Emerging human infectious diseases of aquatic origin: a comparative biogeographic approach using Bayesian spatial modelling.

BACKGROUND: With the increase in unprecedented and unpredictable disease outbreaks due to human-driven environmental changes in recent years, we need new analytical tools to map and predict the spatial distribution of emerging infectious diseases and identify the biogeographic drivers underpinning their emergence. The aim of the study was to identify and compare the local and global biogeographic predictors such as landscape and climate that determine the spatial structure of leptospirosis and Buruli Ulcer (BU). METHODS: We obtained 232 hospital-confirmed leptospirosis (2007-2017) cases and 236 BU cases (1969-2017) in French Guiana. We performed non-spatial and spatial Bayesian regression modeling with landscape and climate predictor variables to characterize the spatial structure and the environmental drivers influencing the distribution of the two diseases. RESULTS: Our results show that the distribution of both diseases is spatially dependent on environmental predictors such as elevation, topological wetness index, proximity to cropland and increasing minimum temperature at the month of potential infection. However, the spatial structure of the two diseases caused by bacterial pathogens occupying similar aquatic niche was different. Leptospirosis was widely distributed across the territory while BU was restricted to the coastal riverbeds. CONCLUSIONS: Our study shows that a biogeographic approach is an effective tool to identify, compare and predict the geographic distribution of emerging diseases at an ecological scale which are spatially dependent to environmental factors such as topography, land cover and climate.

Comparison of Mycobacterium ulcerans (Buruli ulcer) and Leptospira sp. (Leptospirosis) dynamics in urban and rural settings.

BACKGROUND: Zoonotic pathogens respond to changes in host range and/or pathogen, vector and host ecology. Environmental changes (biodiversity, habitat changes, variability in climate), even at a local level, lead to variability in environmental pathogen dynamics and can facilitate their transmission from natural reservoirs to new susceptible hosts. Whilst the environmental dynamics of aquatic bacteria are directly linked to seasonal changes of their habitat they also rely on the ecological processes underpining their transmission. However data allowing the comparison of these ecological processes are lacking. Here we compared the environmental dynamics of generalist and vector-borne aquatic bacterial pathogens in the same unit of time and space, and across rural and urban habitats in French Guiana (South America). PRINCIPAL FINDINGS: Using Leptospira sp. and Mycobacterium ulcerans we performed an environmental survey that allowed the detection of both pathogens in urban vs. rural areas, and during rainy vs. dry weather conditions. All samples were subjected to qPCR amplifications of LipL32 (Leptospira sp.) and IS2404 and KR (M. ulcerans) genetic markers. We found (i) a greater presence of M. ulcerans in rural areas compared with Leptospira sp., (ii) that modified urban environments were more favourable to the establishment of both pathogens, (iii) that Leptospira sp. presence was enhanced during the rainy season and M. ulcerans during the dry period, and (iv) differences in the spatial distribution of both bacteria across urban sites, probably due to the mode of dissemination of each pathogen in the environment. CONCLUSIONS: We propose that in French Guiana simplified and modified urban ecosystems might favour leptospirosis and Buruli ulcer emergence and transmission. Moreover, disease risk was also constrained by seasonality. We suggest that the prevention of aquatic bacterial disease emergence in impoverished urban areas of developing countries would benefit from seasonal diseases targeted surveys, which would maximise limited budgets from cash-strapped health agencies.

Mycobacterium ulcerans infection (Buruli ulcer) in French Guiana, South America, 1969-2013: an epidemiological study.

