Short summary

Observational studies show that co-administration of Bacillus-Calmette Guérin vaccine (BCG) and diphtheria-tetanus-pertussis vaccine (DTP) is associated with 43% (27-54%) lower mortality than BCG followed by DTP. We will implement a randomised trial in Guinea-Bissau, including 6000 children, to test the hypothesis that an extra dose of BCG given with DTP3 can reduce death and hospital admissions with 25% between 3 and 12 months of age.

Rationale

Studies in low-income countries show that vaccines can have important non-specific effects on other infections. Live BCG vaccine can train the immune system and reduce susceptibility to unrelated infections. In contrast, non-live diphtheria-tetanus-pertussis (DTP) vaccine enhances susceptibility in females: DTP vs no DTP is associated with 2-fold higher mortality, and in DTP-vaccinated children, females have higher mortality than males. These effects are seen as long as a vaccine is the most recent vaccine. WHO recommends BCG at birth followed by three DTP vaccines. Observational studies show that co-administration of BCG+DTP is associated with 43% (27-54%) lower mortality than BCG followed by DTP. Hence, in a randomised trial in Guinea-Bissau, we will test the hypotheses: - BCG2+DTP3 vs. DTP3 reduces death and hospital admissions by 25% - BCG2+DTP3 reduce the F/M severe morbidity hazard ratio

Description of the cohort

Children registered in the Bandim Health Project urban health and demographic surveillance system will be included at age 14-24 weeks if they have received the second dose of DTP (DTP2) at least 4 weeks prior, are due to receive DTP3, are not ill, and have no severe malformations. The children will be randomised 1:1 in blocks, stratified by sex, to receive BCG2+DTP3 or DTP3. Children are followed from enrolment until death, migration, measles vaccination, age 12 months, or end of study.

Data and biological material

The main data material for the trial is questionnaire data combined with Bandim Health Project registry data. Pending additional funding, 40 infants will be included in an immunological sub study. Two capillary blood samples will be taken before randomisation and after 4 weeks.

Collaborating researchers and departments

Radboud University

• Prof. Dr Mihai Netea