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Crisscrossing the Globe: The Hunt for Medical Interventions and Innovations

The brutal and bloody reign of dictators such as Idi Amin finally behind them, the resilient people of the Republic of Uganda again found themselves seemingly defenseless against an insidious enemy among them.

Slim disease as they referred to it in 1986 was indiscriminately killing vulnerable Ugandans in disturbing numbers. The government of the East African country, headed by President Yoweri Museveni – still in power today, took notice and made an international appeal for help.

That candid request made its way more than 7,500 miles to the campus of Case Western Reserve University and to the office of Nobel Laureate Frederick Robbins, M.D., world renowned for his groundbreaking research that led to the creation of a polio vaccine.

A champion of efforts to improve the health of people in developing countries who faced great challenges and battled devastating infections, Dr. Robbins heeded the call. He led an entourage from the School of Medicine to the landlocked country the size of Oregon where they found the ravages of advanced AIDS and a fear-stricken people facing down the burdensome disease with little to no resources to do so.

That trip was the first collective step forward with Uganda in a continuing collaboration that has spanned more than 20 years and saw the HIV/AIDS prevalence rate drop from 25-30% to 6-10%.

The successful partnership with Uganda is just one international endeavor in which the School of Medicine and its Center for Global Health and Diseases has leveraged its multidisciplinary biomedical strengths to become a powerhouse in global health.

Through sophisticated research and clinical trials, an unflappable commitment to solving complex diseases, and an adventurous spirit, the growing number of prominent researchers devoted to diseases such as malaria, filariasis, Rift Valley Fever Virus, tuberculosis and HIV/AIDS have put the School of Medicine on a short list of institutions with unmatched international reach and impact.

The School of Medicine has $25 million per year in National Institutes of Health (NIH) and other externally-funded grants dedicated to global health research and education in more than ten countries on five continents. “Case Western Reserve has one of the oldest and longstanding programs in international health and research anywhere in the country,” said W. Henry Boom, M.D., Professor of Medicine and Director of the Tuberculosis Research Unit (TBRU). “A lot of people associate international health with barefoot doctoring and feeding the hungry children and saving mankind. Those are very important things, but frankly those are best done by organizations that are not academic institutions.”

The School of Medicine aspires to do what academic institutions do best: educate, train and research to propel science forward.

“Global health, perhaps, allows one to fulfill humanitarian motivations along with career and academic aspirations by applying good science to these kinds of really big health issues in the world,” said James Kazura, M.D., Director of the Center for Global Health and Diseases (CGHD). The CGHD, which was formed in 2002 by merging the Center for International Health and the Division of Geographic Medicine, fosters myriad dynamic domestic and international partnerships and brings together many disciplines at the School to improve the health of developing countries.

GLOBAL FOOTPRINT

Over the last three decades, School of Medicine scientists have helped define the emerging field of global health. Along with Dr. Robbins the list includes such names as Jerrold Ellner, M.D.; Adel Mahmoud, M.D.; Ph.D., Kenneth Warren, M.D.; Thomas Daniels, M.D.; and Charles Carpenter, M.D. They inspired, encouraged and led other doctors to study infectious problems in places such as Kenya, Uganda, South Africa, Papua New Guinea and Brazil. Trained as a hematologist, Dr. Kazura credits his commitment to global health to the opportunity afforded him by Dr. Carpenter, a leading researcher of diarrheal diseases such as cholera in India, who joined the School in 1973 as Chairman of Medicine. Dr. Carpenter was among the first to make a serious commitment to support development of aspiring physician-scientists to careers in global health.

“After spending three months in East Africa working with Drs. Adel Mahmoud and Kenneth Warren on worm infections, I was turned on to this as something I’d commit my career to,” said Dr. Kazura. “I could see that there was great need there. And we’d get a lot of bang for our buck in terms of developing interventions or preventative measures that could have a great impact, at a relatively low cost, on these enormous health issues that had been neglected for the last century.”

Dr. Kazura, a Professor of International Health and Medicine and Editor of the American Journal of Tropical Medicine and Hygiene, went on to study the worm infection known as lymphatic filariasis and was part of a team that discovered that, by using off-patent drugs, they could actually stop the transmission of the disease that affects one billion people in the world. “In 1997, the World Health Assembly declared lymphatic filariasis as the first infectious disease that can be eradicated by using drugs on a worldwide basis,” he said. Today, Dr. Kazura is a representative on panels for the NIH and World Health Organization (WHO), which promulgate policy on how the eradication program for filariasis should progress.

