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
Randomized trial evaluating an mHealth intervention for the early community-based detection and follow-up of cutaneous leishmaniasis in rural Colombia
Castillo M, Alexander N, Rubiano L, Rojas C, Navarro A, Rincon D, Bernal L, Lerma Y, Saravia N, Aronoff-Spencer E. Randomized trial evaluating an mHealth intervention for the early community-based detection and follow-up of cutaneous leishmaniasis in rural Colombia. PLOS Neglected Tropical Diseases 2023, 17: e0011180. PMID: 36972285, PMCID: PMC10079216, DOI: 10.1371/journal.pntd.0011180.Peer-Reviewed Original ResearchConceptsEffectiveness of treatmentIntervention armWeek 26Therapeutic responseCutaneous leishmaniasisHealth systemSerious adverse eventsEnd of treatmentStart of treatmentCutaneous leishmaniasis treatmentProportion of participantsMobile health strategiesPublic health systemCommunity-based detectionTreatment of CLPrimary endpointAdverse eventsMore patientsClinical managementControl armImproved careMedical attentionNational guidelinesParallel armsHealth strategiesCutaneous 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 ResearchConceptsCollaborative 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 ResearchConceptsFractional 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 combinationsDiagnostic 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 detectionAdaptation and performance of a mobile application for early detection of cutaneous leishmaniasis
Rubiano L, Alexander N, Castillo R, Martínez Á, Luna J, Arango J, Vargas L, Madriñán P, Hurtado L, Orobio Y, Rojas C, del Corral H, Navarro A, Saravia N, Aronoff-Spencer E. Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis. PLOS Neglected Tropical Diseases 2021, 15: e0008989. PMID: 33571192, PMCID: PMC7904137, DOI: 10.1371/journal.pntd.0008989.Peer-Reviewed Original ResearchConceptsCommunity health volunteersHealth volunteersCase detectionHealth workersCutaneous leishmaniasisHealth servicesPrediction rulePassive case detectionChance-adjusted agreementCommunity health workersActive case detectionProportion of participantsMobile health technologyStudy physiciansCutaneous ulcersPresumptive diagnosisGeneral practitionersInter-rater reliabilityMedical attentionParasitological diagnosisRisk scoreEvaluation of specificityHealthcare personnelMHealth toolsMunicipality of Tumaco
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 formationSimultaneous 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 modellingHarmonized 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 ResearchConceptsCutaneous 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-9Clinical 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 costsLeishmaniasisCureTreatmentLocal 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
2016
An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections
Saldarriaga OA, Castellanos-Gonzalez A, Porrozzi R, Baldeviano GC, Lescano AG, de Los Santos MB, Fernandez OL, Saravia NG, Costa E, Melby PC, Travi BL. An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections. PLOS Neglected Tropical Diseases 2016, 10: e0004638. PMID: 27115155, PMCID: PMC4845993, DOI: 10.1371/journal.pntd.0004638.Peer-Reviewed Original ResearchConceptsMucosal leishmaniasisDiagnostic testsL. braziliensisPrimary health systemL. panamensisRPA-LFSensitive diagnostic testMost endemic regionsMolecular diagnostic testsChronic lesionsReal-time PCRCutaneous leishmaniasisEndemic regionsParasite burdenHealth systemClinical validationLeishmaniasisL. naiffiMolecular testsParasite DNALeishmania sppTime PCRClinical samplesViannia subgenusRecombinase polymerase amplification
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 samplesCost-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 ResearchMiltefosine treatmentPediatric patientsMeglumine antimoniateCutaneous leishmaniasisAntimoniatePatientsLeishmaniasisFirst 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