BACKGROUND: Mycobacterium ulcerans infection is the third most common mycobacterial disease in the world after tuberculosis and leprosy. To date, transmission pathways from its environmental reservoir to humans are still unknown. In South America, French Guiana has the highest reported number of M ulcerans infections across the continent. This empirical study aimed to characterise the epidemiology of M ulcerans infection in French Guiana between 1969 and 2013. METHODS: Data were collected prospectively mainly by two dermatologists at Cayenne Hospital's dermatology department between Jan 1, 1969, and Dec 31, 2013, for age, date of diagnosis, sex, residence, location of the lesion, type of lesion, associated symptoms, and diagnostic method (smear, culture, PCR, or histology) for all confirmed and suspected cases of M ulcerans. We obtained population data from censuses. We calculated mean M ulcerans infection incidences, presented as the number of cases per 100 000 person-years. FINDINGS: 245 patients with M ulcerans infections were reported at Cayenne Hospital's dermatology department during the study period. M ulcerans infection incidence decreased over time, from 6·07 infections per 100 000 person-years (95% CI 4·46-7·67) in 1969-83 to 4·77 infections per 100 000 person-years (3·75-5·79) in 1984-98 and to 3·49 infections per 100 000 person-years (2·83-4·16) in 1999-2013. The proportion of children with infections also declined with time, from 42 (76%) of 55 patients in 1969-83 to 26 (31%) of 84 in 1984-98 and to 22 (21%) of 106 in 1999-2013. Most cases occurred in coastal areas surrounded by marshy savannah (incidence of 21·08 per 100 000 person-years in Sinnamary and 21·18 per 100 000 person-years in Mana). Lesions mainly affected limbs (lower limbs 161 [66%] patients; upper limbs 60 [24%] patients). We diagnosed no bone infections. INTERPRETATION: The decrease of M ulcerans infection incidence and the proportion of children with infections over a 45 year period in this ultra-peripheral French territory might have been mostly driven by improving living conditions, prophylactic recommendations, and access to health care. FUNDING: Agence Nationale de la Recherche.

Deforestation-driven food-web collapse linked to emerging tropical infectious disease, Mycobacterium ulcerans.

Generalist microorganisms are the agents of many emerging infectious diseases (EIDs), but their natural life cycles are difficult to predict due to the multiplicity of potential hosts and environmental reservoirs. Among 250 known human EIDs, many have been traced to tropical rain forests and specifically freshwater aquatic systems, which act as an interface between microbe-rich sediments or substrates and terrestrial habitats. Along with the rapid urbanization of developing countries, population encroachment, deforestation, and land-use modifications are expected to increase the risk of EID outbreaks. We show that the freshwater food-web collapse driven by land-use change has a nonlinear effect on the abundance of preferential hosts of a generalist bacterial pathogen, Mycobacterium ulcerans. This leads to an increase of the pathogen within systems at certain levels of environmental disturbance. The complex link between aquatic, terrestrial, and EID processes highlights the potential importance of species community composition and structure and species life history traits in disease risk estimation and mapping. Mechanisms such as the one shown here are also central in predicting how human-induced environmental change, for example, deforestation and changes in land use, may drive emergence.

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. .

Heterogeneity among Mycobacterium ulcerans from French Guiana revealed by multilocus variable number tandem repeat analysis (MLVA).

Buruli ulcer is an emerging and neglected tropical disease caused by Mycobacterium ulcerans. Few cases have been reported so far in the Americas. With 250 cases reported since 1969, French Guiana is the only Buruli ulcer endemic area in the continent. Thus far, no genetic diversity studies of strains of M. ulcerans from French Guiana have been reported. Our goal in the present study was to examine the genetic diversity of M. ulcerans strains in this region by using the Multilocus Variable Number Tandem Repeat Analysis (MLVA) approach. A total of 23 DNA samples were purified from ulcer biopsies or derived from pure cultures. MVLA was used in the study of six previously-described Variable Number of Tandem Repeat (VNTR) markers. A total of three allelic combinations were characterized in our study: genotype I which has been described previously, genotype III which is very similar to genotype I, and genotype II which has distinctly different characteristics in comparison with the other two genotypes. This high degree of genetic diversity appears to be uncommon for M. ulcerans. Further research based on complete genome sequencing of strains belonging to genotypes I and II is in progress and should lead soon to a better understanding of genetic specificities of M. ulcerans strains from French Guiana.

Buruli ulcer in traveler from Suriname, South America, to the Netherlands.

We report Buruli ulcer in a man in the Netherlands. Phenotyping of samples indicate the Buruli pathogen was acquired in Suriname and activated by trauma on return to the Netherlands. Awareness of this disease by clinicians in non-Buruli ulcer-endemic areas is critical for identification.

[Paradoxical reactions and responses during antibiotic treatment for Mycobacterium ulcerans infection (Buruli ulcer). Four cases from French Guiana]. / Réponses et réactions paradoxales au cours du traitement médicamenteux de l'infection à Mycobacterium ulcerans (ulcère de Buruli). Quatre observations en Guyane française.

BACKGROUND: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin. PATIENTS AND METHODS: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years. DISCUSSION: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics.

First detection of Mycobacterium ulcerans DNA in environmental samples from South America.

