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 combinations
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 expression
2011
Toll-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
Murine 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
Role of Toll-like receptors in the response of human macrophages to Leishmania panamensis infection (133.17)
Gallego C, Saravia N, Valderrama L, Golenbock D. Role of Toll-like receptors in the response of human macrophages to Leishmania panamensis infection (133.17). The Journal Of Immunology 2009, 182: 133.17-133.17. DOI: 10.4049/jimmunol.182.supp.133.17.Peer-Reviewed Original ResearchToll-like receptorsOutcome of infectionPanamensis infectionHuman macrophagesTLR ligandsL. panamensisExpression of TLR1L. panamensis infectionsLeishmania panamensis infectionActivation of TLR2Production of TNFαAmerican cutaneous leishmaniasisHuman primary macrophagesL. panamensis promastigotesPossible roleHealthy donorsCutaneous leishmaniasisTNFα productionInnate recognitionWild-type (WT) mouse macrophagesInfectionPrimary macrophagesTLR2MacrophagesPhagocytic cells
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
Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis.
Bosque F, Milon G, Valderrama L, Saravia N. Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis. Journal Of Parasitology 1998, 84: 1250-6. PMID: 9920322, DOI: 10.2307/3284682.Peer-Reviewed Original ResearchConceptsPercentage of cellsBlood monocytesInduction of differentiationLeishmania panamensis infectionHuman peripheral blood monocytesHistiocytic cell line UDifferentiated macrophagesExpression of CD68Number of amastigotesPeripheral blood monocytesOutcome of infectionSite of infectionMonocyte-derived macrophagesL. panamensis promastigotesMononuclear phagocytic cellsPhorbol myristate acetatePanamensis infectionNumber of parasitesCell line UBone marrowFresh monocytesLeishmania panamensisMonocytesResident macrophagesStages of differentiation
1996
The inflammatory response promotes cutaneous metastasis in hamsters infected with Leishmania (Viannia) panamensis.
Travi B, Osorio Y, Saravia N. The inflammatory response promotes cutaneous metastasis in hamsters infected with Leishmania (Viannia) panamensis. Journal Of Parasitology 1996, 82: 454-7. PMID: 8636852, DOI: 10.2307/3284085.Peer-Reviewed Original ResearchConceptsInflammatory responseMetastatic lesionsControl animalsL. panamensisLeishmania panamensis infectionType hypersensitivity responseFrequency of metastasisNonspecific inflammatory responseDevelopment of lesionsExperimental groupElicitation of inflammationPanamensis infectionSkin metastasesCutaneous metastasesHind pawsSurgical excisionHypersensitivity responseSite of inductionIntradermal applicationSecondary diseaseHamster modelInflammatory stimuliLeishmania panamensisMetastasisLesions
1994
Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement receptors and correlation of susceptibility in vitro with clinical phenotype.
Robledo S, Wozencraft A, Valencia A, Saravia N. Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement receptors and correlation of susceptibility in vitro with clinical phenotype. The Journal Of Immunology 1994, 152: 1265-76. PMID: 8301130, DOI: 10.4049/jimmunol.152.3.1265.Peer-Reviewed Original ResearchConceptsPeripheral blood monocytesClinical phenotypeHuman monocytesDistinctive clinical outcomesDifferent clinical groupsComplement receptors CR1Human monocyte cell line UPercentage of cellsPatterns of susceptibilityMonocyte infectionPanamensis infectionClinical outcomesDisease 5Number of parasitesStationary phase promastigotesBlood monocytesComplement receptorsCell line UHealthy individualsReceptors CR1Leishmania panamensisExperimental infectionInfectionUnexposed controlsAntireceptor antibodies
1993
Epidemiology of Cutaneous Leishmaniasis in Colombia: Environmental and Behavioral Risk Factors for Infection, Clinical Manifestations, and Pathogenicity
Weigle K, Santrich C, Martinez F, Valderrama L, Saravia N. Epidemiology of Cutaneous Leishmaniasis in Colombia: Environmental and Behavioral Risk Factors for Infection, Clinical Manifestations, and Pathogenicity. The Journal Of Infectious Diseases 1993, 168: 709-714. PMID: 8354913, DOI: 10.1093/infdis/168.3.709.Peer-Reviewed Original ResearchConceptsRisk factorsFarming occupationLeishmania panamensis infectionRisk factor informationBehavioral risk factorsAcquisition of infectionYears of ageRisk of lesionsPanamensis infectionLeishmanial lesionsClinical manifestationsMale sexActive surveillanceLeishmania infectionCase ascertainmentCutaneous leishmaniasisNew infectionsInfectionLeishmania braziliensisLesionsFactor informationStrongest predictorAgeLeishmaniasisSex
1989
The Relationship of Leishmania braziliensis Subspecies and Immune Response to Disease Expression in New World Leishmaniasis
Saravia N, Valderrama L, Labrada M, Holguin A, Navas C, Palma G, Weigle K. The Relationship of Leishmania braziliensis Subspecies and Immune Response to Disease Expression in New World Leishmaniasis. The Journal Of Infectious Diseases 1989, 159: 725-735. PMID: 2647862, DOI: 10.1093/infdis/159.4.725.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntibodies, ProtozoanAntigens, ProtozoanDose-Response Relationship, ImmunologicFluorescent Antibody TechniqueHost-Parasite InteractionsHumansHypersensitivity, DelayedImmune SeraImmunity, CellularKineticsLeishmaniaLeishmania braziliensisLeishmaniasisLeishmaniasis, MucocutaneousLymphocyte ActivationRegression AnalysisConceptsCutaneous DTHLeishmania antigenBraziliensis infectionTegumentary leishmaniasisIFAT titersDisease formsVitro lymphocyte proliferative responseCutaneous DTH responseHuman tegumentary leishmaniasisL. braziliensis infectionLymphocyte proliferative responsesImmune response parametersHigher IFAT titersNew World leishmaniasisPanamensis infectionDTH responseMucocutaneous diseaseClinical presentationLesion durationCutaneous diseaseDisease presentationImmune mechanismsImmune responseProliferative responseTime of evolution