2023
MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection
Zhu W, Passalia F, Hamond C, Abe C, Ko A, Barbosa A, Wunder E. MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection. PLOS Pathogens 2023, 19: e1011313. PMID: 37486929, PMCID: PMC10399853, DOI: 10.1371/journal.ppat.1011313.Peer-Reviewed Original ResearchConceptsOuter membrane proteinsBacterial outer membrane proteinsC-terminal regionSurface-exposed regionsLeptospiral pathogenesisMDCK cell monolayersMembrane proteinsPathogenic LeptospiraImportant virulence factorMutant strainRecombinant proteinsPathogen's abilityVirulence mechanismsLysine residuesKoch's molecular postulatesBinding proteinPlasminogen receptorPathogen disseminationPathogenic spirochetesVirulence factorsProteinBacterial pathogensEssential roleMutantsHost tissuesSimplified sewerage to prevent urban leptospirosis transmission: a cluster non-randomised controlled trial protocol in disadvantaged urban communities of Salvador, Brazil
Cremonese C, Souza F, Palma F, Sodré J, Brito R, dos Santos Ribeiro P, Santana J, Coelho R, Ticona J, Nazaré R, de Oliveira D, Silva C, Eyre M, de Araújo Mendes V, Knee J, Ristow P, Stauber C, López Y, Giorgi E, Diggle P, Reis M, Cumming O, Ko A, Costa F. Simplified sewerage to prevent urban leptospirosis transmission: a cluster non-randomised controlled trial protocol in disadvantaged urban communities of Salvador, Brazil. BMJ Open 2023, 13: e065009. PMID: 37355266, PMCID: PMC10314607, DOI: 10.1136/bmjopen-2022-065009.Peer-Reviewed Original ResearchConceptsBrazilian Clinical Trials RegistryNon-randomised interventionClinical Trials RegistryNational Research Ethics CommitteeMajor health problemQuasi-experimental study designIntervention-control pairsRoute of exposureSecondary outcomesPrimary outcomeTrials RegistryResearch Ethics CommitteeRisk of exposureSerological measurementsStudy protocolTrial protocolPeer-reviewed publicationsHealth problemsControl clustersAetiological agentInfected rodentsStudy designLeptospirosis transmissionEthics CommitteeUrban slums
2022
Leptospira Infection in Rural Areas of Urabá Region, Colombia: A Prospective Study.
Quintero-Vélez J, Rodas J, Rojas C, Ko A, Wunder E. Leptospira Infection in Rural Areas of Urabá Region, Colombia: A Prospective Study. American Journal Of Tropical Medicine And Hygiene 2022, 107: 1267-1277. PMID: 36375452, PMCID: PMC9768283, DOI: 10.4269/ajtmh.21-1103.Peer-Reviewed Original ResearchConceptsOutdoor occupationsLeptospira infectionProspective studyRisk factorsMultivariable modelLeptospira seroprevalenceLogistic regression modelsEco-epidemiological aspectsMultinomial logistic regression modelsMultivariable analysisSerologic testingPrimary exposureMale genderMicroscopic agglutinationPresence of ratsOlder ageRural areasLeptospira serogroupsInfectionSeroincidenceLeptospira speciesSeroprevalenceSerogroupsRegression modelsDirt floorsLinking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil
Eyre MT, Souza FN, Carvalho-Pereira T, Nery N, de Oliveira D, Cruz JS, Sacramento GA, Khalil H, Wunder EA, Hacker KP, Hagan JE, Childs JE, Reis MG, Begon M, Diggle PJ, Ko AI, Giorgi E, Costa F. Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil. ELife 2022, 11: e73120. PMID: 36111781, PMCID: PMC9560157, DOI: 10.7554/elife.73120.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBrazilCohort StudiesEpidemiologic StudiesGeographyHumansLeptospirosisMalePoverty AreasRatsZoonosesConceptsInfection riskSignificant global public health burdenCommunity-based cohort studyGlobal public health burdenPublic health burdenAgents of leptospirosisExposure of interestYears of agePublic health interventionsHigh-risk communitiesJoint spatial modellingZoonotic spilloverCohort studyHuman infection riskMale genderSerological evidenceHealth burdenLeptospira infectionLeptospiral infectionInfection rateHealth interventionsEco-epidemiological studiesHealth surveillanceFundação de Amparo à PesquisaOswaldo Cruz FoundationEvaluation of the impact of chemical control on the ecology of Rattus norvegicus of an urban community in Salvador, Brazil
