Authors' objectives

To quantify the efficacy of vaccination of infants with bacillus Calmette-Guerin (BCG) against tuberculosis.

Searching

MEDLINE was searched (search years unclear) using the index terms 'BCG vaccine', 'tuberculosis' and 'human', and the references of all retrieved articles were reviewed. Unpublished studies were identified by examining previously compiled lists of BCG studies and articles providing an overview of these studies, and by contacting experts on BCG vaccination and knowledgeable individuals (World Health Organization and the Centers for Disease Control and Prevention). The search was not limited to English language articles.

Study selection

Assessment of study quality

For RCTs the criteria included: method of assignment to vaccination or control arms, loss to follow-up, equality of surveillance between control and vaccination arms, diagnostic criteria and preparation of BCG. For case-control studies, diagnostic criteria and potential bias in the collection of information, such as vaccine status, were examined. The authors do not state how the papers were assessed for validity, or how many of the authors performed the validity assessment.

Data extraction

At least two readers independently extracted the data, with adjudication by a third reader if disagreements arose. The categories of data extracted are listed in the paper. Relative risks (RRs) were calculated for each trial and odds ratios (ORs) were calculated for the case-control studies.

Methods of synthesis

Results of the review

Five RCTs and 11 case-control studies were included. The numbers of participants in each trial were not given.

Tuberculosis cases: RCTs (n=4), combined RR 0.258 (95% CI: 0.174, 0.384, p<0.05); case-control studies (n=9), combined OR 0.476 (95% CI: 0.365, 0.621, p<0.05).

Tuberculosis deaths: RCTs (n=5), combined RR 0.352 (95% CI: 0.140, 0.882, p<0.05).

Laboratory confirmed cases: case-control studies (n=3), combined OR 0.174 (95% CI: 0.072, 0.418, p<0.05).

Tuberculous meningitis: case-control studies (n=3), combined OR 0.356 (95% CI: 0.18, 0.70, p<0.05).

Disseminated tuberculosis: case-control studies (n=3), combined OR 0.22 (95% CI: 0.117, 0.419, p<0.05).

Heterogeneity in the case-control studies was not explained by data validity score or distance from the equator. The RCTs were homogeneous.

Most of the duration-specific evidence suggests that BCG efficacy may persist through 10 years after infant vaccination.

Authors' conclusions

BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis by over 50% on average. Protection has been observed across many populations, study designs and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

CRD commentary

The authors use a well-defined specific question and make a good search for unpublished literature, although it would have been useful to search more than one electronic database for published studies. Inclusion criteria are clear, an assessment of validity is undertaken and the data from different study designs are kept appropriately separate. The review could have been improved with more details of primary studies, especially numbers of participants in each study and validity scores, although validity scores were not found to affect the results in a regression model for case-control studies. The authors' conclusions follow from the results presented.

Implications of the review for practice and research

The authors state that future studies might consider whether the administration of a booster dose of vaccine in childhood would further enhance BCG efficacy and extend its duration.

Funding

United States Centers for Disease Control and Prevention.

Bibliographic details

Colditz G A, Berkey C S, Mosteller F, Brewer T F, Wilson M E, Burdick E, Fineberg H V. The efficacy of Bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 1995; 96(1 Part 1): 29-35. [PubMed: 7596718]

Other publications of related interest

1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. 2. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. The efficacy of bacillus Calmette-Guerin vaccination in the prevention of tuberculosis: meta-analysis of the published literature. JAMA 1994;271:698-702.

Indexing Status

Subject indexing assigned by NLM

MeSH

BCG Vaccine /therapeutic use; Case-Control Studies; Clinical Trials as Topic; Humans; Infant; Infant, Newborn; Odds Ratio; Risk; Treatment Outcome; Tuberculosis /prevention & control

AccessionNumber

11995001914

Database entry date

31/01/2000

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.