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Publication Metadata only Oral artesunate dose-response relationship in acute falciparum malaria(2002-02-28) Brian J. Angus; Itaporn Thaiaporn; Kenechanh Chanthapadith; Yupin Suputtamongkol; Nicholas J. White; Mahidol Universityand combination treatment have largely been derived empirically. In order to characterize the in vivo dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia ≥1% were...) pharmacodynamic model typical of a dose-response curve was fitted to the relationship between dose and shortening of parasite clearance time (PCT). The Emaxwas estimated as 28.6 h, and the 50% effective concentration was 1.6 mg/kg of body weight. These resultsPublication Metadata only Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention(2014-01-01) Martin Bergstrand; François Nosten; Khin Maung Lwin; Mats O. Karlsson; Nicholas J. White; Joel Tarning; Uppsala Universitet; Mahidol University; Nuffield Department of Clinical Medicine; Shoklo Malaria Research Unit= 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal Emaxrelationship, wherePublication Metadata only Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures(2009-03-27) Tihana Bicanic; Annemarie E. Brouwer; Graeme Meintjes; Kevin Rebe; Direk Limmathurotsakur; Wirongrong Chierakul; Praprit Teparrakkul; Angela Loyse; Nicholas J. White; Robin Wood; Shabbar Jaffar; Thomas Harrison; University of Cape Town; St George's University of London; GF Jooste Hospital; Mahidol University; Sappasitthiprasong Hospital; Nuffield Department of Clinical Medicine; Radboud University Nijmegen; London School of Hygiene & Tropical MedicineObjectives: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressurePublication Metadata only Lumefantrine and desbutyl-lumefantrine population pharmacokinetic-pharmacodynamic relationships in pregnant women with uncomplicated Plasmodium falciparum malaria on the Thailand-Myanmar border(2015-10-01) Frank Kloprogge; Rose McGready; Warunee Hanpithakpong; Daniel Blessborn; Nicholas P.J. Day; Nicholas J. White; François Nosten; Joel Tarninga; Nuffield Department of Clinical Medicine; Mahidol University; WorldWide Antimalarial Resistance Network (WWARN)Copyright © 2015, Kloprogge et al. Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than those of lumefantrine. Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand. A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border. The best model was used to evaluate therapeutic outcomes with a time-to-event approach. Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an Emax model, both predicted treatment outcomes, but lumefantrine provided better predictive power. A combined model including both lumefantrine and desbutyllumefantrine did not improve the model further. Simulations suggested that cure rates in pregnant women with falciparum malaria could be increased by prolonging the treatment course. (These trials were registered at controlled-trials.com [ISRCTN 86353884].)Publication Metadata only The relationship between the haemoglobin concentration and the haematocrit in Plasmodium falciparum malaria(2008-08-22) Sue J. Lee; Kasia Stepniewska; Nicholas Anstey; Elizabeth Ashley; Karen Barnes; Tran Quang Binh; Umberto D'Alessandro; Nicholas P.J. Day; Peter J. De Vries; Grant Dorsey; Jean Paul Guthmann; Mayfong Mayxay; Paul Newton; Francois Nosten; Piero Olliaro; Lyda Osario; Loretxu Pinoges; Ric Price; Mark Rowland; Frank Smithuis; Robert Taylor; Nicholas J. White; Mahidol University; Royal Darwin Hospital; Shoklo Malaria Research Unit; University of Cape Town; Choray Hospital; Prins Leopold Instituut voor Tropische Geneeskunde; Centre for Clinical Vaccinology and Tropical Medicine; Academic Medical Centre, University of Amsterdam; University of California, San Francisco; Institut de Recherche en Sciences de la Santé; Uganda Malaria Surveillance Program; Epicentre; National University of Laos; University of Oxford; Organisation Mondiale de la Sante; Centro Internatcional de Entrenamiento e Investigaciones Medicas; London School of Hygiene & Tropical Medicinemeasure from the other. Methods. Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries, to assess the haemoglobin/haematocrit relationship at different timePublication Metadata only Comparison of plasma, venous and capillary blood levels of piperaquine in patients with uncomplicated falciparum malaria(2010-01-01) Elizabeth A. Ashley; Kasia Stepniewska; Niklas Lindegardh; Anna Annerberg; Joel Tarning; Rose McGready; Lucy Phaiphun; Pratap Singhasivanon; Nicholas J. White; François Nosten; Shoklo Malaria Research Unit; Mahidol University; Nuffield Department of Clinical Medicine. The aim of this study was to describe the relationship between piperaquine concentrations measured in capillary blood, venous blood and venous plasma. Methods Samples of plasma, whole blood obtained by venesection and capillary blood were taken... in whole blood and plasma levels of piperaquine suggest