Pertile A, Lustosa R, Carvalho-Pereira T, Pedra G, Panti-May J, Oliveira U, Zeppelini C, Souza F, Oliveira D, Khalil H, Reis M, Childs J, Ko A, Begon M, Costa F. Evaluation of the impact of chemical control on the ecology of Rattus norvegicus of an urban community in Salvador, Brazil. PLOS ONE 2022, 17: e0270568. PMID: 35857771, PMCID: PMC9299319, DOI: 10.1371/journal.pone.0270568.Peer-Reviewed Original ResearchConceptsRodent control programsDemographic variablesSpirochete Leptospira interrogansControl interventionsCommunity settingsR. norvegicusChi-squareControl of zoonosesLeptospira interrogansChemical interventionDemographic characteristicsInterventionIntervention campaignsRodentsSynanthropic rodentsMonthsBody massControl programsControl practicesRattus norvegicusControl campaignsUrban poor communitiesPopulationEnvironmental transmissionAnalysis of varianceRainfall and other meteorological factors as drivers of urban transmission of leptospirosis
Cunha M, Costa F, Ribeiro GS, Carvalho MS, Reis RB, Nery N, Pischel L, Gouveia EL, Santos AC, Queiroz A, Wunder EA, Reis MG, Diggle PJ, Ko AI. Rainfall and other meteorological factors as drivers of urban transmission of leptospirosis. PLOS Neglected Tropical Diseases 2022, 16: e0007507. PMID: 35404948, PMCID: PMC9022820, DOI: 10.1371/journal.pntd.0007507.Peer-Reviewed Original Research
2021
Effect of Sewerage on the Contamination of Soil with Pathogenic Leptospira in Urban Slums
Casanovas-Massana A, Souza F, Curry M, de Oliveira D, de Oliveira AS, Eyre MT, Santiago D, Santos M, Serra RMR, Lopes E, Xavier BI, Diggle PJ, Wunder EA, Reis MG, Ko AI, Costa F. Effect of Sewerage on the Contamination of Soil with Pathogenic Leptospira in Urban Slums. Environmental Science And Technology 2021, 55: 15882-15890. PMID: 34767339, PMCID: PMC9302045, DOI: 10.1021/acs.est.1c04916.Peer-Reviewed Original ResearchGenetic Evidence for a Potential Environmental Pathway to Spillover Infection of Rat-Borne Leptospirosis
Casanovas-Massana A, de Oliveira D, Schneider AG, Begon M, Childs JE, Costa F, Reis MG, Ko AI, Wunder EA. Genetic Evidence for a Potential Environmental Pathway to Spillover Infection of Rat-Borne Leptospirosis. The Journal Of Infectious Diseases 2021, 225: 130-134. PMID: 34139761, PMCID: PMC8730487, DOI: 10.1093/infdis/jiab323.Peer-Reviewed Original ResearchConceptsPotential environmental pathwaysEnvironmental reservoirsSpillover infectionsEnvironmental pathwaysHuman leptospirosis casesSevere leptospirosisLeptospirosis infectionLeptospirosis casesMolecular epidemiologyGenetic evidencePathogenic LeptospiraLeptospira interrogansInfectionLeptospirosisUrban slumsSpillover pathwaysRat specimensReservoirPathwayUrban communitiesCommunityEpidemiologyPoverty, sanitation, and Leptospira transmission pathways in residents from four Brazilian slums
Khalil H, Santana R, de Oliveira D, Palma F, Lustosa R, Eyre MT, Carvalho-Pereira T, Reis MG, Ko AI, Diggle PJ, Lopez Y, Begon M, Costa F. Poverty, sanitation, and Leptospira transmission pathways in residents from four Brazilian slums. PLOS Neglected Tropical Diseases 2021, 15: e0009256. PMID: 33788864, PMCID: PMC8041187, DOI: 10.1371/journal.pntd.0009256.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrazilCross-Sectional StudiesFemaleHumansLeptospirosisMaleMiddle AgedPovertyPoverty AreasSanitationSocial ClassHousehold rat infestation in urban slum populations: Development and validation of a predictive score for leptospirosis
Costa F, Zeppelini CG, Ribeiro GS, Santos N, Reis RB, Martins RD, Bittencourt D, Santana C, Brant J, Reis MG, Ko AI. Household rat infestation in urban slum populations: Development and validation of a predictive score for leptospirosis. PLOS Neglected Tropical Diseases 2021, 15: e0009154. PMID: 33657101, PMCID: PMC7959339, DOI: 10.1371/journal.pntd.0009154.Peer-Reviewed Original ResearchA live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus
