Leishmaniasis en Pando-Bolivia: Frontera con Brasil y Perú

En la región Amazónica del este, aparentemente circulan la mayor biodiversidad de especies de Leishmania spp. y de Phlebotominae. Nuestro objetivo pretende presentar la revisión del conocimiento de la leishmaniasis en el departamento de Pando-Bolivia, frontera con Acre y Rondonia-Brasil y Madre de Dios-Perú, mediante el análisis de indicadores eco epidemiológicos, reportes, informes institucionales, tesis e Investigaciones médicas sobre la leishmaniasis en Bolivia y publicaciones de los países vecinos sobre esta región. En los últimos 23 años, el departamento de Pando registró 6,614 casos de Leishmaniasis Cutáneo Americana y un caso de Leishmaniasis Visceral. El sexo masculino fue el más afectado (69,6% de los registros). La forma cutánea (90,2%) predominó en relación con la manifestación clínica mucosas. Las tasas de incidencia por 10,000 habitantes fueron de 49,8 en 2,006; 39,3 en 2,012 y 49,7 en 2,018. Leishmania (V.) braziliensis fue la única especie registrada y se determinó la presencia de 20 especies de Phlebotominae, siendo las más frecuentes Nyssomyia shawi y Psychodopygus carrerari. Concluimos que la intensa migración de población susceptible asociada a la existencia de una alta diversidad conocida de especies de Phlebotominae con competencia vectorial, donde varias de ellas se están adaptando a ambientes modificados incluyendo el espacio peri doméstico, refuerzan la necesidad de investigar profundamente las características epidemiológicas de la leishmaniasis en la región de frontera entre Bolivia, Brasil y Perú, que registra las tasas más altas de Leishmaniasis Cutánea Americana en América del Sur.Fil: Mollinedo, Zoraida Aymara. Universidad Autonoma del Beni; BoliviaFil: Mollinedo, Pavel Elvin. Universidad Tecnica Cosmos; Bolivia. Instituto de Salud y Medio Ambiente; BoliviaFil: Noto, Javier. No especifíca;Fil: Mollinedo, Pavel Sergio. Ministerio de Salud Bolivia; BoliviaFil: Gironda, Wilson J.. Sociedad Boliviana de Entomología; BoliviaFil: Mollinedo, Juan Sergio. Instituto de Salud y Medio Ambiente; BoliviaFil: Salomón, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; Argentin

Leishmaniasis en Bolivia. Comprehensive review and current status in Tarija, in the border with Argentina

ntroducción. En 1997, en el departamento de Tarija, Bolivia, situado en la frontera con Argentina, se notificó por primera vez la presencia de pacientes con úlceras en las partes descubiertas de la piel, cuyas características clínicas y epidemiológicas correspondían a leishmaniasis. Objetivo. Describir y comprobar la presencia de leishmaniasis en Tarija, sexto departamento endémico en Bolivia. Materiales y métodos. Se hizo un estudio del brote (noviembre de 1998 a diciembre de 2002) y un estudio longitudinal (1997 a 2018) en humanos; además, se capturaron Phlebotominae y potenciales reservorios. Resultados. Se registraron 1.250 pacientes de leishmaniasis; 190 y 249 casos, en los brotes de 1998 y 2002, respectivamente, con periodos interepidémicos de 37 casos como promedio anual. El 68 % de los enfermos eran pobladores migrantes del altiplano asentados en viviendas precarias cercanas al bosque residual; el sexo predominante fue el masculino (2/1). El grupo etario económicamente activo (15 a 49 años) fue el más afectado (363/584, 62 %). Hubo 124/584 (21 %) menores de 15 años, 33/584 de menos de cuatro años. En 51/584 (8,7 %) pacientes se presentaron lesiones mucosas. Se aisló y caracterizó Leishmania (V.) braziliensis de úlceras mucosas de perros enfermos y se capturó abundantemente la especie antropofílica Nyssomyia neivai, incriminada como probable vector. Conclusiones. En 1997 se comprobó por primera vez la presencia de leishmaniasis tegumentaria en el municipio de Bermejo y, en el 2018, ya se había extendido a cuatro municipios: Padcaya, Caraparí, Entre Ríos y Yacuiba, en dirección noreste del departamento de Tarija.Introduction: In the department of Tarija in the Bolivian-Argentine border, human cases with ulcers on uncovered parts of the skin plus clinical and epidemiological characteristics related to leishmaniasis were reported for the first time in 1997. Objective: To describe and to verify the presence of leishmaniasis in Tarija, sixth endemic department in Bolivia. Materials and methods: We conducted both an outbreak study (November, 1998, to December, 2002) and a longitudinal study (1997 to 2018) in humans, as well as captures of Phlebotominae and potential reservoirs. Results: A total of 1,250 patients were registered; in the outbreaks, 190 (1998) to 249 cases (2002) were reported and inter-epidemic periods with 37 cases as an annual average; 68% of the patients were highland migrants who inhabited precarious housing near residual forests. The predominant sex was male (ratio 2:1); the most affected group (363/584 cases, 62%) was the economically active (15 to 49 years old); 124/584 cases (21%) were children under 15 years old, 33/584 of them were under 4 years old; 51 patients/584 (8.7%) had mucosal lesions. Leishmania (V.) braziliensis was isolated and characterized from mucous ulcers of sick dogs. Nyssomyia neivai, an abundant anthropophilic species incriminated as a probable vector, was captured. Conclusions: The initial 1997 leishmaniosis presence in the municipality of Bermejo had spread out over four municipalities in 2018 (Padcaya, Carapari, Entre Rios, and Yacuiba), northeast of the department of Tarija.Fil: Mollinedo, Juan Sergio. Instituto de Salud y Medio Ambiente; BoliviaFil: Mollinedo, Zoraida. Universidad Amazónica de Pando; BoliviaFil: Magne, Marcelo. Secretaría Departamental de Salud Tarija; BoliviaFil: Gironda, Wilson J.. Sociedad Boliviana de Entomología; BoliviaFil: Salomón, Oscar Daniel. Ministerio de Salud. Instituto Nacional de Medicina Tropical; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

