Efficiency of rLb6H recombinant protein from Leishma-nia (Viannia) braziliensis for the detection of canine visceral leishmaniasis / Eficiência da proteína recombinante rLb6H de Leishmania (Viannia) brazi-liensis na detecção da leishmaniose visceral canina

Introduction: Visceral leishmaniasis (VL) is a serious endemic disease in many tropical and subtropical countries, with a strong incidence in Brazil. The disease is transmitted by the bite of infected female phlebotomine sandflies, with dogs being the main urban reservoirs of the parasite. The diverse clinical profile and the long incubation period are challenges for the diagnosis of canine visceral leishmaniasis (CVL). Recombinant proteins from Leishmania spp. have been studied as antigens that can increase the accuracy of serological tests. Objective: To evaluate the diagnostic performance of the recombinant protein rLb6H, from Leishmania braziliensis, in comparison to the reference antigens rK39 and rK28, from L. donovani, prioritizing the identification of subclinical infected dogs. Material and Methods: Serum IgG reactivity to rLb6H, rK28, and rK39 recombinant proteins was assessed in dogs with previously parasitological confirmation of CVL, subdivided according to their clinical status, using immunoenzymatic assay (ELISA). Diagnostic accuracy of each ELISA was evaluated by receiver operating characteristic (ROC) curve analysis. Results: While all antigens showed a better performance in detecting CVL in symptomatic dogs (SD), detection of CVL in the oligosymptomatic (OD) and asymptomatic (AD) groups was lower, but rLb6H achieved high sensitivity for asymptomatic CVL. Interestingly, the most reactive CVL samples to rK28 were barely detected by rLb6H, while the less reactive to rK28, mostly from the AD group, presented higher reactivity to rLb6H. Conclusion: The recombinant protein rLb6H showed utility in the detection of asymptomatic CVL, displaying a complementary reactivity to rK39 and rK28. Thus, these results suggest that rLb6H could be incorporated into multi-antigen strategies, to increase diagnostic accuracy of CVL.

Introdução: A leishmaniose visceral (LV) é uma doença endêmica grave em muitos países tropicais e subtropicais, tendo forte incidência no Brasil. A doença é transmitida pela picada de flebotomíneos fêmeas infectadas, sendo os cães os principais reservatórios urbanos do parasito. O perfil clínico diversificado e o longo período de incubação são desafios para o diagnóstico da leishmaniose visceral canina (LVC). Proteínas recombinantes de Leishmania spp. têm sido estudadas como antígenos que podem aumentar a precisão de testes sorológicos. Objetivo: Avaliar o desempenho diagnóstico da proteína recombinante rLb6H, de Leishmania braziliensis, em comparação com os antígenos de referência rK39 e rK28, de L. donovani, priorizando a identificação de cães com infecção subclínica. Material e Métodos: A reatividade de anticorpos IgG séricos às proteínas recombinantes rLb6H, rK28 e rK39 foi avaliada em cães com confirmação parasitológica prévia de LVC, subdivididos de acordo com seu quadro clínico, utilizando ensaio imunoenzimático (ELISA). A precisão diagnóstica de cada ELISA foi avaliada pela análise da curva ROC (receiver operating characteristic curve). Resultados: Enquanto todos os antígenos mostraram um melhor desempenho na detecção de CVL em cães sintomáticos (SD), a detecção de CVL nos grupos oligossintomáticos (OD) e assintomáticos (AD) foi menor, mas rLb6H alcançou alta sensibilidade para CVL assintomática. Curiosamente, as amostras de CVL mais reativas a rK28 foram pouco detectadas por rLb6H, enquanto as menos reativas a rK28, principalmente do grupo AD, apresentaram maior reatividade a rLb6H. Conclusão: A proteína recombinante rLb6H mostrou utilidade na detecção de CVL assintomática, apresentando uma reatividade complementar a rK39 e rK28. Assim, estes resultados sugerem que o rLb6H pode ser incorporado em estratégias multi-antígeno para aumentar a acurácia diagnóstica da leishmaniose visceral.

Bases para un tratamiento con hipertermia moderada en leishmaniosis cutánea / Bases for a treatment of cutaneous leishmaniasis with moderate hyperthermia

Resumen Introducción: La hipertermia regional entre 38 y 39.5 °C ha sido empleada para tratar procesos inflamatorios y, ocasionalmente, infecciones cutáneas. En zonas endémicas de leishmaniosis se aplican compresas calientes como tratamiento antiparasitario. Objetivo: Conocer las bases del tratamiento térmico de la leishmaniosis para regularlo adecuadamente. Métodos: Parásitos Leishmania mexicana cultivados in vitro fueron incubados por periodos variables de 37 °C y después a 25 °C.. Los parásitos se tiñeron con anexina V-FITC y yoduro de propidio para detectar inducción de apoptosis y su viabilidad. Se realizaron curvas de crecimiento postratamiento e identificación del ciclo celular con anticuerpos anticiclinas. Resultados: Después de 30 minutos de exposición a una temperatura de 37 °C, un porcentaje variable de parásitos perdieron su característica forma ovalada y se tornaron esféricos, sin refringencia y con núcleos condensados, cambios que sugirieron apoptosis, la cual fue confirmada mediante tinción con anexina V-FITC. La cantidad de parásitos en proceso de apoptosis fue proporcional al tiempo de exposición. Los parásitos en los que se observó apoptosis se tiñeron con anticuerpos anticiclinas. Conclusiones: La elevación constante, regulada y fisiológica de la temperatura por más de 30 minutos induce apoptosis de parásitos Leishmania mexicana cultivados in vitro, cuando se encuentran en fase activa en el ciclo celular.

