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Publication Open Access Practical PCR genotyping protocols for Plasmodium vivax using Pvcs and Pvmsp1.(2005-04-27) Mallika Imwong; มัลลิกา อิ่มวงศ์; Sasithon Pukrittayakamee; Grüner, Anne Charlotte; Rénia, Laurent; Letourneur, Frank; Sornchai Looareesuwan; ศรชัย หลูอารีย์สุวรรณ; White, Nicholas J.; Snounou, Georges; Mallika Imwong; Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinicalPublication Open Access Rapid clinical assessment to facilitate the triage of adults with falciparum malaria, a retrospective analysis.(2014-01-29) Hanson, Josh; Lee, Sue J.; Mohanty, Sanjib; Faiz, M. Abul; Anstey, Nicholas M.; Price, Ric N.; Prakaykaew Charunwatthana; ประกายแก้ว จรูญวรรธนะ; Yunus, Emran Bin; Mishra, Saroj K.; Tjitra, Emiliana; Ridwanur Rahman; Francois Nosten; Htut, Ye; Maude, Richard J.; Chau, Tran Thi Hong; Phu, Nguyen Hoan; Hien, Tran Tinh; White, Nicholas J.; Day, Nicholas P. J.; Dondorp, Arjen M.; Hanson, Josh; Mahidol University. Faculty of Tropical Medicine. Mahidol Oxford Tropical Medicine Research Unit.as low-risk by this algorithm can be safely managed initially on a general ward whilst awaiting senior clinical review and laboratory data.... most patients with falciparum malaria are managed, decisions regarding patient care must frequently be made using clinical evaluation alone. METHODS: We retrospectively analysed 4 studies of 1801 adults with severe falciparum malaria to determinePublication Open Access Motivations and perceptions of community advisory boards in the ethics of medical research: the case of the Thai-Myanmar border.(2014-02-17) Maung, Lwin K.; Cheah, Phaik Yeong; Cheah, Phaik Kin; White, Nicholas J.; Day, Nicholas P.; Nosten, Francois; Parker, Michael; Parker, Michael; Mahidol University. Faculty of Tropical Medicine. Mahidol Oxford Research Unit.BACKGROUND: Community engagement is increasingly promoted as a marker of good, ethical practice in the context of international collaborative research in low-income countries. There is, however, no widely agreed definition of community engagement... of important ways in which the Community Advisory Board is in practice understood by its members (and perhaps by community members beyond this) to have morally significant roles and responsibilities beyond those usually associated with the successfulPublication Open Access Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies(2016) Rupam Tripura; Peto, Thomas J.; Jeremy Chalk; Lee, Sue J.; Pasathorn Sirithiranont; Chea Nguon; Mehul Dhorda; Seidlein, Lorenz von; Maude, Richard J.; Day, Nicholas P. J.; Mallika Imwong; White, Nicholas J.; Dondorp, Arjen M.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unitof parasitaemia, the entire population of three Cambodian villages in Pailin province were followed for 1 year at three-monthly intervals. A cohort of adult participants found initially to have asymptomatic malaria parasitaemia was followed monthly over the same... period. Results: The initial cross sectional survey in June 2013 (M0) of 1447 asymptomatic residents found that 32 (2.2 %) had Plasmodium falciparum, 48 (3.3 %) had P. vivax, 4 (0.3 %) had mixed infections and in 142/1447 (9.8 %) malaria was detectedPublication 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.BACKGROUND: Primaquine has been the only widely available hypnozoitocidal anti-malarial drug for half a century. Despite this its clinical efficacy is poorly characterized resulting in a lack of consensus over the optimal regimen for the radical... 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 heterogeneityPublication Open Access Genetic marker suitable for identification and genotyping of Plasmodium ovale curtisi and Plasmodium ovale wallikeri.(2013-12) Naowarat Tanomsing; เนาวรัตน์ ถนอมสิงห์; Mallika Imwong; มัลลิกา อิ่มวงศ์; Sutherland, Colin J.; Dolecek,Christiane; Hien,Tran Tinh; Nosten, Francois; Day, Nicholas P. J.; White, Nicholas J.; Snounouh, Georges; Mallika Imwong; 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.; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit.We present a seminested PCR method that specifically discriminates between Plasmodium ovale curtisi and P. ovale wallikeri with high sensitivity. The test is based on species-specific amplification of a size-polymorphic fragment of the tryptophan-rich antigen gene, potra, which also permits discrimination of intraspecific sequence variants at this locus.Publication Open Access Performance of C-reactive protein and procalcitonin to distinguish viral from bacterial and malarial causes of fever in Southeast Asia(2015) Yoel Lubell; Blacksell, Stuart D.; Susanna Dunachie; Ampai Tanganuchitcharnchai; Thomas Althaus; Wanitda Watthanaworawit; Paris, Daniel H.; Mayfong Mayxay; Peto, Thomas J.; Dondorp, Arjen M.; White, Nicholas J.; Day, Nicholas P.J.; François Nosten; Newton, Paul N.; Paul Turner; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU)Background: Poor targeting of antimicrobial drugs contributes to the millions of deaths each year from malaria, pneumonia, and other tropical infectious diseases. While malaria rapid diagnostic tests have improved use of antimalarial drugs, there are no similar tests to guide the use of antibiotics in undifferentiated fevers. In this study we estimate the diagnostic accuracy of two well established biomarkers of bacterial infection, procalcitonin and Creactive protein (CRP) in discriminating between common viral and bacterial infections in malaria endemic settings of Southeast Asia. Methods: Serum procalcitonin and