2022
Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda
Kay K, Goodwin J, Ehrlich H, Ou J, Freeman T, Wang K, Li F, Wade M, French J, Huang L, Aweeka F, Mwebaza N, Kajubi R, Riggs M, Ruiz‐Garcia A, Parikh S. Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda. Clinical Pharmacology & Therapeutics 2022, 113: 660-669. PMID: 36260349, PMCID: PMC9981240, DOI: 10.1002/cpt.2768.Peer-Reviewed Original ResearchConceptsLopinavir-ritonavirLumefantrine concentrationsSensitive parasitesRecurrence riskPopulation PK/PD modelArtemether-lumefantrine treatmentTrimethoprim-sulfamethoxazole prophylaxisPK/PD modelPopulation PK modelFirst-order absorptionHigh transmission regionsAntiretroviral regimensLumefantrine exposureLumefantrine susceptibilityPfcrt K76Pfmdr1 N86Suboptimal dosingArtemether-lumefantrineTwo-compartment modelHIV statusRecurrent infectionsCombination therapyDrug exposurePrimary treatmentArtemisinin resistanceThe Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial
Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Wang K, Li F, Mwebaza N, Aweeka FT, Parikh S. The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial. Clinical Infectious Diseases 2022, 76: 443-452. PMID: 36130191, PMCID: PMC9907485, DOI: 10.1093/cid/ciac783.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineReinfection riskArtemisinin-based combination therapyDay 7 levelsOverall drug exposureHigh transmission settingsYoung childrenAntimalarial exposureUncomplicated malariaExtended regimenRecurrent parasitemiaControlled TrialsPrimary outcomeCombination therapyKaplan-MeierDrug exposureTotal episodesUgandan childrenArtemisinin resistanceLumefantrine concentrationsPharmacodynamic studiesHigh riskPharmacokinetic parametersRecurrence riskDay 7
2020
Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women.
Hughes E, Mwebaza N, Huang L, Kajubi R, Nguyen V, Nyunt MM, Orukan F, Mwima MW, Parikh S, Aweeka F. Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2020, 83: 140-147. PMID: 31929402, PMCID: PMC7061940, DOI: 10.1097/qai.0000000000002237.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlkynesAnti-HIV AgentsAntimalarialsAnti-Retroviral AgentsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsBenzoxazinesCyclopropanesDrug CombinationsDrug InteractionsFemaleHIV InfectionsHumansLumefantrineMalariaMalaria, FalciparumPregnancyProspective StudiesUgandaYoung AdultConceptsEfavirenz-based antiretroviral therapyImpact of efavirenzPregnant womenArtemether-lumefantrineMalaria treatmentAntiretroviral therapyEfavirenz therapyIntensive PK evaluationPK exposure parametersPlasmodium falciparum malariaEffect of efavirenzActive metabolite dihydroartemisininAntimalarial exposureClinical responseFalciparum malariaPregnant HIVTreatment regimenNonsignificant reductionClinical pharmacokinetic studiesPK evaluationDrug interactionsLumefantrine concentrationsHIVTreatment durationPK samples
2016
Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda.
Roh ME, Oyet C, Orikiriza P, Wade M, Mwanga-Amumpaire J, Boum Y, Kiwanuka GN, Parikh S. Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda. American Journal Of Tropical Medicine And Hygiene 2016, 95: 1094-1099. PMID: 27672207, PMCID: PMC5094223, DOI: 10.4269/ajtmh.16-0552.Peer-Reviewed Original ResearchMeSH KeywordsChild, PreschoolCross-Sectional StudiesDiagnostic Tests, RoutineFemaleGene FrequencyGlucosephosphate DehydrogenaseGlucosephosphate Dehydrogenase DeficiencyHumansInfantMalariaMalaria, FalciparumMalaria, VivaxMalePoint-of-Care SystemsPrevalencePrimaquineRural PopulationSensitivity and SpecificityUgandaUrban PopulationConceptsG6PDd prevalenceGlucose-6-phosphate dehydrogenase deficiencyDehydrogenase deficiencySingle-dose primaquinePlasmodium falciparum transmissionSouthwestern UgandaPlasmodium ovale infectionNegative predictive valueMonths of ageCross-sectional surveyViable screening testOvale infectionsDiagnostic modalitiesStandard quantitative assayLow prevalenceRadical curePlasmodium vivaxPredictive valueSectional surveyCare testScreening testPrevalenceSevere deficiencyPrimaquineEnzyme activityAsymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda - Volume 22, Number 8—August 2016 - Emerging Infectious Diseases journal - CDC
