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
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 combinationsNeutrophil Activation: Influence of Antimony Tolerant and Susceptible Clinical Strains of L. (V.) panamensis and Meglumine Antimoniate
Fernández OL, Ramírez G, Díaz-Varela M, Tacchini-Cottier F, Saravia NG. Neutrophil Activation: Influence of Antimony Tolerant and Susceptible Clinical Strains of L. (V.) panamensis and Meglumine Antimoniate. Frontiers In Cellular And Infection Microbiology 2021, 11: 710006. PMID: 34631596, PMCID: PMC8493214, DOI: 10.3389/fcimb.2021.710006.Peer-Reviewed Original ResearchMeglumine antimoniateActivation of neutrophilsClinical strainsActivation markersNET formationExpression of CD62LReactive oxygen speciesMaximal plasma concentrationInnate host responseSusceptible clinical strainsROS productionDrug-sensitive strainsCD66b expressionNeutrophil activationHealthy donorsInflammatory responsePlasma concentrationsTherapeutic effectAntimonial drugsAntimicrobial medicationsDsDNA releaseHost responseNeutrophilsAntileishmanial drugsCD62L
2017
Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility
Barrera MC, Rojas LJ, Weiss A, Fernandez O, McMahon-Pratt D, Saravia NG, Gomez MA. Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility. Acta Tropica 2017, 176: 355-363. PMID: 28843396, PMCID: PMC5633519, DOI: 10.1016/j.actatropica.2017.08.017.Peer-Reviewed Original ResearchConceptsLeishmania resistanceDrug susceptibilityDrug resistanceHost cell gene expressionClinical strainsCell gene expressionExpression of ABCA2THP-1 cellsPrimary human macrophagesLeishmania susceptibilityGene expressionAntimonial drugsCutaneous leishmaniasisInfected macrophagesLeishmania panamensisIntracellular amastigotesHuman macrophagesResistant strainsSusceptible parasitesAntimonialsIntracellular parasitesLeishmania speciesMacrophagesL. panamensisAQP-9
2014
Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia
Fernández OL, Diaz-Toro Y, Ovalle C, Valderrama L, Muvdi S, Rodríguez I, Gomez MA, Saravia NG. Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia. PLOS Neglected Tropical Diseases 2014, 8: e2871. PMID: 24853871, PMCID: PMC4031164, DOI: 10.1371/journal.pntd.0002871.Peer-Reviewed Original ResearchConceptsV. panamensisLine treatmentClinical strainsDrug susceptibilitySecond-line treatmentFirst-line treatmentEmergence of resistancePopulations of LeishmaniaViannia speciesResistant clinical strainsAntimony susceptibilityClinical evidenceMeglumine antimoniatePentavalent antimonialsDermal leishmaniasisEpidemiologic differencesLeishmania VianniaProxy markerIntracellular amastigotesMunicipality of TumacoResistant strainsMiltefosineDisparate susceptibilityDrugsL. panamensis
2012
Novel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp
Fernández O, Diaz-Toro Y, Valderrama L, Ovalle C, Valderrama M, Castillo H, Perez M, Saravia NG. Novel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp. Journal Of Clinical Microbiology 2012, 50: 2207-2211. PMID: 22518860, PMCID: PMC3405580, DOI: 10.1128/jcm.00216-12.Peer-Reviewed Original ResearchConceptsClinical strainsMeglumine antimoniateDrug susceptibilityCell ratioParasite burdenAntileishmanial drugsDrug susceptibility assessmentReduction of infectionParasites/cellIntracellular burdenAntimonial drugsLeishmania panamensisDrug concentrationsEffective dosesHuman macrophagesPresence of drugsL. braziliensisParasite growthHost cell ratioMiltefosineLeishmania sppDrugsL. guyanensisLeishmaniaAntimoniate
2008
Antimony Resistance and Trypanothione in Experimentally Selected and Clinical Strains of Leishmania panamensis
Goyeneche-Patino DA, Valderrama L, Walker J, Saravia NG. Antimony Resistance and Trypanothione in Experimentally Selected and Clinical Strains of Leishmania panamensis. Antimicrobial Agents And Chemotherapy 2008, 52: 4503-4506. PMID: 18824610, PMCID: PMC2592887, DOI: 10.1128/aac.01075-08.Peer-Reviewed Original Research