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Buruli ulcer (BU), a necrotic skin disease caused by Mycobacterium ulcerans , is mainly prevalent in West Africa, but cases have also been reported in other tropical parts of the world. It is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d'Ivoire. Heterogeneity among M. ulcerans from different geographical locations has not been clearly elucidated, and some studies seem to suggest genetic differences between M. ulcerans in humans and in the environment. This study aimed at identifying genetic differences among M. ulcerans strains between two BU endemic countries: Ghana and Côte d'Ivoire. Clinical samples consisting of swabs, fine needle aspirates, and tissue biopsies of suspected BU lesions and environmental samples (e.g., water, biofilms from plants, soil, and detrital material) were analyzed. BU cases were confirmed via acid fast staining and PCR targeting the 16S rRNA, IS 2404 , IS2606 , and ER domain genes present on M. ulcerans. Heterogeneity among M. ulcerans was determined through VNTR profiling targeting 10 loci. Eleven M. ulcerans genotypes were identified within the clinical samples in both Ghana and Côte d'Ivoire, whiles six M. ulcerans genotypes were found among the environmental samples. Clinical M. ulcerans genotypes C, D, F, and G were common in both countries. Genotype E was unique among the Ghanaian samples, whiles genotypes A, Z, J, and K were unique to the Ivorian samples. Environmental isolates were found to be more conserved compared with the clinical isolates. Genotype W was observed only among the Ghanaian environmental samples. Genotype D was found to be prominent in both clinical and environmental samples, suggesting evidence of possible transmission of M. ulcerans from the environment, particularly water bodies and biofilms from aquatic plants, to humans through open lesions on the skin. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans and is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d'Ivoire. M. ulcerans produces mycolactone, an immunosuppressant macrolide toxin, responsible for the characteristic painless nature of the infection. Secondary infection of ulcers before, during and after treatment has been associated with delayed wound healing and resistance to streptomycin and rifampicin. However, not much is known of the bacteria causing these infections as well as antimicrobial drugs for treating the secondary microorganism. This study sought to identify secondary microbial infections in BU lesions and to determine their levels of antibiotic resistance due to the prolonged antibiotic therapy required for Buruli ulcer. Results: Swabs from fifty-one suspected BU cases were sampled in the Amansie Central District from St. Peters Hospital (Jacobu) and through an active case surveillance. Forty of the samples were M. ulcerans (BU) positive. Secondary bacteria were identified in all sampled lesions (N = 51). The predominant bacteria identified in both BU and Non-BU groups were Staphylococci spp and Bacilli spp. The most diverse secondary bacteria were detected among BU patients who were not yet on antibiotic treatment. Fungal species identified were Candida spp, Penicillium spp and Trichodema spp. Selected secondary bacteria isolates were all susceptible to clarithromycin and amikacin among both BU and Non-BU patients. Majority, however, had high resistance to streptomycin. Conclusions: Microorganisms other than M. ulcerans colonize and proliferate on BU lesions. Secondary microorganisms of BU wounds were mainly Staphylococcus spp, Bacillus spp and Pseudomonas spp. These secondary microorganisms were less predominant in BU patients under treatment compared to those without treatment. The delay in healing that are experienced by some BU patients could be as a result of these bacteria and fungi colonizing and proliferating in BU lesions. Clarithromycin and amikacin are likely suitable drugs for clearance of secondary infection of Buruli ulcer. [ABSTRACT FROM AUTHOR]

