BACKGROUND The impact of nutrient availability on the survival of Mycobacterium leprae and the development of leprosy remains largely unknown. Iron is essential for the survival and replication of pathogens, while vitamin D has been involved with pathogen elimination and immunoregulation. OBJECTIVES We evaluated the influence of dietary iron and vitamin D supplementation and restriction on the inflammatory response of mouse immune cells in vitro. METHODS After 30 days of standard or modified diets, peritoneal cells and splenocytes were stimulated with the alive microorganisms and sonicated antigens of M. leprae, respectively. The production of inflammatory cytokines, reactive oxygen species, and cell proliferation were evaluated. FINDINGS In peritoneal cells, vitamin D supplementation and iron restriction reduced the production of IL-6 and TNF in response to M. leprae, while splenocytes presented a reduction in TNF production under the same conditions. Lower levels of IFN-γ and TNF were observed in both iron-supplemented and iron-deficient splenocytes. Besides, iron supplementation also reduced the production of IL-6 and IL-10. No changes in the production of reactive oxygen species or in cell proliferation were observed related to different diets. MAIN CONCLUSIONS Taken together, these data point to an interference of the status of these nutrients on the interaction between the host and M. leprae, with the potential to interfere with the progression of leprosy. Our results highlight the impact of nutritional aspects on this neglected disease, which is significantly associated with unfavourable social conditions. unknown pathogens immunoregulation vitro 3 diets M respectively cytokines IL6 IL 6 IL- conditions IFNγ IFN γ ironsupplemented supplemented irondeficient deficient Besides IL10. IL10 10. 10 IL-10 together disease IL1 1 IL-1

Abstract Although communication capabilities are displayed by many vertebrate groups, some repertoires are poorly known, such as the case of xenarthrans, particularly armadillos, for which vocalization as a source of communicating to others remains poorly understood and relies on punctual reports of sounds. Here we provide the first description of a behavioral response associated with sound emission of two subjects of Dasypus novemcinctus. Both audio and visual registration was performed to subsequent analyses of expressed behaviors and emitted calls, which accounted for 76 vocalizations from a total of eight video recordings randomly collected from 2017 to 2019. Sound is acoustically characterized by both inhale and exhale phases composed of two vocal units, and no harmonic structure was observed. Once the subjects have always produced these vocalizations while cornered and exhibiting defensive behavior against another subject/human disturbance, these vocalizations were termed as distress. Subjects produced a hiss-purr-like sound while trying to avoid contact with another by bowing or lowering their bodies, humping, or even moving elsewhere when sound production ceased. This shows that the sound repertoire of armadillos is still to be unveiled and seems to be much more complex than previously thought.

BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

Resumo: O estudo teve como objetivos identificar o padrão de distribuição da hanseníase em um município brasileiro hiperendêmico e determinar a relação com o quadro clínico-epidemiológico ao longo de 11 anos. Os casos novos foram analisados com o sistema de informação geográfica, MapInfo, estatística scan espacial e índice Moran I. A base cartográfica digital foi usada para mapear os clusters de casos paucibacilares e multibacilares novos e casos em menores de 15 anos. Os indicadores socioeconômicos são mostrados através da técnica de mapeamento coroplético. Entre 2006 e 2010, foram observados uma redução no coeficiente de detecção, aumento no clusters espaciais de alto risco, mudanças marcantes na distribuição de clusters de alto e baixo risco e clusters de alto risco em menores de 15 anos, sugerindo doença recente, a presença de focos ativos e a sobreposição de clusters de alto risco para infecção multibacilar em menores de 15 anos. A hanseníase persiste enquanto problema de saúde pública em Rondonópolis, Mato Grosso; as áreas de alto risco exigem a intensificação de medidas de controle, além de estratégias de busca ativa para detectar casos novos.

Abstract: This study aimed to identify the distribution pattern of leprosy in a hyperendemic municipality in Brazil and determine its relationship with the clinico-epidemiological situation over 11 years. The geographic information system, MapInfo, spatial scan statistics and the Moran I index were used to analyze new cases. The digital cartographic base was used to map clusters of new paucibacillary and multibacillary cases and cases in minors under 15 years old. Socioeconomic indicators are shown using the choropleth mapping technique. A reduction in the detection coefficient, increases in high-risk spatial clusters, marked changes in the distribution of high-risk and low-risk clusters, and high-risk clusters of minors under 15 years old were observed from 2006 to 2010, showing recent illness, the presence of active foci, and overlapping of high-risk clusters of multibacillary infection in minors under 15 years old. Leprosy remains a public health problem in Rondonópolis, Mato Grosso State; the high-risk areas require an intensification of control measures and active search strategies to detect new cases.

