to the drugs. "This field moves so quickly, we need to help our partners be up-to-date," he says. But most important to Lifson is developing a program that lasts.

"It's really important to build something sustainable," he says. "We want to do this in a way that builds infrastructure and that develops local people who can become experts themselves."

SPH professor of biostatistics James Neaton is known internationally for his work conducting large randomized clinical trials on HIV/AIDS. Through the School's Coordinating Centers for Biometric Research (CCBR), he leads a team focused on determining the most effective ways of treating (continued on next page) (continued from page 3) the disease. He and his colleagues have conducted the two largest HIV treatment trials done to date. Researchers are following more than 10,000 people in 33 countries in randomized studies designed and coordinated by CCBR staff.

Antiretroviral therapies for HIV/AIDS are costly and complicated-huge barriers for those seeking treatment in the developing world where the disease has reached epidemic levels. Neaton's team is studying antiretroviral drug-sparing strategies and novel treatments to improve the health of those living with HIV/AIDS. Findings from several completed trials have already made a large impact on HIV care. Ongoing trials-known by acronyms like SMART, ESPRIT, SILCAAT, and the latest, STALWART-also aim to curb the toxicity of the drugs and potential resistance to treatment.

From the foundation of these trials and the international partnerships that launched them, Neaton hopes to build on a global research strategy to treat HIV/AIDS. He recently submitted a proposal to the National Institutes of Health to establish a global collaborative network to conduct research at some 400 sites in 37 countries.

Pandemic Influenza

In the past 30 years, Michael Osterholm's public health work has dealt with some grim subjects-the emergence of HIV/AIDS, SARS, bioterrorism, 9/11. These though, he says, pale in comparison to a potential outbreak of influenza. "There is nothing in my career that has disturbed me more than the issue of pandemic influenza," he says. "It's not a matter of if it is going to happen but when."

Osterholm has been repeating that mantra during countless print and television appearances, including CNN, Oprah, and Nightline. He's been telling it to high-ranking federal officials and business leaders. He's written about it in influential journals like Nature, the New England Journal of Medicine, and Foreign Affairs. His efforts all center on one mission: to ramp up our preparedness. Despite the flurry of media coverage, government discussions, and rise in public awareness, he believes we remain sorely unprepared for what's to come.

Pandemics, like hurricanes or earthquakes, are inevitable forces of nature. Ten influenza pandemics have circled the world in the past 300 years, and three in the past century. The most devastating hit in 1918, infecting about a third of the world's population and killing an estimated 50 to 100 million. It's very possible that the next culprit for the next pandemic will be H5N1, the avian flu virus that since 2003 has killed more than 100 people worldwide, with most of those transmissions going from bird to human. Health experts have warned that the virus could mutate into a form easily transmitted among people, creating a strain capable of killing millions. Most frightening: while the 1918 virus killed just 2 percent of its victims, H5N1 has killed more than half of the people it has infected.

Central to Osterholm's call for pandemic planning is a "just-in-time" economy that has left us with no surge capacity of the supplies-surgical gloves, IV bags, ventilators-needed to control this infectious and deadly disease. He also points out that the raw materials for 80 percent of U.S. pharmaceutical products come from other countries. If international borders are closed in an attempt to manage the pandemic, drug supplies will be severely limited.

Osterholm has called for government at every level to create an operational blueprint for the best way to get through one to two years of the pandemic, including a plan for staffing hospitals and vaccinating health care workers. "I think the U.S. has made some gains in overall preparedness. But with our complicated supply-chain issues, we have a long way to go," says Osterholm. "We need detailed plans at every societal level, in private and public sectors. General statements of action will be meaningless in the face of a pandemic."

When news of avian influenza first started making headlines, virtually all of the coverage focused on how Asia would have to deal with a potential outbreak. But Marguerite Pappaioanou, an SPH professor with expertise in emerging zoonotic infectious diseases, knew the virus could very easily spread to other parts of the world. And she knew something had to be done about it. Pappaioanou, with co-investigators Sagar Goyal in the College of Veterinary Medicine, and Bill Stauffer in the School of Medicine, has received funding from the U.S. Agency for International Development to establish a laboratory-based influenza surveillance program in Tanzania. The country's massive population of migratory birds and borders with several other sub-Saharan countries make it a target for a potential outbreak. University of Minnesota investigators will assist Tanzania's Animal Disease Research Institute (ADRI) in the Ministry of Livestock Development to establish a capacity to test for influenza viruses. Laboratory-based surveillance will begin in a sentinel hospital-based system, as well as in Tanzania's backyard poultry, swine, and wild birds. In addition to early detection efforts aimed at the H5N1 strain, yearly flu viruses will also be monitored. Right now, there is little to no information on influenza's impact on human and animal health in sub-Saharan Africa.

"People in Africa coming to a clinic with a fever and cough frequently are presumptively diagnosed with malaria or pneumonia, when it could be influenza," says Pappaioanou.

Over the next year, Pappaioanou and colleagues will move beyond Tanzanian borders to build capacity for laboratory-based influenza surveillance in East Africa. She's working to strengthen the relationship between the ADRI laboratory in Tanzania and the International Emerging Infections Program with the Kenyan Medical Research Institute and CDC in Nairobi, Kenya. With recent news of the first bird flu cases hitting Africa, Pappaioanou and colleagues are striving to have their work give Tanzania a "head start in early detection and response."

The Human-Animal Connection

It only takes a quick glance at today's emerging infectious diseases to realize that most exist in the interface of human and animal populations. For SPH adjunct professor Will Hueston that fact means educators must train a new type of public health professional. To that end, he directs the School's dual program in veterinary medicine and public health (D.V.M./M.P.H). "These emerging diseases are the norm, not the exception," he says. "We need a workforce that will be prepared, not surprised, when a diseases hits."

Hueston, who directs the Center for Animal Health and Food Safety at the College of Veterinary Medicine, is also committed to educating those currently in the field. Every month he convenes a group of communicators from state agencies to talk about animal and human health issues. The goal is to share information and make sure public messages about emerging diseases are clear and consistent across disciplines and fields.

As a professor in the SPH and Department of Veterinary and Biomedical Sciences, Randall Singer's research focuses on infectious diseases in animals and humans. For the past three years, he has led an ecological study in southern Chile to determine how environmental factors are affecting the water quality of a system of rivers. His team is looking at how wastewater treatment plants, population density, runoff from the land, and hospital waste may be contributing to antibiotic resistance in the people who live there. "We're finding that human wastewater treatment and hospital effluent are the biggest factors so far," he says. "Organisms we've found downstream resemble most closely what's coming out of treatment plants and hospitals."

Completing the environmental circle of "cause-and-affect", the study is also looking at rates of E. coli and other waterborne and foodborne illnesses reported by patients in the hospitals. "Are these infections more resistant because of the environment," asks Singer. "And how do patterns of resistance differ throughout the region?"

Singer's team-which has included five SPH students who have each spent months in Chile analyzing environmental samples-is working closely with the Chilean health department and veterinary school. The aim is to offer guidance on how to manage the environment to improve public health. Singer believes the lessons learned should be seen through a global lens-both because environmental challenges to water safety are applicable to other countries, and counties around the world like ours import Chilean seafood and produce. "The implications certainly are global," he says. "There's no such thing as an isolated environment."

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