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 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
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
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 ResearchMeSH KeywordsAntimonyAntiprotozoal AgentsDrug ResistanceGene Expression ProfilingHost-Parasite InteractionsHumansLeishmania guyanensisLeishmaniasis, CutaneousMacrophagesConceptsLeishmania 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-9Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection
Ehrlich AK, Fernández OL, Rodriguez-Pinto D, Castilho TM, Caridad M, Goldsmith-Pestana K, Saravia NG, McMahon-Pratt D. Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection. Infection And Immunity 2017, 85: 10.1128/iai.00981-16. PMID: 28052994, PMCID: PMC5328479, DOI: 10.1128/iai.00981-16.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsPeripheral blood mononuclear cellsCutaneous leishmaniasisB cellsIL-17IL-13Inflammatory responseMouse modelToll-like receptor 9 ligand CpGAlternate therapeutic approachCurrent treatment optionsBlood mononuclear cellsMixed inflammatory responseRegulatory cell functionProduction of IFNPredominant etiologic agentDose-response effectHost immune responseCell populationsGrowth factor βCpG treatmentRegulatory cellsChemokine responsesIL-10Host ImmunePharmacokinetics 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
2012
Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response
Ramírez C, Díaz-Toro Y, Tellez J, Castilho TM, Rojas R, Ettinger NA, Tikhonova I, Alexander ND, Valderrama L, Hager J, Wilson ME, Lin A, Zhao H, Saravia NG, McMahon-Pratt D. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response. PLOS Neglected Tropical Diseases 2012, 6: e1866. PMID: 23145196, PMCID: PMC3493378, DOI: 10.1371/journal.pntd.0001866.Peer-Reviewed Original ResearchMeSH KeywordsGene Expression ProfilingHost-Pathogen InteractionsHumansLeishmania guyanensisMacrophagesMicroarray AnalysisRNA, MessengerTime FactorsConceptsMRNA abundance profilesMonocyte-derived macrophagesRegulation of genesDistinct biologic responsesAbundance profilesL. panamensisDifferential gene expressionEarly time pointsMacrophage responseEarly macrophage responseImmune responseLeishmania speciesHuman monocyte-derived macrophagesMicroarray evidenceOutset of infectionGene regulationActivation of PKCHuman macrophage responseGene expressionLeishmania panamensis infectionTime pointsCellular responsesAdaptive immune responsesG proteinsEarly inflammatory response
2011
Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis
Gallego C, Golenbock D, Gomez MA, Saravia NG. Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis. Infection And Immunity 2011, 79: 2871-2879. PMID: 21518783, PMCID: PMC3191987, DOI: 10.1128/iai.01388-10.Peer-Reviewed Original ResearchConceptsToll-like receptorsEndosomal Toll-like receptorsTNF-α productionMacrophage activationLeishmania panamensisTumor necrosis factor-alpha secretionNecrosis factor-alpha secretionHost macrophagesL. panamensis infectionsLack of TLR2Specific TLR ligandsBone marrow-derived macrophagesIntracellular parasite survivalTNF-α secretionMurine bone marrow-derived macrophagesMarrow-derived macrophagesHuman primary macrophagesEarly time pointsMyD88/Panamensis infectionMouse macrophage cell lineTLR4 expressionTLR ligandsHost cell responsesAlpha secretion
2008
Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia.
Rodríguez-Barraquer I, Góngora R, Prager M, Pacheco R, Montero LM, Navas A, Ferro C, Miranda MC, Saravia NG. Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia. American Journal Of Tropical Medicine And Hygiene 2008, 78: 276-82. PMID: 18256429, DOI: 10.4269/ajtmh.2008.78.276.Peer-Reviewed Original ResearchConceptsAmerican cutaneous leishmaniasisCutaneous leishmaniasisEtiologic agentLeishmania guyanensisProbable etiologic agentLeishmaniasis control programLarge epidemicsMonoclonal antibodiesLeishmania isolatesLeishmaniasisPeridomestic settingsZoonotic diseaseL. panamensisEpidemicDomestic transmissionControl programsPresent studyIsoenzyme electrophoresisIsolatesAgentsGuyanensisPatientsDiseaseDiagnosisAntibodies
2000
INTRASPECIFIC HETEROGENEITY IN THE MINI-EXON GENE LOCALIZATION OF LEISHMANIA (VIANNIA) PANAMENSIS AND LEISHMANIA (VIANNIA) GUYANENSIS FROM COLOMBIA
Pacheco R, Fernandes O, Salinas G, Segura I, Momen H, Degrave W, Saravia N, Campbell D. INTRASPECIFIC HETEROGENEITY IN THE MINI-EXON GENE LOCALIZATION OF LEISHMANIA (VIANNIA) PANAMENSIS AND LEISHMANIA (VIANNIA) GUYANENSIS FROM COLOMBIA. Journal Of Parasitology 2000, 86: 1250-1253. PMID: 11191900, DOI: 10.1645/0022-3395(2000)086[1250:ihitme]2.0.co;2.Peer-Reviewed Original ResearchConceptsMini-exon gene sequencesGene sequencesGene localizationMini-exon geneChromosomal localizationGenetic variabilityL. guyanensisIntraspecific heterogeneityDifferent karyotypesChromosomesPanamensisKbL. panamensisSpeciesLeishmania panamensisMolecular epidemiologic markerViannia subgenusHuman isolatesDistinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection
Bosque, Saravia, Valderrama, Milon. Distinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection. Scandinavian Journal Of Immunology 2000, 51: 533-541. PMID: 10792848, DOI: 10.1046/j.1365-3083.2000.00724.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedDisease SusceptibilityEndemic DiseasesFemaleHumansHypersensitivity, DelayedImmunity, InnateInterferon-gammaInterleukin-10Leishmania guyanensisLeishmaniasis, MucocutaneousMacrophagesMaleMiddle AgedMonocytesRecombinant ProteinsRecurrenceRisk FactorsTritiumTumor Necrosis Factor-alphaConceptsPeripheral blood mononuclear cellsRecurrent diseaseL. panamensis infectionsCD8 T lymphocytesType hypersensitivity responseBlood mononuclear cellsAcquired Immune ResponsesTumor necrosis factorProduction of interferonEntry of parasitesLeishmania Viannia panamensisPanamensis infectionRecurrent leishmaniasisHypersensitivity responseImmunological basisSkin testMononuclear cellsNecrosis factorT lymphocytesImmune responseSubclinical infectionLinear regression analysisEvidence of differencesDistinct innateIntracellular amastigotes
1998
Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis.
