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
2023
Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study
del Mar Castro M, Rode J, Machado P, Llanos-Cuentas A, Hueb M, Cota G, Rojas I, Orobio Y, Sarmiento O, Rojas E, Quintero J, Pimentel M, Soto J, Suprien C, Alvarez F, Ramos A, dos Santos Arantes R, da Silva R, Arenas C, Vélez I, Lyra M, Saravia N, Arana B, Alexander N. Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study. PLOS Neglected Tropical Diseases 2023, 17: e0011029. PMID: 36689465, PMCID: PMC9894540, DOI: 10.1371/journal.pntd.0011029.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntiprotozoal AgentsChildHumansLeishmaniasis, CutaneousPentamidineRetrospective StudiesTreatment OutcomeConceptsCollaborative retrospective studyRetrospective studyAdverse reactionsCutaneous leishmaniasisAge groupsMedian lesion diameterOverall cure rateOlder adult patientsMost adverse reactionsCutaneous leishmaniasis treatmentYears of ageMonotherapy regimenAdult patientsReferral centerLocal therapyPediatric populationClinical recordsCure rateCL patientsTherapeutic responseClinical trialsDisease presentationMedian numberMild intensityAntileishmanial treatment
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
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 formationHarmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation
Olliaro P, Grogl M, Boni M, Carvalho E, Chebli H, Cisse M, Diro E, Cota G, Erber A, Gadisa E, Handjani F, Khamesipour A, Llanos-Cuentas A, Carvajal L, Grout L, Lmimouni B, Mokni M, Nahzat M, Salah A, Ozbel Y, Pascale J, Molina N, Rode J, Romero G, Ruiz-Postigo J, Saravia N, Soto J, Uzun S, Mashayekhi V, Vélez I, Vogt F, Zerpa O, Arana B. Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation. PLOS Neglected Tropical Diseases 2018, 12: e0006141. PMID: 29329311, PMCID: PMC5785032, DOI: 10.1371/journal.pntd.0006141.Peer-Reviewed Original ResearchMeSH KeywordsAntiprotozoal AgentsClinical Trials as TopicHumansLeishmaniasis, CutaneousTreatment OutcomeConceptsCutaneous leishmaniasisTrial methodologyNew World cutaneous leishmaniasisLocalized Cutaneous LeishmaniasisCurrent treatment recommendationsClinical trial methodologyFuture clinical researchFuture trialsTreatment recommendationsClinical evaluationOutcome measuresCandidate treatmentSystematic reviewClinical sitesClinical researchStandardized assessmentTreatment effectsLeishmaniasisTrialsTreatmentInconsistent methodologyLevel of consensusWeak evidenceSeparate meetingsGuidance paper
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-9Cost-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 costsLeishmaniasisCureTreatmentPharmacokinetics 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
2013
Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival
Gómez MA, Navas A, Márquez R, Rojas LJ, Vargas DA, Blanco VM, Koren R, Zilberstein D, Saravia NG. Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival. Journal Of Antimicrobial Chemotherapy 2013, 69: 139-149. PMID: 23975742, PMCID: PMC3861331, DOI: 10.1093/jac/dkt334.Peer-Reviewed Original ResearchConceptsIntracellular parasite survivalParasite survivalIntracellular pathogensRNA gene knockdownDrug response genesGene expression profilingHost cell mechanismsHost cell determinantsSurvival of LeishmaniaFunctional validationExpression profilingGene knockdownGene expressionDrug transportersQuantitative RT-PCRPhagolysosomal membraneOutcome of treatmentCell-mediated regulationIntracellular parasite killingNovel mechanismPharmacokinetics/pharmacodynamicsPrimary macrophagesMetallothionein 2AHuman macrophagesTransportersClinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment
Blanco VM, Cossio A, Martinez JD, Saravia NG. Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment. American Journal Of Tropical Medicine And Hygiene 2013, 89: 359-364. PMID: 23798581, PMCID: PMC3741260, DOI: 10.4269/ajtmh.12-0784.Peer-Reviewed Original ResearchConceptsLocal treatmentCutaneous leishmaniasisNew World cutaneous leishmaniasisIndividual risk-benefit assessmentHead/neckYears of ageRisk-benefit assessmentWHO criteriaEpidemiologic profileEpidemiological profileOrganization criteriaCase reportChildren 0Months durationSingle lesionInternational guidelinesTreatment alternativesEffectiveness dataLesionsColombian childrenTreatmentChildrenLeishmaniasisNeckEligibility
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
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 ResearchMeSH KeywordsAnimalsAntimonyAntiprotozoal AgentsButhionine SulfoximineDrug ResistanceGlutathioneHumansLeishmaniaLeishmaniasisParasitic Sensitivity TestsSpermidine
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
2004
Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application.
Henao HH, Osorio Y, Saravia NG, Gómez A, Travi B. Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application. Biomédica 2004, 24: 393-402. PMID: 15678803, DOI: 10.7705/biomedica.v24i4.1289.Peer-Reviewed Original ResearchConceptsAnti-Leishmania treatmentNormal serum levelsFirst-line drugsRight hind footSite of injectionParasitological efficacySerum levelsClinical efficacyLesion reductionCure rateLine drugsPentavalent antimonialsSimilar efficacyHepatic alterationsAlanine aminotransferaseLocal toxicityClinical observationsMicroscopic signsTreatment efficacyAnimal modelsHigh dosesLeishmania panamensisAspartate aminotransferaseParasite burdenGlucantime
2003
Antimony Uptake Systems in the Protozoan Parasite Leishmania and Accumulation Differences in Antimony-Resistant Parasites
Brochu C, Wang J, Roy G, Messier N, Wang XY, Saravia NG, Ouellette M. Antimony Uptake Systems in the Protozoan Parasite Leishmania and Accumulation Differences in Antimony-Resistant Parasites. Antimicrobial Agents And Chemotherapy 2003, 47: 3073-3079. PMID: 14506011, PMCID: PMC201146, DOI: 10.1128/aac.47.10.3073-3079.2003.Peer-Reviewed Original Research