2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalariaUnderstanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory
Nahid D, Coffey K, Bei A, Cordy R. Understanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory. PLOS Pathogens 2024, 20: e1012514. PMID: 39298535, PMCID: PMC11412506, DOI: 10.1371/journal.ppat.1012514.Peer-Reviewed Original ResearchConceptsRed blood cellsIntraerythrocytic developmentReactive oxygen speciesPlasmodium falciparum blood stagesMultiple organ systemsP. falciparum mitochondrionStatus of hemoglobinBlood stagesPlasmodium falciparumReactive oxygen species productionO2-sensing mechanismIn vitro experimentsPlasmodiumBlood cellsOxygenation statusOrgan systemsFunctional changesParasite growthOxidative stressOxygen tensionMosquito hostCulture systemDeep tissuesOxygen speciesTwo decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time
Ndiaye Y, Wong W, Thwing J, Schaffner S, Brenneman K, Tine A, Diallo M, Deme A, Sy M, Bei A, Thiaw A, Daniels R, Ndiaye T, Gaye A, Ndiaye I, Toure M, Gadiaga N, Sene A, Sow D, Garba M, Yade M, Dieye B, Diongue K, Zoumarou D, Ndiaye A, Gomis J, Fall F, Ndiop M, Diallo I, Sene D, Macinnis B, Seck M, Ndiaye M, Ngom B, Diedhiou Y, Mbaye A, Ndiaye L, Sy N, Badiane A, Hartl D, Wirth D, Volkman S, Ndiaye D. Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time. Malaria Journal 2024, 23: 205. PMID: 38982475, PMCID: PMC11234717, DOI: 10.1186/s12936-024-05024-8.Peer-Reviewed Original ResearchConceptsPfcrt K76TArtemisinin-based combination therapyPfdhps A437GSeasonal malaria chemopreventionK76TDrug resistance mutationsMolecular surveillanceA437GSulfadoxine-pyrimethamineArtesunate-amodiaquineSingle nucleotide polymorphismsDrug resistance markersResistance mutationsEfficacy of artesunate-amodiaquineWithdrawal of chloroquineMalaria control effortsP. falciparum parasitesResistance markersCombination of single nucleotide polymorphismsParasite drug resistanceWhole-genome sequencingAQ resistanceHaplotype-based analysisMalaria chemopreventionCombination therapy
2023
Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017
Yade M, Dièye B, Coppée R, Mbaye A, Diallo M, Diongue K, Bailly J, Mama A, Fall A, Thiaw A, Ndiaye I, Ndiaye T, Gaye A, Tine A, Diédhiou Y, Mbaye A, Doderer-Lang C, Garba M, Bei A, Ménard D, Ndiaye D. Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017. Malaria Journal 2023, 22: 167. PMID: 37237307, PMCID: PMC10223908, DOI: 10.1186/s12936-023-04588-1.Peer-Reviewed Original ResearchConceptsRing-stage survival assayART resistancePlasmodium falciparum isolatesMost malaria deathsLong-term useCurative treatmentCombination therapyMalaria deathsMinor variantsFalciparum isolatesPfkelch13 geneSurvival assaysParasite susceptibilityResultsAll samplesPfKelch13Spread of parasitesSaharan AfricaExMain determinantsIsolatesTherapySusceptibilityDeep sequencing approachTracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study
Ehrlich H, Somé A, Bazié T, Ebou C, Dembélé E, Balma R, Goodwin J, Wade M, Bei A, Ouédraogo J, Foy B, Dabiré R, Parikh S. Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study. The Lancet Microbe 2023, 4: e461-e469. PMID: 37086737, PMCID: PMC10365133, DOI: 10.1016/s2666-5247(23)00063-0.Peer-Reviewed Original ResearchConceptsMosquito blood mealsAntimalarial drug resistanceSurvey 3Blood-fed mosquitoesBlood samplesSurvey 1Survey 2Blood mealDrug resistanceUltrasensitive quantitative PCRHuman blood samplesCross-sectional studyMargin of equivalenceStrong surveillance systemCross-sectional surveySupplementary Materials sectionMarker of clonalityPragmatic thresholdAntimalarial resistanceDrug susceptibilityInfectious diseasesPlasmodium falciparumNational InstituteTolerabilityMaterial sectionRoutine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers
