Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND: Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS: In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS: Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS: Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION: ISRCT 72102977.

Mycobacterium ulcerans infection imported from Australia to Missouri, USA, 2012.

Buruli ulcer, the third most common mycobacterial disease worldwide, rarely affects travelers and is uncommon in the United States. We report a travel-associated case imported from Australia and review 3 previous cases diagnosed and treated in the United States. The differential diagnoses for unusual chronic cutaneous ulcers and those nonresponsive to conventional therapy should include Mycobacterium ulcerans infection.

[Community-based approaches in the fight against Buruli ulcer : review of the literature]. / Approches communautaires dans la lutte contre l'ulcère de Buruli : revue de la littérature.

Buruli ulcer (BU) is an infectious skin disease caused by Mycobacterium ulcerans. It mainly affects poor communities living close to bodies of water. In the absence of early treatment, this "neglected" disease can cause lasting deformities and may require limb amputation. It is reported in 34 countries and is the third most common mycobacterial disease in immunocompetent patients. Considerable progress has been made in treatment and prevention. The Cotonou Declaration (2009) describes the recommended control strategies. Although effective, current control strategies are limited because they do not take into account all the factors that influence emergence, prevention and cure of the disease. The control of Buruli ulcer mainly depends on intervention on social, cultural and psychosocial factors that influence preventive and self-care behaviour. The health promotion approach requires collaboration with populations in order to perform simultaneous actions on BU factors in the community setting. Although effective on many health problems, health promotion is not applied in the fight against BU due to the absence of action on all factors such as poverty. This article presents a review of the literature on BU strategies and community approaches. 407 relevant articles published in 1998-2013 period were examined. Eleven programmes are based on a top-down approach, which does not include populations in decision-making processes, unlike the bottom-up participatory approaches recommended in health promotion. Three health promotion programmes and 6 community-based participatory approaches were identified and examined. Community participation and empowerment constitute the basis for a community approach in the fight against Buruli ulcer.

An overview of Buruli ulcer in Australia.

BACKGROUND: Buruli ulcer (BU) is caused by Mycobacterium ulcerans, an environmental pathogen that causes severe skin and soft-tissue necrosis. In Australia, cases of BU are acquired in endemic regions, which include Victoria and Far North Queensland, but those who have visited these regions can present to health practitioners anywhere. OBJECTIVE: This article provides Australian general practitioners with an overview of BU, including its epidemiology, transmission, clinical features, diagnosis and management. DISCUSSION: BU can manifest as an ulcer or as a non-ulcerated skin lesion, such as a plaque, nodule or oedema. Diagnosis can be achieved with a dedicated Mycobacterium ulcerans polymerase chain reaction (PCR) test performed on a wound swab. Swabs on non-ulcerated disease have a high false negative rate, and a PCR test should be performed on a tissue biopsy to confirm disease. Most cases are managed with prolonged antibiotic therapy - commonly a combination of oral rifampicin and clarithromycin or fluroquinolone (moxifloxacin or ciprofloxacin) - and wound dressings.

A lesion in two: Buruli ulcer and squamous cell carcinoma coexistence.

The concurrent diagnoses of Buruli ulcer (BU) and cutaneous squamous cell carcinoma (SCC) is a phenomenon not previously described, despite the fact that both conditions are highly prevalent in Australia. This report presents an intriguing case of concurrent diagnoses, with clues alluding to more than one skin condition being present. The case involves a 73-year-old man with BU diagnosed on the scalp, an atypical location, which led to the consideration of malignancy, ultimately revealing concurrent SCC. This case highlights the importance of considering both conditions in patients with epidemiological risk factors, necessitating multiple lines of investigation for accurate diagnosis. Medical practitioners must remain vigilant and incorporate this possibility into their diagnostic algorithms for suspicious skin lesions to optimize treatment and outcomes. This is the first recorded instance of simultaneous diagnosis, underlining the need for enhanced awareness and attention to these unique cases.

[Buruli ulcer: a dynamic transversal research model performed through the international network of Pasteur Institutes]. / L'ulcère de Buruli: un modèle de recherche transversale dynamique au sein du réseau des Instituts Pasteur.