Buruli ulcer, caused by Mycobacterium ulcerans, is highly endemic in West Africa. While the mode of transmission is unknown, many studies associate Buruli ulcer with different types of water exposure. We present results from the largest study to date to test for M. ulcerans in aquatic sites and identify environmental attributes associated with its presence. Environmental samples from 98 aquatic sites in the Greater Accra, Ashanti, and Volta regions of Ghana were tested for the presence of M. ulcerans DNA by polymerase chain reaction. The proportion of aquatic sites positive for M. ulcerans varied by region: Ashanti 66% (N = 39), Greater Accra 34% (N = 29), and Volta 0% (N = 30). We explored the spatial distribution of M. ulcerans positive and negative water bodies and found no significant clusters. We also determined both highly localized water attributes and broad scale remotely sensed land cover and terrain environmental characteristics associated with M. ulcerans presence through logistic regression. Our results concur with published results regarding conditions suitable for M. ulcerans growth and associations with Buruli ulcer disease burden with regards to water characteristics and disturbed environments, but differ from others with regards to spatial associations and topographic effects such as elevation and wetness. While our results suggest M. ulcerans is an environmental organism existing in a specific ecological niche, they also reveal variation in the elements defining this niche across the sites considered. In addition, despite the causal association between Buruli ulcer and M. ulcerans, we observed no significant statistical association between case reports of Buruli ulcer and presence of M. ulcerans in nearby waterbodies. [ABSTRACT FROM AUTHOR]

Background: A recent study detected cutaneous leishmaniasis (CL) in 31.9% of persons with skin ulcers in the Oti Region of Ghana, resulting in a need to investigate other potential causes of the unexplained skin ulcers., Methodology/principal Findings: A community based cross-sectional study was conducted in the Oti region to investigate skin ulcers of undetermined aetiologies. To confirm a diagnosis of cutaneous leishmaniasis, Buruli ulcer, Haemophilus ducreyi ulcers, or yaws, DNA obtained from each patient skin ulcer sample was systematically subjected to polymerase chain reaction (PCR) for Leishmania spp., Mycobacterium ulcerans, Haemophilus ducreyi, and Treponema pallidum sub species pertenue. A total of 101 skin ulcer samples were obtained from 101 persons. Co-infection of more than one organism was observed in 68.3% of the samples. Forty (39.6%) participants had a positive result for Leishmania spp., 68 (67.3%) for Treponema pallidum sub. Sp. pertenue, and 74 (73.3%) for H. ducreyi. Twenty (19.8%) of the patient ulcers were simultaneously infected with Leishmania spp., Treponema pallidum sub. Sp. pertenue, and H. ducreyi. None of the patients' lesions yielded a positive result for Mycobacterium ulcerans., Conclusions/significance: This study detected single and mixed occurrence of the causative organisms of CL, yaws, and H. ducreyi cutaneous ulcers in CL endemic communities of the Oti Region in Ghana. These findings emphasize the importance of integrating multiple skin diseases on a common research platform and calls for the development of a comprehensive guideline for diagnosing and treating tropical ulcers in the study areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Akuffo 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.)

Background: Beyond Mycobacterium ulcerans—specific therapy, sound general wound management is required for successful management of Buruli ulcer (BU) patients which places them among the large and diverse group of patients in poor countries with a broken skin barrier. Methods: Clinically BU suspicious patients were enrolled between October 2013 and August 2015 at a primary health care (PHC) center and a municipal hospital, secondary health care (SHC) center in Ghana. All patients were IS2404 PCR tested and divided into IS2404 PCR positive and negative groups. The course of wound healing was prospectively investigated including predictors of wound closure and assessment of infrastructure, supply and health staff performance. Results: 53 IS2404 PCR positive patients—31 at the PHC center and 22 at the SHC center were enrolled—and additionally, 80 clinically BU suspicious, IS2404 PCR negative patients at the PHC center. The majority of the skin ulcers at the PHC center closed, without the need for surgical intervention (86.7%) compared to 40% at the SHC center, where the majority required split-skin grafting (75%) or excision (12.5%). Only 9% of wounds at the PHC center, but 50% at the SHC center were complicated by bacterial infection. The majority of patients, 54.8% at the PHC center and 68.4% at the SHC center, experienced wound pain, mostly severe and associated with wound dressing. Failure of ulcers to heal was reliably predicted by wound area reduction between week 2 and 4 after initiation of treatment in 75% at the PHC center, and 90% at the SHC center. Obvious reasons for arrested wound healing or deterioration of wound were missed additional severe pathology; at the PHC center (chronic osteomyelitis, chronic lymphedema, squamous cell carcinoma) and at the SHC center (malignant ulceration, chronic lymphedema) in addition to hygiene and wound care deficiencies. When clinically suspicious, but IS2404 PCR negative patients were recaptured in the community, 76/77 (98.7%) of analyzed wounds were either completely closed (85.7%) or almost closed (13%). Five percent were found to have important missed severe pathology (chronic osteomyelitis, ossified fibroma and suspected malignancy). Conclusion: The wounds of most BU patients attending the primary health care level can be adequately managed. Additionally, the patients are closer to their families and means of livelihood. Non-healing wounds can be predicted by wound area reduction between 2 to 4 weeks after initiation of treatment. Patients with clinically BU suspicious, but PCR negative ulcers need to be followed up to capture missed diagnoses. [ABSTRACT FROM AUTHOR]