Rayack E, Askari H, Zirinsky E, Lapidus S, Sheikha H, Peno C, Kazemi Y, Yolda-Carr D, Liu C, Grubaugh N, Ko A, Wyllie A, Spatz E, Oliveira C, Bei A. Routine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers. Frontiers In Public Health 2023, 11: 1003158. PMID: 36817891, PMCID: PMC9936085, DOI: 10.3389/fpubh.2023.1003158.Peer-Reviewed Original ResearchConceptsParents/guardiansOnline patient portalYounger age groupsSARS-CoV-2Age groupsSurveillance programSaliva collectionSARS-CoV-2 testingSARS-CoV-2 screeningWeekly saliva samplesRT-PCR testingChildcare centre staffCritical age groupRoutine surveillance toolRoutine testing programsChildcare centersCOVID-19 transmissionAsymptomatic screeningSaliva collection methodNasal swabsPatient portalsSymptomatic testingPublic health dataSaliva samplesChildcare facilities
2022
Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
Lapidus S, Liu F, Casanovas-Massana A, Dai Y, Huck J, Lucas C, Klein J, Filler R, Strine M, Sy M, Deme A, Badiane A, Dieye B, Ndiaye I, Diedhiou Y, Mbaye A, Diagne C, Vigan-Womas I, Mbengue A, Sadio B, Diagne M, Moore A, Mangou K, Diallo F, Sene S, Pouye M, Faye R, Diouf B, Nery N, Costa F, Reis M, Muenker M, Hodson D, Mbarga Y, Katz B, Andrews J, Campbell M, Srivathsan A, Kamath K, Baum-Jones E, Faye O, Sall A, Vélez J, Cappello M, Wilson M, Ben-Mamoun C, Tedder R, McClure M, Cherepanov P, Somé F, Dabiré R, Moukoko C, Ouédraogo J, Boum Y, Shon J, Ndiaye D, Wisnewski A, Parikh S, Iwasaki A, Wilen C, Ko A, Ring A, Bei A. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein. Scientific Reports 2022, 12: 22175. PMID: 36550362, PMCID: PMC9778468, DOI: 10.1038/s41598-022-26709-7.Peer-Reviewed Original ResearchConceptsCross-reactive antibodiesSARS-CoV-2Positive SARS-CoV-2 antibody resultsPositive SARS-CoV-2 antibodiesSARS-CoV-2 reactivitySARS-CoV-2 antibodiesAcute malaria infectionSpike proteinAntibody test resultsPre-pandemic samplesMalaria-endemic countriesPopulation-level immunityMalaria-endemic regionsSpike S1 subunitNon-endemic countriesSARS-CoV-2 spike proteinSARS-CoV-2 proteinsPopulation-level exposureCOVID-19 transmissionMalaria exposureFalse-positive resultsMalaria infectionDisease burdenPlasmodium infectionAntibody resultsStructure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5
Mangou K, Moore A, Thiam L, Ba A, Orfanó A, Desamours I, Ndegwa D, Goodwin J, Guo Y, Sheng Z, Patel S, Diallo F, Sene S, Pouye M, Faye A, Thiam A, Nunez V, Diagne C, Sadio B, Shapiro L, Faye O, Mbengue A, Bei A. Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5. Scientific Reports 2022, 12: 19403. PMID: 36371450, PMCID: PMC9653458, DOI: 10.1038/s41598-022-23929-9.Peer-Reviewed Original ResearchConceptsImmune evasionSingle nucleotide polymorphismsPopulation prevalenceVaccine-induced protective immunityP. falciparum positive samplesFalciparum positive samplesPlasmodium falciparum antigensMalaria vaccine candidateNovel single nucleotide polymorphismsInhibitory monoclonal antibodiesProtective immunityFalciparum antigensMalaria deathsEffective vaccineEfficacious vaccineVaccine candidatesPfRH5Infected individualsVaccine targetsMonoclonal antibodiesLow overall frequencyReceptor bindingNovel genetic variantsVaccineOverall frequency
