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 ResearchMeSH KeywordsAntiprotozoal AgentsAzolesHumansLeishmania guyanensisLeukocytes, MononuclearPhosphorylcholineConceptsFractional 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 ResearchMeSH KeywordsAntiprotozoal AgentsHumansLeishmaniaLeishmaniasis, CutaneousLeukocytes, MononuclearMeglumine AntimoniateConceptsPeripheral 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
2018
Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships
Kip AE, del Mar Castro M, Gomez MA, Cossio A, Schellens JHM, Beijnen JH, Saravia NG, Dorlo TPC. Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships. Journal Of Antimicrobial Chemotherapy 2018, 73: 2104-2111. PMID: 29757380, PMCID: PMC6251527, DOI: 10.1093/jac/dky143.Peer-Reviewed Original ResearchConceptsExposure-response relationshipProbability of curePopulation PK modelMiltefosine concentrationsDosing simulationsPK targetPK modelNew World cutaneous leishmaniasisPlasma concentration-time curveCutaneous leishmaniasis patientsPopulation pharmacokinetic modelLarge cohort studyPopulation pharmacokinetic modellingConcentration-time curvePlasma concentration ratioDistribution rate constantMiltefosine exposureCohort studyLeishmaniasis patientsPatient populationEffect compartmentCutaneous leishmaniasisDay 1Three-compartment modelPharmacokinetic modelling
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 differences
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
2014
CD4 T cell activation by B cells in human Leishmania (Viannia)infection
Rodriguez-Pinto D, Saravia NG, McMahon-Pratt D. CD4 T cell activation by B cells in human Leishmania (Viannia)infection. BMC Infectious Diseases 2014, 14: 108. PMID: 24568275, PMCID: PMC3937821, DOI: 10.1186/1471-2334-14-108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiotinB-LymphocytesCD4-Positive T-LymphocytesColombiaFemaleFlow CytometryFluorescein-5-isothiocyanateGene Expression RegulationHumansImmunoglobulin MInterferon-gammaInterleukin-6Leishmania braziliensisLeishmaniasis, CutaneousLeukocytes, MononuclearLymphocyte ActivationMaleMiddle AgedOvalbuminTumor Necrosis Factor-alphaYoung AdultConceptsCD4 T cellsCutaneous leishmaniasis patientsT cellsB cellsLeishmaniasis patientsT cell activationLeishmania antigenImmune responseCell activationT-cell activation parametersSpecific CD4 T cellsEffective adaptive immune responseCD4 T cell activationB-cell activation markersCultures of PBMCUpregulation of CD86Cell activation markersCostimulatory molecule CD86Activation markers CD25Adaptive immune responsesHuman cutaneous leishmaniasisPurified B cellsT cell culturesHuman B cell linesHuman B cells
2010
T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species
Díaz YR, Rojas R, Valderrama L, Saravia NG. T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species. The Journal Of Infectious Diseases 2010, 202: 406-415. PMID: 20583921, PMCID: PMC4850829, DOI: 10.1086/653829.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsCoculture TechniquesCytokinesFemaleForkhead Transcription FactorsGATA3 Transcription FactorGene ExpressionGene Expression ProfilingHumansLeishmaniaLeishmaniasisLeukocytes, MononuclearMaleMiddle AgedT-Box Domain ProteinsTh1 CellsTh2 CellsTreatment OutcomeYoung AdultConceptsGATA-3 expressionT cell differentiationTumor necrosis factor alphaT-bet expressionNecrosis factor alphaT-betHuman infectionsGATA-3Th2 responsesAsymptomatic infectionFactor alphaInterleukin-4Cutaneous leishmaniasisInterferon gammaTh1/Th2 cytokine productionTh1/Th2 cytokine responseHigher T-bet expressionTh1/Th2 responseActive recurrent diseaseRecurrent cutaneous leishmaniasisTh2 cytokine responsesExperimental cutaneous leishmaniasisProinflammatory cytokine interferon-gammaInterleukin-10 secretionTh2 cytokine production
2006
Evidence for Leishmania (Viannia) Parasites in the Skin and Blood of Patients Before and After Treatment
Vergel C, Palacios R, Cadena H, Posso CJ, Valderrama L, Perez M, Walker J, Travi BL, Saravia NG. Evidence for Leishmania (Viannia) Parasites in the Skin and Blood of Patients Before and After Treatment. The Journal Of Infectious Diseases 2006, 194: 503-511. PMID: 16845635, DOI: 10.1086/505583.Peer-Reviewed Original ResearchConceptsPeripheral blood monocytesAmerican cutaneous leishmaniasisCutaneous leishmaniasisLeishmania parasitesUnaffected skinAnthroponotic transmissionAcquisition of infectionBlood of patientsSource of infectionSand fliesAdult patientsLesion scarTreatment failureAntimonial drugsPatientsNormal skinLeishmaniasisMonocytesZoonotic diseaseLesion bordersSkinTreatmentMolecular detection methodsPositive resultsInfection
1992
Haemoculture of Leishmania (Viannia) braziliensis from two cases of mucosal leishmaniasis: Re-examination of haematogenous dissemination
Martinez J, Alba, Arias L, Escobar M, Saravia N. Haemoculture of Leishmania (Viannia) braziliensis from two cases of mucosal leishmaniasis: Re-examination of haematogenous dissemination. Transactions Of The Royal Society Of Tropical Medicine And Hygiene 1992, 86: 392-394. PMID: 1440813, DOI: 10.1016/0035-9203(92)90233-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsHumansLeishmania braziliensisLeishmaniasis, MucocutaneousLeukocytes, MononuclearMaleMiddle AgedConceptsMucosal leishmaniasisActive pulmonary tuberculosisMontenegro skin testPeripheral blood leucocytesIsolation of parasitesIndirect fluorescent antibodyCases of leishmaniasisCulture of parasitesHaematogenous disseminationMucosal involvementPulmonary tuberculosisCutaneous lesionsSkin testMucosal diseaseMetastatic spreadMonths durationBlood leucocytesRight legPatientsLeishmania parasitesLeishmania braziliensisL. braziliensisLeishmaniasisFluorescent antibodyLeucocytes