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Current Opinion in Infectious Diseases Apr 2022The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021. (Review)
Review
PURPOSE OF REVIEW
The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021.
RECENT FINDINGS
Mycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned.
SUMMARY
Mycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.
Topics: Animals; Buruli Ulcer; Drug Therapy, Combination; Humans; Leprostatic Agents; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
PubMed: 35067521
DOI: 10.1097/QCO.0000000000000820 -
Emerging Infectious Diseases Dec 2020
Topics: Buruli Ulcer; Humans; Mycobacterium ulcerans; Skin Ulcer
PubMed: 33220026
DOI: 10.3201/eid2612.200744 -
Infection and Drug Resistance 2022Buruli ulcer is a chronic debilitating infectious disease caused by the pathogen , which can be cured if diagnosed and treated in an early stage. However, advanced cases...
Buruli ulcer is a chronic debilitating infectious disease caused by the pathogen , which can be cured if diagnosed and treated in an early stage. However, advanced cases need antibiotic treatment followed by surgical interventions. In this context, an extremely effective and less expensive treatment modality can be developed by means of an extended topical application of certain selected natural clay minerals, most of the time containing illite-smectite having some iron content. There is a scope for developing the speciality, medical geo-microbiology, which is truly a multidisciplinary one, for finding a cure for the severe and advanced cases of BU.
PubMed: 36458199
DOI: 10.2147/IDR.S388005 -
Expert Review of Clinical Pharmacology Apr 2020Pharmacological treatment of Buruli ulcer ( infection; BU) is highly effective, as shown in two randomized trials in Africa. (Review)
Review
INTRODUCTION
Pharmacological treatment of Buruli ulcer ( 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 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.
Topics: Animals; Anti-Bacterial Agents; Buruli Ulcer; Drug Repositioning; Drug Therapy, Combination; Humans; Macrolides; Mycobacterium ulcerans; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 32310683
DOI: 10.1080/17512433.2020.1752663 -
The American Journal of Tropical... Apr 2022Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related...
Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red-stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.
PubMed: 35405654
DOI: 10.4269/ajtmh.21-1327 -
Toxins Jun 2019In the past, it has proved challenging to generate antibodies against mycolactone, the primary lipidic toxin A of causing Buruli ulcer, due to its immunosuppressive...
In the past, it has proved challenging to generate antibodies against mycolactone, the primary lipidic toxin A of causing Buruli ulcer, due to its immunosuppressive properties. Here we show that in vitro display, comprising both phage and yeast display, can be used to select antibodies recognizing mycolactone from a large human naïve phage antibody library. Ten different antibodies were isolated, and hundreds more identified by next generation sequencing. These results indicate the value of in vitro display methods to generate antibodies against difficult antigenic targets such as toxins, which cannot be used for immunization unless inactivated by structural modification. The possibility to easily generate anti-mycolactone antibodies is an exciting prospect for the development of rapid and simple diagnostic/detection methods.
Topics: Antibodies, Monoclonal; Biotinylation; High-Throughput Nucleotide Sequencing; Humans; Macrolides; Recombinant Proteins; Yeasts
PubMed: 31212961
DOI: 10.3390/toxins11060346 -
Tuberculosis (Edinburgh, Scotland) Mar 2020Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria... (Review)
Review
Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.
Topics: Animals; Bacteriology; Biomedical Research; Congresses as Topic; Diffusion of Innovation; Disease Models, Animal; Host-Pathogen Interactions; Humans; Infectious Disease Medicine; Mycobacterium; Mycobacterium Infections, Nontuberculous; Tuberculosis
PubMed: 32279870
DOI: 10.1016/j.tube.2020.101914 -
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 -
Microorganisms Jul 2022Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses...
Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses in humans and animals. The sources of infections often remain undetected except for soil- or water-borne, water-washed, water-based, or water-related infections caused by groups of the complex; and other NTM species, including infection, known as fish tank granuloma, and infection, which is described as a Buruli ulcer. NTM could be considered as water-borne, air-borne, and soil-borne pathogens (sapronoses). A lot of clinically relevant NTM species could be considered due to the enormity of published data on permanent, periodic, transient, and incidental sapronoses. Interest is currently increasing in mycobacterioses diagnosed in humans and husbandry animals (esp. pigs) caused by NTM species present in peat bogs, potting soil, garden peat, bat and bird guano, and other matrices used as garden fertilizers. NTM are present in dust particles and in water aerosols, which represent certain factors during aerogenous infection in immunosuppressed host organisms during hospitalization, speleotherapy, and leisure activities. For this Special Issue, a collection of articles providing a current view of the research on NTM-including the clinical relevance, therapy, prevention of mycobacterioses, epidemiology, and ecology-are addressed.
PubMed: 35893574
DOI: 10.3390/microorganisms10081516