Randomised trial of not providing booster diphtheria-tetanus-pertussis (DTP) vaccination after measles vaccination and child survival: A failed trial

ABSTRACT Background In low-income settings, WHO recommended a booster-dose of DTP (DTP4) and OPV (OPV4) at 18 months of age. Previous studies found DTP after MV to be associated with higher female mortality. We conducted a randomised trial (RCTs) in Guinea-Bissau, in which children from 18 months of age were randomised to receive DTP4+OPV4 vs OPV4-only to assess the impact on survival and hospitalisations, overall and by sex. Methods The trial was conducted from 2005-2012. Children were randomised and followed from 18 months to 4 years of age. Hospitalisations were captured through a surveillance system at the main paediatric ward, and deaths were detected through a demographic surveillance system in the study area and through yearly home visits to the study participants. Data was analysed in Cox proportional hazards models. The RCT aimed to enrol 6,000 children based on an expected annual mortality rate of 3%. During the trial period many new interventions, including many national health campaigns, were carried out. Results The trial enrolled 5,918 children of which 96% (5,673) were included in the analysis. Annual non-accidental mortality rate was 0.56%, 81% lower than the expected rate. There was no difference in mortality between the randomisation groups. With 30 and 35 deaths, the hazard ratio (HR) for DTP4+OPV4 vs OPV4-only was 0.84 (95% CI=0.52-1.37); 0.86 (0.42-1.77) in males and 0.82 (0.42-1.60) in females. The HR for hospitalisations was 0.90 (0.77-1.06); 0.87 (0.70-1.09) in males; 0.94 (0.74-1.20) in females). Conclusion The study found no negative effect of DTP4 and no sex-differential effect of DTP4, but it was strongly underpowered. Furthermore, due to the large number of health interventions, not envisioned at the initiation of the trial, a limited part of the follow-up was a comparison between DTP4+OPV4 vs OPV4 as the most recent vaccinations.