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
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
Local 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 Immune
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 macrophagesFirst report of Warileya rotundipennis (Psychodidae: Phlebotominae) naturally infected with Leishmania (Viannia) in a focus of cutaneous leishmaniasis in Colombia
Moreno M, Ferro C, Rosales-Chilama M, Rubiano L, Delgado M, Cossio A, Gómez MA, Ocampo C, Saravia NG. First report of Warileya rotundipennis (Psychodidae: Phlebotominae) naturally infected with Leishmania (Viannia) in a focus of cutaneous leishmaniasis in Colombia. Acta Tropica 2015, 148: 191-196. PMID: 25917717, PMCID: PMC4654406, DOI: 10.1016/j.actatropica.2015.04.017.Peer-Reviewed Original Research
2013
Detection of Leishmania RNA Virus in Leishmania Parasites
Zangger H, Ronet C, Desponds C, Kuhlmann FM, Robinson J, Hartley MA, Prevel F, Castiglioni P, Pratlong F, Bastien P, Müller N, Parmentier L, Saravia NG, Beverley SM, Fasel N. Detection of Leishmania RNA Virus in Leishmania Parasites. PLOS Neglected Tropical Diseases 2013, 7: e2006. PMID: 23326619, PMCID: PMC3542153, DOI: 10.1371/journal.pntd.0002006.Peer-Reviewed Original ResearchConceptsLeishmania RNA virusCutaneous leishmaniasisSkin lesionsPresence of LRVHyper-inflammatory immune responsePrimary skin lesionsUlcerated skin lesionsOverall exacerbationsSignificant morbidityInfected miceLesion biopsyRNA virusesSecondary lesionsImmune responseHigh riskNew World Leishmania speciesAggressive phenotypeLeishmania strainsLeishmania parasitesPatient samplesViral detectionMonoclonal antibodiesNasopharyngeal tissuesParasite strainsMetastatic phenotype
2011
Leishmania (Viannia) Infection in the Domestic Dog in Chaparral, Colombia
Santaella J, Ocampo CB, Saravia NG, Méndez F, Góngora R, Gomez MA, Munstermann LE, Quinnell RJ. Leishmania (Viannia) Infection in the Domestic Dog in Chaparral, Colombia. American Journal Of Tropical Medicine And Hygiene 2011, 84: 674-680. PMID: 21540374, PMCID: PMC3083732, DOI: 10.4269/ajtmh.2011.10-0159.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisSkin biopsy specimensHuman cutaneous leishmaniasisReservoirs of LeishmaniaEnzyme-linked immunosorbentAmerican cutaneous leishmaniasisPrevalence of infectionBiopsy specimensLeishmania infectionRisk factorsCanine infectionLeishmania guyanensisBuffy coatL. braziliensisDogsInfectionLeishmaniasisPeridomestic transmissionL. guyanensisPositive resultsBlottingMore testsDomestic dogsGuyanensisBiopsyToll-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
2010
T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species
Díaz YR, Rojas R, Valderrama L, Saravia NG. T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species. The Journal Of Infectious Diseases 2010, 202: 406-415. PMID: 20583921, PMCID: PMC4850829, DOI: 10.1086/653829.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsCoculture TechniquesCytokinesFemaleForkhead Transcription FactorsGATA3 Transcription FactorGene ExpressionGene Expression ProfilingHumansLeishmaniaLeishmaniasisLeukocytes, MononuclearMaleMiddle AgedT-Box Domain ProteinsTh1 CellsTh2 CellsTreatment OutcomeYoung AdultConceptsGATA-3 expressionT cell differentiationTumor necrosis factor alphaT-bet expressionNecrosis factor alphaT-betHuman infectionsGATA-3Th2 responsesAsymptomatic infectionFactor alphaInterleukin-4Cutaneous leishmaniasisInterferon gammaTh1/Th2 cytokine productionTh1/Th2 cytokine responseHigher T-bet expressionTh1/Th2 responseActive recurrent diseaseRecurrent cutaneous leishmaniasisTh2 cytokine responsesExperimental cutaneous leishmaniasisProinflammatory cytokine interferon-gammaInterleukin-10 secretionTh2 cytokine productionMurine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease
Castilho TM, Goldsmith‐Pestana K, Lozano C, Valderrama L, Saravia NG, McMahon‐Pratt D. Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease. European Journal Of Immunology 2010, 40: 2816-2829. PMID: 20827674, PMCID: PMC3289133, DOI: 10.1002/eji.201040384.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsChronic DiseaseDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleHumansInterferon-gammaInterleukin-13LeishmaniaLeishmaniasis, CutaneousMaleMiceMice, Inbred BALB CMice, KnockoutMiddle AgedReceptors, Interleukin-4Th1 CellsTh2 CellsTumor Necrosis Factor-alphaYoung AdultConceptsL. panamensis infectionsIL-13Panamensis infectionChronic diseasesImmunodeficient miceMurine modelMixed Th1/Th2 responseBALB/c mouse modelTh1/Th2 responsePrevalent etiologic agentHuman cutaneous leishmaniasisPresence of TNFPrevention of leishmaniasisIL-17Immunological mechanismsTh2 responsesIL-10Recurrent lesionsChronic infectionEvident lesionsMice resemblesT cellsImmune responsePersistent infectionLeishmania organisms