Abstract Introduction: Regional hyperthermia at between 38 and 39.5 °C has been used to treat inflammatory processes and, occasionally, skin infections. In areas where leishmaniasis is endemic, hot compresses are applied as anti-parasitic treatment. Objective: To identify the bases of leishmaniasis thermal treatment in order to properly regulate it. Methods: In vitro-cultured Leishmania mexicana parasites were incubated for variable periods at 37 and then, to 25 °C. The parasites were then stained with Annexin V-FITC to detect apoptosis induction and with propidium iodide for viability. Post-treatment growth curves and cell cycle identification with anti-cyclin antibodies were performed. Results: After 30 minutes of exposure to a temperature of 37 °C, a variable proportion of parasites lost their characteristic oval shape and became spherical, without refringence and with condensed nuclei, with these changes suggesting apoptosis, which was confirmed by Annexin V-FITC staining. The number of parasites that underwent apoptosis was proportional to exposure time. Parasites in which apoptosis was observed were stained with anti-cyclin antibodies. Conclusions: Constant, regulated and physiological elevation of temperature for more than 30 minutes induces apoptosis of in vitro-cultured L. mexicana parasites when they are in an active phase of the cell cycle.

Guinea Pigs Naturally Infected by Leishmania enriettii: Clinical Analyses, Parasite Isolation and Identification

Abstract Leishmania enriettii has only been found in Curitiba metropolitan region, southern Brazil were it was first observed in Cavia porcellus from the vivarium of Instituto de Biologia e Pesquisas Tecnológicas (IBPT - today named TECPAR) by Medina, 1944. Despite more than a half century from its discovery and several research articles on this species, the natural clinical signs in guinea pigs and the parasite genetic variability is still unclear. The aims of this study were to describe the clinical features, investigate the potential wild reservoirs and, in addition, we intended to understand the polymorphism trait of the species. We analyzed 26 naturally infected guinea pigs from eight Paraná state cities. All animals showed lesions compatible with leishmaniosis, such as skin nodules or ulcers on body extremities. Direct examination of the lesion samples obtained by fine-needle aspiration or punch biopsy was conducted followed by isolation and identification of parasite DNA by random amplification of polymorphic DNA (RAPD)-PCR. Through the direct exam, a large number of intracellular amastigote forms were observed in the lesions. Different strains of the parasite, isolated from the 26 animals, were grouped in 5 clusters of approximately 65% similarity. We looked for L. enriettii in other potential reservoir hosts but the parasite was not observed. These results confirm that distinct strains of L. enriettii circulate in guinea pigs from Paraná state, more specifically in the Atlantic forest region, where we believe it serves as the center for dispersion of the species.

Molecular detection of Leishmania infantum in donkeys and mules under semiarid conditions in Brazil / Detecção molecular de Leishmania infantum em asininos e muares sob condições semiáridas

Abstract Visceral leishmaniasis is a parasitic zoonosis that mainly affects poorest and most vulnerable populations, and domestic dogs are considered to be the main source of infection to the vector and therefore humans. However, several studies have investigated the role of other vertebrate hosts in the disease cycle. In this context, the aim of the present study was to conduct a survey of Leishmania infantum infection in donkeys and mules living in a semiarid region of Brazil. Whole blood sampled from 72 equids (65 donkeys and 7 mules) was used to perform molecular diagnosis using the real-time polymerase chain reaction (qPCR) technique. A total of 25% of the samples (18/72) were positive through qPCR, but there were no significant differences between the species (donkeys or mules), sex (male or female) and abandonment situation of the animals (yes or no). Donkeys and mules living under semiarid conditions have high frequency of L. infantum infection. It is therefore worth assigning importance to these species in the epidemiological cycle of visceral leishmaniasis, either as potential reservoirs or just as an abundant food source for vectors.

Resumo A leishmaniose visceral é uma zoonose parasitária que afeta principalmente populações mais pobres e vulneráveis, e os cães domésticos são considerados as principais fontes de infecção para o vetor e, portanto, para os humanos. Porém diversos estudos têm pesquisado o papel de outros hospedeiros vertebrados no ciclo da doença. Neste contexto, objetivou-se realizar um levantamento da infecção por Leishmania infantum em asininos e muares, vivendo em região semiárida do Brasil. Foi utilizado sangue total de 72 equídeos (65 asininos e 7 muares) para a realização de diagnóstico molecular por meio da técnica de Reação em Cadeia de Polimerase em Tempo Real (qPCR). Um total de 25% das amostras (18/72) resultaram positivas na qPCR, porém não houve diferença significativa entre as espécies (asininos e muares), sexo (macho e fêmea) e situação de abandono dos animais (sim ou não). Asininos e muares, vivendo em condições semiáridas, apresentam alta frequência de infecção por L. infantum, sendo válido atribuir importância a essas espécies no ciclo epidemiológico da leishmaniose visceral, seja como um reservatório em potencial, seja apenas como uma fonte alimentar abundante para os vetores.

Spatial distribution of canine Leishmania infantum infection in a municipality with endemic human leishmaniasis in Eastern Bahia, Brazil / Distribuição espacial de infecção canina por Leishmania infantum em um município com leishmaniose humana endêmica no leste da Bahia, Brasil

Abstract Efforts to control a zoonotic disease such as visceral leishmaniasis (VL) caused by Leishmania infantum can be successful if they rely on comprehensive data on animal infection. In Bahia state, Brazil, human VL is endemic, yet some areas have no epidemiological data on canine L. infantum infection and canine leishmaniasis (CanL) to date. We aimed to perform an epidemiological study describing the spatial distribution and characterizing canine L. infantum infection in two districts of the municipality of Muritiba, where human cases have occurred. Brazilian official serodiagnostic protocol (ELISA and immunochromatographic tests), PCR and clinical examination were performed in 351 owned dogs. A seroprevalence of 15.7% (55/351) was found, and L. infantum identified in 88.8% (32/36) of PCR tested samples. Spatial distribution of positive dogs indicated infection in both urban and rural districts. There was no association between seropositivity and sex or breed, but dogs older than 2 years were 3.8 times more likely to be seropositive (95% CI 1.57 - 9.18) than younger dogs. Among seropositive dogs, 80% (44/55) had clinical manifestations of CanL: 75% (33/44) presented dermatopathy, 50% (22/44) emaciation, and 29.5% (13/44) ophthalmopathy. This is the first report on canine seroprevalence and natural L. infantum infection in Muritiba, Bahia.