Leishmaniasis en Bolivia, revisión y estado actual en Tarija, frontera con Argentina

Introduction: In the department of Tarija in the Bolivian-Argentine border, human cases with ulcers on uncovered parts of the skin plus clinical and epidemiological characteristics related to leishmaniasis were reported for the first time in 1997.Objective: To describe and to verify the presence of leishmaniasis in Tarija, sixth endemic department in Bolivia.Materials and methods: We conducted both an outbreak study (November, 1998, to December, 2002) and a longitudinal study (1997 to 2018) in humans, as well as captures of Phlebotominae and potential reservoirs.Results: A total of 1,250 patients were registered; in the outbreaks, 190 (1998) to 249 cases (2002) were reported and inter-epidemic periods with 37 cases as an annual average; 68% of the patients were highland migrants who inhabited precarious housing near residual forests. The predominant sex was male (ratio 2:1); the most affected group (363/584 cases, 62%) was the economically active (15 to 49 years old); 124/584 cases (21%) were children under 15 years old, 33/584 of them were under 4 years old; 51 patients/584 (8.7%) had mucosal lesions. Leishmania (V.) braziliensis was isolated and characterized from mucous ulcers of sick dogs. Nyssomyia neivai, an abundant anthropophilic species incriminated as a probable vector, was captured.Conclusions: The initial 1997 leishmaniosis presence in the municipality of Bermejo had spread out over four municipalities in 2018 (Padcaya, Caraparí, Entre Ríos, and Yacuiba), northeast of the department of Tarija.Introducción. En 1997, en el departamento de Tarija, Bolivia, situado en la frontera con Argentina, se notificó por primera vez la presencia de pacientes con úlceras en las partes descubiertas de la piel, cuyas características clínicas y epidemiológicas correspondían a leishmaniasis.Objetivo. Describir y comprobar la presencia de leishmaniasis en Tarija, sexto departamento endémico en Bolivia.Materiales y métodos. Se hizo un estudio del brote (noviembre de 1998 a diciembre de 2002) y un estudio longitudinal (1997 a 2018) en humanos; además, se capturaron Phlebotominae y potenciales reservorios.Resultados. Se registraron 1.250 pacientes de leishmaniasis; 190 y 249 casos, en los brotes de 1998 y 2002, respectivamente, con periodos interepidémicos de 37 casos como promedio anual. El 68 % de los enfermos eran pobladores migrantes del altiplano asentados en viviendas precarias cercanas al bosque residual; el sexo predominante fue el masculino (2/1). El grupo etario económicamente activo (15 a 49 años) fue el más afectado (363/584, 62 %). Hubo 124/584 (21 %) menores de 15 años, 33/584 de menos de cuatro años. En 51/584 (8,7 %) pacientes se presentaron lesiones mucosas. Se aisló y caracterizó Leishmania (V.) braziliensis de úlceras mucosas de perros enfermos y se capturó abundantemente la especie antropofílica Nyssomyia neivai, incriminada como probable vector.Conclusiones. En 1997 se comprobó por primera vez la presencia de leishmaniasis tegumentaria en el municipio de Bermejo y, en el 2018, ya se había extendido a cuatro municipios: Padcaya, Caraparí, Entre Ríos y Yacuiba, en dirección noreste del departamento de Tarija

