Nonspecific effects of vaccines and the reduction of mortality in children.

There is now strong evidence that vaccines have substantial nonspecific (heterologous) effects in children in high-mortality regions. The hypothesis states that, until a different vaccine is given: (1) live vaccines induce a protective nonspecific immune response, whereas inactivate vaccines cause a harmful nonspecific immune response; (2) Bacillus Calmette-Guerin (BCG) vaccine approximately halves mortality from infections other than tuberculosis; (3) provided vitamin A was not given at birth, measles vaccine approximately halves mortality from infections other than measles (this effect may be stronger if the child still has maternal antibody); and (4) whole-cell diphtheria-tetanus-pertussis (DTP) vaccine increases mortality from infections other than diphtheria, tetanus, and pertussis (this effect is stronger in girls than boys). These observations suggest that minor modifications to the routine immunization schedule could reduce child mortality by at least 30%, and they have important implications for the design of randomized trials of vaccines in high-mortality regions.