Dataset Information

BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial.

ABSTRACT:

Background

Although BCG has been found to impart protection against leprosy in many populations, the utility of repeat or booster BCG vaccinations is still unclear. When a policy of giving a second BCG dose to school children in Brazil was introduced, a trial was conducted to assess its impact against tuberculosis, and a leprosy component was then undertaken in parallel.

Objective

to estimate the protection against leprosy imparted by a second dose of BCG given to schoolchildren.

Methods and findings

This is a cluster randomised community trial, with 6 years and 8 months of follow-up.

Study site

City of Manaus, Amazon region, a leprosy-endemic area in Brazil.

Participants

99,770 school children with neonatal BCG (aged 7-14 years at baseline), of whom 42,662 were in the intervention arm (revaccination).

Intervention

BCG given by intradermal injection.

Main outcome

Leprosy (all clinical forms).

Results

The incidence rate ratio of leprosy in the intervention over the control arm within the follow-up, in schoolchildren with neonatal BCG, controlled for potential confounders and adjusted for clustering, was 0.99 (95% confidence interval: 0.68 to 1.45).

Conclusions/significance

There was no evidence of protection conferred by the second dose of BCG vaccination in school children against leprosy during the trial follow-up. These results point to a need to consider the effectiveness of the current policy of BCG vaccination of contacts of leprosy cases in Brazilian Amazon region.

SUBMITTER: Cunha SS

PROVIDER: S-EPMC2238709 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial.

Cunha Sérgio S SS Alexander Neal N Barreto Mauricio L ML Pereira Emilia S ES Dourado Inês I Maroja Maria de Fátima Mde F Ichihara Yury Y Brito Silvana S Pereira Susan S Rodrigues Laura C LC

PLoS neglected tropical diseases 20080213 2

<h4>Background</h4>Although BCG has been found to impart protection against leprosy in many populations, the utility of repeat or booster BCG vaccinations is still unclear. When a policy of giving a second BCG dose to school children in Brazil was introduced, a trial was conducted to assess its impact against tuberculosis, and a leprosy component was then undertaken in parallel.<h4>Objective</h4>to estimate the protection against leprosy imparted by a second dose of BCG given to schoolchildren.< ...[more]

PMID: 18270542

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Project description:INTRODUCTION:Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (M.TB) and other species of the Mycobacterium tuberculosis complex. Globally, TB is ranked as the ninth leading cause of death and the leading cause of death from a single infectious agent. The bacille Calmette-Guerin (BCG) vaccine has been used globally since 1921 for the prevention of TB in humans, and was derived from an attenuated strain of Mycobacterium bovis. Evidence from previous randomised trials show that the efficacy of primary BCG vaccination against pulmonary TB ranged from no protection to very high protection. In addition, some studies suggest a benefit of BCG revaccination. For example, a recent trial conducted in South Africa showed that BCG revaccination of adolescents could reduce the risk of TB infection by half. However, we are not aware of any recent systematic reviews of the effects of BCG revaccination. Thus, the need for this systematic review of the effects of BCG revaccination on protection against TB infection and disease. METHOD AND ANALYSIS:We will search PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, WHO International Clinical Trials Registry Platform and reference lists of relevant publications for potentially eligible studies. We will screen search outputs, select eligible studies, extract data and assess risk of bias in duplicate. Discrepancies will be resolved by discussion and consensus or arbitration. We will use the Grading of Recommendations Assessment, Development and Evaluation method to assess the certainty of the evidence. The planned systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in August 2018. ETHICS AND DISSEMINATION:Publicly available data will be used, hence no formal ethical approval will be required for this review. The findings of the review will be disseminated through conference presentations and publication in an open-access peer-reviewed journal. PROSPERO REGISTRATION NUMBER:CRD42018105916.