2018
Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop, Senegal, Revealed Using Genomic Surveillance
Bei AK, Niang M, Deme AB, Daniels RF, Sarr FD, Sokhna C, Talla C, Faye J, Diagne N, Doucoure S, Mboup S, Wirth DF, Tall A, Ndiaye D, Hartl DL, Volkman SK, Toure-Balde A. Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop, Senegal, Revealed Using Genomic Surveillance. The Journal Of Infectious Diseases 2018, 217: 622-627. PMID: 29325146, PMCID: PMC6279132, DOI: 10.1093/infdis/jix580.Peer-Reviewed Original Research
2017
Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes
Dankwa S, Chaand M, Kanjee U, Jiang RHY, Nobre LV, Goldberg JM, Bei AK, Moechtar MA, Grüring C, Ahouidi AD, Ndiaye D, Dieye TN, Mboup S, Weekes MP, Duraisingh MT. Genetic Evidence for Erythrocyte Receptor Glycophorin B Expression Levels Defining a Dominant Plasmodium falciparum Invasion Pathway into Human Erythrocytes. Infection And Immunity 2017, 85: 10.1128/iai.00074-17. PMID: 28760933, PMCID: PMC5607420, DOI: 10.1128/iai.00074-17.Peer-Reviewed Original ResearchConceptsInvasion pathwaysGlycophorin CGlycophorin BExpression levelsShort hairpin RNA transductionLigand-receptor interactionsErythroid progenitor cellsKnockout linesGenetic evidenceBioinformatics analysisKnockdown cellsProteomic profilingTranscript levelsMultiple proteinsHuman erythrocytesExtensive variationParasite invasionProgenitor cellsInvasion ligandsB expression levelsLaboratory strainsGPC receptorsCulture-adapted strainsPathwayReceptor usageFunctional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen
Bei AK, Ahouidi AD, Dvorin JD, Miura K, Diouf A, Ndiaye D, Premji Z, Diakite M, Mboup S, Long CA, Duraisingh MT. Functional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen. The Journal Of Infectious Diseases 2017, 216: 267-275. PMID: 28605544, PMCID: PMC5853457, DOI: 10.1093/infdis/jix280.Peer-Reviewed Original ResearchConceptsInhibitory immune responsesVaccine candidate antigenImmune responseTransgenic parasite linesMalaria-endemic regionsReticulocyte-binding protein homologuesMalaria vaccine candidateParasite linesWild-type controlsTotal IgGHumoral responseMalaria antigensAntibody responseVaccine candidatesCandidate antigensMalaria endemicityGrowth inhibition assaysInvasion ligandsAntigenic specificityImmunogenic domainsSpecific antibodiesEndemic sitesAntigenStandardized toolsInhibition assaysHigh resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations
Ndiaye YD, Diédhiou CK, Bei AK, Dieye B, Mbaye A, Mze NP, Daniels RF, Ndiaye IM, Déme AB, Gaye A, Sy M, Ndiaye T, Badiane AS, Ndiaye M, Premji Z, Wirth DF, Mboup S, Krogstad D, Volkman SK, Ahouidi AD, Ndiaye D. High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations. Malaria Journal 2017, 16: 153. PMID: 28420422, PMCID: PMC5395743, DOI: 10.1186/s12936-017-1811-2.