Objectives: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy.Methods: A number of days of antimicrobial therapy and patient and lesion characteristics were recorded from charts from a cohort of BU patients treated at Nkawie-Toase hospital between 2008 and 2012. Patients who defaulted from treatment were retrieved, and lesion characteristics and functional limitations were recorded.Results: About 54% of patients defaulted from therapy or wound care. Forty-seven defaulters with follow-up completed had received <56 days of antibiotics. 84% of these patients healed after 32 days or less of antibiotics. There appeared to be an increased rate of healing in smaller lesions; 94% of WHO category I lesions had healed after 32 days or less of antibiotics.Conclusion: Although numbers were small, and a potential for bias exists, our findings suggest that a reduction in the duration of antimicrobial therapy in BU in small, early lesions is feasible. These findings can serve as a basis for future well-designed studies. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. Material and methods A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA , Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans . This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro . This review covered the available literature up to December 2014. Results The majority of reports originated from the three most affected West African countries (Cote d’Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius ) , Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans . Conclusions This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control. [ABSTRACT FROM AUTHOR]

Numerous studies have associated Buruli ulcer (BU) disease with disturbed aquatic habitats; however, the natural reservoir, distribution, and transmission of the pathogen, Mycobacterium ulcerans, remain unknown. To better understand the role of aquatic plants in the ecology of this disease, a large-scale survey was conducted in waterbodies of variable flow throughout three regions of Ghana, Africa. Our objectives were to characterize plant communities and identify potential relationships with M. ulcerans and other mycolactone-producing mycobacteria (MPM). Waterbodies with M. ulcerans had significantly different aquatic plant communities, with submerged terrestrial plants identified as indicators of M. ulcerans presence. Mycobacterium ulcerans and MPM were detected on 14 plant taxa in emergent zones from both lotic and lentic waterbodies in endemic regions; however, M. ulcerans was not detected in the non-endemic Volta region. These findings support the hypothesis that plants provide substrate for M. ulcerans colonization and could act as potential indicators for disease risk. These findings also suggest that M. ulcerans is a widespread environmental bacteria species, but that it is absent or reduced in regions of low disease incidence. A better understanding is needed regarding the mechanistic associations among aquatic plants and M. ulcerans for identifying the mode of transmission of BU disease. [ABSTRACT FROM AUTHOR]

Buruli ulcer (BU) is an emerging, but neglected tropical disease, where there has been a reported association with disturbed aquatic habitats and proposed aquatic macroinvertebrate vectors such as biting Hemiptera. An initial step in understanding the potential role of macroinvertebrates in the ecology of BU is to better understand the entire community, not just one or two taxa, in relation to the pathogen, Mycobacterium ulcerans, at a large spatial scale. For the first time at a country-wide scale this research documents that M. ulcerans was frequently detected from environmental samples taken from BU endemic regions, but was not present in 30 waterbodies of a non-endemic region. There were significant differences in macroinvertebrate community structure and identified potential indicator taxa in relation to pathogen presence. These results suggest that specific macroinvertebrate taxa or functional metrics may potentially be used as aquatic biological indicators of M. ulcerans. Developing ecological indicators of this pathogen is a first step for understanding the disease ecology of BU and should assist future studies of transmission. [ABSTRACT FROM AUTHOR]

