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.

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages

OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1) levels in female and male subjects at various cervical vertebral maturation (CVM) stages. MATERIAL AND METHODS: The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS: Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml). CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at different cervical stages. .

OBJETIVO: o objetivo do presente estudo transversal foi avaliar os níveis do fator de crescimento semelhante à insulina-1 (IGF-1 sérico) em pacientes de ambos os sexos e em diferentes estágios de maturação das vértebras cervicais (MVC). MÉTODOS: a amostra consistiu de 60 pacientes, sendo 30 do sexo masculino e 30 do sexo feminino, com idades entre 8 e 23 anos. Amostras de sangue foram colhidas de todos os pacientes, cujos níveis de IGF-1 sérico foram avaliados por meio do método de imunoensaio quimioluminescente (CLIA). O estágio de MVC foi avaliado por meio de radiografias cefalométricas de perfil por meio do método descrito por Baccetti. O nível de IGF-1 sérico e o estágio de maturação das vertebras cervicais de 30 pacientes do sexo feminino foram avaliados e os dados retirados dos registros de um estudo prévio. Os dados foram submetidos aos testes de Kruskal-Wallis e de Mann-Whitney. A correção de Bonferroni foi calculada e o valor de alfa foi de 0,003. RESULTADOS: o valor de pico do IGF-1 sérico foi encontrado no estágio CS3, para mulheres, e CS4, para homens. Foram encontradas diferenças entre as médias dos valores de IGF-1 entre homens e mulheres nos estágios CS3, 4 e 5. O valor médio mais alto para os níveis de IGF-1 nos homens foi observado no estágio CS4, seguido do estágio CS5 e CS3. Nas mulheres, o valor médio mais alto foi observado em CS3, seguido do estágio CS4 e CS5. Diferenças também foram encontradas quanto à curva do IGF-1, em relação ao estágio de maturação das vértebras cervicais nos pacientes de ambos os sexos. O valor médio de IGF-1 sérico mais alto foi comparado. As pacientes do sexo feminino apresentaram valores ligeiramente mais altos (397ng/ml) em comparação aos pacientes do sexo masculino (394.8ng/ml). CONCLUSÕES: homens e mulheres apresentam valores de IGF-1 diferentes em estágios de maturação das vértebras cervicais diferentes. .

A Clinical, Microbiological, and Pathological Study of Cutaneous Nontuberculous Mycobacterial Infection / 대한피부과학회지

BACKGROUND: As the immunocompromised population has increased in recent years, the number of cutaneous nontuberculous mycobacterial (NTM) infections has also risen. However, since this affliction has no pathognomonic clinical or histological features, the diagnosis and treatment of cutaneous NTM infections are often delayed. OBJECTIVE: The aim of this study was to investigate the microbiological, clinical, and histological findings of cutaneous NTM infections. METHODS: We reviewed medical records and histologic slides of 10 patients diagnosed with cutaneous NTM infections confirmed by culture or polymerase chain reaction. RESULTS: All patients except one were immunocompetent, and 5 of 10 patients had preceding factors including trauma, liposuction, and intralesional triamcinolone injection. Microbiologically, of the 10 infections, 5 were caused by Mycobacterium marinum, 3 by Mycobacterium fortuitum, and 1 each by Mycobacterium chelonae and Mycobacterium ulcerans, respectively. Of the 5 patients with M. marinum, 2 had a fish-related job and 1 reared fish at a home aquarium. The most common clinical presentation was erythematous nodules (7/10). Histologically, irregular acanthosis (4/10), mixed cell infiltrate of lymphocytes, histiocytes, neutrophils (9/10), suppurative granuloma (7/10), microcysts lined by neutrophils (5/10), fibrosis (4/10), and panniculitis (7/10) were identified. CONCLUSION: We found microcysts lined by neutrophils in 50% of the samples and considered this finding to be a diagnostic marker of NTM infection. These clinicopathologic features will assist clinicians in diagnosing NTM infection more rapidly and accurately.

Buruli-like ulcer in a Palestinian woman: a case report with uncertain diagnosis

We report a case of Buruli-like ulcer in a Palestinian woman. The patient presented with a new ulcer on her left hand dorsum preceded by wet minor trauma. In view of the patient's medical history and current remnants of ulceration involving the other hand she was managed ad as a case of Buruli-like ulcer. To our knowledge, no similar cases with our patient's ulcer-features, whether Buruli ulcer, Buruli-like ulcer of Mycolactone Producing Mycobacterium marinum, were reported in the literature from Palestine and Jordan. We report this case to document an ulcer that looked like Buruli ulcer which was not proved by laboratory hard evidence

[Rate of production of inflammatory cytokines TNF and IL- by peripheral blood mononuclear cells stimulated with mycolactone]

