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
Neutrophil 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
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
2018
Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions
Regli IB, Fernández OL, Martínez-Salazar B, Gómez MA, Saravia NG, Tacchini-Cottier F. Resistance of Leishmania (Viannia) Panamensis to Meglumine Antimoniate or Miltefosine Modulates Neutrophil Effector Functions. Frontiers In Immunology 2018, 9: 3040. PMID: 30622537, PMCID: PMC6308327, DOI: 10.3389/fimmu.2018.03040.Peer-Reviewed Original ResearchConceptsNeutrophil effector functionsMeglumine antimoniateNeutrophil extracellular trapsEffector functionsLeishmania panamensisCell surface activation markersHuman neutrophilsExpression of CD66bReactive oxygen speciesSurface activation markersDrug-susceptible strainsOutcome of infectionMain causative agentChronic lesionsActivation markersDrug-resistant linesNeutrophil activationExtracellular trapsCutaneous leishmaniasisDrug susceptibilityNeutrophilsMurine neutrophilsDecreased expressionMiltefosineNET formation
2017
Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis
Martínez-Valencia AJ, Daza-Rivera CF, Rosales-Chilama M, Cossio A, Rincón E, Desai MM, Saravia NG, Gómez MA. Clinical and parasitological factors in parasite persistence after treatment and clinical cure of cutaneous leishmaniasis. PLOS Neglected Tropical Diseases 2017, 11: e0005713. PMID: 28704369, PMCID: PMC5526576, DOI: 10.1371/journal.pntd.0005713.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisParasite persistencePercent of patientsInitiation of treatmentEnd of treatmentViability of LeishmaniaDisease reactivationTonsillar mucosaClinical cureClinical resolutionTreatment initiationProtective immunityMeglumine antimoniatePersistent infectionMucosal tissuesPrevious episodesTherapeutic cureParasitological factorsProtective factorsPatientsParasitological parametersTreatmentLeishmaniasisWeeksHigher proportionCost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis
Berger BA, Cossio A, Saravia NG, del Mar Castro M, Prada S, Bartlett AH, Pho MT. Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis. PLOS Neglected Tropical Diseases 2017, 11: e0005459. PMID: 28384261, PMCID: PMC5404883, DOI: 10.1371/journal.pntd.0005459.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAntiprotozoal AgentsCaregiversChildChild, PreschoolCost-Benefit AnalysisDirectly Observed TherapyDrug CostsFemaleHumansInjections, IntramuscularLeishmaniaLeishmaniasis, CutaneousMaleMeglumineMeglumine AntimoniateMonte Carlo MethodOrganometallic CompoundsPhosphorylcholineSensitivity and SpecificityTreatment OutcomeUnited StatesConceptsPediatric cutaneous leishmaniasisMeglumine antimoniateCutaneous leishmaniasisGovernment payer perspectivePayer perspectivePatient's perspectiveMean differenceSocietal perspectiveCost-effectiveness analysisSurvey of providersOral miltefosineAdverse eventsObserved therapyPrimary outcomeHealthcare utilizationClinical trialsMean costTreatment efficacyDrug effectivenessMiltefosineHome caregiversSocietal costsLeishmaniasisCureTreatment
2015
Cost-Effectiveness of Meglumine Antimoniate and Caretaker Directly Observed Treatment Miltefosine Treatment for Cutaneous Leishmaniasis for Pediatric Patients in Colombia
Berger B, Cossio A, Pho M, Del Mar Castro M, Prada S, Guerrero R, Bartlett A, Saravia N. Cost-Effectiveness of Meglumine Antimoniate and Caretaker Directly Observed Treatment Miltefosine Treatment for Cutaneous Leishmaniasis for Pediatric Patients in Colombia. Open Forum Infectious Diseases 2015, 2: 115. DOI: 10.1093/ofid/ofv131.35.Peer-Reviewed Original ResearchEx 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
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. 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
2007
Pharmacokinetics of Antimony in Children Treated for Leishmaniasis with Meglumine Antimoniate
Cruz A, Rainey PM, Herwaldt BL, Stagni G, Palacios R, Trujillo R, Saravia NG. Pharmacokinetics of Antimony in Children Treated for Leishmaniasis with Meglumine Antimoniate. The Journal Of Infectious Diseases 2007, 195: 602-608. PMID: 17230422, DOI: 10.1086/510860.Peer-Reviewed Original ResearchConceptsPharmacokinetics of antimonyMeglumine antimoniateDrug exposureIntramuscular meglumine antimoniateWeight-adjusted clearancePeak concentrationPotential clinical relevanceTime-concentration curveLower peak concentrationsAntimonial therapyPharmacokinetic differencesCutaneous leishmaniasisClinical relevanceChildren 3Day 20Clearance rateAntimoniateLeishmaniasisAdultsChildrenSecond groupFirst groupPharmacokineticsDaysExposure
2006
Resistance 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