Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin:a randomised controlled trial

BACKGROUND: Surgical intervention was once the mainstay of treatment for Buruli ulcer disease, a neglected tropical disease caused by Mycobacterium ulcerans. Since the introduction of streptomycin and rifampicin for 8 weeks as standard care, surgery has persisted as an adjunct therapy, but its role is uncertain. We investigated the effect of delaying the decision to operate to 14 weeks on rates of healing without surgery. METHODS: In this randomised controlled trial, we enrolled patients aged 3 years or older with confirmed disease at one hospital in Lalo, Benin. Patients were randomly assigned (1:1) to groups assessing the need for excision surgery 8 weeks (standard care) or 14 weeks after initiation of antimicrobial treatment. The primary endpoint was the number of patients healed without the need for surgery (not including skin grafting), assessed in all patients in follow-up at 50 weeks (or last observation for those healed for >10 weeks). A doctor masked to treatment assignment checked the indications for surgery according to predefined criteria. This study is registered with ClinicalTrials.gov, number NCT01432925. FINDINGS: Between July 1, 2011, and Jan 15, 2015, 119 patients were enrolled, with two patients per group lost to follow-up. 55 (96%) of 57 participants in the delayed-decision group and 52 (90%) of 58 participants in the standard-care group had healed lesions 1 year after start of antimicrobial treatment (relative risk [RR] 1·08, 95% CI 0·97-1·19). 37 (67%) of 55 patients in the delayed-decision group had their lesions healed without surgical intervention, as did 25 (48%) of 52 in the standard-care group (RR 1·40, 95% CI 1·00-1·96). The time to heal and residual functional limitations did not differ between the two groups (median time to heal 21 weeks [IQR 10-27] in the delayed-decision group and 21 weeks [10-39] in the standard-care group; functional limitations in six [11%] of 57 and three [5%] of 58 patients; p=0·32). Postponing the decision to operate resulted in reduced median duration of hospitalisation (5 days [IQR 0-187] vs 131 days [0-224]; p=0·024) and wound care (153 days [IQR 56-224] vs 182 days [94-307]; p=0·036). INTERPRETATION: In our study, patients treated for Buruli ulcer benefited from delaying the decision to operate. Even large ulcers can heal with antibiotics alone, without delaying healing rate and without an increase in residual functional limitations. FUNDING: NWO-VENI grant 241500, BUG Foundation, and UBS OPTIMUS

Improving clinical and epidemiological predictors of Buruli ulcer

<div><p>Background</p><p>Buruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by <i>Mycobacterium ulcerans</i>. 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.</p><p>Methodology/Principal findings</p><p>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 IS<i>2404</i> 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).</p><p>Conclusion/Significance</p><p>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.</p></div

ROC analysis for both model A and model B.

<p>ROC analysis for both model A and model B.</p

Clinical characteristics and their association with positive PCR results.

<p>Clinical characteristics and their association with positive PCR results.</p

Predictive model of positive PCR result based on WHO criteria (model A) and predictive model of positive PCR result based on WHO criteria and additional characteristic (model B).

<p>Predictive model of positive PCR result based on WHO criteria (model A) and predictive model of positive PCR result based on WHO criteria and additional characteristic (model B).</p