Mycobacterium ulcerans is the etiological agent of Buruli ulcer [BU]; the third most common mycobacterial infection in humans after tuberculosis and leprosy. BU is now considered by the WHO to be an emerging infection of major concern. M. ulcerans produces mycolactone toxin, which is required for the organism's virulence. Mycolactone destroys tissue and suppresses host immune responses. In this descriptive analytical study, peripheral blood mononuclear cells from three volunteers with no history of buruli ulcer were used. IL-6 and TNF produced by these cells at different preincubation times with LPS and mycolactone were measured by using ELISA kits. This study showed hyper inhibition of IL-6 and TNF production by mycolactone. TNF levels in the control tubes [containing LPS] in 4hours reached its maximum value and then decreased. While the production of IL-6 in the tube with fresh cells [zero time] had the highest value, after 16hours, it reached its minimum. Since TNF and IL-6 are important immunity inflammatory cytokines, it can be well imagined that decrease of TNF production by this bacterium plays a role in weakening of inflammatory response. So Mycobacterium ulcerans destroys macrophages and at the same time prevents TNF production by important cells in innate immune mechanism

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.

Enfermedades infecciosas emergentes y reemergentes en Latinoamérica: lo que el dermatólogo debe saber / Emerging and reemerging infectious diseases in Latin America

En los últimos años nuevas enfermedades infecciosas desconocidas o poco conocidas en Latinoamérica han aparecido en la consulta del dermatólogo. La presente discusión incluye cuatro entidades de este tipo. La úlcera de Buruli es una infección crónica de la piel producida por el Mycobacterium ulcerans y se caracteriza por presentar úlceras de bordes socavados. La infección cutánea por amebas de vida libre, especialmente las causadas por Balamuthia mandrillaris, se presenta clásicamente con una lesión de tipo placa infiltrativa, con frecuencia centrofacial y ocasionalmente en extremidades. La gnathomiasis, típica de aquellos cuyas costumbres culinarias incluyen la ingesta de pescado crudo, se presenta como una paniculitis migratoria que va acompañada de marcada eosinofilia tisular. Por último, la dermatitis infectiva, un cuadro eccematoso en directa conexión con la infección por el virus HTLV1, se caracteriza por compromiso recurrente del cuero cabelludo, cara y zonas intertriginosas.

In recent years new infectious diseases unknown or infrequent in Latin America have appeared in dermatology practice. We present four of these disorders. Buruli ulcer is a chronic skin infection caused by Mycobecterium ulcerans and is characterized by the present of large ulcerations with undermined borders. Cutaneous infections caused by free amebas, especially those caused by Balamuthia mandrillaris, manifest as an infiltrating plaque, commonly located on the central face and occasionally on extremities. Gnathomiasis, typical of people who eat raw fish, present as a migratory paniculitis, accompanied by marked tissue eosinophilia and finally, infective dermatitis, an eczematous process in direct relation to HTLV1 infection, which is characterizes by recurrent involvement of scalp, face and intertriginous areas.

Atypical mycobacteria: classification, clinical syndromes and treatment

Atypical mycobacteria may cause many different types of infections such as septic arthritis, abscesses and skin and bone infection. Mycobacteria are classified according to their rate of growth and ability to produce yellow pigment in the dark or in the light. The varied and diverse group of cutaneous mycobacterial infections arise from a combination of the low innate pathogenicity of the organisms and opportune exposures of the hosts. Mycobacteria may pose an infectious risk for pedicure and manicure customers. Physicians should suspect this cause in patients with persistent furunculosis after exposure to whirlpool footbaths or pedicure procedures. Also an outbreak of M. abscessus was reported in a haemodialysis clinic in many clinics. All physicians should be alert to the current cluster of M. abscessus infections after injections for cosmetic purposes by nonmedical practitioners

Etude des appellations et des representations attachees a l'infection a Mycobacterium ulcerans dans differents pays endemiques d'Afrique

L'objectif de ce travail est de presenter les appellations de l'infection a Mycobacterium ulcerans (ulcere de Buruli) dans les langues africaines et leurs significations. Il vise egalement a explorer les representations attachees a la maladie dans differents pays endemiques d'Afrique. La methodologie utilisee implique l'analyse d' entretiens indivi- duels et de publications scientifiques. Les entretiens individuels ont ete menes aupres de differents chefs de programme et responsables de structures de prise en charge de cette maladie. Les resultats de notre analyse montrent que dans les pays d'Afrique ou l'ulcere de Buruli est endemique (Benin; Cameroun; Congo-Brazzaville; Cote d'Ivoire; Ghana; Ouganda; Republique Democratique du Congo; Sud Soudan et Togo); les appellations de cette maladie peuvent etre classees en trois categories; suivant qu'elles evoquent les origines geographiques de la maladie; les caracteristiques des lesions observees; ou les aspects d'incurabilite et de mystere; en lien avec la sorcellerie. Les representations de cette maladie dans les langues africaines apparaissent identiques et semblent traduire une connaissance relativement bonne de la maladie dans les pays ou l'ulcere de Buruli sevit. L'impact de ces representations influence egalement les types de recours aux soins

Ulcera de Buruli en Tumbes. Presentación de un caso y revisión de la literatura / Ulcer of Buruli in Tumbes. A case report and literature review

La úlcera de Buruli es una enfermedad infecciosa endémica causada por Mycobacterium ulcerans. Se presenta en diversas formas, siendo la ulcerada la más discapacitante. El cuadro clínico fluctúa desde el nódulo indoloro hasta extensas lesiones ulceradas que pueden curar espontáneamente, pero muy lentamente. Presentamos el caso de un varón de 53 años con esta patología. Se revisan los aspectos diagnósticos, de tratamiento y pronósticos.