“Global health studies address many interwoven questions and evolve from basic science studies on how the drugs work; how you do rigorous clinical trials in resource-poor settings; how you deliver the drugs; how you decide where you deliver such interventions; and how you determine whether you have been successful by monitoring progress,” he said.

In Uganda, another area of longstanding strength and prominence is the Tuberculosis Research Unit, headed by Dr. Boom, who sits on a WHO panel that is determining the best way to control the spread of tuberculosis (TB) for human clinical immunology in sub-Saharan Africa and the use of anti-TB drugs in developing countries.

Dr. Boom, who took over the TBRU in 1999, was able to fulfill a personal desire to participate in global medicine and oversee a program that has allowed the School to build advanced laboratories for the culturing and diagnosing of TB, as well as an HIV virology lab in Uganda.

“We have a very integrated approach where we work to understand the host and pathogen in TB and to try to find new ways to treat, diagnose and prevent the disease,” he said. “In addition there’s a long tradition of doing very high quality clinical trials so we can explore new drugs, new approaches to TB treatment, and also epidemiologic studies, and try to understand how TB is transmitted, why some people get sick and some do not, and link those studies with sophisticated laboratory studies.”

Anna Mandalakas, M.D., an Associate Professor of Pediatrics whose research focuses on childhood TB and HIV in high-burden communities in sub-Saharan Africa, is working with some new diagnostic tests to be able to better identify children who are infected with TB.

Every year almost nine million people contract and two million people die from TB. Of those, approximately 15% are children. UNAIDS, the Joint United Nations Program on HIV/AIDS, estimates that 655,000 children are newly infected with HIV each year and 450,000 HIV-infected children die annually.

Dr. Mandalakas, the University’s’ first fellow in Global Child Health, began her work in South Africa five years ago. She is in the midst of two new studies to examine TB and HIV/AIDS in children. One study, funded by the NIH, will enroll 800 children five years of age and younger. The other, funded by the Thrasher Research Fund, will examine older children up to the age of 15.

“If we can accurately identify children who are infected with TB, then we can make it much more cost effective to target treatment of those kids to prevent the development of disease,” she said. “The most important goal of my work is to improve the delivery of preventive therapy to very young vulnerable children.”

There is perhaps no greater champion for the health of all children – both physically and psychologically – than Karen Olness, M.D., Professor of Pediatrics, Family Medicine, Global Health and Diseases, who established global child health initiatives when she joined the School of Medicine faculty in 1987. The following year, she launched the first research studies of HIV in Ugandan children and created the first international health track in a United States pediatric residency program. These accomplishments were supplemented with establishment of the first United States pediatric fellowship in global child health and the development of the first disaster management training programs to focus on the special needs of children in disasters. The global child health residency program and disaster management training are now being replicated at pediatric training institutions across the country.

In collaboration with her colleagues from the School of Medicine’s Department of Pediatrics, Khon Kaen University, and Health Frontiers, Dr. Olness also created the first post-graduate training programs in Laos, a three-year pediatric residency training program which has increased the number of pediatricians in Laos from three to 42 with six or seven new trainees entering the program each year.

Locally, Dr. Olness founded the Adoption Health Service, which serves the needs of internationally-adopted children and their families in Northeast Ohio.

At the School of Medicine, Dr. Olness and colleagues created a course, “Preparation for International Health Service,” which is now in its 22nd year. This course, for medical students, residents, nursing students and the wider Cleveland community, provides preparation related to service, education and research in the global health field.

“Dr. Olness is a visionary. She is always ahead of the curve and able to identify new opportunities to improve children’s health,” said Dr. Mandalakas. Dr. Olness is a world renowned humanitarian who created the Children in Disasters Project, a network of programs that train health professionals and relief workers – both in the United States and overseas – to recognize and respond to the special needs of children in disasters.

“We are doing a lot of good for children worldwide,” said Dr. Mandalakas, who directs the domestic programs. “Our Children in Disasters project has tremendous potential to improve the lives of children. There are at least 32 million people displaced in the world today. Children are the most vulnerable survivors in disaster situations.”

A MULTIDISCPLINARY FRAMEWORK

A hallmark of the School’s global health initiatives is the Framework Program for Global Health, a collaboration of faculty from the College of Arts and Sciences, and schools of Medicine, Engineering and Nursing, that is coordinated by the CGHD and supported by the Fogarty International Program of the NIH.

