Dartmouth Investigators to Study Tuberculosis and New Vaccine in Africa

Hanover, NH -- Dartmouth Medical School announced today that faculty members will begin a study of tuberculosis and HIV infection in Africa early next year. Infectious disease researchers at Dartmouth Medical School have been awarded a $2.4 million grant by the National Institutes of Health to conduct this five-year study. The purpose of the study is to determine why many AIDS patients in Africa develop a severe form of tuberculosis that involves the spread of the organism through the bloodstream and to attempt to prevent this complication with a new booster vaccine. This complication, known as disseminated tuberculosis, has been found in as many as 15 to 20% of persons dying with AIDS in developing countries.

In studies conducted in the early 1990s, Dartmouth investigators collaborated with colleagues in London and Kenya on studies of hospitalized patients with AIDS in Africa. According to Dr. Ford von Reyn, professor of medicine at Dartmouth Medical School and chief of the Infectious Disease Section at Dartmouth-Hitchcock Medical Center, the investigators were surprised to find that 23% of patients dying with AIDS also had tuberculosis in the bloodstream. Subsequently, the Dartmouth group and other investigators documented similar rates of this complication in other developing countries and began to recognize the need for understanding risk factors for this and for developing a strategy to prevent it.

A recent investigation conducted by Dartmouth researchers in Zambia showed that 12% of hospitalized AIDS patients had tuberculosis in their bloodstream, according to Dr. Richard Waddell, who directed the investigation. Because the symptoms of these patients were similar to advanced AIDS, the diagnosis of tuberculosis was generally not recognized, and many of the patients died before discharge from the hospital.

The new NIH-sponsored study will be conducted in Dar es Salaam, Tanzania, with collaborators from the Muhimbili Hospital Medical Center. Over 2,000 persons with early HIV infection will be tested for evidence of immunity to tuberculosis and then followed to determine risk factors for disseminated tuberculosis. According to von Reyn, "A principal objective of the study is to determine why this complication develops in some patients, but not others, and to see if it can be prevented. Our principal collaborator at Muhimbili Hospital, Dr. Kisali Pallangyo, has already shown that 20% of AIDS patients hospitalized in Dar es Salaam have disseminated tuberculosis."

The other main objective of the upcoming Tanzania study is to determine whether a new booster vaccine against tuberculosis can prevent disseminated tuberculosis in AIDS patients. The vaccine to be tested in the African study has been tested in pilot studies by Dartmouth investigators in the United States, Finland and Zambia. The vaccine, known as Mycobacterium vaccae and developed at SR Pharma plc in London, was found to be safe in studies in the United States, and a subsequent vaccine study was then conducted in Zambia. In the Zambia study, people with HIV infection who received five doses of the vaccine had an increase in their immune response against tuberculosis, supporting the likelihood that the vaccine will offer protection against tuberculosis.

According to Waddell, M. vaccae appeared to act as a "booster" vaccine in Zambian adults who had already received the standard BCG vaccine against tuberculosis in childhood. BCG is a live vaccine and could not be safely re-administered to adults with known HIV infection to enhance their immunity against tuberculosis, according to von Reyn. However, M. vaccae is a killed vaccine, similar to vaccines that had been used before BCG was developed, and these killed vaccines had been shown effective in preventing tuberculosis. Dartmouth investigators are hopeful that multiple doses of the inactivated M. vaccae will boost immunity against tuberculosis in persons with HIV infection.

In the Tanzania study, subjects will receive either five doses of the new vaccine or five doses of placebo over a 12-month period. Subjects will then be seen every three months to detect and treat tuberculosis infections and to determine whether the vaccine reduces the risk of tuberculosis.

The principal investigator for the study at Dartmouth Medical School is Dr. C. Ford von Reyn, with co-investigators Drs. Richard Waddell and Bernard Cole. Other investigators in the study include Dr. C. Robert Horsburgh, chairman of epidemiology and biostatistics at Boston University School of Public Health; Dr. Robert Arbeit, assistant director for research at the Boston VA Healthcare System; Dr. Jenni Vuola of the Vaccine Immunology Division of the National Public Health Institute of Finland; Dr. Kisali Pallangyo, dean of the faculty of medicine at Muhimbili Hospital Medical Center in Dar es Salaam, Tanzania; and Dr. Ali Zumla, director of the Center for Infectious Diseases, University College London, Royal Free and University College Medical School, in London, United Kingdom. Vaccine for the study will be donated by SR Pharma plc, London.

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