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Moléculas asociadas a anemia y trombocitopenia en pacientes con malaria por Plasmodium vivax

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dc.contributor.advisorCodirector: Cantero Guevara, Miriamspa
dc.contributor.advisorDirector: Yasnot Acosta, María Fernandaspa
dc.contributor.advisorAsesor internacional: Rodríguez, Anaspa
dc.contributor.advisorUniversidad de Córdobaspa
dc.contributor.authorVelasco Pareja, María Camilaspa
dc.coverage.spatialMontería, Córdobaspa
dc.date.accessioned2020-07-07T16:03:41Zspa
dc.date.available2020-07-07T16:03:41Zspa
dc.date.issued2021-12-30spa
dc.description.abstractPlasmodium vivax es el agente etiológico causal de la malaria con mayor distribución en el mundo. Su curso clínico es variable, tradicionalmente se asoció a enfermedad benigna, sin embargo en la última década se ha demostrado que puede llegar a producir formas complicadas de la enfermedad e incluso la muerte, siendo la anemia y la trombocitopenia las complicaciones más frecuentes. En el departamento de Córdoba la situación no es diferente, la malaria es endémica y la mayoría de casos son atribuidos a P. vivax; es el tercer departamento que más casos reporta en Colombia y las complicaciones hematológicas son frecuentes. Los principales mecanismos fisiopatológicos asociados a la disminución de la hemoglobina y recuentos plaquetarios son las alteraciones en la médula ósea, la respuesta inmune proinflamatoria y autoinmune, así como el secuestro esplénico. Este estudio tuvo como objetivo evaluar el efecto de la infección por Plasmodium vivax sobre las concentraciones plasmáticas de citoquinas, quemoquinas y autoanticuerpos e identificar su rol en la anemia y trombocitopenia asociadas a la infección. Para tal fin, se seleccionaron 165 pacientes con monoinfección por P. vivax sin y con anemia, trombocitopenia o ambas, además de individuos sanos e individuos con malaria sin anemia ni trombocitopenia. A todos los participantes se les diligenció una ficha clínica. La cuantificación plasmática de citoquinas (IL-2, IL-4, IL-1β, TNF-α, IL-17A, IL-6, IL-10, INFγ, IL-12p70, y TGF-β1) y quemoquinas (IP-10, MCP-1 y IL-8), se realizó por citometría de flujo. La evaluación de la autoinmunidad se realizó mediante un Ensayo de Inmunoabsorción Ligado a Enzima (ELISA), empleando como antígeno fosfatidilserina (FS), lisado de glóbulos rojos (LGR) y ácido desoxirribonucleico (ADN). Los análisis estadísticos se realizaron mediante GraphPad Prism versión 7.0. La población se caracterizó por ser en su mayoría adolescentes y adultos jóvenes. Clínicamente esta población de caracterizó por tener una media de 5107 parásitos/µL (DS= 12634p/µL), describieron síntomas correspondientes a la tríada clásica de malaria; el 13% de los pacientes requirió de hospitalización. El 49% de los pacientes con malaria vivax desarrollaron anemia y trombocitopenia concomitante, el 28% trombocitopenia y el 13.9% anemia. Se identificó además que el 9% de los pacientes no desarrollaron ningún tipo de alteración hematológica a pesar de tener un episodio activo de malaria. Se demostró que las citoquinas y quemoquinas proinflamatorias, INFγ, IL-6, MCP-1 e IP-10 tuvieron concentraciones significativamente altas (P<0.005) en pacientes con malaria y trombocitopenia. En cuanto a las citoquinas antiiflamatorias, la IL-10 fue significativamente elevada (P = XXX) en los grupos que cursaron con malaria y anemia y trombocitopenia, mientras que la concentración del TGF-β1 (41pg/mL) se encontró significativamente aumentada en pacientes infectados pero que no desarrollaron ninguna alteración hematológica (P<0.0001). Los anticuerpos anti-FS se encontraron aumentados en pacientes con malaria que desarrollaron anemia y trombocitopenia, con una correlación negativa entre anticuerpos anti-FS vs la hemoglobina y las plaquetas (P<0.05). Se concluye que la trombocitopenia puede estar dada por mecanismos multifactoriales, tales como la fagocitosis potenciada por la inflamación causada por el INFγ y la IL-6, así como también por el desarrollo de autoanticuerpos contra fosfatidilserina, los cuales pueden influir en la destrucción de plaquetas ya sea por la fagocitosis o la activación de la vía clásica del complemento. Así mismo, la anemia puede ser una consecuencia de la opsonización de glóbulos rojos parasitados como no parasitados por anticuerpos anti-FS que pueden generar un mecanismo de destrucción por fagocitosis o por la vía clásica del complemento. Finalmente, se demostró que los pacientes con malaria que no desarrollaron alteraciones hematológicas tenían altas concentraciones de TGF-β1 respecto a aquellos que tuvieron anemia o trombocitopenia (P<0.05), sugiriendo esto un efecto antiinflamatorio eficaz.spa
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Microbiología Tropicalspa
dc.description.tableofcontentsINTRODUCCIÓN.................................................................................................................................................................................18spa
dc.description.tableofcontentsOBJETIVO.................................................................................................................................................................................20spa
dc.description.tableofcontentsCapítulo I: Marco Teórico ..............................................................................................................................................................................21spa
dc.description.tableofcontentsCapítulo II: Aspectos epidemiológicos y clínicos de la malaria por P. vivax en el sur de Córdoba...................................................31spa
