Buruli Ulcer: History and Disease Burden

Röltgen, Katharina; Pluschke, Gerd

doi:10.1007/978-3-030-11114-4_1

Cited by 23 publications

(29 citation statements)

References 134 publications

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“…Sterile-filtered culture supernatants of an African and an Australian M. ulcerans strain both gave positive readouts in the assay (Fig 5), demonstrating that both mycolactone A/B predominantly produced by African strains and mycolactone C predominantly produced by Australian strains that are together responsible for >95% of reported BU ulcer cases [1] are recognized. These supernatants were used directly in the assay without any prior lipid extraction.…”

Section: Detection Of Mycolactone In Biological Samplesmentioning

confidence: 92%

“…Mycobacterium ulcerans is the etiological agent of the chronic necrotizing skin disease Buruli ulcer (BU) that primarily affects children in West and Central Africa [1]. Genomic analyses have shown that M. ulcerans has emerged from a common ancestor with the fish pathogen Mycobacterium marinum [2,3] by acquisition of a virulence plasmid carrying genes that encode polyketide-modifying enzymes and the giant polyketide synthases responsible for the synthesis of the lipid toxin mycolactone [4].…”

Section: Introductionmentioning

confidence: 99%

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Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

et al. 2020

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Mycolactones, macrolide cytotoxins, are key virulence factors of Mycobacterium ulcerans, the etiological agent of the chronic necrotizing skin disease Buruli ulcer. There is urgent need for a simple point-of-care laboratory test for Buruli ulcer and mycolactone represents a promising target for the development of an immunological assay. However, for a long time, all efforts to generate mycolactone-specific antibodies have failed. By using a protein conjugate of a truncated non-toxic synthetic mycolactone derivative, we recently described generation of a set of mycolactone-specific monoclonal antibodies. Using the first mycolactonespecific monoclonal antibodies that we have described before, we were able to develop an antigen competition assay that detects mycolactones. By the systematic selection of a capturing antibody and a reporter molecule, and the optimization of assay conditions, we developed an ELISA that detects common natural variants of mycolactone with a limit of detection in the low nanomolar range. The mycolactone-specific ELISA described here will be a very useful tool for research on the biology of this macrolide toxin. After conversion into a simple point-of-care test format, the competition assay may have great potential as laboratory assay for both the diagnosis of Buruli ulcer and for the monitoring of treatment efficacy.

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Section: Detection Of Mycolactone In Biological Samplesmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

et al. 2020

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“…Demographic variables of BU patients have been reviewed by many authors, with no strict consensus having been achieved as to their role as a risk modifier for disease acquisition [7,50]. Results here obtained point to a bipartisan role of age and sex in the susceptibility to BU, as the disease is more frequently observed among children, particularly males, and in the elderly.…”

Section: Discussionmentioning

confidence: 87%

“…Interestingly, these patterns can also be observed in other studies not fulfilling the inclusion criteria for this systematic review (S10 Table). In younger generations, it has been previously argued that these differences could be explained based on increased exposure to M. ulcerans, mainly due to the more erratic behavior that makes children more prone to skin lesions, as well as their likelihood to stay near aquatic environments [50]. However, more recent data encompassing worse outcomes of BU among the elderly casted a stronger suspicion on age as a modulator of intrinsic processes, likely immunological, a phenomenon that could be transversal across generations [41,51].…”

Section: Discussionmentioning

confidence: 99%

Individual and clinical variables associated with the risk of Buruli ulcer acquisition: A systematic review and meta-analysis

et al. 2020

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Background Buruli ulcer (BU) is a necrotizing skin disease, caused by Mycobacterium ulcerans, with poorly understood acquisition risk factors. This review aims at evaluating the importance of individual-sex, age, family ties with history of BU, gene variants-and clinical-Bacillus Calmette-Gué rin (BCG) immunization, Human Immunodeficiency Virus (HIV) infection-variables in this process. Methods A systematic review was performed considering the following databases: ClinicalTrials.gov, Cochrane Controlled Register of Trials (CENTRAL), Current Contents Connect, Embase, MEDLINE, SciELO, Scopus and Web of Science. Eligible studies were critically appraised with The Joanna Briggs Institute checklists and heterogeneity was assessed with Cochran Q-test and I 2 statistic. Published demographic data was descriptively analysed and clinical data pooled within random-effects modelling for meta-analysis. Results A total of 29 studies were included in the systematic review. Two randomized controlled trials (RCTs) and 21 case-control studies were selected for meta-analysis. Studies show that BU mainly affects age extremes, more preponderately males among children. Data pooled from RCTs do not reveal BCG to be protective against BU (odds ratio (OR) = 0.63; 95% CI = 0.38-1.05; I 2 = 56%), a finding case-control studies appear to corroborate. HIV infection (OR = 6.80; 95% CI = 2.33-19.85; I 2 = 0%) and SLC11A1 rs17235409 A allele (OR = 1.86; 95% CI = 1.25-2.77; I 2 = 0%) are associated with increased prevalence of the disease. No definite conclusions can be drawn regarding the influence of previous family history of BU.

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“…Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing skin disease that primarily affects the subcutaneous fat tissue, leading to ulceration of the overlying dermal and epidermal layers of the skin [32]. The disease is reported from tropical regions worldwide, but has its highest prevalence in West Africa [33], (Figure 1). Three distinct non-ulcerative stages of the disease are described: (i) subcutaneous, painless and movable nodules or papules, (ii) edema, and (iii) plaques.…”

Section: Pathogenesis Of Buruli Ulcermentioning

confidence: 99%

wIRA: hyperthermia as a treatment option for intracellular bacteria, with special focus on Chlamydiae and Mycobacteria

Borel

Sauer-Durand

Hartel

et al. 2020

International Journal of Hyperthermia

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The emergence of antibiotic-resistant bacteria in the last century is alarming and calls for alternative, nonchemical treatment strategies. Thermal medicine uses heat for the treatment of infectious diseases but its use in facultative and obligate intracellular bacteria remains poorly studied. In this review, we summarize previous research on reducing the infectious burden of Mycobacterium ulcerans and Chlamydia trachomatis by using water-filtered infrared A-radiation (wIRA), a special form of heat radiation with high tissue penetration and low thermal load on the skin surface. Mycobacterium ulcerans is a thermosensitive bacterium causing chronic necrotizing skin disease. Therefore, previous data on wIRA-induced improvement of wound healing and reduction of wound infections is summarized first. Then, pathogenesis and treatment of infections with M. ulcerans causing Buruli ulcer and of those with C. trachomatis infecting the ocular conjunctiva and resulting in blinding trachoma are discussed. Both bacteria cause neglected tropical diseases and have similar geographical distributions. Results of previous in vitro and in vivo studies using wIRA on M. ulcerans and C. trachomatis infections are presented. Finally, technical aspects of using wIRA in patients are critically reviewed and open questions driving future research are highlighted. In conclusion, wIRA is a promising tool for reducing infectious burden due to intracellular bacteria such as M. ulcerans and C. trachomatis.

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Buruli Ulcer: History and Disease Burden

Cited by 23 publications

References 134 publications

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

Individual and clinical variables associated with the risk of Buruli ulcer acquisition: A systematic review and meta-analysis

wIRA: hyperthermia as a treatment option for intracellular bacteria, with special focus on Chlamydiae and Mycobacteria

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