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
Diagnostic performance of a Recombinant Polymerase Amplification Test—Lateral Flow (RPA-LF) for cutaneous leishmaniasis in an endemic setting of Colombia
Cossio A, Jojoa J, del Mar Castro M, Castillo R, Osorio L, Shelite T, Saravia N, Melby P, Travi B. Diagnostic performance of a Recombinant Polymerase Amplification Test—Lateral Flow (RPA-LF) for cutaneous leishmaniasis in an endemic setting of Colombia. PLOS Neglected Tropical Diseases 2021, 15: e0009291. PMID: 33909619, PMCID: PMC8081229, DOI: 10.1371/journal.pntd.0009291.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolChromatography, AffinityColombiaCross-Sectional StudiesDNA PrimersDNA, KinetoplastDNA, ProtozoanFemaleHumansLeishmaniaLeishmaniasis, CutaneousMaleMiddle AgedMolecular Diagnostic TechniquesNucleic Acid Amplification TechniquesSensitivity and SpecificityYoung AdultConceptsCommunity health workersHealth workersCutaneous leishmaniasisRPA-LFReference centerHealth systemPrimary health facilitiesBurden of diseaseCross-sectional studyYears of ageRoutine diagnostic testsPublic health systemPositive likelihood ratioLeishmania kinetoplast DNANegative likelihood ratioLikelihood ratioUlcerated lesionsPolymerase chain reaction detectionSpecificity 89Endemic settingsEarly diagnosisHealth facilitiesDiagnostic test performanceWeek evolutionReal-time polymerase chain reaction detection
2018
Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships
Kip AE, del Mar Castro M, Gomez MA, Cossio A, Schellens JHM, Beijnen JH, Saravia NG, Dorlo TPC. Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships. Journal Of Antimicrobial Chemotherapy 2018, 73: 2104-2111. PMID: 29757380, PMCID: PMC6251527, DOI: 10.1093/jac/dky143.Peer-Reviewed Original ResearchConceptsExposure-response relationshipProbability of curePopulation PK modelMiltefosine concentrationsDosing simulationsPK targetPK modelNew World cutaneous leishmaniasisPlasma concentration-time curveCutaneous leishmaniasis patientsPopulation pharmacokinetic modelLarge cohort studyPopulation pharmacokinetic modellingConcentration-time curvePlasma concentration ratioDistribution rate constantMiltefosine exposureCohort studyLeishmaniasis patientsPatient populationEffect compartmentCutaneous leishmaniasisDay 1Three-compartment modelPharmacokinetic modelling
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 proportionLocal 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
2015
Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis
Rosales-Chilama M, Gongora RE, Valderrama L, Jojoa J, Alexander N, Rubiano LC, Cossio A, Adams ER, Saravia NG, Gomez MA. Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis. PLOS Neglected Tropical Diseases 2015, 9: e0004273. PMID: 26659114, PMCID: PMC4684356, DOI: 10.1371/journal.pntd.0004273.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAsymptomatic InfectionsBlotting, SouthernChildCluster AnalysisColombiaDNA, HelminthDNA, KinetoplastFemaleGenetic VariationGenotypeHumansLeishmaniaLeishmaniasis, CutaneousMaleMiddle AgedMolecular Sequence DataPhylogenyPolymerase Chain ReactionRNA, Small CytoplasmicSequence Analysis, DNASignal Recognition ParticleYoung AdultConceptsCutaneous leishmaniasisSubclinical infectionParasitological confirmationAsymptomatic infectionEndemic areasHistory of CLTest-positive individualsImmunological evidenceViability of LeishmaniaMucosal swab samplesPersistent subclinical infectionMucosal tissue samplesReservoir of infectionActive diseaseLeishmania kDNALeishmania infectionPositive individualsPersistent infectionBlood monocytesParasite burdenInfectionParasite populationsSwab samplesTransmission of diseaseTissue samples
2014
Sensitive diagnosis of cutaneous leishmaniasis by lesion swab sampling coupled to qPCR
ADAMS ER, GOMEZ MA, SCHESKE L, RIOS R, MARQUEZ R, COSSIO A, ALBERTINI A, SCHALLIG H, SARAVIA NG. Sensitive diagnosis of cutaneous leishmaniasis by lesion swab sampling coupled to qPCR. Parasitology 2014, 141: 1891-1897. PMID: 25111885, PMCID: PMC4654403, DOI: 10.1017/s0031182014001280.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisMiltefosine 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. panamensisChronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression
Navas A, Vargas DA, Freudzon M, McMahon-Pratt D, Saravia NG, Gómez MA. Chronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression. Infection And Immunity 2014, 82: 2872-2880. PMID: 24752514, PMCID: PMC4097649, DOI: 10.1128/iai.01133-13.Peer-Reviewed Original ResearchConceptsSelf-healed patientsChronic cutaneous leishmaniasisDermal leishmaniasisChemokine gene expressionClinical outcomesBiopsy specimensChronic diseasesInflammatory responseLeishmania panamensisExpression levelsCCR5 receptor geneInduction of CXCL5Montenegro skin testLesion biopsy specimensL. panamensisSelf-healing diseaseNew therapeutic targetsReverse transcription-quantitative PCRTranscription-quantitative PCRChemotactic chemokinesInflammation contributesSkin testAsymptomatic infectionInflammatory activationImmune cellsCD4 T cell activation by B cells in human Leishmania (Viannia)infection
Rodriguez-Pinto D, Saravia NG, McMahon-Pratt D. CD4 T cell activation by B cells in human Leishmania (Viannia)infection. BMC Infectious Diseases 2014, 14: 108. PMID: 24568275, PMCID: PMC3937821, DOI: 10.1186/1471-2334-14-108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB-LymphocytesBiotinCD4-Positive T-LymphocytesColombiaFemaleFlow CytometryFluorescein-5-isothiocyanateGene Expression RegulationHumansImmunoglobulin MInterferon-gammaInterleukin-6Leishmania braziliensisLeishmaniasis, CutaneousLeukocytes, MononuclearLymphocyte ActivationMaleMiddle AgedOvalbuminTumor Necrosis Factor-alphaYoung AdultConceptsCD4 T cellsCutaneous leishmaniasis patientsT cellsB cellsLeishmaniasis patientsT cell activationLeishmania antigenImmune responseCell activationT-cell activation parametersSpecific CD4 T cellsEffective adaptive immune responseCD4 T cell activationB-cell activation markersCultures of PBMCUpregulation of CD86Cell activation markersCostimulatory molecule CD86Activation markers CD25Adaptive immune responsesHuman cutaneous leishmaniasisPurified B cellsT cell culturesHuman B cell linesHuman B cells
2013
Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species
Obonaga R, Fernández O, Valderrama L, Rubiano L, del Mar Castro M, Barrera M, Gomez M, Saravia N. Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species. Antimicrobial Agents And Chemotherapy 2013, 58: 144-152. PMID: 24145529, PMCID: PMC3910710, DOI: 10.1128/aac.01023-13.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultATP Binding Cassette Transporter, Subfamily GATP-Binding Cassette TransportersChildDrug ResistanceFemaleHumansLeishmaniaLeishmaniasis, CutaneousMaleMiddle AgedMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsPhosphorylcholineProspective StudiesTreatment FailureYoung AdultConceptsTreatment failureDermal leishmaniasisQuantitative reverse transcription PCRLoss of susceptibilityMiltefosine susceptibilityDrug susceptibilityIntracellular amastigotesL. panamensis infectionsL. braziliensis infectionPanamensis infectionMucocutaneous diseaseMiltefosine treatmentBraziliensis infectionCutaneous lesionsProspective evaluationMucosal diseaseDrug exposureReverse transcription-PCRClinical failureIndividual patientsGene polymorphismsLeishmania panamensisConcurrent conditionsDecreased expressionTransporter expressionLeishmania 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 macrophagesTransporters
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
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
2007
Treponema pallidum Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow-Cytometric Analysis
Salazar JC, Cruz AR, Pope CD, Valderrama L, Trujillo R, Saravia NG, Radolf JD. Treponema pallidum Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow-Cytometric Analysis. The Journal Of Infectious Diseases 2007, 195: 879-887. PMID: 17299719, PMCID: PMC2131710, DOI: 10.1086/511822.Peer-Reviewed Original ResearchConceptsCellular immune responsesPeripheral bloodT cellsSecondary syphilisBlister fluidImmune responseControl subjectsDC-specific intercellular adhesion molecule 3DC-SIGNSystemic cellular immune responsesAdaptive cellular immune responsesEpidermal suction blistersIntercellular adhesion molecule 3Plasmacytoid dendritic cellsDermal T cellsHealthy control subjectsHuman leukocyte antigenActivation marker CD69Adaptive immune responsesMonocytes/macrophagesFlow cytometric analysisDermal leukocytesLeukocyte immunophenotypesHIV coreceptorsDendritic cells
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