This study reports the first successful application of real-time PCR for the detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), in Ghana, a BU-endemic country. Environmental samples and organs of small mammals were analyzed. The real-time PCR assays confirmed the presence of M. ulcerans in a water sample collected in a BU-endemic village in the Ashanti Region. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of Mycobacterium ulcerans infection is currently accepted as sufficient basis for treating the disease. Inadequate laboratory resources in the highly endemic areas of Africa often limit possibilities for in-country confirmation of clinical judgement. We analysed records of 99 Buruli ulcer (BU) patients diagnosed clinically and treated surgically at Amasaman Health Centre in Ghana, for whom post-treatment diagnostic laboratory tests were performed. Comparison of clinical diagnoses with test results obtained by an in-country laboratory on samples of excised tissue showed a high specificity of clinical judgement. Among lesions with three laboratory tests (microscopy for acid fast bacilli, culture and IS2404 polymerase chain reaction) done, 94% tested positive at least once and 83% twice. Thus correct clinical diagnosis of BU by well trained health workers is achievable, although the quality of clinical diagnosis should be monitored by intermittent testing in national reference laboratories. However, being retrospective, this study did not permit sensitivity and negative predictive value analysis. [ABSTRACT FROM AUTHOR]

Buruli ulcer disease (BUD), a devastating tropical disease caused by Mycobacterium ulcerans, occurs in more than 80% of the administrative districts of Ghana. To elucidate community perceptions and understanding of the aetiology of BUD, attitudes towards Buruli patients and treatment-seeking behaviours, we conducted a survey with 504 heads of households and seven focus group discussions in Ga West District, Ghana. Although 67% of participants regarded BUD as a health problem, 53% did not know its cause. Sixteen per cent attributed the cause to drinking non-potable water, 8.1% mentioned poor personal hygiene or dirty surroundings, and 5.5% identified swimming or wading in ponds as a risk factor. About 5.2% thought that witchcraft and curses cause BUD, and 71.8% indicated that BU sufferers first seek treatment from herbalists and only refer to the hospital as a last resort. The main reasons were prospects of prolonged hospital stay, cost of transport, loss of earnings and opportunity associated with parents attending their children's hospitalization over extended period, delays in being attended by medical staff, and not knowing the cause of the disease or required treatment. The level of acceptance of BUD sufferers was high in adults but less so in children. The challenge facing health workers is to break the vicious cycle of poor medical outcomes leading to poor attitudes to hospital treatment in the community. Because herbalists are often the first people consulted by those who contract the disease, they need to be trained in early recognition of the pre-ulcerative stage of Buruli lesions. [ABSTRACT FROM AUTHOR]

Summary: We studied hospital records of 750 consecutive Buruli ulcer patients in a highly endemic area in Amansie West, Ghana. Although more Buruli ulcer lesions were found on the right side of the body, comparison of lesions on arms and legs showed a bilaterally symmetrical distribution. Upper and lower extremities were affected equally by Buruli ulcers, if correction was made for differences in body surface area. Patients from outside the Amansie West district presented significantly more often with ulcerated lesions, which were more often located on a joint, than patients who lived in Amansie West, suggesting that longer travel distance might have caused delay. Our observations of a bilaterally symmetrical distribution of lesions on extremities and equal upper and lower extremity involvement are compatible with a mode of transmission that involves passive exposure of exposed body parts. An asymmetrical distribution of lesions was found in an earlier study, suggesting transmission by vegetation near the ground, through activities like farming or play. Perhaps, transmission in or near water, e.g. by bites of infected aquatic insects, might favour the pattern of distribution of lesions that we found. [Copyright &y& Elsevier]