CRP levels were measured in stored serum samples from febrile patients enrolled in three prospective studies conducted in Cambodia, Laos and, Thailand. Of the 1372 patients with a microbiologically confirmed diagnosis, 1105 had a single viral, bacterial or malarial infection. Procalcitonin and CRP levels were compared amongst these aetiological groups and their sensitivity and specificity in distinguishing bacterial infections and bacteraemias from viral infections were estimated using standard thresholds. Results: Serum concentrations of both biomarkers were significantly higher in bacterial infections and malaria than in viral infections. The AUROC for CRP in discriminating between bacterial and viral infections was 0.83 (0.81–0.86) compared with 0.74 (0.71–0.77) for procalcitonin (p < 0.0001). This relative advantage was evident in all sites and when stratifying patients by age and admission status. For CRP at a threshold of 10 mg/L, the sensitivity of detecting bacterial infections was 95 % with a specificity of 49 %. At a threshold of 20 mg/L sensitivity was 86 % with a specificity of 67 %. For procalcitonin at a low threshold of 0.1 ng/mL the sensitivity was 90 % with a specificity of 39 %. At a higher threshold of 0.5 ng/ul sensitivity was 60 % with a specificity of 76 %. Conclusion: In samples from febrile patients with mono-infections from rural settings in Southeast Asia, CRP was a highly sensitive and moderately specific biomarker for discriminating between viral and bacterial infections. Use of a CRP rapid test in peripheral health settings could potentially be a simple and affordable measure to better identify patients in need of antibacterial treatment and part of a global strategy to combat the emergence of antibiotic resistance.Publication Open Access Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar.(2017) Bonnington, Craig A.; Aung Pyae Phyo; Ashley, Elizabeth A.; Mallika Imwong; Kanlaya Sriprawat; Parker, Daniel M.; Proux, Stephane; White, Nicholas J.; Nosten, Francois; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit; Mahidol University. Faculty of Tropical Medicine. Mahidol Oxford Research Unit; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype. Methods: Between February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated PPublication 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-treatment, crossover, pharmacokinetic study of paracetamol dosed orally and intramuscularly was conducted. Twenty-one adult patients with uncomplicated falciparum malaria were randomized to receive a single 600 mg dose of paracetamol either as syrup or intramuscular injection on day 0 followed by a single dose administered by the alternative route on day 1. Paracetamol plasma concentrations were quantified frequently and modelled simultaneously using nonlinear mixed-effects modelling. The final population pharmacokinetic model was used for dose optimization simulations. Relationships between paracetamol concentrations with temperature and parasite half-life were investigated using linear and non-linear regression analyses. Results: The population pharmacokinetic properties of paracetamol were best described by a two-compartment disposition model, with zero-order and first-order absorption for intramuscular and oral syrup administration, respectively. The relative bioavailability of oral syrup was 84.4 % (95 % CI 68.2–95.1 %) compared to intramuscular administration. Dosing simulations showed that 1000 mg of intramuscular or oral syrup administered six-hourly reached therapeutic steady state concentrations for antipyresis, but more favourable concentration–time profiles were achieved with a loading dose of 1500 mg, followed by a 1000 mg maintenance dose. This ensured that maximum therapeutic concentrations were reached rapidly during the first 6 h. No significant relationships between paracetamol concentrations and temperature or parasite half-life were found. Conclusions: Paracetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model. Relative oral bioavailability compared to intramuscular dosing was estimated as 84.4 % (95 % CI 68.2–95.1 %). Dosing simulations showed that a loading dose followed by six-hourly dosing intervals reduced the time delay to reach therapeutic drug levels after both routes of administration. The safety and efficacy of loading dose paracetamol antipyretic regimens now needs to be established in larger studies.Publication Open Access Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.(2013-01-02) Takala-Harrisona, Shannon; Clark, Taane G.; Cummings, Michael P.; Miotto,Olivo; Dondorp, Arjen M.; Fukudaf, Mark M.; Nosten, Francois; Noedl, Harald; Mallika Imwong; มัลลิกา อิ่มวงศ์; Bethell, Delia; Se, Youry; Lon, Chanthap; Tyner, Stuart D.; Saunders, David L.; Socheat, Duong; Ariey, Frederic; Phyo, Aung Pyae; Starzengruber, Peter; Fuehrer, Hans-Peter; Swoboda, Paul; Stepniewska, Kasia; Flegg, Jennifer; Arze, Cesar; Cerqueira, Gustavo C.; Silva, Joana C.; Ricklefs, Stacy M.; Porcella, Stephen F.; Stephens, Robert M.; Adams, Matthew; Kenefic, Leo J.; Campino, Susana; Auburn, Sarah; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Su, Xin-zhuan; White, Nicholas J.; Ringwald, Pascal; Plowe, Christopher V.; Plowe, Christopher V.; Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Research Unit.; Mahidol University. Faculty of Tropical Medicine. Department of Molecular Tropical Medicine and Genetics.; Mahidol University. Faculty of Tropical Medicine. Shoklo Malaria Research Unit., aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were