Background Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). In West Africa there is an association between BU and residence in low-lying rural villages where aquatic sources are plentiful. Infection occurs through unknown environmental exposure; human-to-human infection is rare. Molecular evidence for M. ulcerans in environmental samples is well documented, but the association of M. ulcerans in the environment with Buruli ulcer has not been studied in West Africa in an area with accurate case data.Methodology/Principal FindingEnvironmental samples were collected from twenty-five villages in three communes of Benin. Sites sampled included 12 BU endemic villages within the Ouheme and Couffo River drainages and 13 villages near the Mono River and along the coast or ridge where BU has never been identified. Triplicate water filtrand samples from major water sources and samples from three dominant aquatic plant species were collected. Detection of M. ulcerans was based on quantitative polymerase chain reaction. Results show a significant association between M. ulcerans in environmental samples and Buruli ulcer cases in a village (p = 0.0001). A “dose response” was observed in that increasing numbers of M. ulceran- positive environmental samples were associated with increasing prevalence of BU cases (R2 = 0.586).Conclusions/SignificanceThis study provides the first spatial data on the overlap of M. ulcerans in the environment and BU cases in Benin where case data are based on active surveillance. The study also provides the first evidence on M. ulcerans in well-defined non-endemic sites. Most environmental pathogens are more broadly distributed in the environment than in human populations. The congruence of M. ulcerans in the environment and human infection raises the possibility that humans play a role in the ecology of M. ulcerans. Methods developed could be useful for identifying new areas where humans may be at high risk for BU.
Background Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities.ObjectivesThis study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU).DesignCase control study.SettingDepartment of Atlantique, Benin.SubjectsBU-confirmed cases that were diagnosed and followed up at the BU detection and treatment center (CDTUB) of Allada (Department of the Atlantique, Benin) during the period from January 1st, 2006, to June 30th, 2008, with three matched controls (persons who had no signs or symptoms of active or inactive BU) for age, gender and village of residence per case.Main Outcomes MeasuredContact with natural water sources, BU history in the family and the practice of consanguineous marriages.ResultsA total of 416 participants were included in this study, including 104 cases and 312 controls. BU history in the family (p<0.001), adjusted by daily contact with a natural water source (p = 0.007), was significantly associated with higher odds of having BU (OR; 95% CI = 5.5; 3.0–10.0). The practice of consanguineous marriage was not associated with the occurrence of BU (p = 0.40). Mendelian disorders could explain this finding, which may influence individual susceptibility by impairing immunity.ConclusionThis study suggests that a combination of genetic factors and behavioral risk factors may increase the susceptibility for developing BU.
IntroductionBuruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection.ObjectiveGenetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form.MethodsGenetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype) and 300 healthy endemic controls.ResultsThe rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR), 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02).ConclusionOur findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes.
Almost half of patients have functional limitations after treatment of Buruli ulcer disease. Antibiotic treatment (along with surgery) was introduced in the National Program for Buruli ulcer in Benin in 2005. The aim of this study was to compare functional limitations in patients who were treated by antibiotics, surgery, or both, using a validated questionnaire. One hundred seventy-nine former patients in Lalo, Benin were retrieved and interviewed in their village. Hospital records were used to gather data about size of lesion at presentation and treatment provided. No significant differences in resulting functional limitations were found between the different treatments. Larger lesions (> 15 cm cross-sectional diameter) at presentation; lesions on a joint, muscular atrophy, and amputation were all associated with a higher risk for functional limitations. Advantages of antibiotic treatment may involve other domains, like costs of treatment or a change in help-seeking behavior.
