Improving clinical and epidemiological predictors of Buruli ulcer

Background: Buruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after clinical suspicion based on the WHO clinical and epidemiological criteria. This study aimed to estimate the predictive values of these criteria and how they could be improved. Methodology/Principal findings: A total of 224 consecutive patients presenting with skin and soft tissue lesions that could be compatible with BU, including those recognized as unlikely BU by experienced clinicians, were recruited in two BU treatment centers in southern Benin between March 2012 and March 2015. For each participant, the WHO and four additional epidemiological and clinical diagnostic criteria were recorded. For microbiological confirmation, direct smear examination and IS2404 PCR were performed. We fitted a logistic regression model with PCR positivity for BU confirmation as outcome variable. On univariate analysis, most of the clinical and epidemiological WHO criteria were associated with a positive PCR result. However, lesions on the lower limbs and WHO category 3 lesions were rather associated with a negative PCR result (respectively OR: 0.4, 95%CI: 0.3–0.8; OR: 0.5, 95%IC: 0.3–0.9). Among the additional characteristics studied, the characteristic smell of BU was strongest associated with a positive PCR result (OR = 16.4; 95%CI = 7.5–35.6). Conclusion/Significance: The WHO diagnostic criteria could be improved upon by differentiating between lesions on the upper and lower limbs and by including lesion size and the characteristic smell recognized by experienced clinicians. Author summary: Buruli ulcer (BU) is a neglected necrotizing skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after clinical suspicion based on WHO diagnostic criteria. In this study we evaluated the WHO diagnostic guidelines for BU and how these criteria could be improved. A total of 224 patients presenting with skin lesions were recruited in two BU treatment centers in southern Benin between March 2012 and March 2015. Most of the clinical and epidemiological WHO criteria were associated with a confirmed BU diagnosis although lesions on the lower limbs were rather associated with a negative PCR result. Among the additional characteristics studied, the characteristic smell of BU was most strongly associated with a positive PCR result. The WHO diagnostic criteria could therefore be improved upon by discriminating between lesions on the upper and lower limbs and by including lesion size and the characteristic smell recognized by experienced clinicians. The volatiles responsible for this smell could serve as a Point-of-Care diagnostic test, useful for non-invasive confirmation during active case-finding activities, and for training of clinicians.