Publication: Búsqueda y optimización de potenciales alternativas terapéuticas para el tratamiento de la enfermedad de chagas
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2017-05-30
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Universidad Complutense de Madrid
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Abstract
La enfermedad de Chagas, causada por Trypanosoma cruzi, es una parasitosis endémica en 21 países de América Latina, donde se transmite por las heces contaminadas de triatominos, provoca más de 7.000 muertes anuales y cerca de 25 millones de personas están en riesgo de contraer la infección. Clasificada por la OMS como una de las 17 enfermedades tropicales desatendidas, principalmente se extiende entre la población más desfavorecida de las zonas rurales. Sin embargo, vías de trasmisión alternativas como la transfusional o la congénita, y los movimientos migratorios, han hecho de ella una enfermedad emergente en países como EE.UU, Australia o España, afectando a más de 7 millones de personas en el mundo. La fase aguda aparece una semana tras la infección y posee baja mortalidad (<10%), asociada a fallo cardíaco y/o meningoencefalitis. En la mayoría de los casos es asintomática u oligosintomática y se resuelve espontáneamente. Tras 12 meses, la respuesta inmune controla parcialmente la infección y aunque no la erradica, el 6070% de los pacientes nunca la manifiesta (fase indeterminada). El 3040% restante entra en fase crónica durante los 1030 años posteriores, con afectación cardíaca y/o digestiva (megaesófago y megacolon). Después de más de un siglo desde su descubrimiento, no se dispone de fármacos adecuados para su tratamiento, basado en dos nitroderivados introducidos hace más de 40 años: benznidazol (BZ) y nifurtimox, recomendados para tratar los casos agudos y crónicos recientes, pero con actividad limitada en la fase crónica avanzada. Su controvertida eficacia, elevada toxicidad y la aparición de cepas de T. cruzi resistentes, afecta al éxito de estas terapias...
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a parasitic infection transmitted in 21 Latin American countries mainly by the contaminated feces of triatomine vectors. In the endemic area, it provokes more than 7,000 deaths annually and maintains over 25 million people at risk for the infection. The disease has been classified by the WHO as one of the 17 neglected tropical diseases, and its chronic nature mostly affects poorest people of the rural areas. However, non-vectorial routes of transmission (e.g., transfusional or congenital) and population mobility have led to its emergence in non-endemic countries such as USA, Australia or Spain, affecting more than 7 million people worldwide. The acute phase appears one week after infection and presents low mortality (<10%), usually related to heart failure and/or meningoencephalitis. In most cases it is asymptomatic/oligosymtomatic and resolves spontaneously. After 12 months, immune response partially controls the infection and although it is not eradicated, about 6070% of patients never develop clinical manifestations (indeterminate phase). The remaining 3040% manifests the chronic disease 1030 years after initial infection, suffering life-threatening cardiomyopathy and/or digestive problems (i.e., megaesophagous and megacolon). Although more than a century has gone since the discovery of the disease, no suitable drug is still available. The specific treatment is based on two nitrocompounds introduced more than forty years ago: benznidazole (BZ) and nifurtimox, recommended to treat acute and early-chronic cases, but both show limited effectiveness in long-term chronic infections. Their controverted activity, high toxicity and the occurrence of naturally resistant parasite strains, hinders the success of these therapies...
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a parasitic infection transmitted in 21 Latin American countries mainly by the contaminated feces of triatomine vectors. In the endemic area, it provokes more than 7,000 deaths annually and maintains over 25 million people at risk for the infection. The disease has been classified by the WHO as one of the 17 neglected tropical diseases, and its chronic nature mostly affects poorest people of the rural areas. However, non-vectorial routes of transmission (e.g., transfusional or congenital) and population mobility have led to its emergence in non-endemic countries such as USA, Australia or Spain, affecting more than 7 million people worldwide. The acute phase appears one week after infection and presents low mortality (<10%), usually related to heart failure and/or meningoencephalitis. In most cases it is asymptomatic/oligosymtomatic and resolves spontaneously. After 12 months, immune response partially controls the infection and although it is not eradicated, about 6070% of patients never develop clinical manifestations (indeterminate phase). The remaining 3040% manifests the chronic disease 1030 years after initial infection, suffering life-threatening cardiomyopathy and/or digestive problems (i.e., megaesophagous and megacolon). Although more than a century has gone since the discovery of the disease, no suitable drug is still available. The specific treatment is based on two nitrocompounds introduced more than forty years ago: benznidazole (BZ) and nifurtimox, recommended to treat acute and early-chronic cases, but both show limited effectiveness in long-term chronic infections. Their controverted activity, high toxicity and the occurrence of naturally resistant parasite strains, hinders the success of these therapies...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Parasitología, leída el 20-07-2016