Buruli ulcer is an endemic severe human skin disease caused by Mycobacterium ulcerans, which prevails in western Africa in swampy areas and primarily hits children. Its gravity comes from the extent of tissue destruction, created by the toxin mycolactone. We describe here how the Centre Pasteur of Cameroon, with the help of the ministry of Health, gathered a network of multidisciplinary partners to fight against Buruli ulcer starting in the years 2000. The Centre Pasteur develops three missions : patient care, training of health care workers and research on the insect vector. Ten years of efforts resulted in significant medical advances such as the design of an early diagnostic test using PCR, or the observation that bed net use significantly decreased the risk of Buruli ulcer, offering useful prevention ; on the research side, entomological studies on aquatic bugs, coupled with epidemiological data, point to the role of these insects in the transmission of the disease. This study examplifies how an efficient network can contribute to the prevention and treatment of debilitating infectious diseases.

[Profile of Buruli ulcer treated at the National Reference Centre of Togo: a study of 119 cases]. / Profil de l'ulcère de Buruli pris en charge au Centre national de référence du Togo: étude de 119 cas.

The purpose of this study was to describe the epidemiological, clinical, therapeutic profile and the outcome of Buruli ulcer (BU) in the National Reference Center for Buruli ulcer treatment (NRCBUT) in Togo. It was a retrospective and descriptive study of records of patients treated for BU in the NRCBUT between June 2007 and December 2010. During the study period, 119 patients (56.3% males) were treated in the NRCBUT for BU. The median age of patients was 14 years. The proportion of children (< 15 years) was 56.3%. On admission, 85 patients were at ulcer stage and 34 patients at the pre-ulcer stage. BU wounds were mainly located on lower limbs (50.4%), followed by upper limbs (32.6%) and trunk (13.3%). The location of the wounds on the lower limbs were more frequent in patients older than 15 years (P < 0.001), while those on the upper limbs (P = 0.002) and trunk (P = 0.03) were more frequent in patients aged less than 15 years. All patients had received medical treatment which was based on rifampicin-streptomycin combination for eight weeks. This treatment was coupled to surgery in 30 cases. The outcome was punctuated by complications in 7 patients, limb amputation in 3 patients, and sequels in 10 patients. This study confirmed that the BU is the prerogative of young subjects and the exposed areas in the skin facilitates transmission. Apart from these classic features, some unique aspects including the age-dependent distribution are related to the pathogenesis of this disease.

[International cooperation with the neglected tropical disease Buruli ulcer in Togo].

The objectives of this paper are to grasp the current status of an endemic disease, known as Buruli ulcer (BU), in the Republic of Togo and the expansion of international assistance in the field. By adopting the explicit support model, this paper also compares the obtained research results with those of the Republic of Ghana and Benin, to clarify the primary functions played among respective governments, WHO, and NGO. Under the auspices of the WHO Global Buruli Ulcer Initiative (GBUI, 1998-), National Buruli Ulcer Control Programme (NBUCP) in the Togo was initiated in 1999. However, due to the shortage of national budget and politico-economic instabilities of the nation, the actual implementation of NBUCP proved to be problematic. It was after 2007 that the programme began to move forward with the interventions of NGOs like DAHW and Handicap International. Currently, major players involved in the implementation of the policies provided by the GBUI are WHO, NGOs and the targeted governments. In other words, the organizations involved in BU treatment work together by fulfilling their functions. Unlike the neighboring countries, the Togolese government encountered much difficulty in materializing its national programme. Largely due to the political instability and the severe shortage of national budget, stronger assistances from NGOs were required at various levels of the national health measures from formulating to implementing the programme. As the programmes in Togo and Ghana/Benin expanded over the years, the respective support model revealed to be unique and different. In Ghana and Benin, intimate cooperation among WHO, government and NGOs has been established. In Togo, strengthening of collaboration among the three players is expected.

Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli ulcer in the Ga-West and Ga-South Municipalities of Ghana.