The occurrences of many environmentally-persistent and zoonotic infections are driven by ecosystem changes, which in turn are underpinned by land-use modifications that alter the governance of pathogen, biodiversity and human interactions. Our current understanding of these ecological changes on disease emergence however remains limited. Buruli ulcer is an emerging human skin disease caused by the mycobacterium, Mycobacterium ulcerans, for which the exact route of infection remains unclear. It can have a devastating impact on its human host, causing extensive necrosis of the skin and underlying tissue, often leading to permanent disability. The mycobacterium is associated with tropical aquatic environments and incidences of the disease are significantly higher on floodplains and where there is an increase of human aquatic activities. Although the disease has been previously diagnosed in South America, until now the presence of M. ulcerans DNA in the wild has only been identified in Australia where there have been significant outbreaks and in western and central regions of Africa where the disease is persistent. Here for the first time, we have identified the presence of the aetiological agent's DNA in environmental samples from South America. The DNA was positively identified using Real-time Polymerase Chain Reaction (PCR) on 163 environmental samples, taken from 23 freshwater bodies in French Guiana (Southern America), using primers for both IS2404 and for the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes (KR). Five samples out of 163 were positive for both primers from three different water bodies. A further nine sites had low levels of IS2404 close to a standard CT of 35 and could potentially harbour M. ulcerans. The majority of our positive samples (8/14) came from filtered water. These results also reveal the Sinnamary River as a potential source of infection to humans.

A cutaneous ulcer resulting from Mycobacterium ulcerans--Leishmania braziliensis coinfection in South America.

Buruli ulcer is a tropical skin disease caused by Mycobacterium ulcerans. Its mode of transmission is not yet clearly understood. We report here a cutaneous ulcer in a European traveler in South America resulting from a coinfection detected specifically for Mycobacterium ulcerans and Leishmania braziliensis DNA with real-time polymerase chain reaction. This observation of a unique cutaneous ulcer raises the issue about possible modes of transmission of those two pathogens by the same vector.

Buruli ulcer in United Kingdom tourist returning from Latin America.

We report a case of Buruli ulcer in a tourist from the United Kingdom. The disease was almost certainly acquired in Brazil, where only 1 case had previously been reported. The delay in diagnosis highlights the need for physicians to be aware of the disease and its epidemiology.

Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas.

Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.

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.

Mycobacterium ulcerans disease, Peru.

Eight adult patients (ages 18-58, 5 women) with Buruli ulcer (BU) confirmed by at least 2 diagnostic methods were seen in a 10-year period. Attempts to culture Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from the swampy northern coast of Peru. The patients had 1-5 lesions, most of which were on the lower extremities. One patient had 5 clustered gluteal lesions; another patient had 2 lesions on a finger. Three patients were lost to follow-up. All 5 remaining patients had moderate disease. Diverse treatments (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial drug treatment for BU, and for 3 patients, excision surgery) were successful. Only 1 patient (patient 7) received the specific drug treatment recommended by WHO. BU is endemic in Peru, although apparently infrequent. Education of populations and training of health workers are first needed to evaluate and understand the full extent of BU in Peru.

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.

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.

The local immune response in ulcerative lesions of Buruli disease.

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-gamma, interleukin (IL)-10, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-gamma was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-gamma, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.

Ulcerative cutaneous mycobacteriosis due to Mycobacterium ulcerans: report of two Mexican cases.

We report two patients from Central Mexico, with ulcerated cutaneous lesions containing acid-fast bacilli (AFB) and ultimately diagnosed as Mycobacterium ulcerans disease. The first patient had a long history (11 years) of disease involving multiple lesions of both upper and lower extremities. Histopathological changes included necrosis of the subcutaneous tissue with large numbers of extracellular AFB. Cultures at 32 degrees C were "positive for mycobacteria," but were not further identified. The polymerase chain reaction for M. ulcerans performed on skin bopsies was positive. The lesions improved after treatment with rifampin and isoniazid (INH) for one month, followed by ethambutol and streptomycin. The second case followed trauma to the right hand, which spread over 2 years to the right upper extremity, the back, and both legs, with a loss of digits and metacarpal bones of the right hand. The histopathological findings were similar to the first case, including presence of AFB. PCR for M. ulcerans on extracts of skin biopsies was positive. Rifampin, INH, pyrazinamide, and levofloxacin resulted in marked improvement of the ulcer; ethambutol and streptomycin were later used, also. We report these cases because they are rare (approximately 6 previous cases were reported from Mexico), and both are unusually disseminated. They are significant in alerting the medical community to M. ulcerans infection, which is still active in Mexico, and the treatment used has not been reported previously.