Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans.

In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, Mycobacterium leprae and Mycobacterium ulcerans, are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.

Changes in Inflammatory Markers in Patients Treated for Buruli Ulcer and Their Ability to Predict Paradoxical Reactions.

Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as paradoxical reactions (PRs), occur in some patients during or after antibiotic treatment. We investigated the clinical and biological features of PRs in a prospective cohort of 41 patients with Buruli ulcer from Benin. Neutrophil counts decreased from baseline to day 90, and interleukin 6 (IL-6), granulocyte colony-stimulating factor, and vascular endothelial growth factor were the cytokines displaying a significant monthly decrease relative to baseline. PRs occurred in 10 (24%) patients. The baseline biological and clinical characteristics of the patients presenting with PRs did not differ significantly from those of the other patients. However, the patients with PRs had significantly higher IL-6 and tumor necrosis factor alpha (TNF-α) concentrations on days 30, 60, and 90 after the start of antibiotic treatment. The absence of a decrease in IL-6 and TNF-α levels during treatment should alert clinicians to the possibility of PR onset.

Quantifying Population Burden and Effectiveness of Decentralized Surveillance Strategies for Skin-Presenting Neglected Tropical Diseases, Liberia.

We evaluated programmatic approaches for skin neglected tropical disease (NTD) surveillance and completed a robust estimation of the burden of skin NTDs endemic to West Africa (Buruli ulcer, leprosy, lymphatic filariasis morbidity, and yaws). In Maryland, Liberia, exhaustive case finding by community health workers of 56,285 persons across 92 clusters identified 3,241 suspected cases. A total of 236 skin NTDs (34.0 [95% CI 29.1-38.9]/10,000 persons) were confirmed by midlevel healthcare workers trained using a tailored program. Cases showed a focal and spatially heterogeneous distribution. This community health worker‒led approach showed a higher skin NTD burden than prevailing surveillance mechanisms, but also showed high (95.1%) and equitable population coverage. Specialized training and task-shifting of diagnoses to midlevel health workers led to reliable identification of skin NTDs, but reliability of individual diagnoses varied. This multifaceted evaluation of skin NTD surveillance strategies quantifies benefits and limitations of key approaches promoted by the 2030 NTD roadmap of the World Health Organization.

A cluster randomized trial for improving mental health and well-being of persons affected by leprosy or buruli ulcer in Nigeria: A study protocol.

This protocol describes a study in which we would assess the effect of using community lay counselors, self-help groups (SHGs), and trained frontline health workers to reduce mental disorders and improve quality of life (QOL) of persons affected by leprosy or Buruli ulcer (BU). A cluster randomized controlled study design will be employed. The study will involve persons affected by leprosy or BU. Ten local government areas (clusters) with the highest number of notified leprosy or BU cases between 2014 and 2018 in Southern Nigeria will be purposively selected. The clusters will be randomized into intervention and control groups using a computer-generated list of random numbers. At baseline, data were collected using the following validated questionnaires, Patient Health Questionnaire, Generalized Anxiety Disorder questionnaire, Stigma Assessment and Reduction of Impact Scale, World Health Organization QOL BREF and Warwick-Edinburgh Mental Well-being scale among persons affected by leprosy or BU. The intervention will last for 2 years and will involve use of community lay counselors, SHGs, and appropriately trained frontline health workers in reducing mental disorders and improving QOL of persons affected by leprosy or BU. This project postulates that the reduction of burden of mental health problems and improved QOL among persons affected by leprosy or BU could be achieved through a holistic approach involving SHGs, appropriately trained community opinion leaders, and general health-care workers as well as a functional referral system. If successful, the model will be integrated into the activities of the National Tuberculosis and Leprosy Control Programme and scaled up nationwide. Trial registration: ISRCTN Registry: ISRCTN 83649248. https://trialsearch. who.int/Trial2.aspx? TrialID % ISRCTN83649248 Prospectively registered.

Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin.

BACKGROUND: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. METHODS: We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. DISCUSSION: If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections). TRIAL REGISTRATION: ClinicalTrials.gov NCT05169554 . Registered on 27 December 2021.

Analysis of key genes in Mycobacterium ulcerans reveals conserved RNA structural motifs and regions with apparent pressure to remain unstructured.

Buruli Ulcer is a neglected tropical disease that results in disfiguring and dangerous lesions in affected persons across a wide geographic area, including much of West Africa. The causative agent of Buruli Ulcer is Mycobacterium ulcerans, a relative of the bacterium that causes tuberculosis and leprosy. Few therapeutic options exist for the treatment of this disease beyond antibiotics in the early stages, which are frequently ineffective, and surgical removal in the later stage. In this study we analyze six genes in Mycobacterium ulcerans that have high potential of therapeutic targeting. We focus our analysis on a combined in silico and comparative sequence study of potential RNA secondary structure across these genes. The result of this work was the comprehensive local RNA structural landscape across each of these significant genes. This revealed multiple sites of ordered and evolved RNA structure interspersed between sequences that either have no bias for structure or, indeed, appear to be ordered to be unstructured and (potentially) accessible. In addition to providing data that could be of interest to basic biology, our results provide guides for efforts aimed at targeting this pathogen at the RNA level. We explore this latter possibility through the in silico analysis of antisense oligonucleotides that could potentially be used to target pathogen RNA.

Effectiveness of self-care interventions for integrated morbidity management of skin neglected tropical diseases in Anambra State, Nigeria.

BACKGROUND: Lymphatic filariasis (LF), Buruli ulcer (BU) and leprosy are neglected tropical diseases (NTDs) of the skin co-endemic in some communities in Nigeria. Not enough is known about the effectiveness of integrated morbidity management and disability prevention in people with these conditions. An integrated self-care intervention was carried out for people with these skin NTDs in two endemic communities of Anambra state, Nigeria. The objective of the study was to assess the effectiveness of self-care practices on costs of care, disability status and health-related quality of life. METHODS: This study utilised a quasi-experimental pre-test/post-test design to assess the effectiveness of the self-care interventions for people affected by NTDs to care for these impairments at home. Data were collected using questionnaires administered at the beginning and at the end of the intervention on monthly cost of morbidity care, and on participants' disability status and their quality of life (QoL). Focus group discussions (FGDs) were held with both the participants and healthcare workers at follow-up. RESULTS: Forty-eight participants were recruited. Thirty participants (62.5%) continued the self-care interventions until the end of the project. Of those, 25 (83%) demonstrated improvement from their baseline impairment status. The mean household costs of morbidity care per participant decreased by 66% after the intervention, falling from US$157.50 at baseline to US$53.24 after 6 months of self-care (p = 0.004). The mean disability score at baseline was 22.3; this decreased to 12.5 after 6 months of self-care (p < 0.001). Among the 30 participants who continued the interventions until the end of the project, 26 (86.7%) had severe disability score (i.e. a score of 10-46) at baseline, and the number with severe disability fell to 18 (60%) of the 30 after the intervention. The mean QoL score increased from 45.7 at baseline to 57.5 at the end of the intervention (p = 0.004). CONCLUSIONS: The 6-month self-care intervention for participants affected by BU, leprosy, or LF led to lower costs of care (including out-of-pocket costs and lost earnings due to morbidity), improved QoL scores, and reduced disability status. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN20317241 ; 27/08/2021, Retrospectively registered.

Road map to the treatment of neglected tropical diseases: Nanocarriers interventions.

