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Seminars in Immunopathology Jun 2020Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing... (Review)
Review
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.
Topics: Buruli Ulcer; Humans; Mycobacterium; Mycobacterium ulcerans; Skin
PubMed: 32100087
DOI: 10.1007/s00281-020-00790-4 -
Mammalian Genome : Official Journal of... Aug 2018Mycobacterial diseases are caused by members of the genus Mycobacterium, acid-fast bacteria characterized by the presence of mycolic acids within their cell walls.... (Review)
Review
Mycobacterial diseases are caused by members of the genus Mycobacterium, acid-fast bacteria characterized by the presence of mycolic acids within their cell walls. Claiming almost 2 million lives every year, tuberculosis (TB) is the most common mycobacterial disease and is caused by infection with M. tuberculosis and, in rare cases, by M. bovis or M. africanum. The second and third most common mycobacterial diseases are leprosy and buruli ulcer (BU), respectively. Both diseases affect the skin and can lead to permanent sequelae and deformities. Leprosy is caused by the uncultivable M. leprae while the etiological agent of BU is the environmental bacterium M. ulcerans. After exposure to these mycobacterial species, a majority of individuals will not progress to clinical disease and, among those who do, inter-individual variability in disease manifestation and outcome can be observed. Susceptibility to mycobacterial diseases carries a human genetic component and intense efforts have been applied over the past decades to decipher the exact nature of the genetic factors controlling disease susceptibility. While for BU this search was mostly conducted on the basis of candidate genes association studies, genome-wide approaches have been widely applied for TB and leprosy. In this review, we summarize some of the findings achieved by genome-wide linkage, association and transcriptome analyses in TB disease and leprosy and the recent genetic findings for BU susceptibility.
Topics: Animals; Buruli Ulcer; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Host-Pathogen Interactions; Humans; Leprosy; Mycobacterium; Mycobacterium Infections; Quantitative Trait Loci; Tuberculosis
PubMed: 30116885
DOI: 10.1007/s00335-018-9765-4 -
Infectious Diseases of Poverty Aug 2021Buruli ulcer disease (BUD) is a necrotic skin neglected tropical disease (NTD) that has both a mental and physical health impact on affected individuals. Although there...
BACKGROUND
Buruli ulcer disease (BUD) is a necrotic skin neglected tropical disease (NTD) that has both a mental and physical health impact on affected individuals. Although there is increasing evidence suggesting a strong association between neglected tropical diseases (NTDs) and mental illness, there is a relative lack of information on BUD's impact on the mental health and quality of life (QoL) of affected individuals in Ghana. This study is to assess the impact of BUD on mental health and quality of life of patients with active and past BUD infection, and their caregivers.
METHODS
We conducted a case control study in 3 BUD endemic districts in Ghana between August and November 2019. Face-to-face structured questionnaire-based interviews were conducted on BUD patients with active and past infection, as well as caregivers of BUD patients using WHO Quality of Life scale, WHO Disability Assessment Schedule, Self-Reporting Questionnaire, Buruli Ulcer Functional Limitation Score and Hospital Anxiety and Depression Scale data tools. Descriptive statistics were used to summarize the characteristics of the study participants. Participant groups were compared using student t test and chi-square (χ) or Fisher's exact tests. Mean quality of life scores are reported with their respective 95% confidence intervals. Data was analysed using STATA statistical software.
RESULTS
Our results show that BUD patients with active and past infection, along with their caregivers, face significant levels of distress and mental health sequelae compared to controls. Depression (P = 0.003) was more common in participants with active (27%) and past BU infection (17%), compared to controls (0%). Anxiety was found in 42% (11/26) and 20% (6/29) of participants with active and past BUD infection compared to 14% (5/36) of controls. Quality of life was also significantly diminished in active BUD infection, compared to controls. In the physical health domain, mean QoL scores were 54 ± 11.1 and 56 ± 11.0 (95% CI: 49.5‒58.5 and 52.2‒59.7) respectively for participants with active infection and controls. Similarly in the psychological domain, scores were lower for active infection than controls [57.1 ± 15.2 (95% CI: 50.9‒63.2) vs 64.7 ± 11.6 (95% CI: 60.8‒68.6)]. Participants with past infection had high QoL scores in both physical [61.3 ± 13.5 (95% CI: 56.1‒66.5)] and psychological health domains [68.4 ± 14.6 (95% CI: 62.7‒74.0)].
