13 results
Search Results
Now showing 1 - 10 of 13
Publication Open Access Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria(2016) Thanaporn Wattanakul; Pramote Teerapong; Plewes, Katherine; Newton, Paul N.; Wirongrong Chierakul; Kamolrat Silamut; Kesinee Chotivanich; Ronnatrai Ruengweerayut; White, Nicholas J.; Dondorp, Arjen M.; Tarning, Joel; Mahidol University. Faculty of Tropical Medicine. Mahidol‑Oxford Tropical Medicine Research Unit.Background: Fever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take... the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed. Methods: A randomized, open-label, two-treatmentPublication Open Access Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda.(2012-08-22) Tarning, Joel; Kloprogge, Frank; Piola, Patrice; Dhorda, Mehul; Muwanga, Sulaiman; Turyakira, Eleanor; Nitra Nuengchamnong; นิทรา เนื่องจำนงค์; Nosten, François; Day, Nicholas P.J.; White, Nicholas J.; Guerin, Philippe J.; Lindegardh, Niklas; Tarning, Joel; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.BACKGROUND: Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. METHODS: Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies. RESULTS: The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches. CONCLUSION: The population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated P. falciparum malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group.Publication Open Access Microsatellite genotyping of Plasmodium vivax infections and their relapses in pregnant and non-pregnant patients on the Thai-Myanmar border(2013) Supinya Thanapongpichat; McGready, Rose; Luxemburger, Christine; Day, Nicholas PJ.; White, Nicholas J.; Nosten, Francois; Snounou, Georges; Mallika Imwong; Mahidol University. Faculty of Tropical Medicine. Molecular Tropical Medicine and Geneticsin pregnant and non-pregnant patients, and/or between the admission infections and recurrent episodes during follow-up. Methods: Blood samples were collected from 18 pregnant and 18 non-pregnant patients, who had at least two recurrent episodes during... markers. Analyses of the genetic diversity, multiplicity of infection (MOI), and a comparison of the genotypes in the samples from each patient were conducted. Results: The P. vivax parasites present in the samples exhibited high genetic diversity (6Publication Open Access Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized,non-inferiority, trial(2010-04) Awab, Ghulam Rahim; Sasithon Pukrittayakamee; ศศิธร ผู้กฤตยาคามี; Mallika Imwong; มัลลิกา อิ่มวงศ์; Dondorp, Arjen M.; Woodrow, Charles J.; Lee, Sue Jean; Day, Nicholas P.J.; Pratap Singhasivanon; ประตาป สิงหศิวานนท์; White, Nicholas J.; Kaker, Faizullah; White, Nicholas J.; Mahidol University. Faculty of Tropical Mediicne. Therapeutic responses across Afghanistan have not been evaluated in detail. METHODS: Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and overPublication Open Access Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos.(2012-06-8) Mayfong Mayxay; Maniphone Khanthavong; Odai Chanthongthip; Mallika Imwong; มัลลิกา อิ่มวงศ์; Tiengkham Pongvongsa; Bouasy Hongvanthong; Samalane Phompida; Viengxay Vanisaveth; White, Nicholas J.; Newton, Paul N; Mayfong Mayxay; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Geneticsmalaria. RESULTS: Of 630 patients with P. falciparum enrolled in the trial of thiamin treatment, 549 (87%, 357 children ≤15 years and 192 adults) were included in this study. The per protocol 42-day cure rates were 97% (524/541) [96% (337/352... of patients who remained parasitaemic at day 1 after treatment was significantly higher in children [33% (116/356)] compared to adults [15% (28/192)] (p < 0.001) and only one adult patient had detectable parasitaemia on day 2. There were no serious adversePublication Open Access In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.(2012-10-26) Hien, Tran Tinh; Thuy-Nhien, Nguyen Thanh; Phu, Nguyen Hoan; Boni, Maciej F.; Thanh, Ngo Viet; Nha-Ca, Nguyen Thuy; Thai, Le Hong; Thai, Cao Quang; Toi, Pham Van; Thuan, Phung Duc; Long, Le Thanh; Dong, Le Thanh; Merson, Laura; Dolecek, Christiane; Stepniewska, Kasia; Ringwald, Pascal; White, Nicholas J.; Farrar, Jeremy; Wolbers, Marcel; Hien, Tran Tinh; Mahidol University. Faculty of Tropical Medicineclearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. RESULTS: 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2....72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasitePublication Open Access Primaquine radical cure of Plasmodium vivax: a critical review of the literature(2012-08-17) John, George K.; Douglas, Nicholas M.; Seidlein, Lorenz von; Nosten, Francois; Baird, J. Kevin; White, Nicholas J.; Price, Ric N.; Price, Ric N.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit.stratifying by total treatment dose and duration of study follow up. RESULTS: Data could be retrieved from 87 clinical trials presenting data in 59,735 patients enrolled into 156 treatment arms, conducted in 20 countries. There was marked heterogeneity... was no different from patients who did not receive primaquine (OR = 0.60, 95%CI 0.33-1.09, p = 0.09), whereas for the low dose regimens a significant difference was reported in 50% (6/12) of studies (overall OR = 0.14, 95%CI: 0.06-0.35, p < 0.001). Two studiesPublication Open Access Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria(2012-08-16) Thiranut Ramutton; Hendriksen, Ilse CE; Mwanga-Amumpaire, Juliet; Mtove, George; Olaosebikan, Rasaq; Tshefu, Antoinette K.; Onyamboko, Marie A.; Karema, Corine; Maitland, Kathryn; Gomes, Ermelinda; Gesase, Samwel; Reyburn, Hugh; Kamolrat Silamut; Kesinee Chotivanich; เกศินี โชติวานิช; Kamoltip Promnares; Fanello, Caterina I.; Seidlein, Lorenz von; Day, Nicholas P.J.; White, Nicholas J.; Dondorp, Arjen M.; Mallika Imwong; มัลลิกา อิ่มวงศ์; Woodrow, Charles J.; Woodrow, Charles J.; Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. METHODS: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in sevenPublication Open Access Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan(2013-03-15) Awab, Ghulam R; Sasithon Pukrittayakamee; ศศิธร ผู้กฤตยาคามี; Natsuda Jamornthanyawat; นาถสุดา จามรธัญญวาท; Yamin, Fazel; Dondorp, Arjen M.; Day, Nicholas P.J.; White, Nicholas J.; Woodrow, Charles J.; Mallika Imwong; มัลลิกา อิ่มวงศ์; Mallika Imwong; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU); Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics; Mahidol University. Center for Emerging and Neglected Infectious Diseasesthe current state of drug susceptibility to the SP component, and can also provide information on the likely efficacy of other potential forms of artemisinin-combination therapy. METHODS: During the years 2007 to 2010, 120 blood spots from patients with P... to be assessed in significant numbers of patients, but these results are clearly concerning since they suggest a higher degree of SP resistance than previously detected. Further focused molecular and clinical studies in this region are urgently required.Publication Open Access A review of mixed malaria species infections in anopheline mosquitoes(2011-08-31) Mallika Imwong; มัลลิกา อิ่มวงศ์; Supatchara Nakeesathit; Day, Nicholas P.J.; White, Nicholas J.; White, Nicholas J.; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU)BACKGROUND: In patients with malaria mixed species infections are common and under reported. In PCR studies conducted in Asia mixed infection rates often exceed 20%. In South-East Asia, approximately one third of patients treated for falciparum... detection and speciation were tabulated. The entomological results in South East Asia were compared with mixed infection rates documented in patients in clinical studies. RESULTS: In total 63 studies were identified. Individual anopheline mosquitoes were