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildChild, PreschoolDihydropteroate SynthaseDrug ResistanceGenotypeGenotyping TechniquesHumansMalaria, FalciparumMolecular Diagnostic TechniquesPlasmodiumPoint-of-Care SystemsPolymerase Chain ReactionPolymorphism, Restriction Fragment LengthSenegalTanzaniaTetrahydrofolate DehydrogenaseTransition TemperatureYoung AdultConceptsMalaria endemic sitesDrug resistanceHigh prevalenceUncomplicated Plasmodium falciparum malariaPolymerase chain reaction-restriction fragment length polymorphism methodologyAnti-malarial drug usePlasmodium falciparum malariaEndemic sitesEmergence of resistanceMultiplicity of infectionFalciparum malariaFragment length polymorphism methodologyDHFR mutationsBlood samplesMalaria endemicityPCR-RFLP genotypingPCR/RFLPTreatment policyCodon 540Drug usePlasmodium populationsMixed allelesEarly detectionCodons 51Mixed infectionsContinued Transmission of Zika Virus in Humans in West Africa, 1992–2016
Herrera BB, Chang CA, Hamel DJ, Mboup S, Ndiaye D, Imade G, Okpokwu J, Agbaji O, Bei AK, Kanki PJ. Continued Transmission of Zika Virus in Humans in West Africa, 1992–2016. The Journal Of Infectious Diseases 2017, 215: 1546-1550. PMID: 28398562, PMCID: PMC5853591, DOI: 10.1093/infdis/jix182.Peer-Reviewed Original ResearchGenetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal
Wong W, Griggs AD, Daniels RF, Schaffner SF, Ndiaye D, Bei AK, Deme AB, MacInnis B, Volkman SK, Hartl DL, Neafsey DE, Wirth DF. Genetic relatedness analysis reveals the cotransmission of genetically related Plasmodium falciparum parasites in Thiès, Senegal. Genome Medicine 2017, 9: 5. PMID: 28118860, PMCID: PMC5260019, DOI: 10.1186/s13073-017-0398-0.Peer-Reviewed Original ResearchConceptsPolygenomic infectionsRelatedness of strainsMalaria elimination activitiesPlasmodium falciparum parasitesPublic health interventionsEpidemiology modelFalciparum parasitesHealth interventionsDrug resistanceInfectionParasite populationsConclusionsOur findingsCotransmissionSuperinfection modelElimination activitiesTransmission intensityGenetic relatedness analysisGenetic profileInterventionParasitesMajor contributorPatientsPopulationSuperinfectionThiès
2016
Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
Dankwa S, Lim C, Bei AK, Jiang RH, Abshire JR, Patel SD, Goldberg JM, Moreno Y, Kono M, Niles JC, Duraisingh MT. Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite. Nature Communications 2016, 7: 11187. PMID: 27041489, PMCID: PMC4822025, DOI: 10.1038/ncomms11187.Peer-Reviewed Original ResearchConceptsInvasion ligandsSialic acid-independent pathwaysHuman RBCsZoonotic malaria parasiteAbsence of Neu5GcPlasmodium knowlesiMalaria parasitesCell surface receptorsN-glycolylneuraminic acidZoonotic parasitesSialic acid variantsSurface receptorsRBCsReceptorsNeu5GcMacaquesInvasionParasitesCMAHAcetylneuraminic acidAcid variantsHumansMalariaKnowlesi
2015
Malaria Vaccine Development: Focusing Field Erythrocyte Invasion Studies on Phenotypic Diversity The West African Merozoite Invasion Network (WAMIN)
: T, Ahouidi AD, Amambua-Ngwa A, Awandare GA, Bei AK, Conway DJ, Diakite M, Duraisingh MT, Rayner JC, Zenonos ZA. Malaria Vaccine Development: Focusing Field Erythrocyte Invasion Studies on Phenotypic Diversity The West African Merozoite Invasion Network (WAMIN). Trends In Parasitology 2015, 32: 274-283. PMID: 26725306, PMCID: PMC7021314, DOI: 10.1016/j.pt.2015.11.009.Peer-Reviewed Original ResearchConceptsVaccine candidatesBlood-stage vaccine candidatePromising vaccine targetPlasmodium falciparum merozoitesRelevant evidence baseFalciparum merozoitesVaccine targetsEvidence baseErythrocyte invasionStandardized assaysParasite survivalInvasion phenotypeInvasion studiesTrue extentField isolatesInvasionMost studiesLigands differsThe Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity
Tubman VN, Mejia P, Shmukler BE, Bei AK, Alper SL, Mitchell JR, Brugnara C, Duraisingh MT. The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity. Antimicrobial Agents And Chemotherapy 2015, 60: 613-616. PMID: 26459896, PMCID: PMC4704178, DOI: 10.1128/aac.01668-15.Peer-Reviewed Original ResearchConceptsGardos channel inhibitorChannel inhibitorsSickle cell diseaseC57BL/6 miceClinical trialsCell diseaseAntimalarial developmentPlasmodium growthErythrocyte dehydrationGardos channelSenicapocBlood stagesBiochemical profileAntimalarial activityPrimate plasmodiaVitro growthInhibitorsPatientsParasitemiaBlockadeDiseaseMiceTrialsMeasuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry
Bei AK, Duraisingh MT. Measuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry. Methods In Molecular Biology 2015, 1325: 167-186. PMID: 26450388, DOI: 10.1007/978-1-4939-2815-6_14.Peer-Reviewed Original ResearchConceptsPlasmodium falciparum merozoite invasionParasite multiplication rateErythrocyte invasion phenotypesInvasion of erythrocytesFlow cytometry methodVaccine mechanismDisease severityInvasion inhibitionEx vivoFlow cytometryMerozoite invasionCytometry methodRing stageInvasion phenotypeInvasionResearch settingsVivoImportant determinantLow levelsAlternative pathwayParasitesParasitemia
2014
Immune Characterization of Plasmodium falciparum Parasites with a Shared Genetic Signature in a Region of Decreasing Transmission
Bei AK, Diouf A, Miura K, Larremore DB, Ribacke U, Tullo G, Moss EL, Neafsey DE, Daniels RF, Zeituni AE, Nosamiefan I, Volkman SK, Ahouidi AD, Ndiaye D, Dieye T, Mboup S, Buckee CO, Long CA, Wirth DF. Immune Characterization of Plasmodium falciparum Parasites with a Shared Genetic Signature in a Region of Decreasing Transmission. Infection And Immunity 2014, 83: 276-285. PMID: 25368109, PMCID: PMC4288878, DOI: 10.1128/iai.01979-14.Peer-Reviewed Original ResearchConceptsQuantitative reverse transcription PCRCommon genetic signatureSurface antigenClinical isolatesVar genesPlasmodium falciparum parasite populationsVariant surface antigensPlasmodium falciparum parasitesParasite-infected erythrocytesImmune characterizationMajor variant surface antigenSpecific parasite genotypesReverse transcription-PCRImmune responseFalciparum parasitesImmune recognitionMalaria transmissionVar transcriptsInfected erythrocytesParasite growthParasite clonesTranscription-PCRAntibodiesParasite correlatesParasite genotypesSTEVOR Is a Plasmodium falciparum Erythrocyte Binding Protein that Mediates Merozoite Invasion and Rosetting
Niang M, Bei AK, Madnani KG, Pelly S, Dankwa S, Kanjee U, Gunalan K, Amaladoss A, Yeo KP, Bob NS, Malleret B, Duraisingh MT, Preiser PR. STEVOR Is a Plasmodium falciparum Erythrocyte Binding Protein that Mediates Merozoite Invasion and Rosetting. Cell Host & Microbe 2014, 16: 81-93. PMID: 25011110, PMCID: PMC4382205, DOI: 10.1016/j.chom.2014.06.004.Peer-Reviewed Original ResearchConceptsMerozoite invasionFalciparum erythrocyte membrane protein 1P. falciparum erythrocyte membrane protein 1Erythrocyte membrane protein 1Variant surface antigensErythrocyte binding proteinInfected erythrocyte surfaceErythrocyte-binding proteinsMembrane protein 1STEVOR expressionMalaria pathogenesisRed blood cell surfaceImmune evasionSurface antigenUninfected RBCsBlood cell surfaceGlycophorin CInfected RBCsErythrocyte surfaceParasite infectionProtein 1Invasive merozoitesForm rosettesSTEVORSchizont stage