The Nonspecific Effects of Vaccines and the Expanded Program on Immunization

(See the article by Aaby et al, on pages 245–52.) There is now clear evidence that the simplistic conventional model of immunization is invalid [1]. We can no longer assume that a vaccine acts independently of other vaccines, or that it influences only infections caused by the target disease. Strong evidence from randomized trials suggests that bacillus Calmette-Guérin vaccine (BCG) reduces mortality from infections other than tuberculosis and that measles vaccine reduces mortality from infections other than measles [1–4]. However, there is worrying evidence that whole-cell diphtheria-tetanus-pertussis vaccine (DTP) may increase mortality from infections other than diphtheria, tetanus, or pertussis in high-mortality areas [1, 3–8]. These nonspecific effects of BCG, measles vaccine, and DTP are generally stronger in girls, appear to be maximal in the first 6 months after immunization, and are largely determined by the most recent vaccine administered [1]. Randomized trials show that measles vaccine has strong nonspecific effects. Providing it is not given after vitamin A or followed by DTP, measles vaccine reduces mortality from diseases other than measles by 45% (95% confidence interval [CI], 14%–65%) when given at 4.5 months of age [9], and by 47% (95% CI, 23%–63%) when given to girls at 9 to 10 months of age [1].