BACKGROUND: Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of socio-cultural research on BU. Examining distinctive experiences and meanings for pre-ulcers and ulcers of BU may clarify the disease burden, illness experience and local perceptions of causes and spread, and environmental features of BU, which are useful to guide public health programmes and future research. This study aimed to explain local meanings and experiences of BU for persons with pre-ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. METHODS: Semi-structured interviews based on the Explanatory Model Interview Catalogue framework were administered to 181 respondents comprising 15 respondents with pre-ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to compare categories of illness experiences (PD) and perceived causes (PC) among respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used to compare the most troubling PD and the most important PC variables. Qualitative phenomenological analysis of respondents' narratives clarified illness experiences and meanings with reference to PC and PD variables. RESULTS: Families of respondents with pre-ulcers and the respondents themselves were often anxious about disease progression, while families of respondents with ulcers, who had to give care, worried about income loss and disruption of school attendance. Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a perceived cause and considered it as the most important PC (53.3%). Respondents with ulcers frequently attributed their BU illness to witchcraft (64.5%) and respondents who claimed they had no water contact, questioned the credibility of health messages CONCLUSIONS: Affected persons with pre-ulcers are likely to delay treatment because of social and financial constraints and the absence of pain. Scepticism on the role of water in disease contagion and prolonged healing is perceived to make ideas of witchcraft as a PC more credible, among respondents with ulcers. Health messages should address issues of locally perceived risk and vulnerability. Guided by study findings, further research on the role of environmental, socio-cultural and genetic factors in BU contagion, is also needed to clarify and formulate health messages and strengthen public health initiatives.

Methods and Approaches for Buruli Ulcer Surveillance in Africa: Lessons Learnt and Future Directions.

Over 95% of the global burden of Buruli ulcer disease (BU) caused by Mycobacterium ulcerans occurs in equatorial Africa. National and sub-national programs have implemented various approaches to improve detection and reporting of incident cases over recent decades. Regional incidence rates are currently in decline; however, surveillance targets outlined in 2012 by WHO have been missed and detection bias may contribute to these trends. In light of the new 2030 NTD roadmap and disease-specific targets, BU programs are required to strengthen case detection and begin a transition towards integration with other skin-NTDs. This transition comes with new opportunities to enhance existing BU surveillance systems and develop novel approaches for implementation and evaluation.In this review, we present a breakdown and assessment of the methods and approaches that have been the pillars of BU surveillance systems in Africa: (1) Passive case detection, (2) Data systems, (3) Clinical training, (4) Active case finding, (5) Burden estimation, and (6) Laboratory confirmation pathways. We discuss successes, challenges, and relevant case studies before highlighting opportunities for future development and evaluation including novel data collection tools, risk-based surveillance, and integrated skin-NTD surveillance. We draw on both experience and available literature to critically evaluate methods of BU surveillance in Africa and highlight new approaches to help achieve 2030 roadmap targets.

Experiences of Buruli Ulcer Patients Following Discharge in the Greater Accra Region of Ghana.

Buruli ulcer (BU) is one of the skin diseases that causes physical deformity, loss of function of the affected part, social stigmatization, and financial burden to individuals affected. Annually, an approximated 6000 cases of BU are reported worldwide especially from West Africa, Central Africa, and Asia. The aim of the study was to assess the experiences of BU patients in the Greater Accra Region of Ghana following discharge from the hospital. The study employed a qualitative descriptive phenomenological approach using snowballing sampling technique to sample 15 participants from the Greater Accra Region of Ghana who have been treated and discharged home. Data were collected through face-to-face interviews that was later transcribed and coded using qualitative content analysis. Findings from this study revealed that individuals with BU goes through several challenges during admission and after discharge including feeling of embarrassment, financially handicapped, and marital conflicts. The study concluded that BU has not been totally eradicated from the country, hence must be given the attention it deserves to help individuals cope better.

Nineteen cases of Buruli ulcer diagnosed in Japan from 1980 to 2010.

The etiology, clinical manifestations, and treatment of 19 sporadic cases of Buruli ulcer (BU) in Japan are described. The cases originated in different regions of Honshu Island, with no evidence of patient contact with an aquatic environment. The majority (73.7%) of cases occurred in females, with an average age of 39.1 years for females and 56.8 years for males. All patients developed ulcers on exposed areas of the skin (e.g., face, extremities). Most ulcers were <5 cm in diameter (category I), except in one severe progressive case (category II). Pain was absent in 10 of the 19 cases. Fourteen ulcers were surgically excised, and nine patients needed skin grafting. All cases were treated with various antibiotic regimens, with no reported recurrences as of March 2011. Mycobacterium ulcerans-specific IS2404 was detected in all cases. Ten isolates had identical 16S rRNA gene sequences, which were similar to those of M. ulcerans. However, the rpoB gene showed a closer resemblance to Mycobacterium marinum or Mycobacterium pseudoshottsii. PCR identified pMUM001 in all isolates but failed to detect one marker. DNA-DNA hybridization misidentified all isolates as M. marinum. The drug susceptibility profile of the isolates also differed from that of M. ulcerans. Sequence analysis revealed "Mycobacterium ulcerans subsp. shinshuense" as the etiologic agent of BU in Japan. Clinical manifestations were comparable to those of M. ulcerans but differed as follows: (i) cases were not concentrated in a particular area; (ii) there was no suspected connection to an aquatic environment; (iii) drug susceptibility was different; and (iv) bacteriological features were different.

