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Vincent Q.B.,French Institute of Health and Medical Research | Vincent Q.B.,University of Paris Descartes | Saint-Andre J.-P.,Angers University Hospital Center | Cottin J.,Angers University Hospital Center | And 10 more authors.
The Lancet Global Health | Year: 2014

Background: Buruli ulcer, caused by Mycobacterium ulcerans, was identified as a neglected emerging infectious disease by WHO in 1998. Although Buruli ulcer is the third most common mycobacterial disease worldwide, understanding of the disease is incomplete. We analysed a large cohort of laboratory-confirmed cases of Buruli ulcer from Pobè, Benin, to provide a comprehensive description of the clinical presentation of the disease, its variation with age and sex, and its effect on the occurrence of permanent functional sequelae. Methods: Between Jan 1, 2005, and Dec 31, 2011, we prospectively collected clinical and laboratory data from all patients with Buruli ulcer diagnosed at the Centre de Dépistage et de Traitement de l'Ulcère de Buruli in Pobè, Benin. We followed up patients to assess the frequency of permanent functional sequelae. All analyses were done on cases that were laboratory confirmed. Findings: 1227 cases of laboratory-confirmed Buruli ulcer were included in the analysis. Typically, patients with Buruli ulcer were children (median age at diagnosis 12 years) presenting with a unique (1172 [96%]) large (≥15 cm, 444 [36%]) ulcerative (805 [66%]) lesion of the lower limb (733 [60%]). Atypical clinical presentation of Buruli ulcer included Buruli ulcer osteomyelitis with no identifiable present or past Buruli ulcer skin lesions, which was recorded in at least 14 patients. The sex ratio of Buruli ulcer widely varied with age, with male patients accounting for 57% (n=427) of patients aged 15 years and younger, but only 33% (n=158) of those older than 15 years (odds ratio [OR] 2·59, 95% CI 2·04-3·30). Clinical presentation of Buruli ulcer was significantly dependent on age and sex. 54 (9%) male patients had Buruli ulcer osteomyelitis, whereas only 28 (4%) of female patients did (OR 2·21, 95% CI 1·39-3·59). 1 year after treatment, 229 (22% of 1043 with follow-up information) patients presented with permanent functional sequelae. Presentation with oedema, osteomyelitis, or large (≥15 cm in diameter), or multifocal lesions was significantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29-11·31) and operationally defines severe Buruli ulcer. Interpretation: Our findings have important clinical implications for daily practice, including enhanced surveillance for early detection of osteomyelitis in boys; systematic search for M ulcerans in osteomyelitis cases of non-specific aspect in areas endemic for Buruli ulcer; and specific disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our findings also suggest a crucial underestimation of the burden of Buruli ulcer in Africa and raise key questions about the contribution of environmental and physiopathological factors to the recorded heterogeneity of the clinical presentation of Buruli ulcer. Funding: Agence Nationale de la Recherche (ANR), Fondation Raoul Follereau, Fondation pour la Recherche Médicale (FRM), and Institut des Maladies Génétiques (IMAGINE). © 2014 Vincent et al. Open Access article distributed under the terms of CC BY-NC-SA. Source


