A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions

Cesario L Martins, Christine S Benn, Andreas Andersen, Carlito Balé, Frederik Schaltz-Buchholzer, Vu An Do, Amabelia Rodrigues, Peter Aaby, Henrik Ravn, Hilton Whittle, May-Lill Garly, Cesario L Martins, Christine S Benn, Andreas Andersen, Carlito Balé, Frederik Schaltz-Buchholzer, Vu An Do, Amabelia Rodrigues, Peter Aaby, Henrik Ravn, Hilton Whittle, May-Lill Garly

Abstract

Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32-.86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of 0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558.

Keywords: Edmonston-Zagreb; hospital admissions; measles infection; measles vaccination; morbidity reduction; nonspecific effects of vaccine.

Figures

Figure 1.
Figure 1.
The cumulative incidence of hospital admissions, according to randomization group. Early recipients received measles vaccine at 4.5 and 9 months of age, and controls received vaccine at 9 months of age.

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