Neglected tropical disease (NTD) is a set of 20 deadliest endemic diseases which shows its presence in most of the developing countries worldwide. Nearly 1 billion of the population are affected by it and suffered from poverty yearly. These diseases offer their own unique challenges and limitations towards effective prevention and treatment methods. Neglected tropical diseases are severe infections they may not kill the patient but debilitate the patient by causing severe skin deformities, disfigurement and horrible risks for several infections. Existing therapies for neglected diseases suffer from the loopholes like high degree of toxicity, side effects, low bioavailability, improper targeting and problematic application for affected populations. Progress in the field of nanotechnology in last decades suggested the intervention of nanocarriers to take over and drive the research and development to the next level by incorporating established drugs into the nanocarriers rather than discovering the newer drugs which is an expensive affair. These nanocarriers are believed to be a sure shot technique to fight infections at root level by virtue of its nanosize and ability to reach at cellular level. This article highlights the recent advances, rationale, targets and the challenges that are being faced to fight against NTDs and how the novel therapy tactics are able to contribute to its importance in prevention and treatment of NTDs.

Reconstructive surgery for sequellae of Mycobacterium ulcerans infection (Buruli ulcer) of the upper limb.

INTRODUCTION: Infection by Mycobacterium ulcerans constitutes a neglected tropical disease whose prevalence seems to have overrun those of cutaneous tuberculosis and leprosy. Its aggressivity depends on a mycolactone toxin. Lesions may involve skin, tendon and bone with a large spectrum of manifestations: non-ulcerative (papules, nodules, plaques), ulcerative and oedematous presentations as well as osteomyelitis with muscular contraction and ankylosis. Upper limbs account for more than two thirds of the infection sites. Surgical treatment may involve tendon transpositions, partial and total skin grafts. Amputation is relegated to extreme cases. MATERIAL AND METHODS: Selected iconography from patients during the last 15 years is presented. At least 1500 cases had partial skin grafts (anterior thigh). Total skin grafts (inguinal region) were used in about 200 cases. Complex lesions involved 9 ilioinguinal flaps (5 boys, 4 girls, mean age 11.2 years, range 2-16 years), 5 tendon transfers (4 boys, one girl, mean age 15.4 years, range 12-19 years) and 3 resections of the first carpal row (2 girls, 1 boy, mean age 8 years, range 4-15 years). RESULTS AND DISCUSSION: Out of 9 ilioinguinal flaps mild, marginal necrosis was the only complication in 2 patients without flap loss. Mean hospital stay was 26.44 days (range, 18-41 days), with return to full weight-bearing after a mean of 12 weeks (range 9-25 weeks) after discharge. Functional thumb opposition to allow pencil prehension was achieved in all three cases of resection of first carpal row resection without postoperative complications.

Novel Diagnostics for Kaposi Sarcoma and Other Skin Diseases in Resource-Limited Settings.

In resource-limited settings, point-of-care diagnostic devices have the potential to reduce diagnostic delays and improve epidemiologic surveillance of dermatologic conditions. We outline novel-point-of care diagnostics that have recently been developed for dermatologic conditions that primarily affect patients living in resource-limited settings, namely, Kaposi sarcoma, cutaneous leishmaniasis, leprosy, Buruli ulcer, yaws, onchocerciasis, and lymphatic filariasis. All of the technologies described in this article are prototypes, and some have undergone field testing. These devices still require validation in real-world settings and effective pricing to have a major impact on dermatologic care in resource-limited settings.

Evaluation of the national tuberculosis surveillance and response systems, 2018 to 2019: National Tuberculosis, Leprosy and Buruli Ulcer Control Programme, Abuja, Nigeria.

