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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 -
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 -
Emerging Infectious Diseases Dec 2020
Topics: Buruli Ulcer; Humans; Mycobacterium ulcerans; Skin Ulcer
PubMed: 33220026
DOI: 10.3201/eid2612.200744 -
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 -
Ghana Medical Journal Mar 2011
Topics: Anti-Bacterial Agents; Buruli Ulcer; Ghana; Humans; Incidence; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Neglected Diseases
PubMed: 21572816
DOI: No ID Found -
Japanese Journal of Infectious Diseases 2013Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however,... (Review)
Review
Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however, it has been reported worldwide, including in some non-tropical areas. "M. ulcerans subsp. shinshuense" is proposed as a subspecies of M. ulcerans, which have been reported from Japan and China. A total of 35 BU cases have been reported as of November 2012. Although M. ulcerans is categorized as nontuberculous mycobacteria, it has some unique characteristics that could only be observed in this bacterium. It possesses a giant virulent plasmid, composed of 174-kbp nucleotides, coding polyketide synthase to produce macrolide toxin called mycolactone. The discovery of such a linkage of plasmid and its pathogenesis has not been reported in other human disease-causing mycobacteria.
Topics: Africa South of the Sahara; Buruli Ulcer; China; Communicable Diseases, Emerging; Humans; Japan; Macrolides; Mycobacterium ulcerans; Plasmids; Polyketide Synthases; Virulence Factors
PubMed: 23514902
DOI: 10.7883/yoken.66.83 -
PLoS Neglected Tropical Diseases Dec 2010Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after... (Review)
Review
Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis. Cases have been reported from at least 32 countries in Africa (mainly west), Australia, Southeast Asia, China, Central and South America, and the Western Pacific. Large lesions often result in scarring, contractual deformities, amputations, and disabilities, and in Africa, most cases of the disease occur in children between the ages of 4-15 years. This environmental mycobacterium, Mycobacterium ulcerans, is found in communities associated with rivers, swamps, wetlands, and human-linked changes in the aquatic environment, particularly those created as a result of environmental disturbance such as deforestation, dam construction, and agriculture. Buruli ulcer disease is often referred to as the "mysterious disease" because the mode of transmission remains unclear, although several hypotheses have been proposed. The above review reveals that various routes of transmission may occur, varying amongst epidemiological setting and geographic region, and that there may be some role for living agents as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult mosquitoes or other biting arthropods. We discuss traditional and non-traditional methods for indicting the roles of living agents as biologically significant reservoirs and/or vectors of pathogens, and suggest an intellectual framework for establishing criteria for transmission. The application of these criteria to the transmission of M. ulcerans presents a significant challenge.
Topics: Age Factors; Animals; Buruli Ulcer; Communicable Diseases, Emerging; Disease Reservoirs; Disease Vectors; Ecosystem; Environmental Microbiology; Humans; Mycobacterium ulcerans
PubMed: 21179505
DOI: 10.1371/journal.pntd.0000911 -
Clinical Microbiology Reviews Jan 2018Buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in Africa, Asia, Oceania, and South America. The causative... (Review)
Review
Buruli ulcer is a noncontagious disabling cutaneous and subcutaneous mycobacteriosis reported by 33 countries in Africa, Asia, Oceania, and South America. The causative agent, , derives from by genomic reduction and acquisition of a plasmid-borne, nonribosomal cytotoxin mycolactone, the major virulence factor. -specific sequences have been readily detected in aquatic environments in food chains involving small mammals. Skin contamination combined with any type of puncture, including insect bites, is the most plausible route of transmission, and skin temperature of <30°C significantly correlates with the topography of lesions. After 30 years of emergence and increasing prevalence between 1970 and 2010, mainly in Africa, factors related to ongoing decreasing prevalence in the same countries remain unexplained. Rapid diagnosis, including laboratory confirmation at the point of care, is mandatory in order to reduce delays in effective treatment. Parenteral and potentially toxic streptomycin-rifampin is to be replaced by oral clarithromycin or fluoroquinolone combined with rifampin. In the absence of proven effective primary prevention, avoiding skin contamination by means of clothing can be implemented in areas of endemicity. Buruli ulcer is a prototype of ecosystem pathology, illustrating the impact of human activities on the environment as a source for emerging tropical infectious diseases.
Topics: Anti-Infective Agents; Buruli Ulcer; Ecosystem; Humans; Mycobacterium ulcerans
PubMed: 29237707
DOI: 10.1128/CMR.00045-17 -
Tropical Medicine & International... Sep 2014Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of... (Review)
Review
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.
Topics: Africa; Anti-Bacterial Agents; Anti-HIV Agents; Buruli Ulcer; CD4 Lymphocyte Count; Coinfection; Endemic Diseases; Guidelines as Topic; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 24946829
DOI: 10.1111/tmi.12342 -
Journal of Clinical Microbiology Apr 2018Buruli ulcer is caused by This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria... (Review)
Review
Buruli ulcer is caused by This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performing PCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.
Topics: Africa, Western; Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Humans; Macrolides; Mycobacterium Infections; Mycobacterium ulcerans; Neglected Diseases; Polymerase Chain Reaction; Rifampin; Skin Diseases, Bacterial; Streptomycin
PubMed: 29343539
DOI: 10.1128/JCM.01507-17