Resumo O sucesso dos esforços para controlar uma doença zoonótica como a leishmaniose visceral (LV), causada por Leishmania infantum, depende de dados abrangentes sobre a infecção animal. Na Bahia, Brasil, embora a LV humana seja endêmica, diversos municípios, como Muritiba, ainda não dispõem de dados epidemiológicos sobre infecção por L. infantum e leishmaniose canina (LCan). Objetivou-se realizar um estudo epidemiológico para descrever a distribuição espacial e caracterizar a infecção canina por L. infantum em dois distritos de Muritiba, onde notificam-se casos humanos. Foi aplicado o protocolo sorodiagnóstico oficial brasileiro (ELISA e imunocromatografia), PCR e exame clínico em 351 cães domiciliados. Encontrou-se uma soroprevalência de 15,7% (55/351) e positividade de 88,8% (32/36) na PCR para L. infantum. A distribuição espacial dos cães positivos indicou infecção em ambos os distritos, urbano e rural. Não houve associação entre soropositividade e sexo ou raça, mas cães com idade acima de 2 anos foram 3,8 vezes mais soropositivos (IC 95% 1,57 - 9,18). Dentre os cães soropositivos, 80% (44/55) apresentavam manifestações clínicas de LCan: 75% (33/44) apresentavam dermatopatia; 50% (22/44) emagrecimento e 29,5% (13/44) oftalmopatia. Este é o primeiro estudo a determinar a soroprevalência e confirmar a circulação natural de L. infantum e LCan em cães de Muritiba.

Caracterización clínico epidemiológica de la leishmaniosis visceral infantil / Clinical epidemiological characterization of children visceral leishmaniasis

Introducción: La leishmaniosis visceral es la más grave de las formas clínicas de la leishmaniosis, afecta principalmente a los niños y es potencialmente fatal. Objetivo: Exponer la caracterización clínico-epidemiológica de la leishmaniosis visceral en población pediátrica y su respuesta terapéutica. Métodos: Se realizó un estudio retrospectivo, longitudinal y descriptivo en el Hospital Italiano, Ciudad de Djibouti en el período septiembre 2016-agosto 2017. El universo lo conformaron 166 menores de 15 años que ingresaron con diagnóstico de fiebre prolongada sin foco de localización, la muestra fue de 22 niños con diagnóstico confirmado de leishmaniosis visceral. La información se obtuvo de las historias clínicas. Se operacionalizaron 20 variables: sociodemográficas, clínicas, analíticas, terapéuticas y evolutivas. Se utilizó el procesador Epidat 3.1. Los resultados se expresaron en valores absolutos y porcentajes. Resultados: Se diagnosticó leishmaniosis visceral en 13,2 por ciento de niños hospitalizados por fiebre prolongada, 90,9 por ciento de procedencia rural y 59,1 por ciento desnutridos. El 77,3 por ciento de los casos recibió antimoniales, 90,9 por ciento tuvo estadía hospitalaria mayor de 21 días y el 36,4 por ciento se complicó con neumonía. Conclusiones: La leishmaniosis visceral es una entidad relativamente frecuente en niños admitidos por fiebre prolongada en el Hospital Italiano, predominan los varones desnutridos, mayores de cinco años de edad, procedentes de zonas rurales. La fiebre y la esplenomegalia son manifestaciones clínicas constantes, la anemia y la leucopenia los principales hallazgos de laboratorio. La aplicación de antimoniales es el tratamiento electivo, con larga estadía hospitalaria y la neumonía es la complicación más frecuente(AU)

Introduction: Visceral leishmaniasis is the most severe clinical form of leishmaniasis that mainly affects children and is potentially fatal. Objective: To explain the clinical-epidemiological characterization of visceral leishmaniasis in the pediatric population and its therapeutic response. Methods: It was conducted a retrospective, longitudinal and descriptive study in the Italian Hospital, Djibouti City in the period from September 2016 to August 2017. The sample group was formed by 166 children under 15 years old that were admitted with a diagnosis of prolonged fever without localization focus and the sample was of 22 children with confirmed diagnosis of visceral leishmaniasis. The information was obtained from the clinical records. Twenty variables were operationalized: sociodemographic, clinical, analytical, therapeutic and evolutive ones. Epidat 3.1 proccessor was used. The results were expressed in absolute values and percentages. Results: Visceral leishmaniasis was diagnosed in 13.2 percent children that were admitted in hospital due to prolonged fever, 90.9 percent of them were from rural areas and 59.1 percent were undernourished. 77,3 percent of the cases had antimonial treatment, 90.9 percent had hospital stay for more than 21 days and the 36.4 percent had complications due to pneumonia. Conclusions: Visceral leishmaniasis is a relatively frequent entity in children admitted in the Italian Hospital due to prolonged fever with a predominance of undernourished males, older that five years and from rural areas. Fever and splenomegaly are constant clinical manifestations, and anemia and leucopenia are the main laboratory findings. The use of antimonials is the election treatment with long hospital stay, and pneumonia is the most frequent complication(AU)

TERAPIA LARVAL CON Musca domestica EN EL TRATAMIENTO DE LA ÚLCERA LEISHMÁNICA EN UN MODELO MURINO / Larval therapy with Musca domestica in the treatment of leishmanian ulcer in a murine model

RESUMEN La leishmaniosis es una enfermedad con gran impacto en salud pública dado a las características de las lesiones tegumentarias. El tratamiento experimental con terapia larval (TL) ha mostrado su uso potencial para la cura de la leishmaniosis, sin embargo, se han utilizado especies de moscas para TL en heridas causadas por Leishmanial que no son de fácil colecta y cultivo bajo condiciones de laboratorio como Lucilia sericata o Calliphora vicina. El objetivo del presente trabajo fue usar una especie de mosca de fácil colecta, y de alta fecundidad como la Musca domestica para aplicarlas en TL de úlceras leishmánicas. Se realizó un estudio cuali-cuantitativo, de tipo descriptivo, mediante un diseño experimental empleado un modelo animal (Mesocricetus auratus), infectado con Leishmania amazonensis para evaluar el efecto terapéutico de la TL y comparar los resultados con el tratamiento químico antimonial de la droga experimental "Ulamina". Se evidencia cicatrización y cura de la úlcera leishmánica en el 66,66 % de los animales tratados con TL en aplicación simple y del 100 % en TL combinada con Ulamina. El uso combinado de TL+Ulamina, muestra un efecto potenciador de la cura clínica de las úlceras, pero con persistente inflamación. Se observó una efectividad óptima de la TL con M. domestica, sobre las úlceras, aunque no se evidenció un efecto sobre L. amazonensis dado a la presencia de amastigotes en los frotis y a los amplicones obtenidos de 480 bp desde las improntas de los animales.

