A two-centre randomised trial of an additional early dose of measles vaccine: Effects on mortality and measles antibody levels

Abstract

Background

Besides protecting against measles, measles vaccine (MV) may have beneficial non-specific effects. We tested the effect of an additional early MV on mortality and measles antibody levels.

Methods

Children aged 4-7 months in two rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomised 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus-influenzae-type-b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrolment to 3 years of age in Cox proportional hazards models, censoring for subsequent non-trial MV. Subgroups of participants had blood sampled at enrolment, before the 9 months MV and in the second year of life to assess measles antibody level.

Results

Among 8309 children enrolled July 18, 2012-December 3, 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomisation group (hazard ratio=1.05 (95%CI: 0.75-1.46)).At enrolment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By 9 months of age, no measles-unvaccinated/unexposed child had protective levels, while 92% (306/333) of early MV recipients had. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels.

Conclusion

Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at 4-7 months and responded with high antibody levels to early MV.