Background: Buruli ulcer is a tissue necrosis infection caused by an environmental mycobacterium called Mycobacterium ulcerans (MU). The disease is most prevalent in rural areas with the highest rates in West and Central African countries. The bacterium produces a toxin called mycolactone which can lead to the destruction of the skin, resulting in incapacitating deformities with an enormous economic and social burden on patients and their caregivers. Even though there is an effective antibiotic treatment for BU, the control and management rely on early case detection and rapid diagnosis to avert morbidities. The diagnosis of Mycobacterium ulcerans relies on smear microscopy, culture histopathology, and PCR. Unfortunately, all the current laboratory diagnostics have various limitations and are not available in endemic communities. Consequently, there is a need for a rapid diagnostic tool for use at the community health centre level to enable diagnosis and confirmation of suspected cases for early treatment. The present study corroborated the diagnostic performance and utility of fluorescent-thin layer chromatography (f-TLC) for the diagnosis of Buruli ulcer., Methodology/principal Findings: The f-TLC method was evaluated for the diagnosis of Buruli ulcer in larger clinical samples than previously reported in an earlier preliminary study Wadagni et al. (2015). A total of 449 patients suspected of BU were included in the final data analysis out of which 122 (27.2%) were positive by f-TLC and 128 (28.5%) by PCR. Using a composite reference method generated from the two diagnostic methods, 85 (18.9%) patients were found to be truly infected with M. ulcerans, 284 (63.3%) were uninfected, while 80 (17.8%) were misidentified as infected or noninfected by the two methods. The data obtained was used to determine the discriminatory accuracy of the f-TLC against the gold standard IS2404 PCR through the analysis of its sensitivity, specificity, positive (+LR), and negative (-LR) likelihood ratio. The positive (PPV) and negative (NPV) predictive values, area under the receiver operating characteristic curve Azevedo et al. (2014), and diagnostic odds ratio were used to assess the predictive accuracy of the f-TLC method. The sensitivity of f-TLC was 66.4% (85/128), specificity was 88.5% (284/321), while the diagnostic accuracy was 82.2% (369/449). The AUC stood at 0.774 while the PPV, NPV, +LR, and-LR were 69.7% (85/122), 86.9% (284/327), 5.76, and 0.38, respectively. The use of the rule-of-thumb interpretation of diagnostic tests suggests that the method is good for use as a diagnostic tool., Conclusions/significance: Larger clinical samples than previously reported had been used to evaluate the f-TLC method for the diagnosis of Buruli ulcer. A sensitivity of 66.4%, a specificity of 88.5%, and diagnostic accuracy of 82.2% were obtained. The method is good for diagnosis and will help in making early clinical decisions about the patients as well as patient management and facilitating treatment decisions. However, it requires a slight modification to address the challenge of background interference and lack of automatic readout to become an excellent diagnostic tool., Competing Interests: The authors have no competing interest.

Background: Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic., Methods: A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders., Results: A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly., Conclusion: The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU., Competing Interests: The authors have declared that no competing interests exist.

