Background Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. The exact mode of transmission remains elusive; yet, some studies identified environmental, socio-sanitary, and behavioral risk factors. The purpose of this study was to assess the association of such factors to contracting BU in Tiassalé, south C?te d’Ivoire. Methodology A case-control study was conducted in 2012. Cases were BU patients diagnosed according to clinical definition put forth by the World Health Organization, readily confirmed by IS2404 polymerase chain reaction (PCR) analysis prior to our study and recruited at one of the health centers of the district. Two controls were matched for each control, by age group (to the nearest 5 years), sex, and living community. Participants were interviewed after providing oral witnessed consent, assessing behavioral, environmental, and socio-sanitary factors. Principal Findings A total of 51 incident and prevalent cases and 102 controls were enrolled. Sex ratio (male:female) was 0.9. Median age was 25 years (range: 5–70 years). Regular contact with unprotected surface water (adjusted odds ratio (aOR) = 6.5; 95% confidence interval (CI) = 2.1–19.7) and absence of protective equipment during agricultural activities (aOR = 18.5, 95% CI = 5.2–66.7) were identified as the main factors associated with the risk of contracting BU. Etiologic fractions among exposed to both factors were 84.9% and 94.6%, respectively. Good knowledge about the risks that may result in BU (aOR = 0.3, 95% CI = 0.1–0.8) and perception about the disease causes (aOR = 0.1, 95% CI = 0.02–0.3) showed protection against BU with a respective preventive fraction of 70% and 90%. Conclusions/Significance Main risk factors identified in this study were the contact with unprotected water bodies through daily activities and the absence of protective equipment during agricultural activities. An effective strategy to reduce the incidence of BU should involve compliance with protective equipment during agricultural activities and avoidance of contact with surface water and community capacity building through training and sensitization.
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