dc.description.tableofcontentsIntroducción............................................................................................................................................................................................31spa
dc.description.tableofcontentsObjetivo...................................................................................................................................................................................................32spa
dc.description.tableofcontentsMetodología......................................................................................................................................................................................32spa
dc.description.tableofcontentsResultados.............................................................................................................................................................................................35spa
dc.description.tableofcontentsCAPÍTULO III: Citoquinas y quemoquinas involucradas en la anemia y la trombocitopenia en pacientes con malaria por P. vivax...................................................................................................................................................................................................................42spa
dc.description.tableofcontentsIntroducción.....................................................................................................................................................................................................42spa
dc.description.tableofcontentsObjetivo.............................................................................................................................................................................................................43spa
dc.description.tableofcontentsMetodología....................................................................................................................................................................................................43spa
dc.description.tableofcontentsResultados......................................................................................................................................................................................................46spa
dc.description.tableofcontentsDiscusión...................................................................................................................................................................................................61spa
dc.description.tableofcontentsCAPÍTULO IV: Autoanticuerpos asociados a la anemia y la trombocitopenia en pacientes con malaria por P. vivax...................67spa
dc.description.tableofcontentsIntroducción.....................................................................................................................................................................................................67spa
dc.description.tableofcontentsObjetivo............................................................................................................................................................................................................68spa
dc.description.tableofcontentsResultados........................................................................................................................................................................................................70spa
dc.description.tableofcontentsDiscusión..........................................................................................................................................................................................................76spa
dc.description.tableofcontentsConclusiones generales.................................................................................................................................................................................80spa
dc.description.tableofcontentsPerspectivas......................................................................................................................................................................................................81spa
dc.description.tableofcontentsReferencias......................................................................................................................................................................................................82spa
dc.format.mimetypeApplication/pdfspa
dc.identifier.uriHttps://repositorio.unicordoba.edu.co/handle/ucordoba/3106spa
dc.language.isospaspa
dc.publisher.facultyFacultad de Medicina Veterinaria y Zootecniaspa
dc.publisher.programMaestría en Microbiología Tropicalspa
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dc.rightsCopyright Universidad de Córdoba, 2019spa
dc.rights.accessrightsInfo:eu-repo/semantics/closedAccessspa
dc.rights.creativecommonsAtribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)spa
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.keywordsPlasmodium vivax, anemia, thrombocytopenia, proinflammatory cytokines, anti-inflammatory cytokinesspa
dc.subject.proposalPlasmodium vivax, anemia, trombocitopenia, citoquinas proinflamatorias, citoquinas antiiflamatorias.spa
dc.titleMoléculas asociadas a anemia y trombocitopenia en pacientes con malaria por Plasmodium vivaxspa
dc.typeTrabajo de grado - Pregradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_7a1fspa
dc.type.contentTextspa
dc.type.driverInfo:eu-repo/semantics/bachelorThesisspa
dc.type.redcolhttps://purl.org/redcol/resource_type/TPspa
dc.type.versionInfo:eu-repo/semantics/publishedVersionspa
dspace.entity.typePublication
oaire.accessrightshttp://purl.org/coar/access_right/c_14cbspa
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85spa
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