Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease).

BACKGROUND: Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery. OBJECTIVES: To summarize the evidence of drug treatments for treating Buruli ulcer. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.Rifampicin combined with streptomycinWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).An additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.Rifampicin combined with clarithromycinTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phaseOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).Novel combination therapyTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%. AUTHORS' CONCLUSIONS: While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, ß tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. RESULTS: Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and ß tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. CONCLUSION: Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection.

[Squamous cell carcinoma secondary to Buruli ulcer in West Africa]. / Carcinomes épidermoïdes sur cicatrices d'ulcère de Buruli en Afrique de l'Ouest.

BACKGROUND: Buruli ulcer is an infection caused by Mycobacterium ulcerans occurring in tropical areas. In West Africa, it is an emerging threat mainly affecting children aged under 15years. This chronic disease is complicated by dystrophic scars in which squamous cell carcinoma can occur in the long term. PATIENTS AND METHODS: This is a retrospective study of squamous cell carcinomas in Buruli ulcer scars seen at the Treichville University Hospital (Abidjan, Ivory Coast) over a five-year period. RESULTS: During the study period, 8cases were observed and concerned young adults presenting Buruli ulcer in their childhood. Tumours were restricted to the limbs, with loco-regional invasion. Treatment was primarily surgical. Four of the patients died. DISCUSSION: The risk of recurrence of cancer in these scars remains poorly evaluated, highlighting the importance of long-term monitoring strategies for human patients in order to ensure rapid identification of any changes in Buruli ulcer scars.

Management of BU-HIV co-infection.

BACKGROUND: Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking. METHODS: Initiated by WHO, a panel of experts in BU and HIV management developed guidance principles for the management of BU-HIV co-infection based on review of available scientific evidence, current treatment experience, and global recommendations established for management of HIV infection and tuberculosis. RESULTS: The expert panel agreed that all BU patients should be offered quality provider-initiated HIV testing and counselling. In areas with high prevalence of malaria and/or bacterial infections, all patients with HIV co-infection should be started on cotrimoxazole preventative therapy. Combination antibiotic treatment for BU should be commenced before starting antiretroviral therapy (ART) and provided for 8 weeks duration. The suggested combination is rifampicin (10 mg/kg daily up to a maximum of 600 mg/day) plus streptomycin (15 mg/kg daily). An alternative regimen is rifampicin plus clarithromycin (7.5 mg/kg twice daily up to a maximum of 1000 mg daily) although due to drug interactions with antiretroviral drugs this regimen should be used with caution. ART should be initiated in all BU-HIV co-infected patients with symptomatic HIV disease (WHO clinical stage 3 or 4) regardless of CD4 cell count and in asymptomatic individuals with CD4 count ≤500 cells/mm(3) . If CD4 count is not available, BU-HIV co-infected individuals with category 2 or 3 BU disease should be offered ART. For eligible individuals, ART should be commenced as soon as possible within 8 weeks after commencing BU treatment, and as a priority in those with advanced HIV disease (CD4 ≤ 350 cells/mm(3) or WHO stage 3 or 4 disease). All co-infected patients should be actively screened for tuberculosis before commencing BU treatment and before starting ART. Programmes should implement a monitoring and reporting system to document the outcomes of BU-HIV interventions. CONCLUSIONS: Knowledge of the clinical and epidemiological interactions between BU and HIV disease is limited. While awaiting more urgently needed evidence, current management practice of both diseases has been useful to build simple 'common sense' preliminary guidance on how to manage BU-HIV co-infection.

[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.

Nutritional status and wound healing in patients with Mycobacterium ulcerans disease (Buruli ulcer): a pilot study from rural Côte d'Ivoire

Background: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans which manifests as deep ulceration of the skin. Wounds from any cause heal slowly if individuals are malnourished. Objectives: To assess the impact of nutritional status on wound healing, we carried out a nutritional assessment of 11 patients diagnosed with BU in rural Côte d'Ivoire, and followed them longitudinally through the wound healing process. Materials & Methods: We conducted patient interviews to collect data on their socioeconomic characteristics, food intake and perception of nutrition. We then prospectively carried out clinical observations to assess their wound healing until complete healing or the end of the study period (median follow-up period: 19 weeks). Results: The age of the patients ranged from 6 to 66 years (median: 24; interquartile range: 20.5-52). Nine patients had normal nutritional status, one had mild malnutrition and one had moderate malnutrition as assessed by their body mass index and/or mid-upper arm circumference. Three (60%) of the five patients with adequate caloric intake, but only 1/6 (17%) of the patients with an inadequate caloric intake achieved complete healing during follow-up. Low food intake from appetite loss primarily due to wound pain and odour was reported by seven patients after developing wounds. Conclusion: Our study is the first of its kind, and the findings highlight the importance of integrating nutritional interventions into wound management protocols, and properly assessing and controlling wound pain in patients with BU.

Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation.

Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.

[Buruli ulcer - beyond the skin, impact on skeletal muscle]. / L'ulcèrede Buruli - Au-delà de la nécrose cutanée, répercussions sur le tissu musculaire.

Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans (M. ulcerans). Clinical observations from infected patients in the endemic zone of the West Africa reveal that severe M. ulcerans infections can induce skeletal muscle contracture and atrophy leading to significant invalidity. Although significant advances have been made for the epidemiological, clinical and therapeutic aspects of the disease in the past ten years, several questions remained unanswered on the muscle physiopathology of the M. ulcerans. This article is one of the first attempts to shed some light on this neglected disease and unravel the impact of M. ulcerans on skeletal muscle.

Squamous cell carcinoma secondary to Buruli ulcer: a clinical case report in a young girl.

Buruli Ulcer, a common tropical disease, is endemic in West Africa in particular in Cote d'Ivoire, where it represents the second mycobacterial disease after Tuberculosis. The late diagnosis and treatment as well as, the lack of surveillance, lead to large skin ulcerations, local or multifocal osteomylitis and some time it may lead to neoplasia which contribute to worse the prognosis of the patient. We presented a case report in a girl of 16 years old, who died from an aggressive squamous cell carcinoma of the upper limb secondary to Buruli Ulcer. This case report showed the importance of early detection and treatment, a specific surveillance for Buruli Ulcer infected patients, a need for them to be vigilant and to report any suspected skin lesions even after healing, and the need for a good prevention strategy in Buruli Ulcer endemic areas.

"Buruli ulcer and leprosy, they are intertwined": Patient experiences of integrated case management of skin neglected tropical diseases in Liberia.

BACKGROUND: Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them. METHODS: To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers. FINDINGS: The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as 'intertwined': related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services. SIGNIFICANCE: Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases.

The co-infection of Buruli ulcer and cutaneous leishmaniasis in Sudanese patient: An association by choice or by chance?

Buruli ulcer and cutaneous leishmaniasis both have the similar cutaneous clinical presentation. Therefore, relying on clinical diagnosis can be challenging. We present a case of 45 years old woman diagnosed with cutaneous leishmaniasis, confirmed by skin biopsy. She received different modalities of anti-leishmanial treatment (fluconazole 450mg daily for 4 weeks, sodium stibogluconate (SSG) followed by thermal therapy, SSG/IV 20mg/kg for 30 days combined with paromomycin 15mg/kg IM for 17 days). These treatments were associated with partial improvement of the ulcer and failure of healing. A second biopsy demonstrated the presence of Mycobacterium ulcerans and hence the diagnosis of Buruli ulcer as a cause of the delayed healing of the ulcer. M. ulcerans releases a toxin known as mycolactone, which decreases immune system function and results in tissue death. M. ulcerans, is regarded as the third most prevalent Mycobacterium after M. tuberculosis and M. leprae. Treatment with streptomycin intramuscular injections 1g daily and rifampicin 600mg daily for 8 weeks was associated with complete healing of the ulcer. To our knowledge, this is the first report that describes the co-infection of Buruli ulcer and cutaneous leishmaniasis in Sudan.

A case of squamous cell carcinoma occurring on a scar of Buruli ulcer in Bouake, Ivory Coast.

