Oral Treatment for Mycobacterium ulcerans Infection: Results From a Pilot Study in Benin

Mycobacterium ulcerans infection is responsible for severe skin lesions in sub-Saharan Africa. We enrolled 30 Beninese patients with Buruli ulcers in a pilot study to evaluate efficacy of an oral chemotherapy using rifampicin plus clarithromycin during an 8-week period. The treatment was well tolerated, and all patients were healed by 12 months after initiation of therapy without relaps

Clinical epidemiology of laboratory-confirmed Buruli ulcer in Benin: a cohort study

Background Buruli ulcer, caused by Mycobacterium ulcerans, was identifi ed 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-confi rmed 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 eff ect 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 confi rmed. Findings 1227 cases of laboratory-confi rmed 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 identifi able 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 signifi cantly 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 signifi cantly associated with occurrence of permanent functional sequelae (OR 7·64, 95% CI 5·29–11·31) and operationally defi nes severe Buruli ulcer. Interpretation Our fi ndings 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-specifi c aspect in areas endemic for Buruli ulcer; and specifi c disability prevention for patients presenting with osteomyelitis, oedema, or multifocal or large lesions. Our fi ndings 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

Establishment of Quantitative PCR (qPCR) and Culture Laboratory Facilities in a Field Hospital in Benin: 1-Year Results

International audienceNo simple diagnostic tool is available to confirm Mycobacterium ulcerans infection, which is an emerging disease reported in many rural areas of Africa. Here, we report the 1-year results of a hospital laboratory that was created in an area of endemicity of Benin to facilitate the diagnosis of M. ulcerans infection.</p

Localisation of Buruli ulcer patients in Nigeria.

<p>(A) Nigerian districts where Buruli ulcer patients were already described at least once, and neighbouring countries areas where Buruli ulcer is endemic. The number of cases described since 1967 is indicated for each Nigerian district. (B) Location of Benin and Nigerian patients coming in CDTUB-Pobè for treatment of Buruli ulcer.</p

A typical category III lesion of Buruli ulcer.

<p>Most Nigerian patients presented in medical center of Pobè in Benin with extensive ulcerative lesions. On the picture, the lesion of a Nigerian 10 years old child on the right thigh and with the typical characteristic of a late stage of the disease: large painless ulceration with presence of necrosis and undermined edges.</p

Clinico-epidemiological features of Buruli ulcer patients from Nigeria.

<p>*no available for 2 patients.</p><p>Clinico-epidemiological features of Buruli ulcer patients from Nigeria.</p

Buruli ulcer Nigerian patients.

<p>(A) Number of new Buruli ulcer patients coming from Nigeria and treated in Buruli ulcer treatment centre of Pobè, Benin between 2005 and 2013. (B) Age of patients by gender, *** <i>P</i> = 0.0001. (C) Distribution of patient consultation delay.</p

Changes in inflammatory markers in patients treated for Buruli ulcer and their ability to predict paradoxical reactions

International audienceAbstract Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as paradoxical reactions, occur in some patients during or after antibiotic treatment. We investigated the clinical and biological features of PRs in a prospective cohort of BU patients from Benin including forty-one patients. Neutrophil counts decreased from baseline to day 90 and IL-6, G-CSF and VEGF were the cytokines displaying a significant monthly decrease relative to baseline. Paradoxical reactions occurred in 10 (24%) patients. The baseline biological and clinical characteristics of the patients presenting PRs did not differ significantly from those of the other patients. However, the patients with PRs had significantly higher IL-6 and TNF-α concentrations on days 30, 60 and 90 after the start of antibiotic treatment. The absence of a decrease in IL-6 and TNF-α levels during treatment should alert clinicians to the possibility of PR onset

Promising Clinical Efficacy of Streptomycin-Rifampin Combination for Treatment of Buruli Ulcer (Mycobacterium ulcerans Disease)▿

According to recommendations of the 6th WHO Advisory Committee on Buruli ulcer, directly observed treatment with the combination of rifampin and streptomycin, administered daily for 8 weeks, was recommended to 310 patients diagnosed with Buruli ulcer in Pobè, Bénin. Among the 224 (72%) eligible patients for whom treatment was initiated, 215 (96%) were categorized as treatment successes, and 9, including 1 death and 8 losses to follow-up, were treatment failures. Of the 215 successfully treated patients, 102 (47%) were treated exclusively with antibiotics and 113 (53%) were treated with antibiotics plus surgical excision and skin grafting. The size of lesions at treatment initiation was the major factor associated with surgical intervention: 73% of patients with lesions of >15 cm in diameter underwent surgery, whereas only 17% of patients with lesions of <5 cm had surgery. No patient discontinued therapy for side effects from the antibiotic treatment. One year after stopping treatment, 208 of the 215 patients were actively retrieved to assess the long-term therapeutic results: 3 (1.44%) of the 208 retrieved patients had recurrence of Mycobacterium ulcerans disease, 2 among the 107 patients treated only with antibiotics and 1 among the 108 patients treated with antibiotics plus surgery. We conclude that the WHO-recommended streptomycin-rifampin combination is highly efficacious for treating M. ulcerans disease. Chemotherapy alone was successful in achieving cure in 47% of cases and was particularly effective against ulcers of less than 5 cm in diameter