ABSTRACT Leishmaniasis is a disease with significant impact on public health, given the characteristics of the tegumentary lesions. Experimental treatment with larval therapy (LT) has shown its potential use for the cure of leishmaniosis. However, fly species not easy to collect and/or colonize have been used. The objective of the present work was to use a fly of accessible collection and high fecundity, not a producer of human myiasis, such as Musca domestica. A qualitative-quantitative study of a descriptive type was carried out through an experimental design with an animal model (Mesocricetus auratus) with infection by Leishmania amazonensis to evaluate the therapeutic effect of LT and compare the results with the antimonial chemical treatment of the drug experimental "Ulamina". Scarring were observed with the use of LT in 66.66 % with TL-simple and 100 % with TL-combined. However, the combined use of LT + Ulamina, shows an enhancing effect of the clinical cure of the lesions, but with persistent inflammation. Optimal effectiveness of TL with M. domestica was observed on the ulcers; however, an effect on L. amazonensis was not observed given the presence of amastigotes in the smears and the 480 bp amplicons from the tissue of the ulcers of animals.

Cytological and molecular detection of Leishmania spp. in different biological tissues of dogs in areas endemic for visceral leishmaniasis / Detecção citológica e molecular de Leishmania spp. em diferentes amostras biológicas de cães em áreas endêmicas para leishmaniose visceral

Devido à ampla distribuição da leishmaniose visceral (LV) no Brasil e à importância dos cães no ciclo de transmissão dessa zoonose, o presente estudo teve como objetivo avaliar a ocorrência de Leishmania spp. e caracterizar a espécie circulante em diferentes tecidos biológicos de cães da Baixada Cuiabana, Mato Grosso, Brasil. Amostras de sangue, linfonodo e medula óssea foram coletadas de 205 cães para realização de análise parasitológica por citologia e análise molecular por meio da nested PCR (nPCR) e do sequenciamento . Dos 205 cães estudados, 34 (16,58%) animais foram positivos pela nPCR, dos quais 12 possuíam formas amastigotas de Leishmania spp. na citologia. Amostras positivas na nPCR foram sequenciadas e caracterizadas como Leishmania (Leishmania) infantum. A sensibilidade da nPCR nas amostras de medula óssea, linfonodo e sangue foi de 94,87%, 91,8% e 98%, respectivamente, enquanto a especificidade foi de 100% para todas as amostras. O presente estudo relata a ocorrência de LV canina em 16,58% dos cães analisados, caracterizando a L. infantum como agente causador. Entre as amostras avaliadas, a medula óssea foi a única a apresentar concordância substancial entre as técnicas de nPCR e citologia (k = 0,643), sendo considerada a amostra mais adequada para o diagnóstico da doença. Os resultados ampliam o conhecimento de espécies de Leishmania infectando cães no Brasil, destacando a importância da identificação etiológica em áreas com escassos dados moleculares.(AU)

La impronta como método no invasivo de toma de muestra para el diagnóstico molecular de la leishmaniosis cutánea en población militar de colombia / The imprint as a non-invasive method of sampling for the molecular diagnosis of cutaneous leishmaniasis in colombia's military population / In print como método não invasivo de coleta de amostra para o diagnóstico molecular da leishmaniose cutânea em população militar da colômbia

Resumen Teniendo en cuenta que los métodos tradicionales de toma de muestra y diagnóstico para la leishmaniosis cutánea presentan limitaciones, como el frotis directo, cuya sensibilidad depende de la pericia del profesional, el aspirado de lesión que puede ser usado para detección de parásitos en lámina, su ADN o para cultivos es demorado y exigente, y la biopsia de la lesión que es invasiva y dolorosa se comparó con el método de impronta en papel filtro de la lesión ulcerativa contra el método tradicional de aspirado mediante la técnica de POR convencional utilizando como blanco una región del ADN del kinetoplasto del parásito. En el presente trabajo, la por obtuvo una sensibilidad para impronta del 90,07% comparado con el aspirado, el 86,3%, que, además, por ser un método de toma de muestra no invasivo, con pocas exigencias para el transporte, se puede tomar directamente en el área de operaciones a muy bajo costo, resulta ser beneficioso para ser usado en los pacientes con leishmaniosis cutánea del Ejército Nacional de Colombia, que se encuentran en las diferentes áreas de operaciones.

Abstract Taking into account that the traditional methods of sampling and diagnosis for cutaneous leishmaniasis , have limitations, such as direct smear, whose sensitivity depends on the professional's expertise, the lesion aspiration that can be used to detect parasites in the lamina, DNA or cultures takes a long time and is demanding, and the biopsy of the lesion that is invasive and painful were compared with the imprinting method on the filter paper of the ulcerative lesion against the traditional method of aspiration by means of the conventional PCR technique using as a target a DNA region of the parasite kinetoplast. In this present work, PCR obtained an imprinting sensitivity of 90.07% compared to the aspirate of 86.3%, which, besides being a non-invasive sampling method, with few transport requirements, it can be taken directly in the area of operations at a very low cost, which turns out to be beneficial to be used in patients with cutaneous leishmaniasis of the National Army of Colombia, who are in different operations areas.