2009
Detection of Leishmania in Unaffected Mucosal Tissues of Patients with Cutaneous Leishmaniasis Caused by Leishmania (Viannia) Species
Figueroa RA, Lozano LE, Romero IC, Cardona MT, Prager M, Pacheco R, Diaz YR, Tellez JA, Saravia NG. Detection of Leishmania in Unaffected Mucosal Tissues of Patients with Cutaneous Leishmaniasis Caused by Leishmania (Viannia) Species. The Journal Of Infectious Diseases 2009, 200: 638-646. PMID: 19569974, PMCID: PMC5056532, DOI: 10.1086/600109.Peer-Reviewed Original ResearchConceptsKinetoplast minicircle DNAMucosal tissuesCutaneous leishmaniasisMucocutaneous leishmaniasisNasal mucosaSwab samplesMucosa of patientsLeishmania speciesPresence of LeishmaniaDetection of LeishmaniaMucosal leishmaniasisMucosal diseaseCutaneous diseaseLeishmania infectionPolymerase chain reactionParasitological evaluationPatientsLeishmania panamensisLeishmania guyanensisMucosaNatural historyLeishmaniasisLeishmania braziliensisChain reactionAsymptomatic presence
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 ResearchEtiologic 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
2006
Resistance to Oxidative Stress Is Associated with Metastasis in Mucocutaneous Leishmaniasis
Acestor N, Masina S, Ives A, Walker J, Saravia NG, Fasel N. Resistance to Oxidative Stress Is Associated with Metastasis in Mucocutaneous Leishmaniasis. The Journal Of Infectious Diseases 2006, 194: 1160-1167. PMID: 16991092, DOI: 10.1086/507646.Peer-Reviewed Original ResearchConceptsMucocutaneous leishmaniasisMetastatic phenotypeMetastatic diseaseCutaneous lesionsMicrobicidal responsesMetastatic disseminationGolden hamstersNasopharyngeal tissuesCytoplasmic peroxiredoxinOxidative stressLeishmania promastigotesNonmetastatic clonesL. panamensisLeishmaniasisHost cellsParasitesPhenotypePatientsMetastasisHeat shockPathogenesisLesionsPeroxidase activityDiseaseDisseminationEvidence 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
2005
Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes
Fadili K, Messier N, Leprohon P, Roy G, Guimond C, Trudel N, Saravia NG, Papadopoulou B, Légaré D, Ouellette M. Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes. Antimicrobial Agents And Chemotherapy 2005, 49: 1988-1993. PMID: 15855523, PMCID: PMC1087671, DOI: 10.1128/aac.49.5.1988-1993.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimonyAntimony Sodium GluconateATP-Binding Cassette TransportersCell LineCysteineDNA, ProtozoanDrug ResistanceGlutathioneLeishmania infantumMembrane GlycoproteinsMicroscopy, ConfocalMonocytesOligonucleotide Array Sequence AnalysisProtozoan ProteinsRibonucleoproteinsSaccharomyces cerevisiae ProteinsSpermidineTransfectionConceptsABC transporter MRPAAntimony resistanceSodium stibogluconate (SSG) resistanceTreatment of infectionsMRPA geneSodium stibogluconateAntimonial compoundsMain drugsAmastigote parasitesPutative alterationsIntracellular amastigotesLevel of expressionProtozoan parasite LeishmaniaIntracellular parasitesAxenic amastigotesButhionine sulfoximineLevels of cysteineAmastigote stageDNA microarraysS-adenosylhomocysteine hydrolaseParasite LeishmaniaPotassium antimonyl tartrateAmastigotesLeishmaniaGenesAmplification of human DNA by primers targeted to Leishmania kinetoplast DNA and post-genome considerations in the detection of parasites by a polymerase chain reaction.
Vergel C, Walker J, Saravia NG. Amplification of human DNA by primers targeted to Leishmania kinetoplast DNA and post-genome considerations in the detection of parasites by a polymerase chain reaction. American Journal Of Tropical Medicine And Hygiene 2005, 72: 423-9. PMID: 15827280, DOI: 10.4269/ajtmh.2005.72.423.Peer-Reviewed Original ResearchConceptsMolecular amplification techniquesPerformance of primersPolymerase chain reaction productsAmplification techniquesMonocyte DNADNA probesLeishmania kinetoplast DNANew applicationsChain reaction productsDNA amplificationHuman DNA sequencesDNA sequencesDetection of parasitesPolymerase chain reaction
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