INTRODUCTION: Nigeria is among the countries with high Tuberculosis (TB) burden by global rating signifying the relevance of TB surveillance system evaluation in improving performance and capacity of the existing system. Hence, this evaluation was conducted in order to determine the gaps and proffer solution to enhance the TB surveillance system performance. METHODS: questionnaires were administered to eight key informants using face-to-face interview method; data obtained was analyzed. Total number of TB cases and estimated number of cases for year 2018 was obtained. Percentage of positive cases using the GeneXpert test for 6 months (January to June 2019) was obtained. Available documents and publications on the National Tuberculosis, Leprosy and Buruli Ulcer Control Programme (NTBLCP) were also sought for information. RESULTS: the NTBLCP has over 5,300 TB service points and 1,602 microscopy Centre's distributed across the country. Acceptance for the standard TB case definition was 100%, forms used are easy to fill and diagnosis is laboratory-based requiring specialized trainings for laboratory personnel. The system had 25% sensitivity, high data quality with 100% timeliness. The TB surveillance system is representative of all ages. The system was first designed as TB and Leprosy Control Programme but later Buruli ulcer was incorporated into the Programme. First quarter supervisory visits are skipped due to late funding and delayed budget approval. Major share of the funding comes from donor partners. CONCLUSION: the system is useful, representative, acceptable, has good data quality, timely, and sensitive. The system is stable but needs to be funded more by the government. There is need for early funding and budget approval to avoid skipping of supervisory visits due to funding challenges. The system is not simple due the various test that need to be conducted before, during and after treatment to detect and verify that the patient is cured. We recommend continuous training of health workers, routine monitoring and evaluation, integration of TB care and prevention into other health services programmes like HIV/AIDS and active case search at all levels to increase the sensitivity of the system. Speed up the process of integration of NTBLCP surveillance system with IDSR for data harmonization in the country.

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.

Pharmacologic management of Mycobacterium ulcerans infection.

INTRODUCTION: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. AREAS COVERED: We review BU drug treatment - in vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. EXPERT OPINION: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.

The immunology of other mycobacteria: M. ulcerans, M. leprae.

Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases.

Bacille Calmette-Guerin (BCG) vaccination is widely practiced around the world to protect against the mycobacterial infection tuberculosis. BCG is also effective against the pathogenic mycobacteria that cause leprosy and Buruli's ulcer. BCG is part of the standard of care for bladder cancer where, when given as an intravesicular irrigant, BCG acts as an immunomodulating agent and lessens the risk of recurrence. Mycobacterium avium ss. paratuberculosis (MAP) causes a fatal enteritis of ruminant animals and is the putative cause of Crohn's disease of humans. MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn's, sarcoidosis, Blau syndrome, Hashimoto's thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson's disease. Epidemiologic evidence points to BCG providing a "heterologous" protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases. This article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP. Other autoimmune diseases, having a concomitant genetic risk for mycobacterial infection as well as cross-reacting antibodies against mycobacterial heat shock protein 65 (HSP65), could reasonably be considered to respond to BCG vaccination. The rare autoimmune disease, relapsing polychondritis, is one such disease and is offered as an example. Recent studies suggesting a protective role for BCG in Alzheimer's disease are also explored. BCG-induced energy shift from oxidative phosphorylation to aerobic glycolysis provides the immunomodulating boost to the immune response and also mitigates mycobacterial infection-this cellular mechanism unifies the impact of BCG on the disparate diseases of this article.

An integrated assessment of leprosy, Buruli ulcer, and yaws around the irrigated perimeters of Bagré and Kompienga in Burkina Faso.

Burkina Faso shares its borders with six countries that regularly report cases of Buruli ulcer, yaws, and leprosy (Hansen disease), three neglected tropical diseases with dermatological manifestations. Treatment of leprosy has shown excellent results, and it appears to be essentially eliminated. The same cannot be said for Buruli ulcer or yaws, the epidemiology of which remains poorly elucidated. In this context, it was essential to review the situation of these three diseases through a joint survey in the health districts bordering the Côte d'Ivoire, Ghana and the irrigated areas around the dams of Kompienga and Bagré. Our team led a disease survey in these irrigated areas, and we report the results. To determine the current scale of the Buruli ulcer, leprosy, and yaws in the irrigated areas around these two dams and to formulate recommendations. This single-pass survey from April 10-18 was a transverse descriptive study, with sampling based on proximity to the dams. Overall, 1482 people were consulted. Among them, 413 (27.9%) presented dermatosis, distributed as follows: 28 suspected cases of yaws (6.8%), 7 suspected cases of Buruli ulcer (1.7%), 1 case of multibacillary leprosy (0.24%) in an 8-year-old girl, and 377 cases of other dermatoses, dominated by those of fungal origin. A large-scale investigation including all other irrigated areas might make it possible to understand the real situation.

