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  A native of South Africa, Keith Klugman remains committed to improving health conditions there. His landmark pneumonia vaccine study of South African children concluded that the pneumonia vaccine could save thousands of lives.  
  SOUTH AFRICA is a place of contradictions—extreme natural beauty and stark urban landscapes, an infrastructure as modern as any in western Europe in some places and conditions as primitive as the poorest countries in others.  
  The incongruent, sometimes surreal nature of things in South Africa shaped Keith Klugman, a physician and microbiologist born and raised there. Growing up in Johannesburg could offer anyone a unique perspective on disease and disability in the developing world. And Klugman, the world’s premier expert on antibiotic resistance among pneumococcal bacteria, has put his insider knowledge to good use on the world stage. Recently named the first William H. Foege Professor of Global Health at the Rollins School of Public Health (RSPH), Klugman is a prolific scientist, a mover and shaker on the international public health funding scene, and a congenial fellow on top of it all.
     Even though he now lives and works in Atlanta, he never loses sight of what developing countries are up against in their often losing battles against death in children. So many young South Africans die every year of respiratory infections that he decided to make preventing and treating those infections his life’s work. The AIDS epidemic has made this work more important than ever.
     “Pneumonia is a big problem at the extremes of life everywhere in the world,” he says, “but it is astonishing in South Africa. Plotting age against incidence of pneumonia typically produces a U curve. But now in South Africa, the curve is like a W, because of the huge burden of HIV. Huge numbers of people are dying of AIDS-related pneumonia at the prime of their life, and because of it, the average life expectancy is dropping into the 30s.”
From 1995 to 2000, Klugman served as director of the South African Institute for Medical Research, the country’s parallel agency to the CDC. In 2001, he decided to plant his flag at Emory.
     “His presence has placed our school at the cutting edge of infectious disease research in Atlanta and around the world,” says Dean James Curran. “A real scientific force, he has more than 300 publications in major peer-reviewed journals, and his studies are supported by many government, foundation, and industry sources. He is a world leader and is helping make our school a world leader as well.”
     Leaving the top public health job in South Africa was largely a matter of politics, says Klugman. “Like our current CDC, South African health agencies have become more politically oriented, and the top job became a political appointment. The government in South Africa decided that the head of it should be a financial business person rather than a scientist. So there was a parting of the ways. I decided to retain my research unit in South Africa but look for opportunities in global health internationally.”
     Klugman remains deeply committed to improving health conditions in South Africa. He maintains a cohort of almost 40,000 children in Soweto and directs the University of Witwatersrand Respiratory and Meningeal Pathogens Research Unit in Johannesburg. Although he returns often to South Africa for work, coming to Emory has given his work a more global reach.
He travels literally around the world several times a year. Klugman’s latest trip took him to South Africa, China, and then London for an interview for the BBC and a meeting with the Wellcome Trust, for which he chairs the Tropical Interview Committee.
  For many years, the president of South Africa denied that HIV causes AIDS, and a clear “anti-science bias” emerged within the government. Although the climate is improving, thanks to lawsuits brought by HIV-infected people demanding treatment, the place where politics and science intersect remains murky in South Africa. Klugman was recently mystified, but not too surprised, by a letter thanking him for his services to a South African government vaccine advisory group but notifying him that the group was being dissolved. The news came on the heels of Klugman’s landmark pneumonia vaccine trial published in 2003 in the New England Journal of Medicine. The study of almost 40,000 South African children concluded overwhelmingly that the pneumonia vaccine could save thousands of lives among HIV-positive as well as HIV-negative children.
     “Vaccine use must be directed by good science, and developing countries like South Africa with a high burden of disease have enormous challenges to meet,” Klugman says. Once people are sick, diagnosing and treating pneumonia can be expensive, requiring tests like X-rays not readily accessible in developing countries. Lack of access to diagnostic tools is a key barrier to appropriate care, he says.
       He is a member of an international group of researchers who recently received a Grand Challenge grant from the Bill and Melinda Gates Foundation. The program seeks creative, yet scientifically sound solutions to obstacles to overcoming disease and death in developing countries. The proposition submitted by Klugman and his colleagues was among 43 selected out of more than 1,500 submitted by scientists in 75 countries. The group hopes to design an end point for clinical trials that would act as a substitute for more expensive vaccine trials for prevention of pneumonia.
     Since the leading cause of pneumonia is pneumococcus, Klugman wondered if prevention of carriage of the organism in the back of the nose in young children might indicate vaccine-attributable prevention of pneumonia. “We wanted to work out whether just demonstrating the impact of vaccine on carriage could be a surrogate for demonstrating protection against pneumonia. Our group and others are conducting new studies to define the relationship between carriage of pneumococci—in which a person carries the bacteria in the back of the throat but isn’t sick—and the development of pneumonia. So far, it seems that carriage is a necessary precursor to invasive disease. It could well be that the impact of the pneumococcal vaccine on pneumonia is through its ability to protect against carriage.”