Buruli ulcer is infectious necrotizing panniculitis due to Mycobacterium ulcerans. Buruli ulcer is healed by leaving dystrophic, fibrous and retractile scars. On these scars can occur long-term squamous cell carcinoma. We report the first case of squamous cell carcinoma occurring on healing of Buruli ulcer. A 32-year-old woman with Buruli ulcer who has been cured for about 10 years is seen for ulcero-bulging knee swelling. The examination had revealed a large swelling of about ten centimeters in diameter, ulcero-budding, with an easily bleeding cauliflower appearance. The diagnosis of squamous cell carcinoma being retained without metastasis, resection of the tumor with scarring after one month without chemotherapy. There was no recurrence after six months of decline. The epidemiology of Buruli ulcer, responsible for scarring, explains the young age of our patient and the localization of carcinoma on the limb. The carcinomatous degeneration of scars, especially the scars of old burns, is constantly reported. The characteristics of Buruli ulcer scars, which bring them closer to burn scars, may explain why they are particularly affected by carcinomatous degeneration. One could also mention the chronicity of the wound in this infection, or wonder if the mycobacteria itself could play a role in carcinogenesis. This observation is, in our opinion, an alarm signal. We must fear an outbreak of cases in the years to come. To this end, preventive measures should already be taken by sensitizing the patients for an early consultation before any modification of their scars. After recovery, Buruli ulcer seems to present a risk of long-term evolution to a cancer. The scars of this condition, which could be considered precancerous lesions.

Challenges associated with the treatment of Buruli ulcer.

Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), is the third most important mycobacterial diseases after tuberculosis and leprosy in immunocompetent individuals. Although the mode of transmission remains an enigma, disease incidence has been strongly linked to disturbed environment and wetlands. The blunt of the diseases is recorded in West African countries along the Gulf of Guinea, and children 15 years and below account for about 48% of all cases globally. Prior to 2004, wide surgical excisions and debridement of infected necrotic tissues followed by skin grafting was the accepted definitive treatment of BU. However, introduction of antibiotic therapy, daily oral rifampicin (10 mg/kg) plus intramuscular injection of streptomycin (15 mg/kg), for 8 weeks by the WHO in 2004 has reduced surgery as an adjunct for correction of deformities and improved wound healing. An all-oral regimen is currently on clinical trial to replace the injectable. It is thought that a protective cloud of the cytotoxic toxin mycolactone kills infiltrating leucocytes leading to local immunosuppression and down-regulation of the systemic immune system. Our studies of lesions from BU patients treated with SR have demonstrated treatment-associated initiation of vigorous immune responses and the development of ectopic lymphoid tissue in the BU lesions. Despite these interventions, there are still challenges that bedevil the management of BU including paradoxical reactions, evolution of lesions after therapy, prolong viability of MU in BU lesions, and development of secondary bacterial infection. In this paper, we will mainly focus on the critical and pertinent challenges that undermine BU treatment toward effective control of BU.

Mycobacterium ulcerans infection as a cause of chronic diarrhea in an AIDS patient: a case report.

Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS). Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients. Among the NTM, Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients. However, NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet. We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.

Laboratory confirmation of Buruli ulcer cases in Ghana, 2008-2016.

BACKGROUND: Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana. METHOD/PRINCIPAL FINDINGS: Pathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions of Ghana (Ashanti, Brong Ahafo, Central, Eastern, Greater Accra, Northern and Volta). The mean annual positivity rate was 46.2% and ranged between 14.6% and 76.2%. The yearly positivity rates from 2008 to 2016 were 52.3%, 76.2%, 56.7%, 53.8%, 41.2%, 41.5%, 22.9%, 28.5% and 14.6% respectively. Of the 1,020 confirmed cases, the ratio of female to male was 518 and 502 respectively. Patients who were 15 years of age and below accounted for 39.8% of all cases. The median age was 20 years (IQR = 10-43). Ulcerative lesions were 69.2%, nodule (9.6%), plaque (2.9%), oedema (2.5%), osteomyelitis (1.1%), ulcer/oedema (9.5%) and ulcer/plaque (5.2%). Lesions frequently occurred on the lower limbs (57%) followed by the upper limbs (38%), the neck and head (3%) and the least found on the abdomen (2%). CONCLUSIONS/SIGNIFICANCE: Our findings show a decline in microbiological confirmed rates over the years and therefore call for intensive education on case recognition to prevent over-diagnosis as BU cases decline.

Support needs of people living with Mycobacterium ulcerans (Buruli ulcer) disease in a Ghana rural community: a grounded theory study.