CONCLUSIONS
BUD is associated with significant mental health distress and reduced quality of life in affected persons and their caregivers in Ghana. There is a need for integration of psychosocial interventions in the management of the disease.
Topics: Buruli Ulcer; Case-Control Studies; Ghana; Humans; Mental Health; Quality of Life
PubMed: 34404483
DOI: 10.1186/s40249-021-00891-8 -
Immunological Reviews May 2021Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life-long deformity and... (Review)
Review
Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life-long deformity and disability. Differently from other mycobacterial pathogens, M ulcerans produces mycolactone, a diffusible lipid factor with unique cytotoxic and immunomodulatory properties. Both traits result from mycolactone targeting Sec61, the entry point of the secretory pathway in eukaryotic cells. By inhibiting Sec61, mycolactone prevents the host cell's production of secreted proteins, and most of its transmembrane proteins. This molecular blockade dramatically alters the functions of immune cells, thereby the generation of protective immunity. Moreover, sustained inhibition of Sec61 triggers proteotoxic stress responses leading to apoptotic cell death, which can stimulate vigorous immune responses. The dynamics of bacterial production of mycolactone and elimination by infected hosts thus critically determine the balance between its immunostimulatory and immunosuppressive effects. Following an introduction summarizing the essential information on Buruli ulcer disease, this review focuses on the current state of knowledge regarding mycolactone's regulation and biodistribution. We then detail the consequences of mycolactone-mediated Sec61 blockade on initiation and maintenance of innate and adaptive immune responses. Finally, we discuss the key questions to address in order to improve immunity to M ulcerans, and how increased knowledge of mycolactone biology may pave the way to innovative therapeutics.
Topics: Buruli Ulcer; Humans; Macrolides; Mycobacterium ulcerans; Tissue Distribution
PubMed: 33607704
DOI: 10.1111/imr.12956 -
The Cochrane Database of Systematic... Dec 2018
Topics: Anti-Infective Agents; Buruli Ulcer; Humans; Mycobacterium ulcerans
PubMed: 30556580
DOI: 10.1002/14651858.ED000128 -
Emerging Infectious Diseases Dec 2019Buruli ulcer is a neglected tropical disease caused by Myocobacterium ulcerans; it manifests as a skin lesion, nodule, or ulcer that can be extensive and disabling. To...
Buruli ulcer is a neglected tropical disease caused by Myocobacterium ulcerans; it manifests as a skin lesion, nodule, or ulcer that can be extensive and disabling. To assess the global burden and the progress on disease control, we analyzed epidemiologic data reported by countries to the World Health Organization during 2010-2017. During this period, 23,206 cases of Buruli ulcer were reported. Globally, cases declined to 2,217 in 2017, but local epidemics seem to arise, such as in Australia and Liberia. In 2013, the World Health Organization formulated 4 programmatic targets for Buruli ulcer that addressed PCR confirmation, occurrence of category III (extensive) lesions and ulcerative lesions, and movement limitation caused by the disease. In 2014, only the movement limitation goal was met, and in 2019, none are met, on a global average. Our findings support discussion on future Buruli ulcer policy and post-2020 programmatic targets.
