malaria
PharmacologyPredicting the Disposition of the Antimalarial Drug Artesunate and Its Active Metabolite Dihydroartemisinin Using Physiologically Based Pharmacokinetic ModelingArtemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically based pharmacokinetic (PBPK) modeling.
Mechanisms of ResistanceSelection of Cytochrome b Mutants Is Rare among Plasmodium falciparum Patients Failing Treatment with Atovaquone-Proguanil in CambodiaAtovaquone-proguanil remains effective against multidrug-resistant Plasmodium falciparum in Southeast Asia, but resistance is mediated by a single point mutation in cytochrome b (cytb) that can arise during treatment. Among 14 atovaquone-proguanil treatment failures in a clinical trial in Cambodia, only one recrudescence harbored the cytb...
Mechanisms of ResistanceAtypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in Plasmodium falciparumThe continued emergence of drug-resistant Plasmodium falciparum parasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt) bc1 complex, which is an essential component of the mitochondrial electron transport chain (...
Clinical TherapeuticsDefining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparumThe spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum.
PharmacologyIn Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic AnaloguesBisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 2′-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant...
Epidemiology and SurveillanceContinued Low Efficacy of Artemether-Lumefantrine in Angola in 2019Biennial therapeutic efficacy monitoring is a crucial activity for ensuring the efficacy of currently used artemisinin-based combination therapy in Angola. Children with acute uncomplicated Plasmodium falciparum infection in sentinel sites in the Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate-amodiaquine (ASAQ)...
Mechanisms of Action: Physiological EffectsInhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and SurvivalOne of the major barriers in the prevention and control of malaria programs worldwide is the growing emergence of multidrug resistance in Plasmodium parasites, and this necessitates continued efforts to discover and develop effective drug molecules targeting novel proteins essential for parasite survival. In recent years, epigenetic regulators have evolved as an attractive drug target option owing to their crucial role in...
Experimental TherapeuticsChloroquine Potentiates Primaquine Activity against Active and Latent Hepatic Plasmodia Ex Vivo: Potentials and PitfallsFor a long while, 8-aminoquinoline compounds have been the only therapeutic agents against latent hepatic malaria parasites. These have poor activity against the blood-stage plasmodia causing acute malaria and must be used in conjunction with partner blood schizontocidal agents. We examined the impacts of one such agent, chloroquine, upon the activity of primaquine, an 8-aminoquinoline, against hepatic stages of...
Mechanisms of ResistanceAssociations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant WomenIntermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of...
Experimental TherapeuticsEvaluation of the Combination of Azithromycin and Naphthoquine in Animal Malaria ModelsCombination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in Plasmodium falciparum has led to a need for the...