Roh ME, Oyet C, Orikiriza P, Wade M, Kiwanuka GN, Mwanga-Amumpaire J, Parikh S, Boum Y. Asymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda - Volume 22, Number 8—August 2016 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2016, 22: 1494-1498. PMID: 27434741, PMCID: PMC4982177, DOI: 10.3201/eid2208.160619.Peer-Reviewed Original ResearchConceptsMicroscopy-positive samplesLow malaria transmission settingsInfectious Diseases journal - CDCAsymptomatic Plasmodium infectionsMalaria transmission settingsRapid diagnostic testsP. falciparum parasitesRoutine diagnostic testingP. ovale parasitesAsymptomatic childrenPlasmodium infectionPlasmodium malariaeP. malariaeTransmission settingsFalciparum parasitesDiagnostic testingDiagnostic testsMalariaeChildrenParasitesInfectionPopulation Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
Tchaparian E, Sambol NC, Arinaitwe E, McCormack SA, Bigira V, Wanzira H, Muhindo M, Creek DJ, Sukumar N, Blessborn D, Tappero JW, Kakuru A, Bergqvist Y, Aweeka FT, Parikh S. Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria. The Journal Of Infectious Diseases 2016, 214: 1243-1251. PMID: 27471317, PMCID: PMC5034953, DOI: 10.1093/infdis/jiw338.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineRecurrent parasitemiaLumefantrine exposurePopulation pharmacokineticsUgandan childrenYoung Ugandan childrenPlasmodium falciparum malariaDay 7 concentrationsAge 6 monthsFirst-order absorptionWhole blood concentrationsYoung childrenUncomplicated malariaFalciparum malariaBlood concentrationsTreatment outcomesLumefantrine concentrationsSignificant positive correlationParasitemiaOlder childrenPharmacokineticsLumefantrineMalariaExposure levelsOpen modelAntiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children
Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clinical Infectious Diseases 2016, 63: 414-422. PMID: 27143666, PMCID: PMC4946019, DOI: 10.1093/cid/ciw291.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrine treatmentLPV/rRecurrent malariaLumefantrine exposureDrug exposureCritical drug-drug interactionsFirst-line antiretroviral therapy regimensArtemisinin-based combination therapyLopinavir/ritonavirAntiretroviral therapy regimensPlasmodium falciparum malariaHuman immunodeficiency virusDay 7 concentrationsMalaria-endemic regionsDrug-drug interactionsAntimalarial exposureAntimalarial componentPharmacokinetic samplingArtemether-lumefantrineFalciparum malariaClinical outcomesDosing regimensTherapy regimensImmunodeficiency virusCombination therapy
2015
Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria
Nyunt MM, Nguyen VK, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Mwima MW, Achan J, Aweeka F, Parikh S, Mwebaza N. Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria. Antimicrobial Agents And Chemotherapy 2015, 60: 1274-1282. PMID: 26666942, PMCID: PMC4775973, DOI: 10.1128/aac.01605-15.Peer-Reviewed Original ResearchConceptsNonpregnant adultsPregnant womenArtemether-lumefantrineFalciparum malariaUncomplicated Plasmodium falciparum malariaPharmacokinetics of artemetherPregnant Ugandan womenSix-dose regimenFirst-line regimenUncomplicated falciparum malariaPlasmodium falciparum malariaHigh transmission settingsUncomplicated malariaClinical responsePharmacokinetic exposureTerminal eliminationClinical outcomesThird trimesterTreatment responseAntimalarial efficacyProphylactic periodUgandan womenPharmacokineticsDrug resistanceOverall pharmacokineticsPopulation Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin‐Piperaquine for Uncomplicated Malaria