Background: Biting aquatic insects belonging to the order Hemiptera have been suggested as potential vectors of Mycobacterium ulcerans in endemic areas for Buruli ulcer (BU). If this is the case, these insects would be expected to co-exist with M. ulcerans in the same geographical areas. Here, we studied the geographical distribution of six aquatic Hemiptera families that are thought to be vectors of M. ulcerans and explored their potential geographical overlapping with communities reporting BU cases in endemic countries., Methods: We have developed ensemble ecological models of predicted distribution for six families of the Hemiptera (Naucoridae, Belostomatidae, Notonectidae, Nepidae, Corixidae and Gerridae) applying a robust modelling framework over a collection of recorded presences and a suite of environmental and topographical factors. Ecological niche factor analysis (ENFA) was first used to identify factors that best described the ecological niches for each hemipteran family. Finally, we explored the potential geographical co-occurrence of these insects and BU in two endemic countries, Cameroon and Ghana., Results: Species of the families Naucoridae and Belostomatidae, according to our models, are widely distributed across Africa, although absent from drier and hotter areas. The other two families of biting Hemiptera, the Notonectidae and Nepidae, would have a more restricted distribution, being more predominant in western and southern Africa. All these four families of biting water bugs are widely distributed across coastal areas of West Africa. They would thrive in areas where annual mean temperature varies between 15-22 °C, with moderate annual precipitation (i.e. 350-1000 mm/annual) and near to water courses. Species of all hemipteran families show preference for human-made environments such as agricultural landscapes and urbanized areas. Finally, our analysis suggests that M. ulcerans and species of these aquatic insects might coexist in the same ecological niches, although there would be variation in species diversity between BU endemic areas., Conclusions: Our findings predict the geographical co-existence of some species of aquatic hemipteran families and BU. Considering the existing biological evidence that points to some of these aquatic insects as potential phoretic vectors of M. ulcerans, its presence in BU endemic areas should be considered a risk factor. The ecological models here presented may be helpful to inform future environmental based models intended to delineate the potential geographical distribution of BU in the African region.

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical disease frequently leading to permanent disabilities. The ulcers are treated with rifampicin and streptomycin, wound care and, if necessary surgical intervention. Professionals have exclusively shaped the research agenda concerning management and control, while patients' perspective on priorities and preferences have not explicitly been explored or addressed., Methodology/principal Findings: To get insight into patient perception of the management and control of Buruli ulcer a mixed methods research design was applied with a questionnaire and focus group discussions among former BU patients. Data collection was obtained in collaboration with a local team of native speakers in Ghana. A questionnaire was completed by 60 former patients and four focus group discussions were conducted with eight participants per group. Former patients positively evaluated both the effectiveness of the treatment and the financial contribution received for the travel costs to the hospitals. Pain experienced during treatment procedures, in particular wound care and the streptomycin injections, and the side-effects of the treatment were negatively evaluated. Former patients considered the development of preventive measures and knowledge on the transmission as priorities. Additionally, former patients asked for improved accessibility of health services, counselling and economic support., Conclusions: These findings can be used to improve clinical management and to guide the international research agenda., Competing Interests: The authors have declared that no competing interests exist.

Buruli ulcer (BU) is a disease affecting the skin, subcutaneous fat, and bone tissues. Wound care is important in the prevention of disabilities. Awareness of current wound care practices in BU-endemic regions is necessary for future wound care interventions. Thirty-one health care workers in Ghana and Benin were interviewed with a semi-structured interview, complemented by structural observations. Quantitative data were analyzed through t tests and one-way analysis of variance, and qualitative data through descriptive statistics. There appeared to be a general understanding of wound assessment. A large variety of different topical antiseptics was reported to be used, pressure irrigation was never reported. Gauze was the main dressing type and a moist environment was preferred, but could not be maintained. Bleeding and pain were observed frequently. Standard of wound care differed importantly between health care personnel and between institutions and adherence to World Health Organization guidelines was low., (© The American Society of Tropical Medicine and Hygiene.)

During August 2010-December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer.

This study examined sociocultural features of help-seeking for Buruli ulcer-affected persons with pre-ulcers and ulcers in a disease-endemic area in Ghana. A sample of 181 respondents were purposively selected. Fisher's exact test was used to compare help-seeking variables for pre-ulcers and ulcers. Qualitative phenomenologic analysis of narratives clarified the meaning and content of selected quantitative help-seeking variables. For pre-ulcers, herbal dressings were used to expose necrotic tissues and subsequently applied as dressings for ulcers. Analgesics and left-over antibiotics were used to ease pain and reduce inflammation. Choices for outside-help were influenced by the perceived effectiveness of the treatment, the closeness of the provider to residences, and family and friends. Health education is required to emphasize the risk of self-medication with antibiotics and the importance of medical treatment for pre-ulcers, and to caution against the use of herbs to expose necrotic tissues, which could lead to co-infections.