Cutaneous Mycobacterial Infections.

Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Cutaneous mycobacterial infections may cause a wide range of clinical manifestations, which are divided into four main disease categories: (i) cutaneous manifestations of Mycobacterium tuberculosis infection, (ii) Buruli ulcer caused by Mycobacterium ulcerans and other related slowly growing mycobacteria, (iii) leprosy caused by Mycobacterium leprae and Mycobacterium lepromatosis, and (iv) cutaneous infections caused by rapidly growing mycobacteria. Clinically, cutaneous mycobacterial infections present with widely different clinical presentations, including cellulitis, nonhealing ulcers, subacute or chronic nodular lesions, abscesses, superficial lymphadenitis, verrucous lesions, and other types of findings. Mycobacterial infections of the skin and subcutaneous tissue are associated with important stigma, deformity, and disability. Geography-based environmental exposures influence the epidemiology of cutaneous mycobacterial infections. Cutaneous tuberculosis exhibits different clinical phenotypes acquired through different routes, including via extrinsic inoculation of the tuberculous bacilli and dissemination to the skin from other sites, or represents hypersensitivity reactions to M. tuberculosis infection. In many settings, leprosy remains an important cause of neurological impairment, deformity, limb loss, and stigma. Mycobacterium lepromatosis, a mycobacterial species related to M. leprae, is linked to diffuse lepromatous leprosy of Lucio and Latapí. Mycobacterium ulcerans produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. Mycobacterium marinum, a close relative of M. ulcerans, is an important cause of cutaneous sporotrichoid nodular lymphangitic lesions. Among patients with advanced immunosuppression, Mycobacterium kansasii, the Mycobacterium avium-intracellulare complex, and Mycobacterium haemophilum may cause cutaneous or disseminated disease. Rapidly growing mycobacteria, including the Mycobacterium abscessus group, Mycobacterium chelonei, and Mycobacterium fortuitum, are increasingly recognized pathogens in cutaneous infections associated particularly with plastic surgery and cosmetic procedures. Skin biopsies of cutaneous lesions to identify acid-fast staining bacilli and cultures represent the cornerstone of diagnosis. Additionally, histopathological evaluation of skin biopsy specimens may be useful in identifying leprosy, Buruli ulcer, and cutaneous tuberculosis. Molecular assays are useful in some cases. The treatment for cutaneous mycobacterial infections depends on the specific pathogen and therefore requires a careful consideration of antimicrobial choices based on official treatment guidelines.

Knowledge and practices of health practitioners on treatment of Buruli ulcer in the Mbonge, Ekondo Titi and Muyuka Health Districts, South West Region, Cameroon.