Project description:BackgroundMore than 200,000 new cases of leprosy were reported by 105 countries in 2011. The disease is a public health problem in Brazil, particularly within high-burden pockets in the Amazon region where leprosy is hyperendemic among children.MethodologyWe applied geographic information systems and spatial analysis to determine the spatio-temporal pattern of leprosy cases in a hyperendemic municipality of the Brazilian Amazon region (Castanhal). Moreover, we performed active surveillance to collect clinical, epidemiological and serological data of the household contacts of people affected by leprosy and school children in the general population. The occurrence of subclinical infection and overt disease among the evaluated individuals was correlated with the spatio-temporal pattern of leprosy.Principal findingsThe pattern of leprosy cases showed significant spatio-temporal heterogeneity (p<0.01). Considering 499 mapped cases, we found spatial clusters of high and low detection rates and spatial autocorrelation of individual cases at fine spatio-temporal scales. The relative risk of contracting leprosy in one specific cluster with a high detection rate is almost four times the risk in the areas of low detection rate (RR = 3.86; 95% CI = 2.26-6.59; p<0.0001). Eight new cases were detected among 302 evaluated household contacts: two living in areas of clusters of high detection rate and six in hyperendemic census tracts. Of 188 examined students, 134 (71.3%) lived in hyperendemic areas, 120 (63.8%) were dwelling less than 100 meters of at least one reported leprosy case, 125 (66.5%) showed immunological evidence (positive anti-PGL-I IgM titer) of subclinical infection, and 9 (4.8%) were diagnosed with leprosy (8 within 200 meters of a case living in the same area).Conclusions/significanceSpatial analysis provided a better understanding of the high rate of early childhood leprosy transmission in this region. These findings can be applied to guide leprosy control programs to target intervention to high risk areas.

Project description:BackgroundTrials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi.MethodsThe Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality.FindingsFollow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54).InterpretationWe found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits.FundingBritish Leprosy Relief Association (LEPRA); Wellcome Trust.

Project description:BackgroundRecent Mycobacterium tuberculosis infection confers a predisposition to the development of tuberculosis disease, the leading killer among global infectious diseases. H4:IC31, a candidate subunit vaccine, has shown protection against tuberculosis disease in preclinical models, and observational studies have indicated that primary bacille Calmette-Guérin (BCG) vaccination may offer partial protection against infection.MethodsIn this phase 2 trial, we randomly assigned 990 adolescents in a high-risk setting who had undergone neonatal BCG vaccination to receive the H4:IC31 vaccine, BCG revaccination, or placebo. All the participants had negative results on testing for M. tuberculosis infection on the QuantiFERON-TB Gold In-tube assay (QFT) and for the human immunodeficiency virus. The primary outcomes were safety and acquisition of M. tuberculosis infection, as defined by initial conversion on QFT that was performed every 6 months during a 2-year period. Secondary outcomes were immunogenicity and sustained QFT conversion to a positive test without reversion to negative status at 3 months and 6 months after conversion. Estimates of vaccine efficacy are based on hazard ratios from Cox regression models and compare each vaccine with placebo.ResultsBoth the BCG and H4:IC31 vaccines were immunogenic. QFT conversion occurred in 44 of 308 participants (14.3%) in the H4:IC31 group and in 41 of 312 participants (13.1%) in the BCG group, as compared with 49 of 310 participants (15.8%) in the placebo group; the rate of sustained conversion was 8.1% in the H4:IC31 group and 6.7% in the BCG group, as compared with 11.6% in the placebo group. Neither the H4:IC31 vaccine nor the BCG vaccine prevented initial QFT conversion, with efficacy point estimates of 9.4% (P=0.63) and 20.1% (P=0.29), respectively. However, the BCG vaccine reduced the rate of sustained QFT conversion, with an efficacy of 45.4% (P=0.03); the efficacy of the H4:IC31 vaccine was 30.5% (P=0.16). There were no clinically significant between-group differences in the rates of serious adverse events, although mild-to-moderate injection-site reactions were more common with BCG revaccination.ConclusionsIn this trial, the rate of sustained QFT conversion, which may reflect sustained M. tuberculosis infection, was reduced by vaccination in a high-transmission setting. This finding may inform clinical development of new vaccine candidates. (Funded by Aeras and others; C-040-404 ClinicalTrials.gov number, NCT02075203 .).

Dataset Information

BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial.

Background

Objective

Methods and findings

Study site

Participants

Intervention

Main outcome

Results

Conclusions/significance

Publications

BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial.

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