Resumo Considerando que os métodos tradicionais de coleta de amostra e diagnóstico para a leishmaniose cutânea apresentam limitações, como exame direto de esfregaços, cuja sensibilidade depende da perícia do profissional, o raspado de lesão que pode ser usado para a detecção de parasitas em lâmina, seu DNA ou para culturas é demorado e exigente, e a biopsia da lesão que é invasiva e dolorosa, comparou-se com o método in print em papel filtro da lesão ulcerativa contra o método tradicional de aspirado mediante a técnica de PCR convencional utilizando como alvo uma região do DNA do cinetoplasto do parasita. No presente trabalho, a PCR obteve uma sensibilidade para in print de 90,07% comparado com o aspirado, 86,3%, que, além disso, por ser um método de coleta de amostra não invasivo, com poucas exigências para o transporte, pode ser coletado diretamente na área de operações a muito baixo custo, resulta ser benéfico para ser usado nos pacientes com leishmaniose cutânea do Exército Nacional da Colômbia, que se encontram nas diferentes áreas de operações.

Carcinoma basocelular de piel y diagnóstico diferencial de leishmaniosis mucocutánea / Basal cell carcinoma of the skin and differential diagnosis mucocutaneous leishmaniasis

Contexto: la leishmaniosis es una enfermedad parasitaria causada por veinte especies diferentes del protozoario Leishmania y transmitida al hombre por la picadura del mosquito hembra del género Phlebotomine. Las manifestaciones clínicas son variables y se relacionan con la especie infestante, su relación con el medio ambiente y respuesta inmune del hospedero. La leishmaniosis cutánea (LC) y mucocutánea (LMC) afecta a piel y mucosas de vías respiratorias superiores; está presente en Latinoamérica donde es producida principalmente por la especie Leishmania (Viannia) braziliensis. Los signos iniciales son eritema y ulceraciones a nivel de orificios nasales seguido por inflamación destructiva que puede extenderse hasta afectar el septo nasal y en algunos casos faringe o laringe, desfigurando gravemente el rostro y comprometer la vida del paciente. Presentación de caso: se presenta el caso de un hombre de 90 años de edad, procedente del noroccidente de la Provincia de Pichincha; exhibe varias lesiones ulcerativas localizadas a nivel del puente nasal derecho, ángulo interno del ojo derecho y mejilla homolateral, cubriendo un área aproximada de 4 cm de diámetro. Inicialmente se sospechó de LMC y se aplicaron varias dosis de antimonio pentavalente (Glucantime©). Se realizaron exámenes diagnósticos para leishmaniosis (frotis, cultivo y prueba cutánea de Montenegro) los cuales resultaron negativos. El estudio histopatológico determinó que se trataba de un carcinoma basocelular de piel (CBC). Conclusiones: en zonas endémicas de LC y LMC, es necesario realizar un adecuado diagnóstico diferencial con otras patologías que causan lesiones ulcerativas, entre las que se incluye el carcinoma basocelular de piel, evitando administrar antimonio pentavalente de manera indiscriminada.

Context: Leishmaniasis is a parasitic disease caused by twenty different species of the Leishmania protozoan and transmitted to man by the bite of the female mosquito of the genus Phle- botomine. The clinical manifestations are variable and are related to the infestant species, its relationship with the environment and the host's immune response. Cutaneous and mucocutaneous (LMC) leishmaniasis affects the skin and mucous membranes of the upper respiratory tract; It is present in Latin America where it is mainly produced by the species Leishmania (Viannia) braziliensis. The initial signs are erythema and ulcerations at the level of nostrils followed by destructive inflammation that can extend to affect the nasal septum and in some cases pharynx or larynx, seriously disfiguring the face and compromising the patient's life. Case presentation: The case of a 90-year-old man from the northwest of the Pichincha Province is presented; It presents several ulcerative lesions located at the level of the right nasal bridge, internal angle of the right eye and homolateral cheek, covering an area approximately 4 cm in diameter. Initially, CML was suspected and several doses of pentavalent antimony (Glucantime©) were applied. Diagnostic tests were performed for leishmaniasis (smear, culture and skin test of Montenegro) which were negative. The histopathological study determined that it was a basal cell carcinoma of the skin (CBC). Conclusions: In endemic areas of LC and CML, it is necessary to make an adequate differential diagnosis with other pathologies that cause ulcerative lesions, including basal cell carcinoma of the skin, avoiding administering pentavalent antimony indiscriminately.

La leishmaniosis cutánea en Costa Rica: prevención, diagnóstico y tratamiento / Cutaneous leishmaniasis in Costa Rica: prevention, diagnosis and treatment

Resumen El objetivo de esta investigación fue describir el estado actual de la leishmaniosis en Costa Rica, profundizar en las diferentes manifestaciones clínicas y en las especies identificadas a la fecha causantes de la enfermedad, para recomendar tratamientos de acuerdo con estas, así como describir su comportamiento epidemiológico con el propósito de recomendar estrategias de prevención y control en los grupos identificados. Como fuentes de información se utilizaron la base de datos del Registro Colectivo del Ministerio de Salud de Costa Rica, de 2011 a 2016 y las estimaciones de población del Instituto Nacional de Estadísticas y Censos. La incidencia promedio de leishmaniosis en el trienio 2005-07 fue de 35,5 casos por 100 000 y pasó a 30,5 en el trienio 2014-16. Los grupos más afectados fueron los menores de 15 años con: 44,42 casos por cien mil. En San Ramón, Guatuso, Turrialba y Talamanca las tasas de incidencia superan la tasa de incidencia promedio.

Abstract The purpose of the present research was to describe the different species of Leishmania sp. in Costa Rica so as to recommend specific treatment; also, we wish to describe the epidemiological behavior of the different species in order to suggest prevention and control strategies. Our sources were Collective Registry Data of the Ministry of Health estimates (2011 to 2016) and population data from the National Institute of Statistics and the Census. The average incidence rate from 2005 through 2007 was 35.5 cases per 100,000; the rate went down to 30.5 during the years 2011 through 2016. The most affected age group were those younger than 15 years with a rate of 44.42 per 100,000. Since 2005, the areas in which incidence rates are higher than the average national incidence rate are: San Ramón, Guatuso, Turrialba and Talamanca. Management must be carried out according to: the identified species of the parasite and also according to the experience of experts in Costa Rica. Prevention must be directed to the identified risk groups.

