Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls. A randomised trial from Guinea-Bissau

Background: Combined vaccination with diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) has been associated with increased mortality in observational studies. Among children missing MV and a dose of DTP and oral polio vaccine (OPV), we conducted a randomised trial of providing MV + DTP + OPV simultaneously, as currently recommended, or MV + OPV only, and examined the effect on morbidity and growth. We hypothesised that the MV + OPV group would experience less morbidity and grow better. Due to previous observations of sex differences in the non-specific effects of vaccinations, we analysed all data stratified by sex. Methods: At the Bandim Health Project in Guinea-Bissau. 568 children who were due to receive MV and who were missing either DTP3 or DTP booster were enrolled in the study. A subgroup of 332 children was followed intensively to register adverse events and infections in the first month after vaccination. A subgroup of 276 children was followed every third month for a year to monitor growth. All children were followed for one year for infectious diseases, consultations, and hospitalisations. Results: As expected, adverse events were more common in the MV + DTP + OPV group; diarrhoea and use of medication were increased among girls but not among boys (both p = 0.02, test of interaction between DTP and sex). Febrile disease with vesicular rash, as well as consultations and hospitalisations tended to be more common in the MV + DTP + OPV group than in the MV + OPV group; the hazard ratio (HR) for febrile disease with vesicular rash was 1.86 (1.00; 3.47). The strongest tendencies for more febrile diseases and hospitalisations in the MV + DTP + OPV group were found in girls. Overall, growth did not differ by randomisation group. However, results differed by sex. Girls in the MV + DTP + OPV group had a consistent pattern of worse z-scores for weight, height, and mid-upper-arm-circumference (MUAC) than girls in the MV + OPV group. The effect was opposite for boys, with boys in the MV + OPV group faring worse than those in the MV + DTP + OPV group, the interaction test for sex and DTP being significant for weight at 6 and 9 months, for MUAC at 12 months and for weight-for-height at 3 and 9 months after randomisation. Conclusion: This is the first randomised trial of the non-specific effects of DTP and supports that these effects may be sex-differential and of clinical and anthropometric importance. Combined vaccination with DTP + MV + OPV may be detrimental for girls. (C) 2010 Elsevier Ltd. All rights reserved.