2022
Pentoxifylline in the Treatment of Cutaneous Leishmaniasis: A Randomized Clinical Trial in Colombia
del Mar Castro M, Cossio A, Navas A, Fernandez O, Valderrama L, Cuervo-Pardo L, Marquez-Oñate R, Gómez MA, Saravia NG. Pentoxifylline in the Treatment of Cutaneous Leishmaniasis: A Randomized Clinical Trial in Colombia. Pathogens 2022, 11: 378. PMID: 35335703, PMCID: PMC8949591, DOI: 10.3390/pathogens11030378.Peer-Reviewed Original ResearchAddition of pentoxifyllinePeripheral blood mononuclear cellsMeglumine antimoniate treatmentPlacebo-controlled trialCutaneous leishmaniasis patientsBlood mononuclear cellsInflammatory gene expressionAntimoniate treatmentOral pentoxifyllineTrial patientsAdverse eventsInflammatory mediatorsMucosal leishmaniasisLeishmaniasis patientsAntimonial treatmentClinical benefitMononuclear cellsStandard treatmentMultiple lesionsTherapeutic failureTherapeutic responseClinical trialsFailure rateStudy groupSingle lesion
2021
Potency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection
Fernández OL, Rosales-Chilama M, Quintero N, Travi BL, Wetzel DM, Gómez MA, Saravia NG. Potency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection. Antimicrobial Agents And Chemotherapy 2021, 66: e01425-21. PMID: 34694879, PMCID: PMC8765415, DOI: 10.1128/aac.01425-21.Peer-Reviewed Original ResearchConceptsFractional inhibitory concentration indexPeripheral blood mononuclear cellsL. panamensisHuman peripheral blood mononuclear cellsClinical strainsLeishmania panamensis infectionOral azole drugsOral combination therapyFailure of treatmentBlood mononuclear cellsEfficacy of treatmentNovel therapeutic strategiesEffectiveness of treatmentHigh potencyReduction of infectionEx vivo modelInhibitory concentration indexFree drug concentrationPanamensis infectionPreclinical evidenceCombination therapyMononuclear cellsAntimonial drugsCutaneous leishmaniasisDrug combinations
2020
Immuno-pharmacokinetics of Meglumine Antimoniate in Patients With Cutaneous Leishmaniasis Caused by Leishmania (Viannia)
Gómez MA, Navas A, Prieto M, Giraldo-Parra L, Cossio A, Alexander N, Saravia N. Immuno-pharmacokinetics of Meglumine Antimoniate in Patients With Cutaneous Leishmaniasis Caused by Leishmania (Viannia). Clinical Infectious Diseases 2020, 72: e484-e492. PMID: 32818964, PMCID: PMC8130027, DOI: 10.1093/cid/ciaa1206.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMeglumine antimoniateCutaneous leishmaniasisBlood mononuclear cellsHuman cutaneous leishmaniasisIntracellular drug concentrationImmune gene expressionPK evidenceClinical cureParasite clearanceClinical resolutionDrug regimensMononuclear cellsPharmacodynamic parametersPharmacodynamic relationshipsLeishmania VianniaDrug treatmentTargeted immunomodulationTherapeutic outcomesImmune dynamicsDrug efficacyGene signatureDrug concentrationsProfile of expressionMicrobial killProfiles of Local and Systemic Inflammation in the Outcome of Treatment of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia)
Navas A, Fernández O, Gallego-Marín C, del Mar Castro M, Rosales-Chilama M, Murillo J, Cossio A, McMahon-Pratt D, Saravia N, Gómez MA. Profiles of Local and Systemic Inflammation in the Outcome of Treatment of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia). Infection And Immunity 2020, 88: 10.1128/iai.00764-19. PMID: 31818959, PMCID: PMC7035935, DOI: 10.1128/iai.00764-19.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsOutcome of treatmentInnate immune responseCutaneous leishmaniasisTreatment failureCL patientsBiopsy specimensImmune responseResponse of PBMCLocal innate immune responseTreatment of CLBlood mononuclear cellsEnd of treatmentLesion biopsy specimensHuman cutaneous leishmaniasisEfficacy of treatmentGene expression profilesImmune response genesImmune correlatesClinical cureSystemic inflammationPretreatment expressionMeglumine antimoniateMononuclear cellsCare treatment