     Why the normally benign physiologic state of carriage leads to pneumonia is another question Klugman is seeking to answer. “We have really good evidence that viral infections such as influenza can upset the immunologic balance that keeps the bacteria in check,” he says. “If pneumococci are present, then influenza can allow the bacteria to invade. It does this in many ways but mainly seems to disrupt the integrity of the epithelial lining of the back of the nose, making it vulnerable to bacterial invasion.”
     Klugman’s paper in the August 2004 issue of Nature Medicine shows that the new pneumonia vaccine decreases the number of severe influenza-related hospitalizations among young children. Some people die of the actual influenza viral infection, but a large proportion of deaths stem from the secondary bacterial infections that follow influenza. “So this paper showed that children who got the pneumococcal vaccine had less influenza-related pneumonia,” says Klugman.
     The study showed that a nine-valent pneumococcal vaccine prevented 31% of pneumonias associated with any of seven respiratory viruses. It thus confirmed a role for the pneumococcus in virus-associated pneumonia.
  HIV infection, however, drives the incidence of pneumonia out of kilter everywhere in Africa, and particularly in South Africa.
     “Even in communities where HIV is very common in adults and even where there are programs to halt transmission from mothers to children with the use of antiretroviral drugs during pregnancy, you still get about 10% transmission, so at least 3% of all kids born are HIV infected,” says Klugman.
     That small fraction of children carry such a huge burden of pneumonia that the total burden of pneumonia has increased about three-fold in the community at large because this group of children has 100 times increased risk of getting pneumonia.
“That’s a 300% increase in the burden of pneumonia in the community,” says Klugman.
      “In our vaccine trial we found that the pneumococcal vaccine prevented pneumonia in HIV-positive and HIV-negative children. That was a landmark finding and establishes a good foundation for inoculating all HIV-positive children with the pneumococcal vaccine.”
     And HIV amplifies the need for all measures to prevent infectious disease.
  Klugman’s work to prevent pneumonia through vaccines also includes a vaccine to protect against Hemophilus influenzae type B (HIB), the second leading cause of pneumonia in children in developing countries. This vaccine is commonly available in the United States and other western countries but is largely unavailable in the developing world. “I’m trying to find strategies for both of these vaccines to be more affordable and to be introduced more rapidly into developing countries,” he says.
     Surveillance of infectious diseases is another important area of Klugman’s work. “Infectious diseases are pliable—they can change and adapt, as in the case of antibiotic resistance. There is also the real threat of new emerging infections,” he says. “We must help developing countries develop the capacity for surveillance. My research unit in South Africa pioneered surveillance for a lot of important diseases including pneumococcus, HIB, and Neisseria meningitidus, which is the third leading cause of meningitis. We also have surveillance there now for opportunistic infections such as cryptococcal disease—a severe kind of fungal meningitis particularly associated these days with HIV infection.”

  Now that solid infectious disease surveillance programs are established in South Africa, Klugman hopes to spread them to the rest of the developing world. In July 2005, he was appointed chair of the International Committee of the American Society for Microbiology (ASM), a group with more than 40,000 members and a large full-time staff in Washington, D.C. He hopes to leverage this role to increase surveillance capacity and improve training for microbiologists in developing countries. For example, the ASM recently collected more than $30,000 to boost infectious disease surveillance in the wake of the tsunami in Banda Aceh, Indonesia.
     No matter where Klugman goes, he knows that politics are part and parcel of all public health work. Like Bill Foege, the namesake of the chair he holds, he values leveraging public resources to gain the most public good. He is now lending his experience and expertise to the U.S. government. This past year, his ASM committee received funding from the President’s Emergency Plan for AIDS Relief, a five-year, $15 billion initiative to combat the HIV/AIDS pandemic worldwide. The program aims to provide antiretroviral drugs for 2 million HIV-infected people, prevent 7 million new infections, care for 10 million people, including orphans, affected by the disease, and build health care capacity in Africa and the Caribbean.
     Klugman is well qualified to advise the government on how to accomplish such sweeping goals. Indeed, he knows how to move on the ground, adapt to changing times and conditions, and make a lot out of a little. These skills, honed in the turbulent dust of South Africa, now reach out to the world from a corner office in the Hubert Department of Global Health. Although this thoroughly modern scientist has found a home in the richest country in the world, he remains, at heart, a true son of Africa.
  Valerie Gregg is a freelance writer in Atlanta and former editor of this magazine.  


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