Involvement of Raft Aggregates Enriched in Fas/CD95 Death-Inducing Signaling Complex in the Antileukemic Action of Edelfosine in Jurkat Cells

BACKGROUND: Recent evidence suggests that co-clustering of Fas/CD95 death receptor and lipid rafts plays a major role in death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: By a combination of genetic, biochemical, and ultrastructural approaches, we provide here compelling evidence for the involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein (FADD), and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine, the prototype compound of a promising family of synthetic antitumor lipids named as synthetic alkyl-lysophospholipid analogues. Co-immunoprecipitation assays revealed that edelfosine induced the generation of the so-called death-inducing signaling complex (DISC), made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts. Electron microscopy analyses allowed to visualize the formation of raft clusters and their co-localization with DISC components Fas/CD95, FADD, and procaspase-8 following edelfosine treatment of Jurkat cells. Silencing of Fas/CD95 by RNA interference, transfection with a FADD dominant-negative mutant that blocks Fas/CD95 signaling, and specific inhibition of caspase-8 prevented the apoptotic response triggered by edelfosine, hence demonstrating the functional role of DISC in drug-induced apoptosis. By using radioactive labeled edelfosine and a fluorescent analogue, we found that edelfosine accumulated in lipid rafts, forming edelfosine-rich membrane raft clusters in Jurkat leukemic T-cells. Disruption of these membrane raft domains abrogated drug uptake and drug-induced DISC assembly and apoptosis. Thus, edelfosine uptake into lipid rafts was critical for the onset of both co-aggregation of DISC in membrane rafts and subsequent apoptotic cell death. CONCLUSIONS/SIGNIFICANCE: This work shows the involvement of DISC clusters in lipid raft aggregates as a supramolecular and physical entity responsible for the induction of apoptosis in leukemic cells by the antitumor drug edelfosine. Our data set a novel framework and paradigm in leukemia therapy, as well as in death receptor-mediated apoptosis

Inhibition of granulomatous inflammation and prophylactic treatment of schistosomiasis with a combination of edelfosine and Praziquantel

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Background]: Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. This parasitic disease is due to immunologic reactions to Schistosoma eggs trapped in tissues. Egg-released antigens stimulate tissue-destructive inflammatory and granulomatous reactions, involving different immune cell populations, including T cells and granulocytes. Granulomas lead to collagen fibers deposition and fibrosis, resulting in organ damage. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. [Methodology/Principal Findings]: Using in vitro and in vivo approaches, we have found that the alkylphospholipid analog edelfosine kills schistosomula, and displays anti-inflammatory activity. The combined treatment of PZQ and edelfosine during a few days before and after cercariae infection in a schistosomiasis mouse model, simulating a prophylactic treatment, led to seven major effects: a) killing of Schistosoma parasites at early and late development stages; b) reduction of hepatomegaly; c) granuloma size reduction; d) down-regulation of Th1, Th2 and Th17 responses at late post-infection times, thus inhibiting granuloma formation; e) upregulation of IL-10 at early post-infection times, thus potentiating anti-inflammatory actions; f) down-regulation of IL-10 at late post-infection times, thus favoring resistance to re-infection; g) reduction in the number of blood granulocytes in late post-infection times as compared to infected untreated animals. [Conclusions/Significance]: Taken together, these data suggest that the combined treatment of PZQ and edelfosine promotes a high decrease in granuloma formation, as well as in the cellular immune response that underlies granuloma development, with changes in the cytokine patterns, and may provide a promising and effective strategy for a prophylactic treatment of schistosomiasis.This work was supported by grants from the Junta de Castilla y León (SA342U13, CSI052A11-2, and CSI221A12-2), Real Federación Española de Fútbol-Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013), Spanish Ministerio de Economía y Competitividad (SAF2011-30518, SAF2014-59716-R, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), and European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS).Peer Reviewe

In vitro and in vivo anti-schistosomal activity of the alkylphospholipid analog edelfosine

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites. [Methodology/Principal Findings]: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis. [Conclusions/Significance]: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni -infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo.This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF2011-30518, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), European Community's Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS), Junta de Castilla y León (CSI052A11-2and SA342U13), Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013) and the Universidad de Salamanca (USAL17008).Peer Reviewe