Babonneau J.,French Institute of Health and Medical Research | Bernard C.,SR2B | Kempf M.,Angers University Hospital Center | Robert R.,SR2B | And 15 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Background: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans. This skin disease is the third most common mycobacterial disease and its rapid diagnosis and treatment are necessary. Polymerase chain reaction (PCR) is considered to be the most sensitive method for the laboratory confirmation of Buruli ulcer. However, PCR remains expensive and involves reagents unsuitable for use in tropical countries with poor storage conditions, hindering the development of reliable quantitative PCR (qPCR) diagnosis. We aimed to overcome this problem by developing a ready-to-use dry qPCR mix for the diagnosis of M. ulcerans infection. Methodology/Principal Findings: We compared the efficiency of three different dry qPCR mixes, lyophilized with various concentrations of cryoprotectants, with that of a freshly prepared mixture, for the detection of a standard range of M. ulcerans DNA concentrations. We evaluated the heat resistance of the dry mixes, comparing them with the fresh mix after heating. We also evaluated one of the dry mixes in field conditions, by analyzing 93 specimens from patients with suspected Buruli ulcers. The dry mix was (i) highly resistant to heat; (ii) of similar sensitivity and efficiency to the fresh mix and (iii) easier to use than the fresh mix. Conclusions: Dry qPCR mixes are suitable for use in the diagnosis of M. ulcerans infection in endemic countries. The user-friendly format of this mix makes it possible for untrained staff to perform diagnostic tests with a limited risk of contamination. The possibility of using this mix in either vial or strip form provides considerable flexibility for the management of small or large amounts of sample. Thus, dry-mix qPCR could be used as a reliable tool for the diagnosis of Buruli ulcer in the field. © 2015 Babonneau et al. Source


Alferink M.,University of Groningen | De Zeeuw J.,University of Groningen | Sopoh G.,Programme de Lutte Contre la Lepre et lUlcere de Buruli | Agossadou C.,Programme de Lutte Contre la Lepre et lUlcere de Buruli | And 9 more authors.
PLoS ONE | Year: 2015

Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. People living in remote areas in tropical Sub Saharan Africa are mostly affected. Wound care is an important component of BU management; this often needs to be extended for months after the initial antibiotic treatment. BU is reported in the literature as being painless, however clinical observations revealed that some patients experienced pain during wound care. This was the first study on pain intensity during and after wound care in BU patients and factors associated with pain. In Ghana and Benin, 52 BU patients above 5 years of age and their relatives were included between December 2012 and May 2014. Information on pain intensity during and after wound care was obtained during two consecutive weeks using the Wong-Baker Pain Scale. Median pain intensity during wound care was in the lower range (Mdn = 2, CV = 1), but severe pain (score > 6) was reported in nearly 30% of the patients. Nevertheless, only one patient received pain medication. Pain declined over time to low scores 2 hours after treatment. Factors associated with higher self-reported pain scores were; male gender, fear prior to treatment, pain during the night prior to treatment, and pain caused by cleaning the wound. The general idea that BU is painless is incorrect for the wound care procedure. This procedural pain deserves attention and appropriate intervention. © 2015 Alferink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.DOI:. Source


Alferink M.,University of Groningen | van der Werf T.S.,University of Groningen | Sopoh G.E.,Programme de Lutte Contre la Lepre et lUlcere de Buruli | Agossadou D.C.,Programme de Lutte Contre la Lepre et lUlcere de Buruli | And 6 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background: Delay in seeking treatment at the hospital is a major challenge in current Buruli ulcer control; it is associated with severe sequelae and functional limitations. Choosing alternative treatment and psychological, social and practical factors appear to influence delay. Objectives were to determine potential predictors for pre-hospital delay with Leventhal's commonsense model of illness representations, and to explore whether the type of available dominant treatment modality influenced individuals' perceptions about BU, and therefore, influenced pre-hospital delay. Methodology: 130 healthy individuals aged >18 years, living in BU-endemic areas in Benin without any history of BU were included in this cross-sectional study. Sixty four participants from areas where surgery was the dominant treatment and sixty six participants from areas where antibiotic treatment was the dominant treatment modality were recruited. Using a semi-structured interview we measured illness perceptions (IPQ-R), knowledge about BU, background variables and estimated pre-hospital delay. Principal Findings: The individual characteristics 'effectiveness of treatment' and 'timeline acute-chronic' showed the strongest association with pre-hospital delay. No differences were found between regions where surgery was the dominant treatment and regions where antibiotics were the dominant treatment modality. Conclusions: Individual characteristics, not anticipated treatment modality appeared predictors of pre-hospital delay. © 2013 Alferink et al. Source

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