“We currently have three Fogarty Training Programs at this institution for education in health research for people from Uganda, Kenya and Papua New Guinea,” Dr. Kazura said. “We also have a program to develop an interdisciplinary curriculum in global health for biomedical students, students in the medical school, the school of nursing, and the school of dental medicine, but also for undergraduate education and students in anthropology or mathematics.”

“Each year, 25 to 30 medical students travel abroad for study and research. And there are many graduate students from Kenya and Uganda working in laboratories throughout the School of Medicine,” Dr. Kazura said.

The education and training abroad can be profound. The School of Medicine recently celebrated its 20-year anniversary in Uganda, with more than 25 completed or ongoing clinical trials and more than 200 employees involved in research there. The milestone was marked by a theme of looking toward the next 20 years and all that can be accomplished by working together.

Beyond the state-of-the-art laboratories, improved technology, and generating valuable medical knowledge, the School of Medicine has trained many Ugandans – more than 35 have earned master’s and doctorate degrees – to become the new generation of leaders, said Robert A. Salata, M.D., Executive Vice Chair of the Department of Medicine and Chief of the Division of Infectious Diseases and HIV Medicine. He has been a force in the HIV/AIDS research in Uganda since 1996.

“We leave a lot behind and I think that’s one of the reasons we have been so successful,” Dr. Salata said.

Uganda, and its capital city Kampala, is now, in many ways, a beacon for biomedical research.

“Kampala is crawling with investigators from all over the world – not just because it’s an easy place to do research but because there are a lot of well-trained Ugandans who can help projects get going,” Dr. Boom said. “That has made it a very attractive place for researchers. It attracts grants, attracts funding, and attracts more development.”

BI-DIRECTIONAL AND MEANINGFUL

Traditionally rooted in field-based studies and research of diseases prevalent in developing countries, global health has evolved into a more substantive interplay on both sides of the logistical equation.

“It’s a real partnership and it’s bi-directional. We’re not just over there serving those underserved people. We get a lot out of it, too,” said Dr. Mandalakas, who is Chief of the Division of Global Child Health and continuing the work begun by Dr. Olness. “Our work overseas brings so much back to Northeast Ohio at all levels of education – from undergraduates all the way to senior physicians who may be starting to slow down in their practice and want to get more involved in global health initiatives.”

It is without question that the more physician-scientists and biomedical researchers understand disease, “…globally from a health perspective, the more we can put our own problems in perspective,” said Dr. Salata. He also was a part of the first preventative HIV-vaccine trial in the continent of Africa that ultimately was unsuccessful, but the three-year endeavor proved such an ambitious program could be implemented there.

“The funding agencies are recognizing this, too. When many of us first started in these areas it was very difficult to procure the research funding to push on these studies. That is becoming easier to do,” he said. “I think it’s from a recognition, at the highest levels, that this is a global issue. We have to fund these things because the findings will have implications back here at home, too.”

Take childhood TB for example. “We have just as difficult a time figuring out what children have TB infection in the United States as they do overseas,” Dr. Mandalakas said. “The diagnostic test most commonly used is more than 100 years old. We are just starting now to look at new blood-based tests…Data on use of these tests in children overseas will be directly relevant to the use of these tests in kids in the United States.”

ONLY CONSTANT IS CHANGE

The field – even the definition – of global health is one that is always evolving, responding and pulsating with the drumbeat of disease around the world. In fact as the developing countries become more “westernized,” chronic medical problems – the leading causes of death here in United States -- are on the rise.

“We are beginning to see health problems that are non-contagious or non-infectious in nature such as heart disease, diabetes, hypertension, kidney disease, lung disease and cancer,” Dr. Salata said. “These have always been there but they have been overshadowed by infectious disease issues. There will be opportunities for us to use the infrastructure and the relationships that we already have in place to expand the collaboration and include research and study of the areas beyond infectious diseases.”

That being said, a country’s ability to address major health issues such as malaria, tuberculosis nd HIV/AIDS, can have a profound impact on its future.

“If you have a lot sick young adults, you’re going to have a hard time developing a robust economy,” Dr. Boom said. “That means that if you’re interested in making the world a safer place where more people have economic opportunity and are less likely to go into crime or terrorism…health has an important role to play in that.”

Global health, in turn, can be a wonderful tool of diplomacy, Dr. Kazura said.

“Whether it’s our university or it’s the NIH taxpayer money, it’s contributing to research – clinical or basic research – and to health issues that really affect some of the poorest of the poor people in the world,” he said. “I think it’s a tremendously important thing in terms of the image of the United States around the world and it’s in our own self interest.”