INTRODUCTION/BACKGROUND: Mycobacterium ulcerans (also known as Buruli ulcer) disease is a rare skin disease which is prevalent in rural communities in the tropics mostly in Africa. Mortality rate is low, yet morbidity and consequent disabilities affect the quality of life of sufferers. AIMS: The aim of this paper is to use the grounded theory method to explore the support needs of people living with the consequences of Buruli ulcer in an endemic rural community in Ghana. METHODS: We used the grounded theory research approach to explore the experiences of people living with Mycobacterium ulcerans in a rural district in Ghana and provide a basis to understand the support needs of this group. RESULTS: The key support needs identified were: functional limitations, fear and frequency of disease recurrence, contracture of limbs and legs, loss of sensation and numbness in the affected body area, lack of information from health professionals about self-care, feeling tired all the time, insomnia, lack of good diet, lack of access to prostheses, having to walk long distances to access health services, and loss of educational opportunities. DISCUSSIONS: The study discusses how the systematically derived qualitative data has helped to provide a unique insight and advance our understanding of the support needs of people living with BU and how they live and attempt to adapt their lives with disability. We discuss how the availability of appropriate interventions and equipment could help them self-manage their condition and improve access to skin care services. CONCLUSIONS: The support needs of this vulnerable group were identified from a detailed analysis of how those living with BU coped with their lives. A key issue is the lack of education to assist self-management and prevent deterioration. Further research into the evaluation of interventions to address these support needs is necessary including self-management strategies.

Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon.

BACKGROUND: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. METHOD: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. RESULTS/ DISCUSSION: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). CONCLUSION: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status.

Pre-emptive steroids for a severe oedematous Buruli ulcer lesion: a case report.

INTRODUCTION: Severe oedematous forms of Buruli ulcer (BU) often result in extensive tissue destruction, even with the institution of appropriate antibiotic treatment, leading to reconstructive surgery and long-term disability. We report a case of a patient with severe oedematous BU, which describes for the first time the pre-emptive use of prednisolone therapy commenced at the time of antibiotic initiation aimed at limiting the ongoing tissue destruction and its secondary sequelae. CASE PRESENTATION: A 91-year-old Australian-born Caucasian woman presented with a WHO category 3 oedematous BU lesion on the anterior aspect of her right ankle that she had first noticed three weeks earlier. Treatment was commenced with an antibiotic combination of rifampicin and ciprofloxacin. At the same time, pre-emptive prednisolone was commenced (a dose of 0.5mg/kg daily). Treatment resulted in rapid and significant reduction in the size of the induration associated with the lesion, and no significant increase in the size of the skin ulceration. Antibiotics were continued for 56 days and prednisolone therapy ceased 130 days after antibiotics commenced. No surgery was required. The wound healed completely after 10 months and there was no long-term limitation of movement at the ankle joint. CONCLUSIONS: Pre-emptive corticosteroid therapy may prevent further progressive tissue necrosis and the need for secondary reconstructive surgery that commonly occurs during the antibiotic treatment of severe odematous forms of BU.

Assessment and Treatment of Pain during Treatment of Buruli Ulcer.

BACKGROUND: Buruli ulcer (BU) is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment. Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU. METHODOLOGY: A mixed methods approach was used, consisting of information retrieved from medical records on prescribed pain medication from Ghana and Benin, and semi-structured interviews with health care personnel (HCP) from Ghana on pain perceptions, assessment and treatment. Medical records (n = 149) of patients treated between 2008 and 2012 were collected between November 2012 and August 2013. Interviews (n = 11) were audio-taped, transcribed verbatim and qualitatively analyzed. PRINCIPAL FINDINGS: In 113 (84%) of the 135 included records, pain medication, mostly simple analgesics, was prescribed. In 48% of the prescriptions, an indication was not documented. HCP reported that advanced BU could be painful, especially after wound care and after a skin graft. They reported not be trained in the assessment of mild pain. Pain recognition was perceived as difficult, as patients were said to suppress or to exaggerate pain, and to have different expectations regarding acceptable pain levels. HCP reported a fear of side effects of pain medication, shortage and irregularities in the supply of pain medication, and time constraints among medical doctors for pain management. CONCLUSIONS: Professionals perceived BU disease as potentially painful, and predominantly focused on severe pain. Our study suggests that pain in BU deserves attention and should be integrated in current treatment.