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
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 formation
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-9
2014
Miltefosine 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 expression
2008
Antimony Resistance and Trypanothione in Experimentally Selected and Clinical Strains of Leishmania panamensis
Goyeneche-Patino DA, Valderrama L, Walker J, Saravia NG. Antimony Resistance and Trypanothione in Experimentally Selected and Clinical Strains of Leishmania panamensis. Antimicrobial Agents And Chemotherapy 2008, 52: 4503-4506. PMID: 18824610, PMCID: PMC2592887, DOI: 10.1128/aac.01075-08.Peer-Reviewed Original Research
2006
Resistance to Oxidative Stress Is Associated with Metastasis in Mucocutaneous Leishmaniasis
Acestor N, Masina S, Ives A, Walker J, Saravia NG, Fasel N. Resistance to Oxidative Stress Is Associated with Metastasis in Mucocutaneous Leishmaniasis. The Journal Of Infectious Diseases 2006, 194: 1160-1167. PMID: 16991092, DOI: 10.1086/507646.Peer-Reviewed Original ResearchConceptsMucocutaneous leishmaniasisMetastatic phenotypeMetastatic diseaseCutaneous lesionsMicrobicidal responsesMetastatic disseminationGolden hamstersNasopharyngeal tissuesCytoplasmic peroxiredoxinOxidative stressLeishmania promastigotesNonmetastatic clonesL. panamensisLeishmaniasisHost cellsParasitesPhenotypePatientsMetastasisHeat shockPathogenesisLesionsPeroxidase activityDiseaseDisseminationResistance 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
2005
Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes
Fadili K, Messier N, Leprohon P, Roy G, Guimond C, Trudel N, Saravia NG, Papadopoulou B, Légaré D, Ouellette M. Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes. Antimicrobial Agents And Chemotherapy 2005, 49: 1988-1993. PMID: 15855523, PMCID: PMC1087671, DOI: 10.1128/aac.49.5.1988-1993.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimonyAntimony Sodium GluconateATP-Binding Cassette TransportersCell LineCysteineDNA, ProtozoanDrug ResistanceGlutathioneLeishmania infantumMembrane GlycoproteinsMicroscopy, ConfocalMonocytesOligonucleotide Array Sequence AnalysisProtozoan ProteinsRibonucleoproteinsSaccharomyces cerevisiae ProteinsSpermidineTransfectionConceptsABC transporter MRPAAntimony resistanceSodium stibogluconate (SSG) resistanceTreatment of infectionsMRPA geneSodium stibogluconateAntimonial compoundsMain drugsAmastigote parasitesPutative alterationsIntracellular amastigotesLevel of expressionProtozoan parasite LeishmaniaIntracellular parasitesAxenic amastigotesButhionine sulfoximineLevels of cysteineAmastigote stageDNA microarraysS-adenosylhomocysteine hydrolaseParasite LeishmaniaPotassium antimonyl tartrateAmastigotesLeishmaniaGenes