Respuesta doméstica a las recomendaciones sanitarias de intervención sobre ambiente y perros en una localidad con transmisión de leishmaniasis visceral (Pto. Iguazú, Argentina, 2014­2016) / Domestic response to intervention based on health recommendations on the environment and dogs in a locality with transmission of visceral leishmaniosis (Pto. Iguazú, Argentina, 2014-2016)

Introducción: La leishmaniasis visceral (LV) es una enfermedad parasitaria emergente en Argentina. En Puerto Iguazú, frontera con Brasil y Paraguay, en 2010 se registró presencia del vector y casos caninos; y en 2014-2015 dos casos humanos. Objetivo: Este artículo tiene como objetivo analizar los cambios en el nivel micro escala después de dar a conocer a los convivientes el diagnóstico de LV canina (LVC), informándoles estrategias de manejo ambiental para reducir el contacto con el vector. Método: Es una investigación descriptiva, que indagó en dos momentos (2014 y 2016) una muestra no probabilística distribuida en base al criterio de mejor escenario para la presencia del vector (n = 55) en la que se seleccionaron, luego de un primer rastrillaje entomológico y de diagnóstico veterinario, puntos de muestreo con presencia de vectores y al menos un perro con LVC (n = 6/55). Resultados: Un único hogar implementó las modificaciones sugeridas. Esos cambios no resultaron suficientes para controlar la transmisión. La hipótesis es que las medidas de control requieren intervención a meso escala (el vecindario y no el domicilio), atendiendo al radio real de dispersión de vectores. Conclusiones: El riesgo de infección humana por LV se relaciona con el modo de vida, incluyendo las relaciones interespecie. Las relaciones humano-perro combinan especismo y poshumanismo, acotando la efectividad de la "tenencia responsable" como modelo de vínculo saludable.

Introduction: Visceral leishmaniasis (VL) is an emerging parasitic disease in Argentina. In Puerto Iguazú, border with Brazil and Paraguay, vector and canine cases were registered in 2010; and in 2014 and 2015 there were two human cases. Objective: The objective of this article is to analyze changes at the micro-scale level after informing the cohabitants of the diagnosis of canine LV (LVC), letting them know the environmental management strategies to reduce contact with the vector. Method: It is a descriptive researh, which investigated in two moments (2014 and 2016) a non-probabilistic sample distributed based on the criterion of the best scenario for the presence of the vector (n = 55). Sampling points with the presence of vectors and at least one dog with LVC (n = 6/55) were selected, after a first entomological and veterinary diagnosis raking. Results: A single household implemented the suggested modifications. The changes were not enough to control the transmission. The hypothesis is that the control measures require intervention at a meso-scale (the neighborhood instead of the home), taking into account the real radius of vector dispersion. Conclusions: The risk of human infection due to VL is related to the way of life, including interspecies relationships. The human-dog relationships combine speciesism and post-humanism, which limits the effectiveness of "responsible ownership" as model of a healthy bond.

Pertinencia intercultural de la atención en salud. El camino a seguir en Leishmaniosis Tegumentaria Americana / Intercultural relevance of health care. The way to follow in American Tegumentary Leishmaniosis

La Leishmaniosis tegumentaria americana (LTA) es considerada un problema de salud pública por su elevada incidencia. Además, es una patología abordada en muchos países a través de programas sanitarios con estructura vertical, sin contacto social y sin considerar la cultura de los grupos poblacionales, a sabiendas que existen diferencias en cuanto a ésta en el tratamiento de la enfermedad. El objetivo es la descripción y análisis de la pertinencia cultural del proceso de atención en salud en el caso de LTA, con base en la revisión bibliográfica de literatura científica sobre esta patología y sobre el papel de la cultura sobre la misma como aporte de ideas y de conocimientos para el debate necesario en el diseño de políticas y programas sanitarios de control de patologías parasitarias.(AU)

American tegumentary Leishmaniasis (LTA) is considered a public health problem because of its high incidence. In addition, it is a pathology addressed in many countries through health programs with vertical structure, without social contact and without considering the culture of the population groups, knowing that there are differences in the treatment of the disease. The objective is the description and analysis of the cultural relevance of the health care process in the case of LTA, based on the bibliographical review of scientific literature on this pathology and on the role of culture in the same as contribution of ideas and of knowledge for the necessary debate in the design of health policies and programs to control parasitic diseases.(AU)

Situación epidemiológica de las leishmaniosis y percepción de actores claves en el departamento de alto Paraná, Paraguay / Epidemiological situation of leishmaniasis and perception of key actors in the department of alto Paraná, Paraguay

Las leishmaniosis cutánea y mucocutánea son endémicas en el departamento de Alto Paraná. En los últimos años ha disminuido el número de casos y se han diagnosticado los primeros pacientes y perros positivos con leishmaniosis visceral. Con el objetivo de describir la situación actual de las leishmaniosis en este departamento e identificar la percepción de actores políticos, agentes del sistema de salud e informantes claves de la comunidad en relación a diferentes formas de la enfermedad, se realizó una revisión documental sobre el control, diagnóstico y tratamiento, además de un estudio exploratorio observacional, descriptivo y cualitativo con los entrevistados. En zonas urbanas conocían la enfermedad en todas sus formas, no así en zonas rurales, donde los funcionarios jóvenes de salud, no identificaron signos ni síntomas debido a la alta rotación, mientras que la capacitación en las veterinarias a nivel rural es limitada. El SENEPA trabaja en coordinación con las municipalidades y las Unidades de Salud Familiar. El diagnóstico está centralizado en los Centros de Salud y en el Hospital Regional de Ciudad del Este, donde se reciben los medicamentos por parte del Programa para el tratamiento. Las Unidades de Salud Familiar no poseen laboratorios y no disponen de fichas ni de insumos para el diagnóstico y tratamiento. La principal dificultad para el tratamiento es su discontinuidad y las dificultades económicas de la población para trasladarse a la ciudad, lo que dificulta el acceso a exámenes de laboratorio u otros estudios diagnósticos que sólo ahí se brindan.

