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
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. guyanensisLeishmaniaAntimoniateNoninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children
Rubiano L, Miranda M, Arenas S, Montero L, Rodríguez-Barraquer I, Garcerant D, Prager M, Osorio L, Rojas M, Pérez M, Nicholls R, Saravia N. Noninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children. The Journal Of Infectious Diseases 2012, 205: 684-692. PMID: 22238470, PMCID: PMC3266136, DOI: 10.1093/infdis/jir816.Peer-Reviewed Original ResearchConceptsPediatric cutaneous leishmaniasisMeglumine antimoniateCutaneous leishmaniasisTreatment failureInitiation of treatmentNoninferiority clinical trialPercent of childrenLow response rateOral miltefosineAdverse eventsMasked evaluationPrimary outcomeTreat analysisWeek 26Clinical trialsOral administrationAntimonial drugsTreatment groupsResponse rateAntimoniateLeishmania panamensisLeishmania guyanensisMiltefosineLeishmaniasisElimination rate
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 resultsInfectionResistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection
Rojas R, Valderrama L, Valderrama M, Varona MX, Ouellette M, Saravia NG. Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection. The Journal Of Infectious Diseases 2006, 193: 1375-1383. PMID: 16619185, DOI: 10.1086/503371.Peer-Reviewed Original ResearchConceptsTreatment failureMeglumine antimoniatePrimary resistanceAntimonial drugsSecondary resistanceDrug resistanceHuman Leishmania infectionsEffective immune responseAnthroponotic visceral leishmaniasisAmerican cutaneous leishmaniasisAntimonial therapyStandard treatmentCutaneous diseaseLeishmania infectionTherapeutic responseImmune responseCutaneous leishmaniasisVisceral leishmaniasisAnthroponotic transmissionResistant organismsEffective doseIntracellular amastigotesSusceptible strainsAntimoniatePatients
1998
Sensitivity of Leishmania viannia panamensis to Pentavalent Antimony Is Correlated with the Formation of Cleavable DNA-Protein Complexes
Lucumi A, Robledo S, Gama V, Saravia N. Sensitivity of Leishmania viannia panamensis to Pentavalent Antimony Is Correlated with the Formation of Cleavable DNA-Protein Complexes. Antimicrobial Agents And Chemotherapy 1998, 42: 1990-1995. PMID: 9687395, PMCID: PMC105721, DOI: 10.1128/aac.42.8.1990.Peer-Reviewed Original ResearchConceptsSbv/Sodium stibogluconateAntimonial drugsHuman promonocytic cell line UCleavable complexLeishmania Viannia panamensisAntimonial agentsMedian ED50Meglumine antimoniateCell line UEffective doseEffects of camptothecinPentavalent antimonyPromastigotes of LeishmaniaReports of inhibitionInhibitors of topoisomeraseInhibition of topoisomeraseLeishmania donovaniL. panamensisLeishmaniaAntimoniatePatientsRelapseStibogluconateLine U