Resumen: Este estudio tuvo como objetivo identificar la distribución de los patrones de lepra en una municipalidad hiperendémica en Brasil y determinar su relación con la situación clínico-epidemiológica durante 11 años. El sistema de información geográfica, MapInfo, estadísticas de escaneo espacial y el índice de Moran se usaron para analizar nuevos casos. La base cartográfica digital se usó para mapear clústeres de nuevos casos multibacilares y paucibacilares, así como casos en menores por debajo de 15 años de edad. Los indicadores socioeconómicos se presentan usando la técnica de mapeo de coropletas. La reducción en la detección del coeficiente, se incrementa en los clústeres de alto riesgo espaciales, asimismo, se observaron de 2006 a 2010 cambios considerables en la distribución de los clústeres de alto riesgo y bajo riesgo, así como en clústeres de alto riesgo con menores con menos de 15 años de edad, mostrando los casos de enfermedad reciente la presencia de focos activos, así como solapando clústeres de alto riesgo de infección multibacilar en menores por debajo de los 15 años de edad. La lepra continúa siendo un problema de salud pública en Rondonópolis, Mato Grosso; las áreas de alto riesgo necesitan una intensificación de las medidas de control y una búsqueda activa de estrategias, con el fin de detectar nuevos casos.

Resumo: O estudo teve como objetivos identificar o padrão de distribuição da hanseníase em um município brasileiro hiperendêmico e determinar a relação com o quadro clínico-epidemiológico ao longo de 11 anos. Os casos novos foram analisados com o sistema de informação geográfica, MapInfo, estatística scan espacial e índice Moran I. A base cartográfica digital foi usada para mapear os clusters de casos paucibacilares e multibacilares novos e casos em menores de 15 anos. Os indicadores socioeconômicos são mostrados através da técnica de mapeamento coroplético. Entre 2006 e 2010, foram observados uma redução no coeficiente de detecção, aumento no clusters espaciais de alto risco, mudanças marcantes na distribuição de clusters de alto e baixo risco e clusters de alto risco em menores de 15 anos, sugerindo doença recente, a presença de focos ativos e a sobreposição de clusters de alto risco para infecção multibacilar em menores de 15 anos. A hanseníase persiste enquanto problema de saúde pública em Rondonópolis, Mato Grosso; as áreas de alto risco exigem a intensificação de medidas de controle, além de estratégias de busca ativa para detectar casos novos.

Abstract: This study aimed to identify the distribution pattern of leprosy in a hyperendemic municipality in Brazil and determine its relationship with the clinico-epidemiological situation over 11 years. The geographic information system, MapInfo, spatial scan statistics and the Moran I index were used to analyze new cases. The digital cartographic base was used to map clusters of new paucibacillary and multibacillary cases and cases in minors under 15 years old. Socioeconomic indicators are shown using the choropleth mapping technique. A reduction in the detection coefficient, increases in high-risk spatial clusters, marked changes in the distribution of high-risk and low-risk clusters, and high-risk clusters of minors under 15 years old were observed from 2006 to 2010, showing recent illness, the presence of active foci, and overlapping of high-risk clusters of multibacillary infection in minors under 15 years old. Leprosy remains a public health problem in Rondonópolis, Mato Grosso State; the high-risk areas require an intensification of control measures and active search strategies to detect new cases.

Resumen: Este estudio tuvo como objetivo identificar la distribución de los patrones de lepra en una municipalidad hiperendémica en Brasil y determinar su relación con la situación clínico-epidemiológica durante 11 años. El sistema de información geográfica, MapInfo, estadísticas de escaneo espacial y el índice de Moran se usaron para analizar nuevos casos. La base cartográfica digital se usó para mapear clústeres de nuevos casos multibacilares y paucibacilares, así como casos en menores por debajo de 15 años de edad. Los indicadores socioeconómicos se presentan usando la técnica de mapeo de coropletas. La reducción en la detección del coeficiente, se incrementa en los clústeres de alto riesgo espaciales, asimismo, se observaron de 2006 a 2010 cambios considerables en la distribución de los clústeres de alto riesgo y bajo riesgo, así como en clústeres de alto riesgo con menores con menos de 15 años de edad, mostrando los casos de enfermedad reciente la presencia de focos activos, así como solapando clústeres de alto riesgo de infección multibacilar en menores por debajo de los 15 años de edad. La lepra continúa siendo un problema de salud pública en Rondonópolis, Mato Grosso; las áreas de alto riesgo necesitan una intensificación de las medidas de control y una búsqueda activa de estrategias, con el fin de detectar nuevos casos.