Bosque F, Milon G, Valderrama L, Saravia N. Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis. Journal Of Parasitology 1998, 84: 1250-6. PMID: 9920322, DOI: 10.2307/3284682.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCells, CulturedCricetinaeCulture MediaHumansLeishmania guyanensisMacrophagesMonocytesTime FactorsConceptsPercentage of cellsBlood monocytesInduction of differentiationLeishmania panamensis infectionHuman peripheral blood monocytesHistiocytic cell line UDifferentiated macrophagesExpression of CD68Number of amastigotesPeripheral blood monocytesOutcome of infectionSite of infectionMonocyte-derived macrophagesL. panamensis promastigotesMononuclear phagocytic cellsPhorbol myristate acetatePanamensis infectionNumber of parasitesCell line UBone marrowFresh monocytesLeishmania panamensisMonocytesResident macrophagesStages of differentiationSensitivity 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
1997
Carbohydrate and LPG expression in Leishmania viannia subgenus.
Muskus C, Segura I, Oddone R, Turco S, Leiby D, Toro L, Robledo S, Saravia N. Carbohydrate and LPG expression in Leishmania viannia subgenus. Journal Of Parasitology 1997, 83: 671-8. PMID: 9267410, DOI: 10.2307/3284245.Peer-Reviewed Original ResearchConceptsGrowth phaseLogarithmic phase promastigotesRepeat unitsViannia subgenusLPG repeat unitsSpecies referenceL. donovani lipophosphoglycanLPG expressionMolecular determinantsSubgeneraCell surfaceGlycosylated moleculesStationary phase promastigotesL. donovaniDistinct populationsBiochemical analysisExpression of carbohydratesSpeciesExpressionL. panamensisL. guyanensisSuch moleculesL. braziliensisLeishmania promastigotesFlow cytometry
1996
The inflammatory response promotes cutaneous metastasis in hamsters infected with Leishmania (Viannia) panamensis.
Travi B, Osorio Y, Saravia N. The inflammatory response promotes cutaneous metastasis in hamsters infected with Leishmania (Viannia) panamensis. Journal Of Parasitology 1996, 82: 454-7. PMID: 8636852, DOI: 10.2307/3284085.Peer-Reviewed Original ResearchConceptsInflammatory responseMetastatic lesionsControl animalsL. panamensisLeishmania panamensis infectionType hypersensitivity responseFrequency of metastasisNonspecific inflammatory responseDevelopment of lesionsExperimental groupElicitation of inflammationPanamensis infectionSkin metastasesCutaneous metastasesHind pawsSurgical excisionHypersensitivity responseSite of inductionIntradermal applicationSecondary diseaseHamster modelInflammatory stimuliLeishmania panamensisMetastasisLesions
1995
Genotypic polymorphisms in experimental metastatic dermal leishmaniasis
Pacheco R, Martinez J, Valderrama L, Momen H, Saravia N. Genotypic polymorphisms in experimental metastatic dermal leishmaniasis. Molecular And Biochemical Parasitology 1995, 69: 197-209. PMID: 7770084, DOI: 10.1016/0166-6851(94)00212-6.Peer-Reviewed Original Research
1994
Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement receptors and correlation of susceptibility in vitro with clinical phenotype.
Robledo S, Wozencraft A, Valencia A, Saravia N. Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement receptors and correlation of susceptibility in vitro with clinical phenotype. The Journal Of Immunology 1994, 152: 1265-76. PMID: 8301130, DOI: 10.4049/jimmunol.152.3.1265.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCell LineFibronectinsHumansIn Vitro TechniquesLeishmania guyanensisLeishmaniasis, MucocutaneousMonocytesReceptors, ComplementConceptsPeripheral blood monocytesClinical phenotypeHuman monocytesDistinctive clinical outcomesDifferent clinical groupsComplement receptors CR1Human monocyte cell line UPercentage of cellsPatterns of susceptibilityMonocyte infectionPanamensis infectionClinical outcomesDisease 5Number of parasitesStationary phase promastigotesBlood monocytesComplement receptorsCell line UHealthy individualsReceptors CR1Leishmania panamensisExperimental infectionInfectionUnexposed controlsAntireceptor antibodies