Published 24 July 2008, doi:10.1136/bmj.a661
Cite this as: BMJ 2008;337:a661

Research

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

Cesário L Martins, clinician, PhD student1, May-Lill Garly, senior researcher1,2, Carlito Balé, clinician1, Amabelia Rodrigues, research director1, Henrik Ravn, senior statistician1,2, Hilton C Whittle, professor3, Ida M Lisse, senior registar4, Peter Aaby, professor1,2

1 Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau, 2 Bandim Health Project, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark, 3 MRC Laboratories, Fajara, Gambia, 4 Department of Pathology, Herlev University Hospital, Denmark

Correspondence to: P Aaby p.aaby{at}bandim.org

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] [ClinicalTrials.gov].


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

Early vaccination against measles in developing countries
H Broutin and M A Miller
BMJ 2008 337: a406. [Extract] [Full Text]

Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries
Peter Aaby, Badara Samb, Francois Simondon, Awa Marie Coll Seck, Kim Knudsen, and Hilton Whittle
BMJ 1995 311: 481-485. [Abstract] [Full Text]

This article has been cited by other articles:

  • Reyes-del Valle, J., Hodge, G., McChesney, M. B., Cattaneo, R. (2009). Protective Anti-Hepatitis B Virus Responses in Rhesus Monkeys Primed with a Vectored Measles Virus and Boosted with a Single Dose of Hepatitis B Surface Antigen. J. Virol. 83: 9013-9017 [Abstract] [Full text]  
  • Wolfson, L. J, Grais, R. F, Luquero, F. J, Birmingham, M. E, Strebel, P. M (2009). Estimates of measles case fatality ratios: a comprehensive review of community-based studies. Int J Epidemiol 38: 192-205 [Abstract] [Full text]  
  • Broutin, H, Miller, M A (2008). Early vaccination against measles in developing countries. BMJ 337: a406-a406 [Full text]  

Rapid Responses:

Read all Rapid Responses

Early Admistration of measles vaccination
N.P. Viswanathan
bmj.com, 28 Jul 2008 [Full text]
Advancement of measles vaccineto 4.5 months
N.P. viswanathan
bmj.com, 29 Jul 2008 [Full text]
Correction to my response
N.P. Viswanathan
bmj.com, 29 Jul 2008 [Full text]
Re-reevaluation of Edmonston Zagreb measles vaccine may be unethical
Bedangshu Saikia, et al.
bmj.com, 18 Sep 2008 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