by Valerie Gregg ormally, pneumococcal bacteria live a peaceful life in the back of the human throat. The immune system keeps the colony in check but doesn't kill it off completely. But sometimes, the bacteria get the upper h and. They multiply and travel to the lungs, the middle ear, or through the bloodstream to the brain, causing ear infections and potentially fatal pneumonia and meningitis. Each year, more than a million people worldwide die of pneumococcal infections. Although antibiotics save many lives, they have also complicated the relationship between bacteria and humans. Bacteria adapt quickly to changing environments -- including those flooded regularly with antibiotics. Widespread immune suppression due to HIV infection has also played in favor of the pneumococcus. South African scientist and physician Keith Klugman, a newly appointed professor of international health, has grappled with these problems for much of his career. The place where drug-resistant microbes and HIV collide is his special area of expertise. In developing countries, pneumococcal diseases cause one-fifth of all deaths among children under 5 and almost one-third of infant deaths. In South Africa, which has one of the highest HIV infection rates in the world, about 30% of pregnant women are HIV positive. Five percent of all babies are born infected with the virus. "About 73% of bloodstream pneumococcal infections in South Africa are now associated with HIV," he says. "It's devastating and overwhelming. And anti-retroviral drugs are unavailable to the public. The official government stance has been that providing these drugs would be too expensive. But many South African scientists feel strongly about at least providing them to pregnant women to stop transmission to children. The South African scientific community is working hard to provide the science to prove t hat preventing transmission of HIV to babies from infected mothers is cost-effective." In this troubled environment, Klugman worries most about the children. In South Africa, HIV is transmitted from an infected mother to her newborn child 25% to 30% of the time. These children are particularly vulnerable to recurring pneumococcal infections. Because these children are treated so often with antibiotics, they are easy prey for drug-resistant strains. Klugman's South African research team is investigating immunological strategies to head off drug-resistant infections before they start. About 40,000 children in Soweto are now enrolled in a trial of a pediatric pneumococcal conjugate vaccine very simi lar to one recently approved by the FDA in the United States. "We hope to find out if the vaccine is effective in preventing pneumonia. We also want to know if the vaccine will prevent pneumonia in HIV-infected children," he says. "Up until now, there have been no studies of the efficacy of vaccines to prevent op portunistic infections in HIV-infected children." The US vaccine is based on the seven most common types of pneumococcus in the United States. The experimental version Klugman is studying includes protection against those seven pneumococcal serotypes and two others found in developing countries. The v accine itself consists of the sugar capsules that surround each type of pneumococcus. Vaccination enables the immune system to recognize and fight the real thing. Previous vaccine studies in South Africa have shown that there is less transmission of pneumococci among groups of vaccinated children. "If a vaccinated child is exposed to pneumonia of a serotype included in the vaccine, they are less likely to be col onized," says Klugman. Because vaccinated children are less likely to require antibiotics to fight infections, the bacteria living in their bodies become less resistant to drugs over time. Vaccines may be the most successful way to combat antibiotic resistance globally, beca use they limit the need for antibiotic drugs in the first place, Klugman says. Previous studies of physicians' prescription habits are telling. "At the societal level, prescription patterns tell us much about the trends in antibiotic-resistant bacteria within a region," says Klugman. "For example, a study in Atlanta showed that bacterial infections among inner city children are less likely to be antibiotic resistant than those among more well-off children in the suburbs, who have better access to health care and antibiotics.

"We have seen contrasting results in South Africa. In lower socioeconomic groups there tends to be a lot of penicillin resistance because penicillin is frequently given out at public health clinics. In more affluent communities, there is less res istance to penicillin but more resistance to erythromycin, because that's what doctors there more often prescribe. Prescription patterns also relate to a patient's age. Young children tend to get more antibiotics and thus have more resistance. In South Af rica, the most dire problem with antibiotic-resistant bacteria is associated with HIV infection. The reason is that, like very young children, HIV-infected patients tend to be prescribed antibiotics more often." Before moving to the United States, Klugman was a professor at the University of Witwatersrand in Johannesburg. He plans to continue his work there as director of the Pneumococcal Diseases Research Unit of the Medical Research Council. In addition to h is primary position at RSPH, he holds joint appointments in the Emory School of Medicine and the Centers for Disease Control and Prevention. A physician with a PhD in physiology and postdoctoral degrees in pathology and microbiology, Klugman has authored more than 200 publications in major peer-reviewed journals. He has settled in nicely at his new office on the seventh floor of the Grace Crum Rollins Public Health Building, where he enjoys a view of the Atlanta skyline. He is busy mapping out a new public health course on global microbial resistance and is ass embling a research team to focus on the problem as well. Reynaldo Martorell, chair of International Health at RSPH, is clearly delighted to add Klugman to the faculty. "His presence will expand our expertise in fields at the cutting edge of infectious disease research and strengthen our links to the infectious disease community in Atlanta and around the world," says Martorell. "Keith is extremely approachable and eas ygoing, and a great collaborator. He projects an incredible sense of energy and is quick to articulate plans for research, public health application, and teaching. He's a great catch."

Microscopic Survivors In the ongoing battle between humans and pneumococcus, natural selection sides with bacteria. Here's why: Mutations occur randomly with reproduction in any population, including bacteria. Because bacteria can reproduce quickly and in great numbers, mutations frequently arise.   Over time, a few bacteria will reproduce with mutations that allow them to evade antibiotics. Some gain features like "molecular pumps" to eject antibiotics. Others create enzymes that neutralize drugs.   After treatment with a course of antibiotic, susceptible bacteria are eliminated, but the mutant bacteria remain. These drug-resistant survivors, now adapted to an environment commonly flooded with antibiotic agents, proliferate.