Is susceptibility to severe infection in low-income countries inherited or acquired?

From a low-income country perspective, we need to emphasize factors which affect acquired susceptibility to severe infection. Such factors may lend themselves to modification by public health interventions. The present paper reviews the experience with understanding the causes of severe measles infection and the impact of health interventions in Guinea-Bissau over a 28-year period. In the 1970s, acquired susceptibility because of malnutrition was considered to be the main cause of high mortality. However, we found no association between nutritional status and subsequent risk of dying of measles. Instead, crowding and intensity of exposure were the main determinants of severe measles. Factors related to transmission have been substantiated for measles, chickenpox, whooping cough and polio. We found measles vaccination to be associated with a major reduction in mortality, particularly for girls. This suggested that measles vaccine has a beneficial nontargeted immune stimulatory effect. The importance of nontargeted effects was clearly documented when World Health Organization introduced a new high-titre measles vaccine (HTMV). HTMV was fully protective but associated with twofold higher mortality for girls. Bacille Calmette Guérin (BCG), diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) have also shown nontargeted effects, the effect being beneficial for BCG and OPV but negative for DTP. Both beneficial and negative effects are strongest for girls. There are many acquired factors, which affect susceptibility to infection in ways which have not been explored by medical science. They may have a major impact on child survival in low-income countries.