A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Abstract

Background:

In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels.

Methods:

Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 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 enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels.

Results:

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

Conclusions:

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

Clinical Trials Registration:

NCT01644721.

• Authors: Ane B Fisker, Eric Nebie, Anja Schoeps, Cesario Martins, Amabelia Rodrigues, Alphonse Zakane, Moubassira Kagone, Stine Byberg, Sanne M Thysen, Justin Tiendrebeogo, Boubacar Coulibaly, Osman Sankoh, Heiko Becher, Hilton C Whittle, Fiona R M van der Klis, Christine S Benn, Ali Sie, Olaf Müller, Peter Aaby
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 66 Issue 10 Pg. 1573-1580 (05 02 2018) ISSN: 1537-6591 [Electronic] United States
• PMID: 29177407 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Measles Vaccine

Topics

• Antibodies, Viral (blood)
• Burkina Faso (epidemiology)
• Female
• Guinea-Bissau (epidemiology)
• Humans
• Immunization Schedule
• Infant
• Male
• Measles (blood, immunology, prevention & control)
• Measles Vaccine (administration & dosage, immunology)
• Measles virus (immunology)