Cutaneous and mucocutaneous leishmaniases are endemic in the department of AltoParaná. In recent years, the number of cases has decreased and the first patients andpositive dogs with visceral leishmaniasis have been diagnosed. In order to describe thecurrent situation of leishmaniasis in this department and to identify the perception ofpolitical actors, agents of the health system and key community informants in relation todifferent forms of the disease, a documentary review about the control, diagnosis and treatment was performed. An exploratory, observational, descriptive and qualitative studywith the interviewees was also carried out. In urban areas they knew the disease in all itsforms, but not in rural areas, where young health officials did not identify signs orsymptoms due to their high turnover while training in veterinary medicine at the rural levelis limited. SENEPA works in coordination with the municipalities and the Family Health Units. The diagnosis is centralized in the Health Centers and in the Regional Hospital of Ciudad delEste, where medicines are received from the Treatment Program. The Family Health Unitsdo not have laboratories and do not have supplies for diagnosis and treatment. The maincomplication for treatment is the discontinuity and the economic problems of the populationto move to the city, making difficult the access to laboratory tests or other diagnosticstudies that are only available there.

Estudio de factores de riesgo para transmisión de leishmaniosis cutánea americana en una área endémica de la Provincia de Pichincha / Study of risk factors for transmission of American cutaneous leishmaniasis in an endemic area of ​​the Province of Pichincha

Contexto: En Ecuador, la leishmaniosis cutánea americana se reporta en 20 de 22 provincias, con una incidencia anual de 3.000 a 4.500 casos. En la Provincia de Pichincha, esta forma clínica de leishmaniosis se ha expandido a las zonas tropicales del noroeste y el conocimiento epidemiológico es exiguo. Objetivos: investigar el perfil epidemiológico y factores de riesgo de leishmaniosis cutánea americana. Material y métodos: el estudio efectuado en la Provincia de Pichincha vinculó a 1081 individuos mediante la aplicación de una encuesta con variables epidemiológicas relacionadas al parásito, evaluación de actitudes, conocimientos y prácticas de la población sobre la enfermedad. Resultados: el 15,7% de los encuestados sufrieron leishmaniosis cutánea americana en el pasado. Se observó la presencia de cánidos (56,4%) y aves de corral (37%) en las inmediaciones de las viviendas. La recolección de basura beneficia al 86,7% de inmuebles, donde el 87,7% de habitantes permanecen entre 18 a 22 horas diarias. El 51,9% de encuestados usan habitualmente insecticidas para el control de vectores. El 70,4% conocen sobre la leishmaniosis cutánea americana y el 25,6% saben cómo prevenirla mediante control químico (12%), control físico (18,9%), limpieza peridomiciliaria (11,7%) y selección adecuada del sitio para edificar viviendas distantes de vegetaciones (2,2%). Conclusión: es mandatorio iniciar campañas educativas para mejorar conocimientos, actitudes y prácticas sobre prevención. (AU)

Context: In Ecuador, American cutaneous leishmaniasis is reported in 20 of 22 provinces, with an annual incidence of 3,000 to 4,500 cases. In the Province of Pichincha, this clinical form of leishmaniasis has spread to the tropical zones of the northwest and the epidemiological knowledge is meager. Objective: to investigate the epidemiological profile and risk factors of American cutaneous leishmaniasis. Material and methods: The study carried out in the Province of Pichincha involved 1081 individuals, through the application of a survey with epidemiological variables related to the parasite, evaluation of attitudes, knowledge and practices of the population about the disease. Results: 15.7% of the respondents suffered from American cutaneous leishmaniasis in the past. The presence of canids (56.4%) and poultry (37%) were observed in the immediate vicinity of the dwellings. Garbage collection benefits 86.7% of properties, where 87.7% of inhabitants remain between 18 to 22 hours a day. 51.9% of respondents routinely use insecticides for vector control. 70.4% know about American cutaneous leishmaniasis and 25.6% know how to prevent it by chemical control (12%), physical control (18.9%), peridomiciliary cleaning (11.7%) and adequate site selection to build houses far from vegetation (2.2%). Conclusion: It is mandatory to initiate educational campaigns to improve knowledge, attitudes and prevention practices. (AU)

Rol del Consultorio de Leishmaniosis en las investigaciones del IICS / Leishmaniasis Consulting Room at the IICS: its role in research

La leishmaniosis tegumentaria es una enfermedad desatendida y descontrolada que afecta a sectores sensibles de la población. El IICS, a través de este consultorio especializado, brinda los servicios de establecer el diagnóstico y acompañar el tratamiento de los casos que se presentan, así como de realizar seguimiento de los casos curados. Esta labor aporta permanentemente datos y suscita discusiones científicas que se convierten en fuentes de trabajos de investigación para la Institución. Y estamos hablando de una enfermedad con bastantes aspectos aún desconocidos, que amerita ser estudiada con prioridad en nuestro país

Tegumentary leishmaniasis is a neglected and uncontrolled disease affecting sensitive sectors of the population. The IICS, through this specialized practice, provides the services of establishing the diagnosis and to accompany the treatment of the cases presented, as well as to follow up the cured cases. This work provides data permanently and raises scientific discussions that become sources of research to the institution. And we are talking about a disease with many still unknown aspects that deserve to be studied with priority in our country.

Avaliação de estratégia de organização de serviços de saúde para prevenção e controle da leishmaniose visceral / Evaluation of the organization of health services as a strategy for the prevention and control of visceral leishmaniasis / Evaluación de la organización de los servicios de salud como estrategia para la prevención y control de la leishmaniosis visceral en Brasil

OBJETIVO: avaliar a estratégia de organização de serviços de saúde para prevenção e controle da leishmaniose visceral (LV) em Ribeirão das Neves, Minas Gerais, Brasil, de 2010 a 2012. MÉTODOS: pesquisa avaliativa de tipo estudo de caso, sobre o grau de implantação de uma estratégia voltada à integração dos serviços de assistência, controle de zoonoses e vigilância epidemiológica; consistiu de observação do processo de trabalho, entrevistas com profissionais e análise de dados secundários dos sistemas de informações. RESULTADOS: a implantação mostrou-se parcialmente adequada (84%); na estrutura, o fator de recursos humanos obteve a pior avaliação (64%), e no processo, a reorganização da assistência (80%) e da vigilância (77%); no período 2010-2012, houve aumento de 20% nas notificações de casos de LV e redução de 20% no intervalo entre notificação e início do tratamento. CONCLUSÃO: a estratégia contribuiu para a melhoria da organização das ações de prevenção e controle da LV.