compartmentalisation of the drug within blood cells, as also occurs with the structurally related quinoline chloroquine. The relationship between piperaquine concentrations in the venous plasma, venousPublication Metadata only Intrahost modeling of artemisinin resistance in Plasmodium falciparum(2011-01-04) Sompob Saralamba; Wirichada Pan-Ngum; Richard J. Maude; Sue J. Lee; Joel Tarning; Niklas Lindegårdh; Kesinee Chotivanich; François Nosten; Nicholas P J Day; Duong Socheat; Nicholas J. White; Arjen M. Dondorp; Lisa J. White; Mahidol University; Nuffield Department of Clinical Medicine; Shoklo Malaria Research Unit; National Center for Parasitology, Entomology and Malaria Controlpharmacokinetic-pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where... 10 scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration-effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stagesPublication Metadata only The relationship between age and the manifestations of and mortality associated with severe malaria(2008-07-15) Arjen M. Dondorp; Sue J. Lee; M. A. Faiz; Saroj Mishra; Ric Price; Emiliana Tjitra; Marlar Than; Ye Htut; Sanjib Mohanty; Emran Bin Yunus; Ridwanur Rahman; Francois Nosten; Nicholas M. Anstey; Nicholas P.J. Day; Nicholas J. White; Mahidol University; Shoklo Malaria Research Unit; University of Oxford; Dhaka Medical College; Chittagong Medical College; Ispat General Hospital; Menzies School of Health Research; Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia; Defence Services General Hospital; Department of Medical ResearchBackground. The reported case-fatality rate associated with severe malaria varies widely. Whether age is an independent risk factor is uncertain. Methods. In a large, multicenter treatment trial conducted in Asia, the presenting manifestations and outcome of severe malaria were analyzed in relation to age. Results. Among 1050 patients with severe malaria, the mortality increased stepwise, from 6.1% in children (age, <10 years) to 36.5% in patients aged >50 years (P < .001). Compared with adults aged 21-50 years, the decreased risk of death among children (adjusted odds ratio, 0.06; 95% confidence interval, 0.01-0.23; P < .001) and the increased risk of death among patients aged >50 years (adjusted odds ratio, 1.88; 95% confidence interval, 1.01-3.52; P = .046) was independent of the variation in presenting manifestations. The incidence of anemia and convulsions decreased with age, whereas the incidence of hyperparasitemia, jaundice, and renal insufficiency increased with age. Coma and metabolic acidosis did not vary with age and were the strongest predictors of a fatal outcome. The number of severity signs at hospital admission also had a strong prognostic value. Conclusion. Presenting syndromes in severe malaria depend on age, although the incidence and the strong prognostic significance of coma and acidosis are similar at all ages. Age is an independent risk factor for a fatal outcome of the disease. © 2008 by the Infectious Diseases Society of America. All rights reserved.Publication Metadata only Community engagement and the social context of targeted malaria treatment: a qualitative study in Kayin (Karen) State, Myanmar(2017-02-14) Kate Sahan; Christopher Pell; Frank Smithuis; Aung Kyaw Phyo; Sai Maung Maung; Chanida Indrasuta; Arjen M. Dondorp; Nicholas J. White; Nicholas P.J. Day; Lorenz Von Seidlein; Phaik Yeong Cheah; University of Oxford; University of Amsterdam; Medical Action Myanmar; Nuffield Department of Clinical Medicine; Mahidol University; Amsterdam Institute for Global Health and Developmentpotential benefits. Community engagement was seen by staff as integral to the TMT project as a whole and not a sub-set of activities. Attitudes towards TMT (including towards community engagement) showed that developing trusting relationships helped foster... community even though staff faced time constraints. Understanding the social context of engagement helped TMT to foster respectful and trusting relationships. The complex relationship between the local context and community engagement complicated evaluationPublication Metadata only How much fat is necessary to optimize lumefantrine oral bioavailability?(2007-02-01) Elizabeth A. Ashley; Kasia Stepniewska; Niklas Lindegårdh; Anna Annerberg; Am Kham; Al Brockman; Pratap Singhasivanon; Nicholas J. White; François Nosten; Shoklo Malaria Research Unit; Mahidol University; Churchill Hospital; Menzies School of Health Researchrelationship between coadministration of fat and relative lumefantrine bioavailability, in order to determine the minimum amount of fat necessary to optimize absorption. Method: We conducted a multiple crossover pharmacokinetic study in 12 healthy volunteers... volumes of milk supplements were tested in all subjects with a 3- to 4-week washout period in-between. Results: A dose-response relationship was demonstrated between the volume of soya milk administered and lumefantrine bioavailability. AL administration