2024
Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Goodwin J, Kajubi R, Wang K, Li F, Wade M, Orukan F, Huang L, Whalen M, Aweeka F, Mwebaza N, Parikh S. Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children. Nature Communications 2024, 15: 3817. PMID: 38714692, PMCID: PMC11076639, DOI: 10.1038/s41467-024-48210-7.Peer-Reviewed Original ResearchConceptsDay 7 lumefantrine concentrationsArtemether-lumefantrine treatmentRing-stage parasitesEarly post-treatmentEarly post-treatment periodArtemether-lumefantrineArtemisinin resistanceDay regimenMulticlonal infectionsEfficacious therapyFollow-upRandomized trialsPersistent clonesTransmission settingsEffective treatmentPost-treatment periodRegimensAntimalarial studiesStandard diagnosticsStandard 3DaysPost-treatmentChildrenTreatmentTherapy
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
Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis
Saito M, Mansoor R, Kennon K, Anvikar AR, Ashley EA, Chandramohan D, Cohee LM, D'Alessandro U, Genton B, Gilder ME, Juma E, Kalilani-Phiri L, Kuepfer I, Laufer MK, Lwin KM, Meshnick SR, Mosha D, Mwapasa V, Mwebaza N, Nambozi M, Ndiaye JA, Nosten F, Nyunt M, Ogutu B, Parikh S, Paw MK, Phyo AP, Pimanpanarak M, Piola P, Rijken MJ, Sriprawat K, Tagbor HK, Tarning J, Tinto H, Valéa I, Valecha N, White NJ, Wiladphaingern J, Stepniewska K, McGready R, Guérin PJ. Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis. The Lancet Infectious Diseases 2020, 20: 943-952. PMID: 32530424, PMCID: PMC7391007, DOI: 10.1016/s1473-3099(20)30064-5.Peer-Reviewed Original ResearchConceptsArtemisinin-based combination therapyIndividual patient dataQuinine-based treatmentsUncomplicated falciparum malariaPregnant womenArtemether-lumefantrineFalciparum malariaTreatment failureOne-stage individual patient dataSystematic reviewPatient dataObservational cohort studyAcute adverse eventsClinical Trials RegistryGametocyte carriageQuinine monotherapyAsexual parasitaemiaFever clearanceAdverse eventsCohort studyParasite clearanceTreatment guidelinesTrials RegistryCombination therapyRisk factorsEfavirenz-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
2018
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
Kloprogge F, Workman L, Borrmann S, Tékété M, Lefèvre G, Hamed K, Piola P, Ursing J, Kofoed PE, Mårtensson A, Ngasala B, Björkman A, Ashton M, Hietala S, Aweeka F, Parikh S, Mwai L, Davis TME, Karunajeewa H, Salman S, Checchi F, Fogg C, Newton PN, Mayxay M, Deloron P, Faucher JF, Nosten F, Ashley EA, McGready R, van Vugt M, Proux S, Price RN, Karbwang J, Ezzet F, Bakshi R, Stepniewska K, White NJ, Guerin PJ, Barnes KI, Tarning J. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis. PLOS Medicine 2018, 15: e1002579. PMID: 29894518, PMCID: PMC5997317, DOI: 10.1371/journal.pmed.1002579.Peer-Reviewed Original ResearchConceptsPregnant womenArtemether-lumefantrineCure rateClinical studiesYoung childrenCurrent standard treatment regimenUncomplicated Plasmodium falciparum malariaPharmacokinetic modelAbsorption of lumefantrinePre-treatment parasitaemiaVenous plasma dataAlternative dosing regimensPlasmodium falciparum malariaStandard treatment regimenProspective clinical studyNon-pregnant adultsLow cure ratePopulation pharmacokinetic modelRelevant clinical studiesUseful therapeutic lifeFrequency of dosingConcentration-time dataHigher individual dosesLumefantrine exposureLumefantrine levels
2016
Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children
Kajubi R, Huang L, Were M, Kiconco S, Li F, Marzan F, Gingrich D, Nyunt MM, Ssebuliba J, Mwebaza N, Aweeka FT, Parikh S. Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children. Open Forum Infectious Diseases 2016, 3: ofw217. PMID: 28018925, PMCID: PMC5170492, DOI: 10.1093/ofid/ofw217.Peer-Reviewed Original ResearchParasite clearanceArtemether-lumefantrineDHA exposureUgandan childrenHuman immunodeficiency virus (HIV) infectionArtemether-lumefantrine treatmentDaily blood smearsEarly parasite clearanceInitial parasite clearanceImmunodeficiency virus infectionLopinavir/ritonavirHuman immunodeficiency virusParasite clearance ratesAL efficacyArtemisinin pharmacokineticsAntiretroviral therapyHIV statusImmunodeficiency virusPK exposureArtemisinin resistanceTreatment outcomesVirus infectionHIVPharmacokinetic parametersBlood smearsPopulation 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 pharmacokineticsThe epidemiological impact of HIV antiretroviral therapy on malaria in children
Greenhalgh S, Ndeffo M, Galvani AP, Parikh S. The epidemiological impact of HIV antiretroviral therapy on malaria in children. AIDS 2015, 29: 473-482. PMID: 25486414, PMCID: PMC4391884, DOI: 10.1097/qad.0000000000000550.Peer-Reviewed Original ResearchConceptsHIV protease inhibitorsRecurrent malariaMalaria transmissionAntiretroviral therapyArtemether-lumefantrineAnnual incidenceProtease inhibitorsFirst-line antiretroviral regimenFirst-line antiretroviral therapyArtemether-lumefantrine treatmentHIV-negative childrenFirst-line antimalarialsHIV prevalence settingsHIV antiretroviral therapyRecent clinical trialsHIV prevalence levelsMalaria transmission settingsMalaria transmission intensityAntiretroviral regimenAntimalarial treatmentHIV prevalenceProphylactic effectPrevalence settingsClinical trialsHealth burden
2011
Antimalarial Agents
Parikh S, Lee M, Aweeka F. Antimalarial Agents. Infectious Disease 2011, 561-579. DOI: 10.1007/978-1-61779-213-7_16.Peer-Reviewed Original ResearchOld antimalarial drugMainstay of treatmentCases of malariaDrug-drug interactionsTreatment of malariaImportant infectious diseasesWorld Health OrganizationUncomplicated malariaArtemether-lumefantrinePharmacodynamic interactionsSulfadoxine-pyrimethamineACT drugsCombination therapyPartner drugsProphylactic useArtemisinin drugsDrug interactionsMalaria therapyDrug combinationsOld drugsComplex pharmacologyVirulent human malariaMalaria todayAntimalarial drugsACT exposure
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