BackgroundNeglected Tropical Diseases (NTDs) are a group of several communicable diseases prevalent in the tropical and subtropical areas. The co-endemicity of these diseases, the similarity of the clinical signs, and need to maximize limited financial and human resources have necessitated implementation of integrated approach. Our study aims to share the lessons of this integrated approach in the fight against Buruli ulcer (BU), leprosy and yaws in a rural district in Benin.MethodsIt is a cross-sectional study using a single set of activities data conducted from May 2016 to December 2016. Health workers and community health volunteers involved in this study were trained on integrated approach of the Buruli ulcer, leprosy and yaws. Village chiefs were briefed about the activity. The trained team visited the villages and schools in the district of Lalo in Benin. After the education and awareness raising sessions, all persons with a skin lesion who presented voluntarily to the team were carefully examined in a well-lit area which respected their privacy. Suspected cases were tested as needed. The socio-demographic information and the characteristics of the lesions were collected using a form. A descriptive analysis of the epidemiological, clinical and laboratory variables of the cases was made using Excel 2013 and SPSS version 22.00.Principal findingsIn the study period, 1106 people were examined. The median (IQR) age of those examined was 11 (8; 27) years. Of 34 (3.1%) suspected BU cases, 15 (1.4%) were confirmed by PCR. Only three cases of leprosy were confirmed. The 185 (16.7%) suspected cases of yaws were all negative with the rapid test. The majority of cases were other skin conditions, including fungal infections, eczema and traumatic lesions.ConclusionThe integrated approach of skin NTD allows optimal use of resources and surveillance of these diseases. Sustaining this skin NTD integrated control will require the training of peripheral health workers not only on skin NTD but also on basic dermatology.
Invasive punch or incisional skin biopsy specimens are currently employed for the bacteriological confirmation of the clinical diagnosis of Buruli ulcer (BU), a cutaneous infectious disease caused by Mycobacterium ulcerans. The efficacy of fine-needle aspirates (FNA) using fine-gauge needles (23G by 25 mm) for the laboratory confirmation of BU was compared with that of skin tissue fragments obtained in parallel by excision or punch biopsy. In three BU treatment centers in Benin, both types of diagnostic material were obtained from 33 clinically suspected cases of BU and subjected to the same laboratory analyses: i.e., direct smear examination, IS2404 PCR, and in vitro culture. Twenty-three patients, demonstrating 17 ulcerative and 6 nonulcerative lesions, were positive by at least two tests and were therefore confirmed to have active BU. A total of 68 aspirates and 68 parallel tissue specimens were available from these confirmed patients. When comparing the sensitivities of the three confirmation tests between FNA and tissue specimens, the latter yielded more positive results, but only for PCR was this significant. When only nonulcerative BU lesions were considered, however, the sensitivities of the confirmation tests using FNA and tissue specimens were not significantly different. Our results show that the minimally invasive FNA technique offers enough sensitivity to be used for the diagnosis of BU in nonulcerative lesions.
BackgroundBuruli ulcer (BU) caused by Mycobacterium ulcerans is a necrotizing skin disease usually starting with a subcutaneous nodule or plaque, which may ulcerate and progress, if untreated, over months and years. During the currently recommended antibiotic treatment with rifampicin/streptomycin plaque lesions tend to ulcerate, often associated with retarded wound healing and prolonged hospital stays.Methodology/Principal FindingsIncluded in this study were twelve laboratory reconfirmed, HIV negative BU patients presenting with plaque lesions at the CDTUB in Allada, Benin. Punch biopsies for histopathological and immunohistochemical analysis were taken before start of treatment and after four to five weeks of treatment. Where excision or wound debridement was clinically indicated, the removed tissue was also analyzed. Based on clinical judgment, nine of the twelve patients enrolled in this study received limited surgical excision seven to 39 days after completion of chemotherapy, followed by skin grafting. Lesions of three patients healed without further intervention. Before treatment, plaque lesions were characterized by a destroyed subcutis with extensive necrosis without major signs of infiltration. After completion of antibiotic treatment partial infiltration of the affected tissue was observed, but large necrotic areas remained unchanged.Conclusion/SignificanceOur histopathological analyses show that ulceration of plaque lesions during antibiotic treatment do not represent a failure to respond to antimycobacterial treatment. Based on our results we suggest formal testing in a controlled clinical trial setting whether limited surgical excision of necrotic tissue favours wound healing and can reduce the duration of hospital stays.
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