Topics: Age Factors; Buruli Ulcer; Endemic Diseases; Global Health; History, 21st Century; Humans; Mycobacterium ulcerans; Polymerase Chain Reaction; Population Surveillance; Retrospective Studies; Sex Factors; World Health Organization
PubMed: 31742506
DOI: 10.3201/eid2512.190427 -
PLoS Neglected Tropical Diseases Aug 2021Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rare but chronic debilitating skin and soft tissue disease found predominantly in West Africa and... (Review)
Review
Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rare but chronic debilitating skin and soft tissue disease found predominantly in West Africa and Southeast Australia. While a moderate body of research has examined the distribution of M. ulcerans, the specific route(s) of transmission of this bacterium remain unknown, hindering control efforts. M. ulcerans is considered an environmental pathogen given it is associated with lentic ecosystems and human-to-human spread is negligible. However, the pathogen is also carried by various mammals and invertebrates, which may serve as key reservoirs and mechanical vectors, respectively. Here, we examine and review recent evidence from these endemic regions on potential transmission pathways, noting differences in findings between Africa and Australia, and summarising the risk and protective factors associated with Buruli ulcer transmission. We also discuss evidence suggesting that environmental disturbance and human population changes precede outbreaks. We note five key research priorities, including adoption of One Health frameworks, to resolve transmission pathways and inform control strategies to reduce the spread of Buruli ulcer.
Topics: Animals; Buruli Ulcer; Communicable Disease Control; Ecosystem; Environment; Humans; Mycobacterium ulcerans; One Health
PubMed: 34437549
DOI: 10.1371/journal.pntd.0009678 -
Emerging Infectious Diseases May 2007
Topics: Adolescent; Adult; Buruli Ulcer; Female; Humans; Male; Nigeria; Population Surveillance; World Health Organization
PubMed: 18044041
DOI: 10.3201/eid1305.070065 -
PLoS Neglected Tropical Diseases Aug 2018Buruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after...
BACKGROUND
Buruli ulcer (BU) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans. The treatment with BU-specific antibiotics is initiated after clinical suspicion based on the WHO clinical and epidemiological criteria. This study aimed to estimate the predictive values of these criteria and how they could be improved.
METHODOLOGY/PRINCIPAL FINDINGS
A total of 224 consecutive patients presenting with skin and soft tissue lesions that could be compatible with BU, including those recognized as unlikely BU by experienced clinicians, were recruited in two BU treatment centers in southern Benin between March 2012 and March 2015. For each participant, the WHO and four additional epidemiological and clinical diagnostic criteria were recorded. For microbiological confirmation, direct smear examination and IS2404 PCR were performed. We fitted a logistic regression model with PCR positivity for BU confirmation as outcome variable. On univariate analysis, most of the clinical and epidemiological WHO criteria were associated with a positive PCR result. However, lesions on the lower limbs and WHO category 3 lesions were rather associated with a negative PCR result (respectively OR: 0.4, 95%CI: 0.3-0.8; OR: 0.5, 95%IC: 0.3-0.9). Among the additional characteristics studied, the characteristic smell of BU was strongest associated with a positive PCR result (OR = 16.4; 95%CI = 7.5-35.6).
CONCLUSION/SIGNIFICANCE
The WHO diagnostic criteria could be improved upon by differentiating between lesions on the upper and lower limbs and by including lesion size and the characteristic smell recognized by experienced clinicians.
Topics: Adolescent; Adult; Buruli Ulcer; Child; Female; Humans; Logistic Models; Male; Mycobacterium ulcerans; Odds Ratio; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Skin; World Health Organization; Young Adult
PubMed: 30080870
DOI: 10.1371/journal.pntd.0006713 -
Emerging Microbes & Infections Apr 2017Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus... (Review)
Review
Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.
Topics: Agriculture; Animals; Animals, Wild; Biodiversity; Buruli Ulcer; Communicable Diseases, Emerging; Conservation of Natural Resources; DNA, Bacterial; Disease Reservoirs; Ecosystem; Humans; Mycobacterium ulcerans; Tropical Climate
PubMed: 28442755
DOI: 10.1038/emi.2017.7