A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation. 1. Background The paper discusses the immunology behind the reported nonspecific effects of DTwP and BCG vaccination: increased childhood mortality rates after DTwP and decreased mortality rates after BCG vaccination given during the course of the WHO recommended vaccine programs implemented in Guinea-Bissau and other low-income countries [1, 2]. Both the detrimental and the beneficial effects of vaccination are strongest in females [3–7]. We speculate here that vaccine-induced changes in innate and adaptive immunity may play a role. 2. DTwP Vaccine According to the WHO recommendations children in low-income countries are vaccinated against diphtheria, tetanus, and pertussis at 6, 10, and 14 weeks of age. Most countries use a whole-cell Bordetella pertussis vaccine. A typical DTwP vaccine dose (0.5？mL) from the Serum Institute of India contains diphtheria toxoid (25？Lf), tetanus toxoid (5？Lf), and pertussis toxoid (4？IU), aluminium phosphate (1.5？mg), and a preservative, thiomersal (0.01%). Aluminium phosphate acts primarily as an antigen-adsorbing and Th2-polarizing adjuvant [8]. Intramuscular vaccine injection results in a palpable sore induration at the site of injection in 70% of children. In 9% of the children the induration lasts 4 weeks and there is a significant correlation between local reactivity and fever (J. Agergaard, personal communication). 3. Increased Mortality after DTwP Vaccination The major causes of death in general among children in Guinea-Bissau are related to gastrointestinal infections with diarrhoea and dehydration, pneumonia and septicaemia, whereas the risk of death
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