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 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
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 proportionPharmacokinetics 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 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 macrophages
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. panamensis
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 expressionClinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment
Blanco VM, Cossio A, Martinez JD, Saravia NG. Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment. American Journal Of Tropical Medicine And Hygiene 2013, 89: 359-364. PMID: 23798581, PMCID: PMC3741260, DOI: 10.4269/ajtmh.12-0784.Peer-Reviewed Original ResearchConceptsLocal treatmentCutaneous leishmaniasisNew World cutaneous leishmaniasisIndividual risk-benefit assessmentHead/neckYears of ageRisk-benefit assessmentWHO criteriaEpidemiologic profileEpidemiological profileOrganization criteriaCase reportChildren 0Months durationSingle lesionInternational guidelinesTreatment alternativesEffectiveness dataLesionsColombian childrenTreatmentChildrenLeishmaniasisNeckEligibility
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
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
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
2003
Efficacy of amodiaquine and sulfadoxine/pyrimethamine in the treatment of malaria not complicated by Plasmodium falciparum in Nariño, Colombia, 1999-2002.
González IJ, Padilla JO, Giraldo LE, Saravia NG. Efficacy of amodiaquine and sulfadoxine/pyrimethamine in the treatment of malaria not complicated by Plasmodium falciparum in Nariño, Colombia, 1999-2002. Biomédica 2003, 23: 38-46. PMID: 12696398, DOI: 10.7705/biomedica.v23i1.1196.Peer-Reviewed Original ResearchConceptsSulfadoxine/pyrimethamineTreatment failureUncomplicated Plasmodium falciparum malariaCombination of amodiaquineEfficacy of amodiaquinePlasmodium falciparum malariaSP treatment failureModerate malaria transmissionAntimalarial drug resistanceTreatment of malariaFalciparum malariaAntimalarial treatmentTherapeutic failureAntimalarial resistanceCurrent doseAntimalarial efficacyMalaria transmissionPatientsAntimalarial drugsDrug resistanceAmodiaquinePlasmodium falciparumTreatment regimesMalariaEfficacy
2000
Distinct 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
Frequency of the Asn-108 and Thr-108 point mutations in the dihydrofolate reductase gene in Plasmodium falciparum from southwest Colombia.
Giraldo L, Acosta M, Labrada L, Praba A, Montenegro-James S, Saravia N, Krogstad D. Frequency of the Asn-108 and Thr-108 point mutations in the dihydrofolate reductase gene in Plasmodium falciparum from southwest Colombia. American Journal Of Tropical Medicine And Hygiene 1998, 59: 124-8. PMID: 9684639, DOI: 10.4269/ajtmh.1998.59.124.Peer-Reviewed Original Research
1997
In Situ Characterization of the Human Host Response to Leishmania panamensis
Palma G, Saravia N. In Situ Characterization of the Human Host Response to Leishmania panamensis. American Journal Of Dermatopathology 1997, 19: 585-590. PMID: 9415615, DOI: 10.1097/00000372-199712000-00006.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsAntibodies, ProtozoanAntigen-Antibody ReactionsAntigens, ProtozoanBiomarkersBiopsyCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEpidermisFluorescent Antibody Technique, IndirectGranulocytesGranulomaHumansImmunity, CellularImmunohistochemistryLeishmaniaLeishmaniasisLymphocyte ActivationMaleMiddle AgedNecrosisRegression AnalysisSkinConceptsHuman host responseHost responseLeishmania panamensisPresence of amastigotesT cell subpopulationsImmune response dataIndirect immunoperoxidase methodCD8 ratioDermal infiltrateMale patientsHistopathologic changesParticular cell populationPrognostic indicatorLeishmania infectionSkin biopsiesPlasma cellsT cellsDermal distributionCutaneous leishmaniasisProspective analysisB cellsB lymphocytesUpper dermisImmunoperoxidase methodDisease evolution