Background: Mycobacterium ulcerans (MU) disease causes extensive destruction of tissues leaving large ulcers on the body. Management which consisted of surgical excision of the lesions is gradually being replaced with chemotherapy., Objective: To study the impact on surgery of prior treatment of MU disease with rifampicin and streptomycin., Study Design: Retrospective, from September 2004 to September 2009., Setting: Asunafo, Amansie West, Ahafo Ano and Amansie Central districts of Ghana., Methods: Patients who have completed 8 weeks or a minimum of 4 weeks treatment with rifampicin and streptomycin but have unhealed lesions were selected for surgery., Results: 132 patients had surgery for MU disease; 51 at Tepa (Ahafo Ano); 36 at Agroyesum (Amansie West); 16 from Jacobu (Amansie Central); 29 from Goaso (Asunafo) districts. Their ages ranged from 4 to 98 years, with mean age of 29.90 years, standard deviation of 20.74. Sites involved were: head and neck 1 (0.74%), upper limb 40 (29.63%), lower limb 92 (68.15%), trunk 2 (1.48%) (N=135). The clinical forms were: papule 1 (0.74%), nodule 2 (1.48%), oedematous lesion 4 (2.96%), osteomyelitis 2 (1.48%), ulcers 124 (91.85%), contractures 2 (1.48%). 139 surgical procedures were performed: excision 25 (18.11), skin grafting 36 (26.1%), excision and skin grafting 54 (39.1%), debridem net 10 (7.2%), sequestrectomy 2 (1.4%), regrafting 10 (7.2%), release of contractures 2 (1.4%)., Conclusion: Treatment of MU disease with rifampicin and streptomycin improved the condition and minimised the extent of surgery. Combination of surgery and antibiotics is necessary to prevent the development contractures.

Objectives: To evaluate former Buruli ulcer disease (BUD) patients to assess the factors associated with functional limitations and subsequent employment or schooling., Methods: The previously validated Buruli ulcer functional limitation score (BUFLS) questionnaire and interviews about educational and professional consequences incurred by BUD., Results: Of 638 participants, 362 (57%) had a functional limitation after a median period of almost 4 years after treatment for BUD. A lesion on a joint, older age, female gender, a lesion on a distal part of an extremity and a persistent wound were found to be independent risk factors for stopping work or education. The same risk factors applied to the development of a functional limitation. Both functional limitations and financial difficulties due to BUD disease often led to job loss and school dropout., Conclusions: Rehabilitation programmes are urgently needed to diminish the suffering from the functional limitations and employment or schooling problems caused by BUD.

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, follows an indolent course of initial progression to ulceration accompanied by extensive tissue damage. It has been suggested that healing disease stages are accompanied by a protective immune response. We hypothesized that interleukin-4 (IL-4)- or IL-10-induced downregulation of Th-1 responses plays a key role in the progression of early BUD and that healing is accompanied by an augmented Th-1 response. Gamma interferon (IFN-gamma), IL-4, and IL-10 responses were measured after in vitro stimulation with phytohemagglutinin (PHA) and tuberculin purified protein derivative (PPD) of whole blood from 39 (23 early- and 16 late-stage) BUD patients and 39 healthy control subjects in Ghana. Additionally, 30 patients with active or treated tuberculosis (TB) serving as PPD-responsive positive controls were studied. Early-stage BUD patients produced significantly lower levels of IFN and IFN-gamma/IL-4 ratios compared to late-stage BUD patients after PHA stimulation. Compared to that of controls, IFN-gamma production after tuberculin stimulation was significantly higher in late-stage but not in early-stage BUD patients (P=0.009). IL-10 and IL-4 levels did not differ between BUD patients and controls, although active TB patients had significantly higher IL-10 production levels than did treated TB patients. Multivariate analysis showed no confounding factors. In conclusion, Th-1 down regulation in early BUD appears to reverse in later stages of BUD, although an association with IL-10 or IL-4 production does not emerge from our data. Here we show differences in Th-1-type cytokine production between early- and late-stage BUD that might reflect an improved immune defense over time.

