Abstract

PIP: The Karonga (Malawi) Prevention Trial revealed that repeat BCG vaccinations did not protect against pulmonary tuberculosis (TB) but appeared to provide some protection against glandular TB. They increased protection against leprosy. In fact, a single BCG vaccination conferred 50% protection against leprosy and a repeat BCG vaccination increased protection by another 50%. This trial's findings confirm the need for maintaining BCG vaccination programs in countries where leprosy is a public health problem, for individuals at high risk of leprosy (i.e., contacts of leprosy cases), and because BCG provides some protection against severe forms of TB (i.e., miliary disease and TB meningitis). An alternative TB vaccine needs to be developed, however. The protective efficacy of BCG against pulmonary TB is higher at latitudes far from the equator (80% in northern Europe vs. 0% in India and Malawi). It appears that the immunologic effects of environmental mycobacteria compromise BCG's protective effect against pulmonary TB. There is heterologous immunity between various mycobacterial infections. Low-level delayed-type hypersensitivity (DTH) to tuberculin in non-BCG vaccinated people reflects exposure to environmental mycobacteria. These people are at lower risk of TB than are people with either no DTH or strong DTH to tuberculin. Intradermal exposure to different mycobacteria provides varying degrees of protection against TB in guinea pigs. The warmer and the wetter the environment, the more widespread is colonization by mycobacteria. An area of future research is mapping the distribution of environmental mycobacteria, correlating it with the pattern of DTH responses to tuberculin, and then laboratory work to isolate relevant antigens of the mycobacteria. Another approach is identifying mycobacterial antigens that elicit protective immune responses in vitro so researchers can then identify which antigens and responses are associated with patterns of DTH known to reflect low risk of TB and which response patterns are elicited by BCG against leprosy but not TB antigens. New vaccines are not on the imminent horizon, however.