OBJECTIVE: to evaluate the organization of health services as a strategy for the prevention and control of visceral leishmaniasis (VL) in Ribeirão das Neves, Minas Gerais, Brazil, from 2010 to 2012. METHODS: this was a case study evaluation of the degree of implementation of a strategy for the integration of health care services, control of zoonosis and epidemiological surveillance; it consisted of observing the work process, interviewing health professionals and analysing secondary data from information systems. RESULTS: implementation was partially adequate (84%); in terms of structure, the human resources component had the worst evaluation (64%) whilst in terms of work process, evaluation was 80% for reorganization of care and 77% for surveillance; in the period 2010-2012 there was a 20% increase in reported cases of VL and a 20% reduction in the time interval between reporting a case and starting treatment. CONCLUSION: the strategy contributed to the improvement of the organization of VL prevention and control actions.

OBJETIVO: evaluar la estrategia de organización de servicios de salud para la prevención y control de leishmaniosis visceral (LV) en Ribeirão das Neves, Minas Gerais, Brasil, 2010-2012. MÉTODOS: estudio de caso sobre el grado de implantación de la estructura y el proceso de estrategia centrada en la integración de los servicios de atención en salud, el control de zoonosis y vigilancia epidemiológica; se realizó la observación del proceso de trabajo, entrevistas con profesionales y análisis de datos secundarios de sistemas de información. RESULTADOS: la implementación se mostró parcialmente adecuado (84%); en la estructura, el componente recursos humanos obtuvo la peor puntuación (64%) y en el proceso, la reorganización de la atención (80%) y vigilancia (77%); en el periodo 2010-2012 hubo un aumento (20%) de casos reportados de LV y una reducción (20%) del intervalo de tiempo entre notificaciones e inicio de tratamiento. CONCLUSIÓN: la estrategia contribuyo con la mejora en la organización de las accionesde prevencio y control de la LV.

A probable hybrid female Psychodopygus sp. (Diptera, Psychodidae, Phlebotominae) specimen from Amazonas State, Brazil / Un híbrido probable en una hembra Psychodopygus sp. (Diptera, Psychodidae, Phlebotominae) en el estado de Amazonas, Brasil

Phlebotomine sand flies are vectors of several important etiological agents. Sand fly cibaria and genitalia exhibit morphological characters that are essential for species identification. A morphologically anomalous female sand fly of the subgenus Psychodopygus Mangabeira was found in a faunistic survey of a forested area near Manaus, Amazonas State, Brazil. This specimen possesses two pairs of spermathecae and a cibarium with supernumerary rows of teeth. Most morphological anomalies in sand flies occur in the number and arrangement of spines in structures associated with the male genitalia. In females, the number of cibarial teeth is the most common form of anomaly. The specimen described here constitutes a rare anomalous record.

Los flebótomos son importantes vectores de varios agentes etiológicos. En flebótomos, los caracteres morfológicos del cibario y la genitália, son esenciales para la correcta identificación de las especies. Una hembra morfológicamente anómala del subgénero Psychodopygus Mangabeira, fue encontrada en un levantamiento faunístico en un área de bosque cerca de Manaus, estado de Amazonas, Brasil. Este espécime tiene dos pares de espermatecas y un cibario como hileras de dientes supranumerários. La mayoria de las anomalías morfológicas en los flebótomos ocurre en el número y disposición de las espinas en las estruturas de la genitália masculina. En las hembras, el número de dientes del cibario es la forma mas común de anomalía. El espécimen aqui descrito constituye un raro registro de anomalía.

Vacunas contra Leishmania / As vacinas contra Leishmania / Vaccines against Leishmania

La leishmaniosis, una enfermedad parasitaria de amplia distribución mundial y endémica en muchas regiones, plantea un gran reto al control epidemiológico debido, por un lado, a la toxicidad cada vez mayor de la quimioterapia y a la resistencia a la misma, y por el otro, a que el control del vector se ha tornado extremadamente difícil porque el insecto se ha generalizado y adaptado a múltiples y diferentes microambientes; de allí que se le dé alta prioridad al desarrollo de estrategias profilácticas costo-efectivas para prevenirla, porque la población más afectada vive en países con economías débiles. El objetivo de esta revisión fue actualizar lo hecho en estrategias de vacunación contra Leishmania. Se resume dicha información para guiar a los profesionales de la salud sobre el adecuado proceder en el control de tan importante endemia mundial...

Leishmaniosis, a parasitic disease of worldwide distribution and endemic in many regions, poses a challenge to epidemiological control due, on the one hand, to the increased toxicity of chemotherapy and resistance to it and, on the other, to the fact that vector control has become extremely difficult because the insect is widespread and has adapted to many different microenvironments. Hence, the high priority given to develop prophylactic measures to prevent this disease, that are cost-effective because the affected population lives mostly in countries with weak economies. The subject of this review was to update what is being done in vaccination strategies against Leishmania. We summarize the information in order to guide health professionals in the adequate control of this important worldwide endemic disease...

A leishmaniose, uma doença parasitária amplamente espalhada por todo o mundo, e endêmica em varias regiões, representa um grande desafio para o controle epidemiológico devido, por um lado, ao aumento da toxicidade da quimioterapia e a resistência ao mesmo, e por outro lado, para que o controle do vetor tornou-se extremamente difícil, porque o inseto tem sido espalhado e adaptado a diversas condições ambientais; dai que se dá alta prioridade para o desenvolvimento e estratégias de profilática eficaz em termos de custos para evitar, pois as pessoas mais afetadas vivem em países com economias frágeis. O objetivo da revisão foi o de atualizar o fato em estratégias de vacinação contra Leishmania. Se Resume essa informação para orientar os profissionais de saúde sobre o procedimento adequado para o controle de uma tão importante endemia mundial...

Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents

Objective To evaluate whether hypoxia inducible factor (HIF-1α) targeting pharmacological drugs, echinomycin, resveratrol and CdCl