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Los parásitos son organismos eucariotas (unicelulares o pluricelulares) que viven en el interior o sobre el tejido vivo de otro organismo más organizado denominado hospedador. El término parásito proviene del nombre dado a unos sacerdotes auxiliares que “sentados al lado del alimento” -sentido etimológico- del sacrificio, participaban más tarde de la ofrenda; de aquí el uso despectivo que se le da a dicha palabra que además, tiene el término, desde su origen griego (para, junto a y sitos, trigo, comida). La generalización biológica se debe a los médicos veterinarios romanos que denominaron así a aquellos animales que vivían y se alimentaban a expensas de otros. En las primeras definiciones de los parásitos se trataba de diferenciarlos de los depredadores, insistiendo en que, aunque la asociación era para la adquisición de alimentos, se tendía a conservar la vida del hospedador y a no proporcionarle beneficio alguno, sino al contrario, efectos dañinos o acciones patógenas.Todosestos conceptos se completaron al observar la naturaleza de la asociación; el carácter fisiológico de la misma; la interdependencia bioquímica con tendencia a la estabilidad por pérdida o adquisición mutua de información genética donde los parásitos han desarrollado mecanismos que son capaces de manipular el genoma de su hospedador compatible, orquestando cambios en los nucleos de sus células que alteran la expresión génica en favor del parásito [1, 2]. Recientemente los enfoques más informativos del Ácido Desoxirribonucleico (ADN) (secuencias de genes, polimorfismos de un solo nucleótido del inglés Single Nucleotide Polymorphism (SNP), y los microsatélites) [3], se han utilizado ampliamente para inferir la influencia de la genética en los diferentes aspectos de la biología del parásito., Por otra parte, de forma general, las acciones perjudiciales son mutuas o en ambas direcciones. La posible «bondad» de algunos parasitismos, o del parasitismo, en general, no existe. Algunos hospedadores van cambiando su metabolismo, ganando peso, o modificando su comportamiento. Por el contrario, los parásitos hallan ventajas adaptativas en conservar la expresión génica de la virulencia. Si los factores de virulencia son mantenidos por la selección natural, ocasionando una disminución del bienestar del hospedador, inevitablemente se producirá también la correspondiente selección para la resistencia del hospedador. Así, se mantiene el equilibrio inestable y dinámico de la comunidad antagónica de dos seres vivos de distinta especie en asociación definida como parasitismo [4, 5]. La gran mayoría de los parásitos pertenecen a uno de los siguientes Phylum: Apicomplexa, Microspora, Ciliophora, Plathelminthes, Nematoda y Arthropoda. Los helmintos se encuentran en dos de ellos Plathelminthes y Nematoda. Se han descrito cerca de 25.000 especies de nematodos. Muchos de ellos son parásitos de insectos, plantas o animales, pero también existen especies de vida libre como Caenorhabditis elegans. Sobre la base de las estimaciones mundiales, entre 75.000 y 300.000 especies de helminto nfectan a los vertebrados terrestres y acuáticos; entre estos, 287 son conocidos en los seres humanos, el 95% de los cuales son especies zoonóticas y aproximadamente el 25% de la población mundial está infectada con estos organismos [3]. La gran mayoría de los platelmintos parásitos pertenecen a las clases, Monogenea, Digenea (gr. dis, “doble” y genos, “raza”) y Cestoda (tenias) (figura I.1), y las dos primeras clases son comúnmente denominadas “trematodos”. Todos los trematodos que residen en los seres humanos son de la clase Digenea. Tienen complejos ciclos de vida indirectos, en los que incluyen uno o varios hospedadores intermediarios (Ej. caracoles terrestres), ejemplo de estos parásitos son los e

[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 r

[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 burd

[Background]: The leishmaniases are a complex of neglected tropical diseases caused by more than 20 Leishmania parasite species, for which available therapeutic arsenal is scarce and unsatisfactory. Pentavalent antimonials (SbV) are currently the first-line pharmacologic therapy for leishmaniasis worldwide, but resistance to these compounds is increasingly reported. Alkyl-lysophospoholipid analogs (ALPs) constitute a family of compounds with antileishmanial activity, and one of its members, miltefosine, has been approved as the first oral treatment for visceral and cutaneous leishmaniasis. However, its clinical use can be challenged by less impressive efficiency in patients infected with some Leishmania species, including L. braziliensis and L. mexicana, and by proneness to develop drug resistance in vitro. [Methodology/Principal Findings]: We found that ALPs ranked edelfosine.perifosine.miltefosine.erucylphosphocholine for their antileishmanial activity and capacity to promote apoptosis-like parasitic cell death in promastigote and amastigote forms of distinct Leishmania spp., as assessed by proliferation and flow cytometry assays. Effective antileishmanial ALP concentrations were dependent on both the parasite species and their development stage. Edelfosine accumulated in and killed intracellular Leishmania parasites within macrophages. In vivo antileishmanial activity was demonstrated following oral treatment with edelfosine of mice and hamsters infected with L. major, L. panamensis or L. braziliensis, without any significant side-effect. Edelfosine also killed SbV-resistant Leishmania parasites in in vitro and in vivo assays, and required longer incubation times than miltefosine to generate drug resistance. [Conclusions/Significance]: Our data reveal that edelfosine is the most potent ALP in killing different Leishmania spp., and it is less prone to lead to drug resistance development than miltefosine. Edelfosine is effective in killing Leishmania in culture and

La presente invención se refiere al uso de un compuesto de fórmula general (1) donde preferiblemente el compuesto es edelfosina (1- O-octadecil-2-0-metil-rac-glicero-3-fosfocolina), para la fabricación de un medicamento para la prevención y/o el tratamiento de helmintiasis, es decir, para su uso como antihelmíntico, preferiblemente para la prevención y/o el tratamiento de esquistosomiasis y/o estrong iloidiasis.