Individual and clinical variables associated with the risk of Buruli ulcer acquisition: A systematic review and meta-analysis

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 individual–sex, age, family ties with history of BU, gene variants–and clinical–Bacillus Calmette-Guérin (BCG) immunization, Human Immunodeficiency Virus (HIV) infection–variables 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 I(2) statistic. Published demographic data was descriptively analysed and clinical data pooled within random-effects modelling for meta-analysis. RESULTS: A total of 29 studies were included in the systematic review. Two randomized controlled trials (RCTs) and 21 case-control studies were selected for meta-analysis. Studies show that 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; I(2) = 56%), a finding case-control studies appear to corroborate. HIV infection (OR = 6.80; 95% CI = 2.33–19.85; I(2) = 0%) and SLC11A1 rs17235409 A allele (OR = 1.86; 95% CI = 1.25–2.77; I(2) = 0%) are associated with increased prevalence of the disease. No definite conclusions can be drawn regarding the influence of previous family history of BU. DISCUSSION: While available evidence warrants further robustness, these results have direct implications on current interventions and future research programs, and foster the development of more cost-effective preventive and screening measures. REGISTRATION: The study was registered at PROSPERO with number CRD42019123611.