Caregiver burden in Buruli ulcer disease: Evidence from Ghana.

BACKGROUND: Buruli ulcer disease (BUD) results in disabilities and deformities in the absence of early medical intervention. The extensive role of caregiving in BUD is widely acknowledged, however, associated caregiver burden is poorly understood. In this paper we assessed the burden which caregivers experience when supporting patients with BUD in Ghana. METHOD/ PRINCIPAL FINDINGS: This qualitative study was conducted in 3 districts in Ghana between August and October 2019. 13 semi-structured interviews were conducted on caregivers of BUD patients in the local language of Twi. Data was translated into English, coded into broad themes, and direct content analysis approach was used to analyse results. The results show the caregivers face financial, psychological and health issues as a consequence of their caregiving role. CONCLUSION/ SIGNIFICANCE: This study found significant caregiver burden on family members. It also highlighted the psychological burden caregivers experience and the limited knowledge of the disease within endemic communities. Further research is needed to quantify the caregiver burden of BUD at different economic levels in order to better understand the impact of possible caregiver interventions on patient outcomes.

Perspectives of buruli ulcer patients toward informed consent - An insight from Nigeria.

Introduction: Informed consent is a basic ethical requirement in situations involving sharing of patients' data. It supports and upholds the ethical principle of respect for persons and individual autonomy. For Buruli ulcer (BU) patients, associated stigma renders them vulnerable, hence the need for emphasis on additional protection by ensuring obtaining informed consent before third party use of their data. The authors therefore sought to determine willingness of these patients to give informed consent to the third party use of their data before and after treatment. Methodology: This cross-sectional study was carried out between February and August, 2019. The study involved BU patients from three endemic states in Nigeria. Data were collected using pretested, researcher-administered semi-structured questionnaires. Results: A total of 92 respondents participated in the study. The median age was 23.5 years (range 4-74 years) with the age group <15 years being the modal age group 36 (39.13%). About a quarter of the respondents (23.91%) had suffered some form of discrimination in the course of their disease. Majority 86 (93.48%) were favorably disposed to allowing the use of their data for donor drive, policy development, and teaching/training purposes. A significant greater proportion of respondents 90 (97.83%) were willing to give consent for the use of their oral interview as against pictures and videos both in the pre- and post-treatment periods. Conclusion: The present study provides evidence that majority of the respondents were positively inclined to give consent to use of their data by a third party. However, intrusion into privacy and anonymity were major concerns for the respondents.

RésuméIntroduction: Le consentement éclairé est une exigence éthique de base dans les situations impliquant le partage des données des patients. Il soutient et défend le principe éthique du respect des personnes et de l'autonomie individuelle. Pour les patients atteints d'ulcère de Buruli, la stigmatisation associée les rend vulnérables, d'où la nécessité de mettre l'accent sur une protection supplémentaire en garantissant l'obtention d'un consentement éclairé avant l'utilisation par des tiers de leurs données. Les auteurs ont donc cherché à déterminer la volonté de ces patients de consentir en connaissance de cause à l'utilisation de leurs données par des tiers avant et après le traitement. Les méthodes: Cette étude transversale a été réalisée entre février et août 2019. L'étude a porté sur des patients atteints d'ulcère de Buruli provenant de trois États endémiques du Nigéria. Les données ont été recueillies à l'aide de questionnaires semi-structurés prétestés et administrés par des chercheurs. Résultats: Au total, 92 répondants ont participé à l'étude. L'âge médian était de 23,5 ans (de 4 à 74 ans), le groupe d'âge <15 ans étant le groupe d'âge modal 36 (39,13%). Environ un quart des répondants (23,91%) ont subi une forme de discrimination au cours de leur maladie. La majorité 86 (93,48%) étaient favorables à autoriser l'utilisation de leurs données à des fins de mobilisation des donateurs, d'élaboration de politiques et d'enseignement / formation. Une proportion significativement plus élevée de répondants 90 (97,83%) étaient disposés à donner leur consentement pour l'utilisation de leur entretien oral par rapport aux photos et vidéos à la fois avant et après le traitement. Conclusion: La présente étude prouve que la majorité des répondants étaient positivement enclins à consentir à l'utilisation de leurs données par un tiers. Cependant, l'intrusion dans la vie privée et l'anonymat étaient des préoccupations majeures pour les répondants.

