Search results

Background Tuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette‐Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis. Objectives To assess and summarize the effects of the MVA85A vaccine boosting BCG in humans. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018. Selection criteria We evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status. Data collection and analysis Two review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta‐analyses. Where meta‐analysis was inappropriate, we summarized results narratively. Main results The search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV‐positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV‐exposed infants. The largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition endpoints for active tuberculosis published prior to the trial analysis. MVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing microbiologically confirmed tuberculosis (RR 0.97, 95% CI 0.58 to 1.62; 3439 participants, 2 trials; moderate‐certainty evidence), or the risk of starting on tuberculosis treatment (RR 1.10, 95% CI 0.92 to 1.33; 3687 participants, 3 trials; moderate‐certainty evidence). MVA85A probably has no effect on the risk of developing latent tuberculosis (RR 1.01, 95% CI 0.85 to 1.21; 3831 participants, 4 trials; moderate‐certainty evidence). Vaccinating people with MVA85A in addition to BCG did not cause life‐threatening serious adverse effects (RD 0.00, 95% CI –0.00 to 0.00; 3692 participants, 3 trials; high‐certainty evidence). Vaccination with MVA85A is probably associated with an increased risk of local skin adverse effects (3187 participants, 3 trials; moderate‐certainty evidence), but not systemic adverse effect related to vaccination (144 participants, 1 trial; low‐certainty evidence). This safety profile is consistent with Phase 1 studies which outlined a transient, superficial reaction local to the injection site and mild short‐lived symptoms such as malaise and fever. Authors' conclusions MVA85A delivered by intradermal injection in addition to BCG is safe but not effective in reducing the risk of developing tuberculosis.

BACKGROUND: Tuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette‐Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis. OBJECTIVES: To assess and summarize the effects of the MVA85A vaccine boosting BCG in humans. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018. SELECTION CRITERIA: We evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta‐analyses. Where meta‐analysis was inappropriate, we summarized results narratively. MAIN RESULTS: The search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV‐positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV‐exposed infants. The largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition ...

A retrospective survey, based on a standardized questionnaire sent to qualified public health experts in tuberculosis in 50 European countries, was carried out to evaluate the following: concordance between national vaccination programmes and WHO recommendations on BCG vaccination for prevention of tuberculosis; relation between BCG vaccination and revaccination policy and the tuberculosis epidemiological situation; and differences in BCG vaccination policy between Western and Central-Eastern European countries. The results obtained (from 41 (82%) of the 50 countries) revealed that BCG vaccination programmes met WHO recommendations in 44% of European countries. Mass primary vaccination and general revaccination were extremely common in countries where the prevalence of tuberculosis was high. A highly significant difference was found between Western and Central-Eastern European countries in terms of their adhesion to WHO recommendations. Within Central-Eastern Europe no difference was found between countries that had or had not been part of the former Soviet Union. The implementation of WHO recommendations into national tuberculosis programmes must be intensified, based on the available body of evidence. Preventive methods whose cost-effectiveness has not been properly established should be discouraged.