Wunder EA, Adhikarla H, Hamond C, Bonner K, Liang L, Rodrigues CB, Bisht V, Nally JE, Alt DP, Reis MG, Diggle PJ, Felgner PL, Ko A. A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus. ELife 2021, 10: e64166. PMID: 33496263, PMCID: PMC7837694, DOI: 10.7554/elife.64166.Peer-Reviewed Original ResearchConceptsCross-protective immunityPathogenic Leptospira speciesTerms of morbidityLeptospira speciesTransient bacteremiaSingle doseAntibody responseImmune responseApplicable vaccinesVaccine candidatesAnimal modelsEffective preventionAttenuated mutantsZoonotic diseaseLeptospira genusPotential correlatesDisease transmissionDiseaseLeptospirosisImmunityBacteremiaMorbidityImmunizationVaccineRelevant proteinsKnowledge, Attitude, and Practices regarding Leptospirosis among Visitors to a Recreational Forest in Malaysia
Shafie NJ, Halim N, Zalipah M, Amin N, Esa S, Md-Nor S, Casanovas-Massana A, Ko AI, Palma F, Souza F, Costa F. Knowledge, Attitude, and Practices regarding Leptospirosis among Visitors to a Recreational Forest in Malaysia. American Journal Of Tropical Medicine And Hygiene 2021, 104: 1290-1296. PMID: 33534768, PMCID: PMC8045624, DOI: 10.4269/ajtmh.20-0306.Peer-Reviewed Original ResearchConceptsHigh-risk groupPractice scoresWorldwide public health problemCross-sectional studyPublic health problemHigher practice scoresHigher knowledge scoresAppropriate prevention programsGood practice habitsHigh riskHealth problemsKnowledge scorePrevention programsPractice habitsLeptospirosisMajority of respondentsLeptospirosis transmissionMajor causeDiseaseTransmission routesZoonotic diseaseHigher knowledgePotential outbreaksScoresFinal model
2020
Effects of Accounting for Interval-Censored Antibody Titer Decay on Seroincidence in a Longitudinal Cohort Study of Leptospirosis
Bonner K, Cruz JS, Sacramento GA, de Oliveira D, Nery N, Carvalho M, Costa F, Childs JE, Ko AI, Diggle PJ. Effects of Accounting for Interval-Censored Antibody Titer Decay on Seroincidence in a Longitudinal Cohort Study of Leptospirosis. American Journal Of Epidemiology 2020, 190: 893-899. PMID: 33274738, PMCID: PMC8096484, DOI: 10.1093/aje/kwaa253.Peer-Reviewed Original ResearchMeSH KeywordsBrazilHumansIncidenceItalyLeptospirosisLongitudinal StudiesRisk FactorsSeroepidemiologic StudiesConceptsLongitudinal cohort studyCohort studyMicroscopic agglutination test titersAgglutination test titersHigh transmission settingsPoint-source exposureSeroincidence ratesEstimates of infectionRisk factorsTest titersReported casesEpidemiologic implicationsInfection rateMean infection rateSerological samplesSerological assaysLeptospirosis casesInfectionArboviral diseasesTiter dilutionsSeroincidenceSource exposureLeptospirosisSample size estimationIntervalSeroepidemiology of Leptospira infection in slaughtered cattle in Gauteng province, South Africa
Dogonyaro BB, van Heerden H, Potts AD, Kolo BF, Lotter C, Katsande C, Fasina FO, Ko AI, Wunder EA, Adesiyun AA. Seroepidemiology of Leptospira infection in slaughtered cattle in Gauteng province, South Africa. Tropical Animal Health And Production 2020, 52: 3789-3798. PMID: 33009586, PMCID: PMC10407966, DOI: 10.1007/s11250-020-02417-0.Peer-Reviewed Original ResearchConceptsSeroprevalence of leptospirosisMicroscopic agglutination testRisk factorsCattle populationSeropositive cattleSerogroup SejroeSouth AfricaCattleCross-sectional studyLeptospira sppPublic health importancePredominant serogroupVaccine serogroupsAbattoirLivestockLeptospira infectionGauteng ProvinceCutoff titerBlood samplesLeptospirosisSejroeDemographic dataHealth importanceAgglutination testSeroprevalenceEarly Release - Anicteric Leptospirosis-Associated Meningitis in a Tropical Urban Environment, Brazil - Volume 26, Number 9—September 2020 - Emerging Infectious Diseases journal - CDC
Nabity SA, Araújo GC, Hagan JE, Damião AO, Reis MG, Ko AI, Ribeiro GS. Early Release - Anicteric Leptospirosis-Associated Meningitis in a Tropical Urban Environment, Brazil - Volume 26, Number 9—September 2020 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2020, 26: 2190-2192. PMID: 32818405, PMCID: PMC7454101, DOI: 10.3201/eid2609.191001.Peer-Reviewed Original ResearchEscape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella
Holzapfel M, Bonhomme D, Cagliero J, Vernel-Pauillac F, d’Andon M, Bortolussi S, Fiette L, Goarant C, Wunder EA, Picardeau M, Ko AI, Werling D, Matsui M, Boneca IG, Werts C. Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella. Frontiers In Immunology 2020, 11: 2007. PMID: 32849665, PMCID: PMC7431986, DOI: 10.3389/fimmu.2020.02007.Peer-Reviewed Original ResearchConceptsTLR5 recognitionHuman Toll-like receptorsTLR5-deficient miceToll-like receptorsInnate immune recognitionNOD-like receptorsBacterial cell wall componentsHeat-killed bacteriaInflammatory roleDeficient miceTLR5 activationImmune responseLive leptospiresTLR5Immune recognitionLive strainsStealth pathogenWorldwide zoonosisHost defenseBovine TLR5TLR5 activityLeptospira sppInfectionLeptospiresCentral localizationSevere leptospirosis after rat bite: A case report
Vinholo T, Ribeiro GS, Silva NF, Cruz J, Reis MG, Ko AI, Costa F. Severe leptospirosis after rat bite: A case report. PLOS Neglected Tropical Diseases 2020, 14: e0008257. PMID: 32645040, PMCID: PMC7347098, DOI: 10.1371/journal.pntd.0008257.Peer-Reviewed Original Research
2019
Seroprevalence, Risk Factors, and Rodent Reservoirs of Leptospirosis in an Urban Community of Puerto Rico, 2015
Briskin EA, Casanovas-Massana A, Ryff KR, Morales-Estrada S, Hamond C, Perez-Rodriguez NM, Benavidez KM, Weinberger DM, Castro-Arellano I, Wunder EA, Sharp TM, Rivera-Garcia B, Ko AI. Seroprevalence, Risk Factors, and Rodent Reservoirs of Leptospirosis in an Urban Community of Puerto Rico, 2015. The Journal Of Infectious Diseases 2019, 220: 1489-1497. PMID: 31342075, PMCID: PMC6761939, DOI: 10.1093/infdis/jiz339.Peer-Reviewed Original ResearchConceptsRisk factorsAnti-Leptospira antibodiesBurden of leptospirosisRisk of infectionMicroscopic agglutination testCross-sectional surveyQuantitative polymerase chain reactionSeropositive individualsPrevious infectionPolymerase chain reactionLeptospira infectionLeptospira carriageSerogroup IcterohaemorrhagiaeHigh titersStudy participantsAgglutination testLeptospira exposurePathogenic LeptospiraInfectionRodent reservoirsChain reactionAntibodiesRodent trappingSeroprevalenceCommunity sites
2016
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis
Lindow JC, Wunder EA, Popper SJ, Min JN, Mannam P, Srivastava A, Yao Y, Hacker KP, Raddassi K, Lee PJ, Montgomery RR, Shaw AC, Hagan JE, Araújo GC, Nery N, Relman DA, Kim CC, Reis MG, Ko AI. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLOS Pathogens 2016, 12: e1005943. PMID: 27812211, PMCID: PMC5094754, DOI: 10.1371/journal.ppat.1005943.Peer-Reviewed Original ResearchConceptsHost immune responseHigh bacterial loadBacterial loadAcute leptospirosisCase fatalityFatal casesDisease progressionImmune responseHigher systemic bacterial loadsValuable new therapeutic approachPro-inflammatory cytokine receptorsAdaptive immune signaturesSystemic bacterial loadsIndependent risk factorTime of hospitalizationDuration of illnessHigh case fatalityPoor clinical outcomeNew therapeutic approachesBlood transcriptional profilingLimited study sizeFatal leptospirosisLethal leptospirosisRANTES levelsSerum cathelicidin
2015
Global Morbidity and Mortality of Leptospirosis: A Systematic Review
Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, Stein C, Abela-Ridder B, Ko AI. Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLOS Neglected Tropical Diseases 2015, 9: e0003898. PMID: 26379143, PMCID: PMC4574773, DOI: 10.1371/journal.pntd.0003898.Peer-Reviewed Original ResearchConceptsCase fatality ratioDisease morbidityFatality ratioSystematic reviewMortality of leptospirosisPulmonary hemorrhage syndromeBurden of leptospirosisLife-threatening diseaseDiverse epidemiological settingsResource-poor countriesNumber of deathsHigh morbidityGlobal morbidityGBD regionsGlobal burdenMorbidityZoonotic causesHaemorrhagic feverMortality studyUrban slum dwellersImportant causeDisease statusEpidemiological settingsDisease incidenceWHO regions