INTRODUCTION: After tuberculosis and leprosy, Buruli ulcer (BU) is the third most common mycobacterial infection. Buruli ulcer begins as a localized skin lesion that progresses to extensive ulceration thus leading to functional disability, loss of economic productivity and social stigma. This study is aimed at assessing the knowledge and practices among health practitioners on the treatment of BU in the Mbonge, Ekondo Titi and Muyuka Health Districts of the South West Region of Cameroon. METHODS: This is a cross-sectional study that investigates participants' knowledge and practices on the treatment of BU. The study uses a qualitative method of structured questionnaires in the process of data collection. RESULTS: Seventy percent (70%) of the participants acknowledged they encounter cases of BU in their respective Hospitals or Health centers. Among these, 48% agreed they managed BU in their facilities and up to 91.7% noted that their community members are aware that BU is managed in their facility while seventy percent of the medical practitioners indicated they cannot identify the various stages of BU. Eighty-one percent of the practitioners from Muyuka HD indicated they could not identify the various stages of BU. More than 63% of the practitioners regarded BU patients as normal people in their communities however, practitioners that practiced for less than 5 years were likely not to admit BU patients in the same room with other patients. Beliefs such as being cursed (47.06%) and being possessed (29.41%) were reported by practitioners that acknowledged the existence of traditional beliefs in the community. CONCLUSION: Despite the fact that a majority of the health practitioners knew what BU is, most of them demonstrated lack of knowledge on the identification of the various stages and management of the illness. Practitioners demonstrated positive attitude towards patients although they would not admit them in the same room with other patients. Considering the poor knowledge on identification and management demonstrated by most of the practitioners, management of the disease would be inadequate and may even aggravate the patient's situation. Training and onsite mentorship on screening, identification and management of BU is therefore highly recommended amongst health personnel practicing in endemic areas.

Overview of Cutaneous Mycobacterial Infections.

PURPOSE OF REVIEW: Mycobacterial infections may affect any human organ and produce disseminated disease in immunocompromised individuals. Their most common clinical presentations include pulmonary, cutaneous (skin and soft tissues), and disseminated forms. The skin and soft tissues are frequent targets of affection by mycobacterial pathogens manifesting as localized or diffuse disease. RECENT FINDINGS: Overall, infections due to Mycobacterium leprae, Mycobacterium ulcerans, and Mycobacterium tuberculosis are the most frequently recognized mycobacterial pathogens involving the skin and soft tissues. Additionally, all mycobacterial species of the nontuberculous group may also produce cutaneous disease. Of these, the most commonly identified organisms causing localized infections of the skin and subcutaneous tissues are the rapidly growing species (Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus complex), Mycobacterium marinum, and M. ulcerans. Since the skin and soft tissues are important protective barriers for environmental pathogens, their disruption often represents the portal of entry of nontuberculous environmental mycobacteria (soil, natural water systems, engineered water networks, etc.). Additionally, some mycobacterial diseases affecting cutaneous structures occur after exposure to infected animals or their products (i.e., Mycobacterium bovis). Mycobacterial infections of the skin and soft tissues may manifest with a broad range of clinical phenotypes such as cellulitis, single or multiple abscesses, subacute or chronic nodular lesions, macules, superficial lymphadenitis, plaques, nonhealing ulcers, necrotic plaques, verrucous lesions, and many other dermatologic manifestations. SUMMARY: Geography and environmental exposure play an important role in the epidemiology of cutaneous mycobacterial infections. Mycobacterial infection of the skin and subcutaneous tissue is an important cause of human suffering in terms of morbidity, deformity, dysfunction, and stigma. The diagnosis of cutaneous mycobacterial infections is challenging requiring a low threshold of clinical suspicion for obtaining skin biopsies of cutaneous lesions for acid-fast staining and cultures, and molecular probe assays to detect the presence of mycobacterial pathogens. The choice of antibacterial therapy combinations and length of therapy for cutaneous mycobacterial infections is species-specific.

Mapping biopsy for Buruli ulcer self-medicated with occlusive dressing.

Buruli ulcer is the third most common mycobacterial infection next to tuberculosis and leprosy caused by Mycobacterium ulcerans. Although it affects the skin, subcutaneous tissues, muscles and sometimes bones, there is no reliable evidence to determine the extent of debridement. We present here a case of Buruli ulcer treated successfully with a preoperative mapping biopsy procedure, which had been self-medicated with occlusive dressing. Because Buruli ulcer is accompanied by subtle pain, patients and clinicians tend to initially treat the ulcer with occlusive dressing therapy, which leads to the misdiagnosis of Buruli ulcer as a common bacterial infection only judging from bacterial culture of the surface of the ulcer. We propose the efficacy of mapping biopsy for treating Buruli ulcer.