Abstract Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

Leprosy in children is correlated with community-level factors, including the recent presence of disease and active foci of transmission in the community. We performed clinical and serological examinations of 1,592 randomly selected school children (SC) in a cross-sectional study of eight hyperendemic municipalities in the Brazilian Amazon Region. Sixty-three (4%) SC, with a mean age of 13.3 years (standard deviation = 2.6), were diagnosed with leprosy and 777 (48.8%) were seropositive for anti-phenolic glycolipid-I (PGL-I). Additionally, we evaluated 256 house-hold contacts (HHCs) of the students diagnosed with leprosy; 24 (9.4%) HHC were also diagnosed with leprosy and 107 (41.8%) were seropositive. The seroprevalence of anti-PGL-I was significantly higher amongst girls, students from urban areas and students from public schools (p < 0.0001). Forty-five (71.4%) new cases detected amongst SC were classified as paucibacillary and 59 (93.6%) patients did not demonstrate any degree of physical disability at diagnosis. The results of this study suggest that there is a high rate of undiagnosed leprosy and subclinical infection amongst children in the Amazon Region. The advantages of school surveys in hyperendemic areas include identifying leprosy patients at an early stage when they show no physical disabilities, preventing the spread of the infection in the community and breaking the chain of transmission.

A doença de Jorge Lobo é micose cutânea e subcutânea que afeta pessoas na região Amazônica. O número de pacientes é relativamente pequeno, no entanto, a real prevalência da doença como problema de saúde pública é pouco conhecida. A doença de Jorge Lobo não é de notificação compulsória. Este estudo teve como objetivo determinar a prevalência, as áreas de ocorrência da doença de Jorge Lobo, além de sua evolução clínica. Um estudo retrospectivo foi desenvolvido com base na análise de prontuários de pacientes, incluindo documentação fotográfica dos mesmos, que foram atendidos no Departamento de Dermatologia Sanitária em Rio Branco e no interior do Estado. Foram registrados 249 casos em uma década em Rio Branco, 30 mulheres e 219 homens. Do total 153 apresentavam lesões localizadas, 94 lesões em apenas uma orelha, 55 lesões multifocais e 41 lesões disseminadas. A média de tempo entre o início dos sintomas e o diagnóstico foi de 19 anos. A média de idade no momento do diagnóstico foi de 53 anos, e as idades variaram de 14 a 96 anos.

Jorge Lobo's disease is a cutaneous and subcutaneous mycosis that affects patients in the Amazon region. The number of patients is relatively small, but the real situation of the disease as public health problem is not known, because Jorge Lobo's disease is not a notifiable disease. This study aims to report the clinical evolution in patients affected and to determine the prevalence and areas of occurrence of the disease. A retrospective study was carried out based on the analysis of the clinical records, which included a collection of photographs of patients in the Department of Sanitary Dermatology, in Rio Branco, and patients seen in the interior of the state. In a decade, in Rio Branco, 249 cases of the disease were reported, 30 were females and 219 males. Of these patients, 153 had localized lesions, 94 of them were on one ear, 55 had multifocal lesions and 41 had disseminated lesions. The average time between the onset of symptoms and diagnosis was 19 years. The average age at the time of diagnosis was 53 years, and ages ranged from 14 to 96 years.

Leprosy is still a worldwide public health problem. Brazil and India show the highest prevalence rates of the disease. Natural infection of armadillos Dasypus novemcinctus with Mycobacterium leprae has been reported in some regions of the United States. Identification of bacilli is difficult, particularly due to its inability to grow in vitro. The use of molecular tools represents a fast and sensitive alternative method for diagnosis of mycobacteriosis. In the present study, the diagnostic methods used were bacilloscopy, histopathology, microbiology, and PCR using specific primers for M. leprae repetitive sequences. PCR were performed using genomic DNA extracted from 138 samples of liver, spleen, lymph nodes, and skin of 44 D. novemcinctus, Euphractus sexcinctus, Cabassous unicinctus, and C. tatouay armadillos from the Middle Western region of the state of São Paulo and from the experimental station of Embrapa Pantanal, located in Pantanal da Nhecolândia of Mato Grosso do Sul state. Also, the molecular analysis of 19 samples from internal organs of other road killed species of wild animals, such as Nasua nasua (ring-tailed coati), Procyon cancrivoros (hand-skinned), Cerdocyon thous (dog-pity-bush), Cavia aperea (restless cavy), Didelphis albiventris (skunk), Sphigurrus spinosus (hedgehog), and Gallictis vittata (ferret) showed PCR negative data. None of the 157 analyzed samples had shown natural mycobacterial infection. Only the armadillo inoculated with material collected from untreated multibacillary leprosy patient presented PCR positive and its genomic sequencing revealed 100% identity with M. leprae. According to these preliminary studies, based on the used methodology, it is possible to conclude that wild mammals seem not to play an important role in the epidemiology of leprosy in the Middle Western region of the São Paulo state and in the Pantanal of Mato Grosso do Sul state.