Mycobacterial Infections of the Skin

Meyers, Wayne M.

doi:10.1007/978-3-642-57863-2_9

Cited by 36 publications

(37 citation statements)

References 189 publications

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“…28 Not unexpectedly, AFB were observed more frequently in animals with advanced lesions. Three skin samples collected during necropsy were culture positive for AFB on Lowenstein-Jensen media.…”

Section: Resultsmentioning

confidence: 96%

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Walsh¹,

Meyers²,

Krieg³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Animal models for Mycobacterium ulcerans infections (Buruli ulcer) include guinea pigs, rats, and mice, but each has limitations in replicating the spectrum of human disease. Here, 19 adult nine-banded armadillos were inoculated intradermally with M. ulcerans. Injection sites were examined and skin samples obtained for histologic and microbiology studies. Necropsies were conducted to assess systemic involvement. In group 1 (n ϭ 4), 2 animals developed progressive skin ulcers with undermined borders at the injection sites within 6-10 weeks. Biopsies showed features similar to human disease including extensive necrosis in the deep dermis and subcutaneous fat, mixed cellular infiltrates, and acid-fast bacilli (AFB). In group 2 (n ϭ 15), 5 animals developed progressive skin ulcers, 3 had evanescent papulo-nodules, 3 died shortly after inoculation of unknown causes, and 4 showed no signs of infection. Lesion samples from 3 animals with progressive ulcers were culture positive for AFB. Our findings indicate that nine-banded armadillos are susceptible to M. ulcerans and may develop cutaneous lesions that closely mimic Buruli ulcer.In tropical countries, skin ulcers caused by infectious agents are common. Mycobacterium ulcerans, the causative organism of Buruli ulcer first isolated in Australia, is considered a public health threat, especially in Africa. [1][2][3][4][5][6][7][8][9][10] Recent observations suggest that environmental sources of M. ulcerans include swamps, with subsequent transmission by insects. 11 The clinical features of Buruli ulcer are variable. In uncomplicated disease, painless skin ulcers, typically on the extremities, develop without fever or malaise. 12,13 However, progressive lesions may result in large areas of ulceration, necrosis, and osteomyelitis. Many lesions tend to heal, but this may take years without medical intervention. Advanced disease requires surgical excision and skin grafts or amputation. Crippling contractures and lymphedema may accompany healing. Medical therapies include clofazimine, dapsone, rifampicin, phenytoin, cotrimoxazole, macrolide compounds, and heat. However, cure rates are generally low. [14][15][16][17][18][19] Understanding the pathogenesis of human M. ulcerans infections has been slowed by the lack of an animal model that develops features resembling human disease. Rats, mice, and guinea pigs are used as animal models for M. ulcerans infections, but each is limited in replicating the spectrum of features found in human disease. Rats and mice develop lesions after cutaneous inoculation with M. ulcerans, but lack the extensive ulceration characteristic of human disease. In the mouse footpad, the organisms multiply but necrosis without ulceration destroys the limb and causes death. 20,21 Guinea pigs develop inflammatory lesions at the inoculation sites that usually resolve without ulcer formation. 21,22 The nine-banded armadillo is highly susceptible to M. leprae and has been a useful animal model for leprosy. 23 Here, we report that armadillos are also s...

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Section: Resultsmentioning

confidence: 96%

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Walsh¹,

Meyers²,

Krieg³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…M. ulcerans infection in humans presents three stages: 1) a preulcerative or early stage, which includes nodules, plaques, or edemas; 2) an ulcerative stage during which lesions evolve toward massive ulceration that, without medical care, can reach bones; and 3) spontaneous healing that can occur after a long ulcerative stage without treatment, leading to major infirmities due to retractions and bone destruction (1,15,19) (E. Marion, Y. Delneste, and L. Marsollier, manuscript in preparation). Although the spontaneous healing stage has been observed since the first outbreak of M. ulcerans, it remains poorly described and studied (1,2,(15)(16)(17)(18)(19)(20)(21).…”

Section: Contextmentioning

confidence: 99%

“…This process was often mentioned, but remains poorly described or studied (1,2,(15)(16)(17)(18)(19)(20)(21). We have recently conducted a retrospective epidemiological study reporting that ∼5% of Buruli ulcer patients present clinical features of spontaneous healing process at the diagnosis (E. Marion, Y. Delneste, and L. Marsollier, manuscript in preparation).…”

mentioning

confidence: 99%

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Marion

Jarry

Cano

et al. 2016

The Journal of Immunology

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Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies.

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“…After introduction of the mycobacteria into the dermis or subcutaneous tissue, there is presumably a latent phase during which the slowgrowing bacteria proliferate and elaborate sufficient toxin to destroy the surrounding tissue. The subsequent necrosis, especially of fatty tissue, may then provide a favorable milieu for further proliferation (19). Analyses of the spreading of the mycobacteria may contribute to our understanding of the pathogenesis of Buruli ulcer and guide surgical treatment.…”

Section: Vol 41 2003mentioning

confidence: 99%

“…Even in the most minimal lesions, necrosis of fatty tissue seems to be a primary event (19). In contrast to other pathogenic mycobacteria, M. ulcerans is not a facultative intracellular pathogen but is found primarily as extracellular microcolonies (14,19).…”

mentioning

confidence: 99%

Development and Application of Real-Time PCR Assay for Quantification of Mycobacterium ulcerans DNA

Rondini

Mensah-Quainoo

Troll³

et al. 2003

J Clin Microbiol

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Buruli ulcer, an infection caused by Mycobacterium ulcerans, is, after tuberculosis and leprosy, the third most common mycobacterial disease. The mode of transmission of M. ulcerans is not exactly known, but since Buruli ulcer often occurs in focalized swampy areas, it is assumed that there is a reservoir of the pathogen in stagnant water. Buruli ulcer usually starts as a painless nodule and can lead to massive destruction of skin, subcutaneous tissue, and eventually muscle and bone. Currently the only recommended treatment is wide surgical excision. In this report we describe the development of a real-time PCR method for the quantification of M. ulcerans DNA (IS2404 TaqMan). The highly specific assay is based on the detection of the M. ulcerans specific insertion sequence IS2404. The IS2404 TaqMan assay turned out to be about 10 times more sensitive than the available conventional PCR-based diagnostic test. It is demonstrated that the IS2404 TaqMan assay is suitable for the quantitative assessment of the dissemination of the mycobacteria in Buruli ulcer lesions. Prototype results obtained with excised tissue from a patient with a late preulcerative Buruli ulcer lesion reconfirmed earlier histopathological findings indicating that tissue damage occurs far beyond the regions in which large numbers of mycobacteria are detectable. The IS2404 TaqMan assay should be a useful tool for both diagnosis and research into the pathology and mode of transmission of this still inadequately investigated mycobacterial disease.

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Mycobacterial Infections of the Skin

Cited by 36 publications

References 189 publications

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Development and Application of Real-Time PCR Assay for Quantification of Mycobacterium ulcerans DNA

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