Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Abstract

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...

Infection withMycobacterium ulceransInduces Persistent Inflammatory Responses in Mice

“…On the other hand, the experimental (22,23,38,40,57,75). Therefore, comprehensive analyses of infection with different M. ulcerans clinical isolates were carried out in mice to understand the dynamics of inflammatory responses in an animal model largely used in the study of experimental infections, including mycobacteriosis (18,47), and to compare the histopathological features of M. ulcerans infections in mice and humans.…”

“…Experimental M. ulcerans infections in mice, rats, guinea pigs, and nine-banded armadillos led to contradictory observations regarding induction of inflammatory responses. In some stud-ies, the occurrence of an inflammatory response was reported (38,40,57), but other studies showed minimal inflammation associated with M. ulcerans infection (22,23,75). Moreover, the dynamics of the infection process and host inflammatory response at different stages of infection with M. ulcerans are still poorly understood.…”

Tuberculous and tuberculoid lesions in free living small terrestrial mammals and the risk of infection to humans and animals: a review

“…The HIV/AIDS infection in humans largely contributes to the process. M. fortuitum, M. phlei, M. chelonae, M. marinum, M. smegmatis, M. ulcerans and others are the atypical mycobacteria most commonly isolated from such lesions (Karbe, 1987;Walsh et al, 1999;Bercovier and Vincent, 2001;Portaels et al, 2001;Dega et al, 2002). Accordingly, a comparable complex of mycobacterial species is likely to be found in small terrestrial mammals in the case of their immunosuppression, e.g.…”

Methods used in preclinical assessment of anti-Buruli ulcer agents: A global perspective

“…Experimentation with armadillos showed that nine-banded armadillos are susceptible to M. ulcerans and can develop cutaneous lesions that closely mimic BU in human suggesting that it could be a useful model to investigate the pathogenesis of M. ulcerans (Walsh, Meyers, Krieg, & Walsh, 1999) and to provide further insight into the assessment of new treatments for BU. Addo et al (2006) studied the grasscutter, a hystricomorph rodent as a model for BU.…”

“…Guinea pigs develop inflammatory lesions at the sites of inoculation that habitually resolve without formation of ulcer (Kreig et al, 1974;Read et al, 1974). The nine-banded armadillo is susceptible to M. ulcerans and develops cutaneous lesions after experimental intradermal infection, approximating those of the human disease, but is phylogenetically distant (Walsh et al, 1999). The cynomolgus monkey has shown to be susceptible to M. tuberculosis, and to some extent, M. leprae, and it is usually used in pre-clinical drug and vaccine studies (Walsh et al, 1996).…”