Sambol N, Yan L, Creek D, McCormack S, Arinaitwe E, Bigira V, Wanzira H, Kakuru A, Tappero J, Lindegardh N, Tarning J, Nosten F, Aweeka F, Parikh S. Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin‐Piperaquine for Uncomplicated Malaria. Clinical Pharmacology & Therapeutics 2015, 98: 87-95. PMID: 25732044, PMCID: PMC5088713, DOI: 10.1002/cpt.104.Peer-Reviewed Original ResearchConceptsUncomplicated malariaPopulation pharmacokineticsYoung Ugandan childrenWeight-based dosingChildren 6 monthsAge-specific guidelinesClearance/bioavailabilityFirst-order absorptionDihydroartemisinin-PiperaquinePiperaquine exposureMalaria episodesProspective trialOral dosesUgandan childrenPlasma concentrationsThree-compartment modelDay 7High dosesAge groupsEarly childhoodPiperaquineDosingPharmacokineticsMalariaPhysiological changes
2013
Pharmacokinetic Predictors for Recurrent Malaria After Dihydroartemisinin-Piperaquine Treatment of Uncomplicated Malaria in Ugandan Infants
Creek DJ, Bigira V, McCormack S, Arinaitwe E, Wanzira H, Kakuru A, Tappero JW, Sandison TG, Lindegardh N, Nosten F, Aweeka FT, Parikh S. Pharmacokinetic Predictors for Recurrent Malaria After Dihydroartemisinin-Piperaquine Treatment of Uncomplicated Malaria in Ugandan Infants. The Journal Of Infectious Diseases 2013, 207: 1646-1654. PMID: 23447696, PMCID: PMC4318925, DOI: 10.1093/infdis/jit078.Peer-Reviewed Original ResearchConceptsPiperaquine concentrationsRecurrent malariaDay 7TMP-SMXDihydroartemisinin-piperaquine treatmentPK/PD studiesTMP-SMX prophylaxisTrimethoprim-sulfamethoxazole prophylaxisTime of presentationPK/PD dataYears of ageYoung childrenPiperaquine exposureUgandan infantsUncomplicated malariaMalaria treatmentPharmacodynamic dataDP useDay 28PD studiesMalariaDay 63Strong associationPQ concentrationProphylaxis
2009
Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda
Mwesigwa J, Parikh S, McGee B, German P, Drysdale T, Kalyango JN, Clark TD, Dorsey G, Lindegardh N, Annerberg A, Rosenthal PJ, Kamya MR, Aweeka F. Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda. Antimicrobial Agents And Chemotherapy 2009, 54: 52-59. PMID: 19841149, PMCID: PMC2798532, DOI: 10.1128/aac.00679-09.Peer-Reviewed Original ResearchConceptsArtemisinin-based combination therapyUncomplicated malariaActive metaboliteConcentration-time curveWorld Health OrganizationACT regimensArtesunate-AmodiaquineLast doseArtemether-lumefantrineLevel of exposureDrug regimensVenous samplingCombination therapyUgandan childrenPK parametersPharmacokinetic dataArtemisinin derivativesPK resultsOptimum dosingRegimensLumefantrineHealth OrganizationAdultsChildrenDesethylamodiaquine
2004
Host polymorphisms and the incidence of malaria in Ugandan children.
Parikh S, Dorsey G, Rosenthal PJ. Host polymorphisms and the incidence of malaria in Ugandan children. American Journal Of Tropical Medicine And Hygiene 2004, 71: 750-3. PMID: 15642965, DOI: 10.4269/ajtmh.2004.71.750.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseWild-type childrenUgandan childrenLower incidenceHost polymorphismsParasite densityNitric oxide synthaseLow parasite densitiesIncidence of malariaHigh parasite densitySymptomatic malariaUncomplicated malariaTumor necrosisIncidence rateOxide synthaseHigh incidencePromoter polymorphismGlucose-6-phosphate dehydrogenase AMale hemizygotesMalariaIncidencePreventative measuresGlucose-6-phosphate dehydrogenaseSickle hemoglobinDehydrogenase AMolecular Evaluation of the Natural History of Asymptomatic Parasitemia in Ugandan Children
Nsobya SL, Parikh S, Kironde F, Lubega G, Kamya MR, Rosenthal PJ, Dorsey G. Molecular Evaluation of the Natural History of Asymptomatic Parasitemia in Ugandan Children. The Journal Of Infectious Diseases 2004, 189: 2220-2226. PMID: 15181569, DOI: 10.1086/421281.Peer-Reviewed Original ResearchConceptsSymptomatic malariaPolymerase chain reactionAsymptomatic parasitemiaDetectable parasitemiaNatural historySubsequent clinical malariaClinical malariaAsymptomatic childrenSymptomatic episodesMalarial parasitemiaUgandan childrenPersistent infectionParasitemiaMalariaFirst monthChain reactionMolecular evaluationChildrenHigh ratePrevalenceSimilar ratesMonthsPersistent strainsEpisodesInfection