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

João Fevereiro; Nikta Sajjadi; Alexandra G Fraga; Pedro M Teixeira; Jorge Pedrosa

doi:10.1371/journal.pntd.0008161

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

PLoS Negl Trop Dis. 2020 Apr 8;14(4):e0008161. doi: 10.1371/journal.pntd.0008161. eCollection 2020 Apr.

Authors

João Fevereiro^{1

2}, Nikta Sajjadi^{1

2}, Alexandra G Fraga^{1

2}, Pedro M Teixeira^{1

2}, Jorge Pedrosa^{1

2}

Affiliations

¹ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
² ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.

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 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 I2 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; I2 = 56%), a finding case-control studies appear to corroborate. HIV infection (OR = 6.80; 95% CI = 2.33-19.85; 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.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

BCG Vaccine
Buruli Ulcer / epidemiology
Buruli Ulcer / physiopathology*
Databases, Factual
Genetic Variation
HIV Infections / complications
Humans
Medical History Taking
Mycobacterium ulcerans / pathogenicity*

Substances

BCG Vaccine

Grants and funding

This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER); FEDER, through the Competitiveness Factors Operational Program (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 PD/BD/113699/2015 to JF, UMINHO/BI/427/2018 to NS, DL57/2016(CRP) to AGF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.