Understanding the transmission of Mycobacterium ulcerans: A step towards controlling Buruli ulcer

Muleta, Anthony J.; Lappan, Rachael; Stinear, Timothy P.; Greening, Chris

doi:10.1371/journal.pntd.0009678

Cited by 28 publications

(34 citation statements)

References 129 publications

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“…No human-to-human transmission of this infection has ever been reported. The ecological characteristics and mode of transmission of M. ulcerans are not entirely understood, and several fundamental questions remain unanswered [16,17]. One key concern relates to the routes by which M. ulcerans crosses the human skin barrier.…”

Section: Introductionmentioning

confidence: 99%

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses

Boccarossa

Degnonvi

Brou

et al. 2022

PLOS Glob Public Health

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Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.

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Section: Introductionmentioning

confidence: 99%

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses

Boccarossa

Degnonvi

Brou

et al. 2022

PLOS Glob Public Health

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“…Aquatic environments may represent the natural niches for M. ulcerans . Aquatic insects in West Africa, and mosquitoes in Australia have been proposed as vectors in Buruli ulcer, but their role remains unclear [ 69 ▪▪ ]. Australian opossums have been investigated as animal reservoirs, as they are affected by Buruli ulcer and M. ulcerans DNA has been detected in their faeces [ 69 ▪▪ ].…”

Section: Mycobacterial Skin Infectionsmentioning

confidence: 99%

“…Aquatic insects in West Africa, and mosquitoes in Australia have been proposed as vectors in Buruli ulcer, but their role remains unclear [ 69 ▪▪ ]. Australian opossums have been investigated as animal reservoirs, as they are affected by Buruli ulcer and M. ulcerans DNA has been detected in their faeces [ 69 ▪▪ ]. A few cases of Buruli ulcer have been described also in other mammals in Australia, but animal-to-human transmission has not been demonstrated yet.…”

Section: Mycobacterial Skin Infectionsmentioning

confidence: 99%

Mycobacterial skin infection

Giannotti

Gregori

Matteelli

et al. 2022

Current Opinion in Infectious Diseases

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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.

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“…It is useful to understand the details of Sec61 inhibition by mycolactone, as it applies across the nucleated cells of higher eukaryotic species that harbor M. ulcerans infections ( 41 , 42 ). The Sec61 translocon consists of 3 subunits, Sec61α, Sec61β and Sec61γ, with Sec61α being the dynamic major pore forming subunit.…”

Section: Introductionmentioning

confidence: 99%

The One That Got Away: How Macrophage-Derived IL-1β Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer

et al. 2022

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Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a devastating necrotizing skin disease. Key to its pathogenesis is mycolactone, the exotoxin virulence factor that is both immunosuppressive and cytotoxic. The discovery that the essential Sec61 translocon is the major cellular target of mycolactone explains much of the disease pathology, including the immune blockade. Sec61 inhibition leads to a loss in production of nearly all cytokines from monocytes, macrophages, dendritic cells and T cells, as well as antigen presentation pathway proteins and costimulatory molecules. However, there has long been evidence that the immune system is not completely incapable of responding to M. ulcerans infection. In particular, IL-1β was recently shown to be present in BU lesions, and to be induced from M. ulcerans-exposed macrophages in a mycolactone-dependent manner. This has important implications for our understanding of BU, showing that mycolactone can act as the “second signal” for IL-1β production without inhibiting the pathways of unconventional secretion it uses for cellular release. In this Perspective article, we validate and discuss this recent advance, which is entirely in-line with our understanding of mycolactone’s inhibition of the Sec61 translocon. However, we also show that the IL-1 receptor, which uses the conventional secretory pathway, is sensitive to mycolactone blockade at Sec61. Hence, a more complete understanding of the mechanisms regulating IL-1β function in skin tissue, including the transient intra-macrophage stage of M. ulcerans infection, is urgently needed to uncover the double-edged sword of IL-1β in BU pathogenesis, treatment and wound healing.

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Understanding the transmission of Mycobacterium ulcerans: A step towards controlling Buruli ulcer

Cited by 28 publications

References 129 publications

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses

Mycobacterial skin infection

The One That Got Away: How Macrophage-Derived IL-1β Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer

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