Le traitement traditionnel de l'ulcere de Buruli au Benin

The purpose of this tra n s ve rs ve qualitat ive study on traditional treatment for Buruli ulcer in Benin was to track the tre atment itinera ry of pat i e n s ; the main phases of traditional treatment; cost and effi c a cy of such tre atment ; and the knowledge and skills of traditional practitioners. A total of 20 traditional practitioners; 35 patients treated by traditional therapy; and 35 patients treated by surgery were included. Findings showed that both traditional and surgical treatment was sought at a late stage. Reasons determining the type of tre atment chosen included religion; access to adequate care facilities; constraints involved in surgical treatment; duration of hospitalization; and fear of scarring. The four main steps in traditional treatment were diagnosis; removal of necrotic tissue; wound care; and exorcism. The cost of traditional treatment was high not only in c u rre n cy but also by payment in kind (e.g.; live s t o ck and land). Although it is perfo rmed with patient consent; t raditional tre atment presents a number of risks. Information campaigns are necessary to inform populations about available treatments and the possible risks associated with each modality. Care centers must do more to lessen the constraints involved in surgical treatment both in terms of duration of hospitalization and cosmetic outcome

The Effect of Mycolactone on the Expression of Bcl-2 Family Genes in Hep 3B Hepatoma Cells

Mycolactone is a recently reported lipid toxin of Mycobacterium ulcerans that causes Buruli ulcer, a severe human skin disease. However, the mechanism of cell death by mycolactone is still unclear. In this paper, we demonstrate that mycolactone induces apoptosis in Hep 3B hepatocellular carcinoma (HCC) cells. Morphological and biochemical evidences of apoptosis, such as membrane blebbing, cell shrinkage, increase of TUNEL-positive cells and a sub-G 1 cell population, were observed. To explain the mechanism of mycolactone-induced apoptosis, we examined the expression of Bcl-2 family genes. The mRNA expression of anti-apoptotic BclXL gene was decreased after 8 hours, while that of Mcl-l, another anti-apoptotic gene, was slowly decreased with an initial increase at second hour after treatment. Bcl-2 gene expression was extremely low both in the presence and absence of mycolactone. The expression of other Bcl-2 family genes, such as Bclw, Bad, Bak, and Bax, was not affected. By Western blotting analysis, Mcl-1 expression (not BclXL) was down-regulated. Our results suggest that the down-regulation of Mcl-1 protein expression is involved in the apoptosis of Hep 3B cells by mycolactone.

Detection de mycobacterium ulcerans par la technique de polymerase chain reaction (PCR) et relations avec l'etude histopathologique chez des patients porteurs d'ulcerations cutanees chroniques (ulcere de buruli)

"Ce travail est une etude transversale qui avait pour objectif d'etablir les relations entre la detection de Mycobacterium ulcerans par la technique de polymerase Chain reaction (PCR) et l'etude histopathologique chez 33 patients porteurs d'ulcerations cutanees chroniques evoquant cliniquement un ulcere de Buruli. Les methodes d'etude utilisees ont ete pour la biologie moleculaire la technique de ""Single PCR."" par amplification de la sequence d'insertion IS 2404 specifique de Mycobacterium ulcerans et les techniques d'inclusion et coupe en paraffine suivies des colorations a l'hemateine-eosine et au Ziehl-Neelsen pour l'etude histopathologique. Nos resultats ont ete les suivants: *Le taux de positivite de la PCR effectuee sur les fragments biopsiques etait de 90;90pour cent; *Il existait 3 formes histopathologiques: forme necrosante (39;4pour cent); forme mixte (42;4pour cent); forme granulomateuse (18;2pour cent) ; *La comparaison entre les 2 tests diagnostiques a montre que: -Dans la forme necrosante; la PCR et l'histopathologie avaient le meme rendement diagnostique avec un niveau de concordance de 100pour cent. -Dans la forme mixte le niveau de concordance entre les 2 methodes diagnostiques etait de 92;8.6pour cent. -et de 66;67pour cent dans la forme granulomateuse. En conclusion; ces resultats indiquent d'une part un taux de positivite eleve de la PCR realisee sur des fragments tissulaires et d'autre part la fiabilite de l'etude histopathologique pour la confirmation biologique du diagnostic d'ulcere de Buruli dans ses formes necrosante et mixte. En revanche elle devra etre couplee a la PCR pour plus de fiabilite dans les formes granulomateuses."