2024
Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis
Fernández O, Rosales-Chilama M, Sánchez-Hidalgo A, Gómez P, Rebellón-Sánchez D, Regli I, Díaz-Varela M, Tacchini-Cottier F, Saravia N. Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis. PLOS Neglected Tropical Diseases 2024, 18: e0012156. PMID: 38709850, PMCID: PMC11098511, DOI: 10.1371/journal.pntd.0012156.Peer-Reviewed Original ResearchConceptsAssociated with treatment failureTreatment failureHost risk factorsBALB/c miceRisk factorsDrug susceptibilityClinical strainsOutcome of cutaneous leishmaniasisOdds of treatment failureMeglumine antimoniateParasitological response to treatmentLeishmania (Viannia) panamensisSubgroup of patientsAntimicrobial drug susceptibilityResponse to treatmentU937 macrophagesEvaluate drug susceptibilityCutaneous leishmaniasis patientsCutaneous leishmaniasisFailed treatmentPlasma CmaxTherapeutic responseClinical outcomesPatient's lesionsTreatment outcomes
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
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
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 KeywordsAdultAgedB-LymphocytesBiotinCD4-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