Mycobacterium ulcerans disease starts as a painless, subcutaneous nodule, excision of which prevents the development of large Buruli ulcers. An outreach programme was set up in Ghana to promote nodule recognition and excision. The programme was cost-effective and shifted the pattern of disease presentation. This could from a model for other countries.

Buruli ulcer, caused by Mycobacterium ulcerans, is emerging as the third most common mycobacterial disease after leprosy and tuberculosis in some tropical regions. Although a toxin of the polyketide family is central to the pathogenesis of the disease, there are still several parameters that need clarification. Among them and of crucial interest are the curative drug treatment and the test for early detection of the disease. In this study, we used mouse monoclonal antibodies, raised against synthetic sugars of the terminal trisaccharide of M. leprae PGL-1, to detect the immunoreactivity of this antigen in tissue infected with M. ulcerans. Thirty specimens of skin tissue from Buruli ulcer patients (3 plaques, 10 nodules, 1 ulcerated nodule, 7 deep ulcer beds and 9 ulcers in healing) were obtained from Ghana. Eighty-three percent of the submitted cases were compatible with the lesions of Buruli ulcer. AFB were positive in 33% of plaques, 40% of nodules, 44% of actives ulcers and 22% of the ulcer in healing stage. Immunohistochemically, phenolic glycolipid-1 (PGL-1) was detected in all AFB-positive cases. This observation implies that Mycobacterium ulcerans may express an M. leprae PGL-1-like substance and should tentatively emulate research to further characterize such a substance. The search for an early diagnostic tool for the Buruli disease may benefit from such investigations.

Buruli ulcer is a chronic ulcerative skin disease caused by Mycobacterium ulcerans. It is the third most common mycobacterial disease in immunocompetent people and affects mainly children living in humid areas of the tropical rain forest. The mode of transmission is unknown. The microorganisms penetrate the skin via microinjuries. A few weeks after infection, a subcutaneous nodule develops, followed by necrosis of the subcutaneous fat and finally by a large dermal ulceration. Typical is the lack of an acute inflammatory response, likely due to an immunosuppressive toxin produced by M. ulcerans called mycolactone. The lesions mostly affect the limbs. Constitutional symptoms are normally absent. The only effective treatment consists of wide excision, often followed by skin grafts. Conservative measures are rarely successful. Buruli ulcer is characterized by low mortality and high morbidity. Early recognition and treatment are decisive for the complete cure and prevention of debilitating deformities.

Recently, Buruli ulcer is emerging from the West and Central African countries. The disease come up with necrotizing and immno-suppressive type ulcer in the skin, subcutaneous tissue and bone, infected by Mycobacterium ulcerans, and shows indolent chronic course as mycobacterial infection, like tuberculosis and Hansen's disease. After the transmission to human, the lesion is usually single and begin as firm, painless, subcutaneous nodule and on any area of human body skin, though most frequently on lower limbs. In countries of West Africa, it is suspected that the disease should be spreading most widely in Ghana. During April and June 1999, Ghana Health Service pick up the new patients by nation-wide examination. The author visited Ghana twice at March and September 1999 and made on-the-spot inspections not only at a community and Ga district Health Service Center in Accra region but also at St. Martin's hospital in Agroyesum, Amanse west district, Ashanti region. At the time, the author did see the present state of Buruli ulcer, i.e. health and medical enlightenment. This report, includes the results due to undergoing nation-wide examination on Buruli ulcer at 2 District in Ghana (List 1 and 2), the present states of the patients and the enlightenment provided by the staffs of Ga district Health Service Center (Photografs 1-14). Staffs working for WHO and Ghana Health Service are tackling to Buruli ulcer problems, but conditions of the patients are very hard because these patients must live in tropical wetlands, poor health, poor medical and poor economic conditions.