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malaria

  • Predicting the Disposition of the Antimalarial Drug Artesunate and Its Active Metabolite Dihydroartemisinin Using Physiologically Based Pharmacokinetic Modeling
    Pharmacology
    Predicting the Disposition of the Antimalarial Drug Artesunate and Its Active Metabolite Dihydroartemisinin Using Physiologically Based Pharmacokinetic Modeling

    Artemisinin-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.

    Ryan Arey, Brad Reisfeld
  • Selection of Cytochrome <em>b</em> Mutants Is Rare among <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Patients Failing Treatment with Atovaquone-Proguanil in Cambodia
    Mechanisms of Resistance
    Selection of Cytochrome b Mutants Is Rare among Plasmodium falciparum Patients Failing Treatment with Atovaquone-Proguanil in Cambodia

    Atovaquone-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...

    Jessica T. Lin, Andreea Waltmann, Kara A. Moser, Zackary Park, Yu Bin Na, Ozkan Aydemir, Nicholas F. Brazeau, Panita Gosi, Patrick W. Marsh, Meredith S. Muller, Michele Spring, Somethy Sok, Jeffrey A. Bailey, David L. Saunders, Chanthap Lon, Mariusz Wojnarski
  • Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Mechanisms of Resistance
    Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in Plasmodium falciparum

    The 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 (...

    Heather J. Painter, Joanne M. Morrisey, Michael W. Mather, Lindsey M. Orchard, Cuyler Luck, Martin J. Smilkstein, Michael K. Riscoe, Akhil B. Vaidya, Manuel Llinás
  • Open Access
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Clinical Therapeutics
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum

    The 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.

    James S. McCarthy, Azrin N. Abd-Rahman, Katharine A. Collins, Louise Marquart, Paul Griffin, Anne Kümmel, Aline Fuchs, Cornelis Winnips, Vishal Mishra, Katalin Csermak-Renner, J. Prakash Jain, Preetam Gandhi
  • Open Access
    <em>In Vivo</em> Efficacy and Metabolism of the Antimalarial Cycleanine and Improved <em>In Vitro</em> Antiplasmodial Activity of Semisynthetic Analogues
    Pharmacology
    In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues

    Bisbenzylisoquinoline (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...

    Fidelia Ijeoma Uche, Xiaozhen Guo, Jude Okokon, Imran Ullah, Paul Horrocks, Joshua Boateng, Chenggang Huang, Wen-Wu Li
  • Open Access
    Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019
    Epidemiology and Surveillance
    Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019

    Biennial 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)...

    Pedro Rafael Dimbu, Roberta Horth, Ana Luísa M. Cândido, Carolina Miguel Ferreira, Felismina Caquece, Luzala Elisabeth Armando Garcia, Kialanda André, Garcia Pembele, Domingos Jandondo, Belmira José Bondo, Benjamin Nieto Andrade, Sarah Labuda, Gabriel Ponce de León, Julia Kelley, Dhruviben Patel, Samaly S. Svigel, Eldin Talundzic, Naomi Lucchi, Joana F. M. Morais, Filomeno Fortes, José Franco Martins, Mateusz M. Pluciński
  • Inhibition of PfMYST Histone Acetyltransferase Activity Blocks <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Growth and Survival
    Mechanisms of Action: Physiological Effects
    Inhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and Survival

    One 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...

    Utsav Sen, Akshaykumar Nayak, Juhi Khurana, Deepu Sharma, Ashish Gupta
  • Open Access
    Chloroquine Potentiates Primaquine Activity against Active and Latent Hepatic Plasmodia <em>Ex Vivo</em>: Potentials and Pitfalls
    Experimental Therapeutics
    Chloroquine Potentiates Primaquine Activity against Active and Latent Hepatic Plasmodia Ex Vivo: Potentials and Pitfalls

    For 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...

    Laurent Dembélé, Jean-François Franetich, Valérie Soulard, Nadia Amanzougaghene, Shahin Tajeri, Teun Bousema, Geert-Jan van Gemert, Roger Le Grand, Nathalie Dereuddre-Bosquet, J. Kevin Baird, Dominique Mazier, Georges Snounou
  • Associations between Malaria-Preventive Regimens and <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women
    Mechanisms of Resistance
    Associations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women

    Intermittent 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...

    Patience Nayebare, Victor Asua, Melissa D. Conrad, Richard Kajubi, Abel Kakuru, Joaniter I. Nankabirwa, Dennis Muhanguzi, Grant Dorsey, Moses R. Kamya, Sam Nsobya, Philip J. Rosenthal
  • Evaluation of the Combination of Azithromycin and Naphthoquine in Animal Malaria Models
    Experimental Therapeutics
    Evaluation of the Combination of Azithromycin and Naphthoquine in Animal Malaria Models

    Combination 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...

    Zhu-Chun Bei, Guo-Fu Li, Jing-Hua Zhao, Min Zhang, Xiao-Guang Ji, Jing-Yan Wang

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