03026nas a2200277   4500000000100000008004100001653001700042100001300059700001200072700001400084700002000098700001300118700001200131700001300143700001300156700001800169700001400187700001600201700001400217245014100231856007900372300001300451490000600464520226400470022001402734       2015                            d10aEpidemiology1 aCapela C1 aSopoh G1 aHouezo JG1 aFiodessihoué R1 aDossou A1 aCosta P1 aFraga AG1 aMenino J1 aSilva-Gomes R1 aOuendo EM1 aRodrigues F1 aPedrosa J00aClinical epidemiology of Buruli ulcer from Benin (2005-2013): Effect of time-delay to diagnosis on clinical forms and severe phenotypes.  uhttp://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004005   ae00040050 v93 a<p>Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (&gt;15cm diameter) or WHO Category (WHO Category 3 lesions).</p>

<p>There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed.</p>

<p>To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter &gt;15cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively.</p>

<p>Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.</p>
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