Hosts and transmission of Mycobacterium ulcerans: a systematic review

The control of Buruli ulcer (BU), a debilitating neglected tropical disease, is hampered by the inadequate understanding of the mode of transmission of its causative agent, Mycobacterium ulcerans (M. ulcerans). The DNA of M. ulcerans has been detected in some living organisms and non-living environmental samples of both aquatic and terrestrial sources. However, it is unclear whether the identified organisms support in vivo multiplication of the bacterium or play any role in its transmission. This paper identifies hosts of M. ulcerans, reviews progress made in unravelling the exact mode of transmission of M. ulcerans and identifies research gaps in this aspect of BU epidemiology. Using the search terms, 'niche, Mycobacterium ulcerans' and 'mode of transmission, Mycobacterium ulcerans' as well as defined inclusion criteria, information was obtained from the PubMed database and reviewed to assess their importance to the research question. Aquatic bugs of the genera Appasus and Diplonychus as well as Naucoris cimicoides and possums were identified to support in vivo multiplication of the bacterium. Bite of M. ulcerans contaminated Aedes notoscriptus, bite of aquatic bugs harboring or contaminated with M. ulcerans, and M. ulcerans contaminated skin-puncturing materials present in nature create opportunity for its transmission and infection. Appropriate protective measures may be useful to reduce the risk of exposure to M. ulcerans in BU endemic areas, and incorporation of trophic interactions of aquatic organisms known to support in vivo multiplication of M. ulcerans is needed in future research for better understanding of the spread of M. ulcerans in nature.

Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for

Buruli ulcer (BU), caused by

Secondary bacterial isolates from previously untreated Buruli ulcer lesions and their antibiotic susceptibility patterns in Southern Nigeria

Abstract INTRODUCTION: Mycolactones, secreted by Mycobacterium ulcerans, were previously believed to prevent super infection in Buruli ulcer lesions. However, little is known about secondary bacterial infections in these lesions. This study evaluated contaminating bacterial flora and their antibiotic susceptibility patterns in cases of previously untreated Buruli ulcer disease from three states in Southern Nigeria. METHODS A prospective analysis was conducted between January and June of 2015 using wound swabs from eligible patients with Buruli ulcer disease, confirmed by quantitative-polymerase chain reaction, with active ulcers. Microbiological analyses including isolation of bacteria, species identification of isolates, and drug susceptibility tests were performed. RESULTS Of 51 patients, 27 (52.9%) were female. One or more bacterial species of clinical importance was isolated from each patient. A total of 17 different microbial species were isolated; 76.4% were Gram-negative and 23.6% were Gram-positive isolates. The most common bacterial species detected was Staphylococcus aureus (24%), followed by Aeromonas hydrophila (13%), Pseudomonas aeruginosa (13%), and Klebsiella pneumoniae (11%). Drug susceptibility tests showed a particularly high frequency of resistance to commonly used antimicrobials in Nigeria for Staphylococcus aureus. CONCLUSIONS Super bacterial infections occur in Buruli ulcer lesions in Nigeria, and these infections are associated with high rates of resistance to commonly used antibiotics in the country.

Úlcera de Buruli / Buruli ulcer

A úlcera de Buruli, uma doença infecciosa causada pela Mycobacterium ulcerans (M. ulcerans),é a terceira micobacteriose em ocorrência, após a hanseníase e a tuberculose. Essa micobacteriose atípica tem sido relatada em mais de 30 países, principalmente, nos que têm climas tropicais e subtropicais, mas a sua epidemiologia permanece obscura. Recentemente, os primeiros casos autóctones do Brasil foram relatados, fazendo com que dermatologistas brasileiros estejam atentos a esse diagnóstico. O quadro clínico varia: nódulos, áreas de edema, placas, mas a manifestação mais típica é uma grande úlcera, que ocorre, em geral, nas pernas ou nos braços. Apesar do amplo conhecimento quanto ao seu quadro clínico em países endêmicos, nas outras áreas, esse diagnóstico pode passar despercebido. Assim, médicos devem ser orientados quanto à úlcera de Buruli, pois o diagnóstico precoce, o tratamento específico e a introdução de cuidados na prevenção de incapacidades são essenciais para uma boa evolução.

