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
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
Development and Evaluation of a Novel Loop-Mediated Isothermal Amplification Assay for Diagnosis of Cutaneous and Visceral Leishmaniasis
Adams ER, Schoone G, Versteeg I, Gomez MA, Diro E, Mori Y, Perlee D, Downing T, Saravia N, Assaye A, Hailu A, Albertini A, Ndung'u JM, Schallig H. Development and Evaluation of a Novel Loop-Mediated Isothermal Amplification Assay for Diagnosis of Cutaneous and Visceral Leishmaniasis. Journal Of Clinical Microbiology 2018, 56: 10.1128/jcm.00386-18. PMID: 29695527, PMCID: PMC6018344, DOI: 10.1128/jcm.00386-18.Peer-Reviewed Original ResearchConceptsVisceral leishmaniasisLAMP assayDiagnostic accuracyProspective cohort trialDiagnosis of CLBone marrow aspirateMinicircle kinetoplast DNANear-patient settingIsothermal Amplification AssayCohort trialVL patientsCL diagnosisVL suspectsMarrow aspiratesMalaria parasitesSwab samplesDiagnosisWhole bloodGold standardInvasive samplesAnalytical specificityClinical samplesAmplification assaysPatientsReference standard
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 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 costsLeishmaniasisCureTreatment
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 samplesEx 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
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 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 macrophagesTransportersDetection 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
2012
Regulatory T Cells in the Pathogenesis and Healing of Chronic Human Dermal Leishmaniasis Caused by Leishmania (Viannia) Species
Rodriguez-Pinto D, Navas A, Blanco VM, Ramírez L, Garcerant D, Cruz A, Craft N, Saravia NG. Regulatory T Cells in the Pathogenesis and Healing of Chronic Human Dermal Leishmaniasis Caused by Leishmania (Viannia) Species. PLOS Neglected Tropical Diseases 2012, 6: e1627. PMID: 22545172, PMCID: PMC3335885, DOI: 10.1371/journal.pntd.0001627.Peer-Reviewed Original ResearchMeSH KeywordsAsymptomatic DiseasesCD4 AntigensChronic DiseaseFemaleFlow CytometryForkhead Transcription FactorsGene Expression ProfilingGlucocorticoid-Induced TNFR-Related ProteinHumansImmunophenotypingInterferon-gammaInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLeishmaniaLeishmaniasis, CutaneousMaleSkinT-Lymphocytes, RegulatoryConceptsRegulatory T cellsIFN-γ secretionDermal leishmaniasisPeripheral bloodT cellsSuppressive capacityCD4 T-cell frequenciesImpaired Treg functionParticipation of TregsT cell frequenciesExpression of Foxp3CD4 T cellsEnd of treatmentHealing of lesionsCdLS patientsSkin test sitesSite biopsiesTreg subsetsImmunotherapeutic strategiesTreg functionEffector cellsCutaneous lesionsFoxp3 expressionCutaneous responseInflammatory responseNovel 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
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 dogsGuyanensisBiopsy