2017
Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis
del Mar Castro M, Gomez MA, Kip AE, Cossio A, Ortiz E, Navas A, Dorlo TP, Saravia NG. Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis. Antimicrobial Agents And Chemotherapy 2017, 61: 10.1128/aac.02198-16. PMID: 27956421, PMCID: PMC5328512, DOI: 10.1128/aac.02198-16.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisMiltefosine concentrationsPeripheral blood mononuclear cellsInitiation of treatmentCompletion of treatmentBlood mononuclear cellsEnd of treatmentOutcome of treatmentConcentration-time curvePharmacokinetic clinical trialsClinical responsePediatric patientsPediatric populationMononuclear cellsTherapeutic regimensDrug exposureClinical trialsNoncompartmental analysisParasite eliminationTherapeutic outcomesStudy participantsMiltefosinePatientsLiquid chromatography-tandem mass spectrometryPK differencesLocal Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection
Ehrlich AK, Fernández OL, Rodriguez-Pinto D, Castilho TM, Caridad M, Goldsmith-Pestana K, Saravia NG, McMahon-Pratt D. Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection. Infection And Immunity 2017, 85: 10.1128/iai.00981-16. PMID: 28052994, PMCID: PMC5328479, DOI: 10.1128/iai.00981-16.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsPeripheral blood mononuclear cellsCutaneous leishmaniasisB cellsIL-17IL-13Inflammatory responseMouse modelToll-like receptor 9 ligand CpGAlternate therapeutic approachCurrent treatment optionsBlood mononuclear cellsMixed inflammatory responseRegulatory cell functionProduction of IFNPredominant etiologic agentDose-response effectHost immune responseCell populationsGrowth factor βCpG treatmentRegulatory cellsChemokine responsesIL-10Host Immune
2015
Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators
Gonzalez-Fajardo L, Fernández OL, McMahon-Pratt D, Saravia NG. Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators. PLOS Neglected Tropical Diseases 2015, 9: e0003820. PMID: 26024228, PMCID: PMC4449175, DOI: 10.1371/journal.pntd.0003820.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsOutcome of infectionIL-10Meglumine antimoniateIL-13Therapeutic strategiesAntileishmanial drugsTherapeutic responseCytokine secretionInfected peripheral blood mononuclear cellsParasite survivalHuman peripheral blood mononuclear cellsL. panamensis infectionsCutaneous leishmaniasis patientsPro-inflammatory cytokinesBlood mononuclear cellsIL-13 secretionIntracellular parasite survivalAssessment of hostViability of LeishmaniaEfficacy of treatmentPromising therapeutic strategySecretion of TNFInnovative therapeutic strategiesMonocyte-derived macrophages
2000
Distinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection
Bosque, Saravia, Valderrama, Milon. Distinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection. Scandinavian Journal Of Immunology 2000, 51: 533-541. PMID: 10792848, DOI: 10.1046/j.1365-3083.2000.00724.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedDisease SusceptibilityEndemic DiseasesFemaleHumansHypersensitivity, DelayedImmunity, InnateInterferon-gammaInterleukin-10Leishmania guyanensisLeishmaniasis, MucocutaneousMacrophagesMaleMiddle AgedMonocytesRecombinant ProteinsRecurrenceRisk FactorsTritiumTumor Necrosis Factor-alphaConceptsPeripheral blood mononuclear cellsRecurrent diseaseL. panamensis infectionsCD8 T lymphocytesType hypersensitivity responseBlood mononuclear cellsAcquired Immune ResponsesTumor necrosis factorProduction of interferonEntry of parasitesLeishmania Viannia panamensisPanamensis infectionRecurrent leishmaniasisHypersensitivity responseImmunological basisSkin testMononuclear cellsNecrosis factorT lymphocytesImmune responseSubclinical infectionLinear regression analysisEvidence of differencesDistinct innateIntracellular amastigotes