AbstractThe exact route of transmission of Mycobacterium ulcerans (MU) (causative agent of Buruli ulcer [BU]), risk factors, and reservoir hosts are not clearly known, although it has been identified as an environmental pathogen. This study assessed potential environmental and behavioral risk factors that influence BU infections. We conducted a case-control study where cases were matched by their demographic characteristics and place of residence. A structured questionnaire was administered to solicit information on the environmental and behavioral factors of participants that may expose them to infection. A total of 176 cases and 176 controls were enrolled into the study. Multivariate conditional logistic regression analysis identified farming in swampy areas (odds ratio [OR] = 4.10, 95% confidence interval [CI] = 3.82-7.18), farming while wearing short clothing (OR = 1,734.1, 95% CI = 68.1-44,120.9), insect bite (OR = 988.3, 95% CI = 31.4-31,115.6), and application of leaves on wounds (OR = 6.23, 95% CI = 4.74-18.11) as potential risk factors. Farming in long clothing (OR = 0.000, 95% CI = 0.00-0.14), washing wound with water and soap (OR = 0.37, 95% CI = 0.29-0.98), and application of adhesive bandage on wounds (OR = 0.31, 95% CI = 0.15-0.82) were found to be protective against BU infection. In the absence of the exact MU transmission mechanisms, education of public in BU-endemic zones on the use of protective clothing during farming activities to limit exposure of the skin and proper wound care management would be essential in the fight against BU.