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Research

Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial

BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a661 (Published 24 July 2008) Cite this as: BMJ 2008;337:a661
  1. Cesário L Martins, clinician, PhD student1,
  2. May-Lill Garly, senior researcher12,
  3. Carlito Balé, clinician1,
  4. Amabelia Rodrigues, research director1,
  5. Henrik Ravn, senior statistician12,
  6. Hilton C Whittle, professor3,
  7. Ida M Lisse, senior registar4,
  8. Peter Aaby, professor12
  1. 1Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau
  2. 2Bandim Health Project, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
  3. 3MRC Laboratories, Fajara, Gambia
  4. 4Department of Pathology, Herlev University Hospital, Denmark
  1. Correspondence to: P Aaby p.aaby{at}bandim.org
  • Accepted 19 May 2008

Abstract

Objective To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age.

Design Randomised clinical trial.

Participants 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group.

Setting Urban area in Guinea-Bissau.

Intervention Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age.

Main outcome measures Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age.

Results 28% of the children tested at 4.5 months of age had protective levels of maternal antibodies against measles at enrolment. After early vaccination against measles 92% had measles antibodies at 9 months of age. A measles outbreak offered a unique situation for testing the efficacy of early measles vaccination. During the outbreak, 96 children developed measles; 19% of unvaccinated children had measles before 9 months of age. The monthly incidence of measles among the 441 children enrolled in the treatment arm was 0.7% and among the 892 enrolled in the control arm was 3.1%. Early vaccination with the Edmonston-Zagreb measles vaccine prevented infection; vaccine efficacy for children with serologically confirmed measles and definite clinical measles was 94% (95% confidence interval 77% to 99%), for admissions to hospital for measles was 100% (46% to 100%), and for measles mortality was 100% (−42% to 100%). The number needed to treat to prevent one case of measles between ages 4.5 months and 9 months during the epidemic was 7.2 (6.8 to 9.2). The treatment group tended to have lower overall mortality (mortality rate ratio 0.18, 0.02 to 1.36) although this was not significant.

Conclusions In low income countries, maternal antibody levels against measles may be low and severe outbreaks of measles can occur in infants before the recommended age of vaccination at 9 months. Outbreaks of measles may be curtailed by measles vaccination using the Edmonston-Zagreb vaccine as early as 4.5 months of age.

Trial registration Clinical Trials NCT00168558 [ClinicalTrials.gov].

Footnotes

  • We thank Mario Monteiro (Laboratório Nacional de Saúde Pública, Guinea-Bissau) and Elishia Roberts and Tibeh Faye-Joof (Medical Research Council Laboratories, the Gambia) for collection and analyses of blood samples.

  • Contributors: M-LG, CLM, HCW, IML, and PA designed the study. CLM and M-LG initiated the study routines. CLM and CB treated the children during the outbreak. AR supervised the routine registration system. CLM, PA, and HR analysed the data. CLM and PA wrote the first draft of the paper and all authors contributed to the final version. CLM and PA are guarantors.

  • Funding: The research on maternal antibodies that inspired the present trial was funded by the Thrasher Foundation. The present study was mostly funded by DANIDA and Fonden til Lægevidenskabens Fremme. The Bandim Health Project received support from DANIDA and the Danish National Research Foundation. PA holds a research professorship grant from the Novo Nordisk Foundation. The funding institutions had no role in the implementation and interpretation of the study.

  • Competing interests: None declared.

  • Ethical approval: The protocol was approved by the Danish central ethical committee, the Gambia/Medical Research Council scientific and ethics committees, and the Guinean Ministry of Health’s research coordination committee. Participants had access to free consultations at the local health centres and to essential drugs free of charge.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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