Sociodemographic and Clinical Variables Associated with the Risk of Buruli Ulcer Acquisition: A Systematic Review and Meta-Analysis

Abstract

Background: Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans, with poorly understood acquisition risk factors. This review aims at evaluating the importance of sociodemographic - sex, age and family ties with history of BU - and clinical - Bacillus Calmette-Guerin (BCG) immunization, Human Immunodeficiency Virus (HIV) infection and gene variants - in this process. Methods: A systematic review was performed considering the following databases: ClinicalTrials.gov, Cochrane Controlled Register of Trials (CENTRAL), Current Contents Connect, Embase, MEDLINE, SciELO, Scopus and Web of Science. Eligible studies were critically appraised with The Joanna Briggs Institute checklists and heterogeneity was assessed with Cochran Q-test and I2 statistic. Published demographic data was descriptively analysed and clinical data pooled within random-effects modelling for meta-analysis. Findings: A total of 29 studies were included in the systematic review and two randomised controlled trials (RCTs) and 20 case-control studies were selected for meta-analysis. Studies show BU mainly affects age extremes, more preponderately males among children. Data pooled from RCTs do not reveal BCG to be protective against BU (odds ratio (OR) = 0·63; 95% CI = 0·38-1·05; I2 = 56%), a finding later case-control studies appear to corroborate. HIV infection (OR = 6·40; 95% CI = 2·12-19·29; I2 = 0%) and SLC11A1 rs17235409 A allele (OR = 1·86; 95% CI = 1·25-2·77;I2= 0%) are associated with increased prevalence of the disease. No definite conclusions can be drawn regarding the influence of previous family history of BU. Interpretation: These findings have direct implications on current interventions and future research programs, opening avenues on fundamental research topics and fostering the development of more cost-effective preventive and screening measures. Funding Statement: This work was developed under the scope of the project NORTE-01-0145-FEDE13, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER); FEDER, through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT), under the scope of project POCI-01-0145-FEDER-007038 and POCI-01-0145-FEDER-031312; Infect-ERA grant Infect-ERA/0002/2015; and FCT, through the PhD grant PD/BD/113699/2015 to JF, fellowship UMINHO/BI/427/2018 to NS, and postdoctoral grant SFRH/BPD/112903/2015 to AGF. Declaration of Interests: Authors state that they have no conflict of interest to declare. Ethics Approval Statement: The study was registered at PROSPERO with number CRD42019123611.