Buruli ulcer, an infectious disease caused by Mycobacterium ulcerans, is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. This atypical mycobacteriosis has been reported in over 30 countries, mainly those with tropical and subtropical climates, but its epidemiology remains unclear. The first autochthonous cases of infection in Brazil have recently been described, making this diagnosis important for Brazilian dermatologists. Clinical manifestations vary from nodules, areas of edema, and plaques, but the most typical presentation is a large ulcer, usually in the limbs. Despite considerable knowledge about its clinical manifestations in some endemic countries, in other areas the diagnosis may be overlooked. Therefore, physicians should be educated about Buruli ulcer, since early diagnosis and treatment, including measures to prevent disability, are essential for a good outcome.

Búsqueda de úlcera de Buruli en el Urabá Chocoano y Antioqueño, Colombia 2006 / Search of Buruli in Choco and Antioquia, Uraba Colombia, 2006

Introducción: en Colombia no se ha reportado ningún caso de úlcera de Buruli (UB), aún teniendo regiones con características similares a zonas endémicas. En nuestro medio, la proximidad geográfica y las condiciones ambientales similares con los países de Sur y Centro América donde se han reportado casos, motivan a buscar activamente pacientes sospechosos de UB, y aplicar técnicas de laboratorio moleculares específicas para brindar un adecuado diagnóstico. Objetivo: buscar casos de úlcera de Buruli (UB) en Urabá chocoano y antioqueño, (Colombia) durante el año 2006. Materiales y métodos: se estudiaron casos provenientes de las áreas de estudio, para establecer la causa etiológica de las lesiones utilizando métodos de diagnóstico clínico, microbiológico, histopatológico y molecular. Resultados: en cinco pacientes (6%) no se pudo establecer la causa etiológica de la úlcera (leishmaniosis, micosis, úlceras venosas o arteriales, cáncer). El examen clínico de estos pacientes no fue concluyente de UB, sin embargo debido a la falta de documentación de casos en Colombia, se procesó biopsia de la lesión para detectar ADN de Mycobacterium ulcerans por reacción en cadena de la polimerasa (PCR). Todas las pruebas de PCR fueron negativas para ADN de Mycobacterium ulcerans. Conclusiones: debido a indicadores epidemiológicos que señalan a Colombia con condiciones geográficas y ambientales similares a las que se presentan en regiones endémicas, como Perú, Guyana Francesa, México, Surinam, es necesario continuar con su búsqueda.

Introduction: in Colombia there are no reported cases of Buruli ulcer (BU), however the geographic and environmental characteristics are similar to endemic regions, and the proximity to other countries in South and Central America where there are reported cases, makes it an important issue to search for them, using molecular techniques specific for BU diagnostic. Objectives: to search for Buruli ulcer (BU) at the Urabá region of Chocó and Antioquia in Colombia, during 2006. Materials and methods: patients with skin ulcer from the study region were tested to establish the etiologic cause of the lesions, using clinical, microbiological, pathological and molecular methods. Results: Five patients were tested for BU using PCR test, since other etiologic causes of the ulcer (leishmaniosis, mycosis, venous or arterial ulcer, others) were not determined. Clinical examination of the patients was not conclusive of BU; but due to the lack of documented cases in Colombia, biopsies were taken from patients for detection of M. ulcerans by PCR. All the samples samples tested negative for DNA of Mycobacterium ulcerans. Conclusions: due to the epidemiological indicators that show that Colombia has the geographic and environmental conditions similar to endemic regions, as Perú, French Guyana, México and Surinam it is necessary to continue with the search.