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One current focus is multi-drug resistant TB in resource-poor countries, with a particular emphasis on how drug resistant TB is transmitted in the hospital and other settings, and how it should be treated given the great expense of second line drugs for treatment. Along with several faculty members from New Jersey Medical School, I am involved in extensive research in Uganda, a country that has been greatly impacted by the AIDS epidemic. We are working with faculty from Makerere University in Kampala, Uganda, and the London School of Tropical Medicine and Hygiene to study host and bacterial factors contributing to resistance and susceptibility to TB. A project funded by the NIH looks at lung immunity and is based in Mexico City. We are planning to assess how host immunogenetics and genetics of the bacteria impact on resistance to tuberculosis.

Early on, President Museveni acknowledged that AIDS is a problem and welcomed expatriates and non-governmental organizations to contribute to control measures and research. The result was a loud prevention message. This led to behavior changes with delays in start of sexual activity, greater monogamy/abstinence and increased use of condoms. With declining prevalence, there is the danger that HIV prevention approaches will become lax and the introduction of antiretrovirals will promote unsafe sex. I am somewhat involved in a prevention program funded by the Bill and Melinda Gates Foundation to avoid such a regression.

HIV infection increases the risk of TB 200- to 500-fold by increasing the risk that a latent TB infection will reactivate and a new infection or re-infection will progress to disease. Overall, 30 to 40 percent of AIDS patients die of TB. Before the occurrence of HIV infection, TB was the most common fatal infectious disease in the world. Now the incidence has increased in large part because of HIV. Other factors such as war, social disruption, famine and migration of populations also play a role.

I became involved in TB research before the epidemic spread of HIV infection, at a time when there was little interest in this disease in the U.S. When HIV emerged as the public health problem of our time, I decided to maintain my interest in the interactions of HIV with TB and other mycobacteria rather than switch my research focus entirely to HIV. I was involved in the U.S. through the AIDS Clinical Trials Group in issues related to management and prevention of TB and mycobacterium avium infection in the HIV-infected. I also was asked to take the lead with Dr. Frederick Robbins in developing a proposal to study AIDS in Uganda. Dr. Robbins received the Nobel Prize in Medicine for his role in cultivation of the poliovirus. After serving as chair of pediatrics at the then Cleveland Metropolitan General Hospital, dean of Case Western Reserve University and president of the Institute of Medicine, he returned to Case as Professor Emeritus and took on the challenge of developing an international collaboration in AIDS research. He asked me to help him organize the program and grant proposal, and in 1988 we launched the Case Western Reserve University - Uganda Research Collaboration, which developed to an unprecedented extent, giving me access to large numbers of patients with dual TB and HIV infections. I became the principal investigator of controlled clinical trials of the prevention and management of TB and HIV. David Hom, Robert Wallis and Stephan Schwander, now faculty in the Department of Medicine at NJMS, were involved in these early studies. Bob Wallis and I were jogging in Florence when we had an interesting Eureka moment. It suddenly seemed obvious that TB might accelerate the progression of HIV by activating the immune system. We proved this hypothesis to be correct and proceeded to studies of interventions that are still ongoing.

I used to think the only hope was a preventive vaccine. I organized programs in Uganda related to vaccine preparedness and served as principal investigator of the first AIDS vaccine trial in Africa. Unfortunately, an effective vaccine is not yet in sight. So I have changed my thinking to doing what can be done, short of the "big-fix." Prevention measures of the future potentially will include microbicides for women, treatment of herpes simplex virus infection, adult male circumcision and primary prevention in high risk populations. I do believe that HIV will be eradicated at some point by the development of an effective vaccine and the dying out of the infected populations who represent a reservoir for transmission. Until this happens though, everything possible must be done to prevent the spread of HIV, including treatment of those already infected.