Barriers to Buruli ulcer treatment completion in the Ashanti and Central Regions, Ghana.

BACKGROUND: Buruli ulcer is a chronic ulcerating skin condition, with the highest burden found in Central and West Africa where it disproportionately affects the most vulnerable populations. Treatment is demanding, comprising eight-weeks of daily antibiotics, regular wound care and possible surgical intervention. Treatment completion is key to optimising outcomes, however the degree of and barriers to this are not well understood. Recent change from injectable treatment (SR8) to oral treatment (CR8) has made it feasible to further decentralise care, potentially improving treatment access and completion. However, the impact of this and of other demographic and clinical influences on treatment completion must be explored first to ensure appropriate models of care are developed. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective clinical notes review and secondary data analysis of records from patients diagnosed between 1 January 2006-31 December 2018 at four district hospital clinics in the Ashanti and Central Regions, Ghana. Univariable analyses and multivariable logistic regression were performed to assess the association between explanatory variables and treatment completion. There were 931 patient episodes across the four clinics with overall treatment completion of 84.4%. CR8 was associated with higher treatment completion compared to SR8 (OR 4.1, P = 0.001). There was no statistically significant association found between distance from patient residence to clinic and treatment completion. CONCLUSIONS/SIGNIFICANCE: Improved treatment completion with CR8 supports its use as first line therapy and may enable decentralisation to fully community-based care. We did not find an association between distance to care and treatment completion, though analyses were limited by data availability. However, we did find evidence that distance to care continues to be associated with more severe forms of disease, which may reflect the higher costs of accessing care and lower awareness of the condition the further a patient lives. Decentralised care must therefore also continue to support community engagement and active outreach to identify cases early.

Buruli ulcer in United Kingdom tourist returning from Latin America.

We report a case of Buruli ulcer in a tourist from the United Kingdom. The disease was almost certainly acquired in Brazil, where only 1 case had previously been reported. The delay in diagnosis highlights the need for physicians to be aware of the disease and its epidemiology.

Therapeutic itineraries of patients with ulcerated forms of Mycobacterium ulcerans (Buruli ulcer) disease in a rural health zone in the Democratic Republic of Congo.

OBJECTIVE: To describe lay perceptions of the ulcerated forms of Mycobacterium ulcerans, commonly called Buruli ulcer (BU), and therapeutic itineraries of BU patients in a rural area of the Democratic Republic of Congo. METHODS: Qualitative research consisting of semi-structured interviews of 19 patients with clinical signs of BU and 12 in-depth interviews of confirmed cases allowing for a detailed reconstruction of the itineraries followed. RESULTS: The first symptoms of BU are perceived as mild. The perceived seriousness of the disease increases as the ulceration persists, increases in size or results in complications. Knowledge about the biomedical aetiology of the disease is scarce; it is commonly believed to be due to witches' attacks or bad fate. Four therapeutic paths are taken: self-medication, traditional therapy, the church and the health centre. However lay perception, recourse to traditional treatments and self-medication only partially explain the long delays in diagnosis (on average 6 months); the main problem lies with health providers, particularly the lack of proper diagnostic capability. CONCLUSIONS: Diagnostic capabilities at health centre level need to be strengthened through training and supervision. Engaging with the population and the traditional healers would render health promotion messages on BU more relevant and culturally acceptable.

[Buruli ulcer re-emergent infection]. / Ulcerul de Buruli--infectie reemergenta.

Nowadays, Buruli ulcer caused by Mycobacterium ulcerans remains a highly stigmatizing emerging disease in tropical countries, currently being the third mycobacterian infection in immunocompetent individuals. The purpose of this paper is to gather a number of information (epidemiological, clinical, laboratory and related to current treatment) in order to make the "aura of mysterious disease" fade away. Our work insists on the fact that prevention of Buruli ulcer and its complications is based on a better awareness of the dynamics and evolution of ecosystems as well as on socio-economic factors in tropical countries. Besides prophylactic measures, efficient methods for diagnosis and treatment are emphasized.