Browsing by Author "Bernhards R. Ogutu"

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    Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: An individual patient data meta-analysis
    (2015-09-22) Salim Abdulla; Elizabeth A. Ashley; Quique Bassat; Delia Bethell; Anders Björkman; Steffen Borrmann; Umberto D’Alessandro; Prabin Dahal; Nicholas P. Day; Mahamadou Diakite; Abdoulaye A. Djimde; Arjen M. Dondorp; Socheat Duong; Michael D. Edstein; Rick M. Fairhurst; M. Abul Faiz; Catherine Falade; Jennifer A. Flegg; Carole Fogg; Raquel Gonzalez; Brian Greenwood; Philippe J. Guérin; Jean Paul Guthmann; Kamal Hamed; Tran Tinh Hien; Ye Htut; Elizabeth Juma; Pharath Lim; Andreas Mårtensson; Mayfong Mayxay; Olugbenga A. Mokuolu; Clarissa Moreira; Paul Newton; Harald Noedl; Francois Nosten; Bernhards R. Ogutu; Marie A. Onyamboko; Seth Owusu-Agyei; Aung Pyae Phyo; Zul Premji; Ric N. Price; Sasithon Pukrittayakamee; Michael Ramharter; Issaka Sagara; Youry Se; Seila Suon; Kasia Stepniewska; Stephen A. Ward; Nicholas J. White; Peter A. Winstanley; Ifakara Health Institute; Nuffield Department of Clinical Medicine; Mahidol University; Centro de Investigação em Saúde de Manhiça; Instituto de Salud Global de Barcelona; Armed Forces Research Institute of Medical Sciences, Thailand; Karolinska University Hospital; Kenya Medical Research Institute; Magdeburg University School of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; Medical Research Council Unit; WorldWide Antimalarial Resistance Network (WWARN); University of Bamako; National Center for Parasitology, Entomology and Malaria Control; Australian Army Malaria Institute; National Institute of Allergy and Infectious Diseases; Malaria Research Group and Dev Care Foundation; University of Ibadan; Monash University; University of Portsmouth; Centre de Recerca en Salut Internacional de Barcelona (CRESIB); London School of Hygiene & Tropical Medicine; Epicentre; Novartis Pharmaceuticals Corporation; University of Oxford; Department of Medical Research; Karolinska Institutet; Uppsala Universitet; Mahosot Hospital; University of Health Sciences; University of Ilorin; Medizinische Universitat Wien; Kinshasa School of Public Health; Kintampo Health Research Centre; Muhimbili University of Health and Allied Sciences; Menzies School of Health Research; Universitat Tubingen; Centre de Recherches Médicales de Lambaréné; University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology; Armed Forces Research Institute of Medical Sciences; Liverpool School of Tropical Medicine; Warwick Medical School
    © 2015 WWARN Parasite Clearance Study Group. Background: Artemisinin resistance in Plasmodium falciparum manifests as slow parasite clearance but this measure is also influenced by host immunity, initial parasite biomass and partner drug efficacy. This study collated data from clinical trials of artemisinin derivatives in falciparum malaria with frequent parasite counts to provide reference parasite clearance estimates stratified by location, treatment and time, to examine host factors affecting parasite clearance, and to assess the relationships between parasite clearance and risk of recrudescence during follow-up. Methods: Data from 24 studies, conducted from 1996 to 2013, with frequent parasite counts were pooled. Parasite clearance half-life (PC1/2) was estimated using the WWARN Parasite Clearance Estimator. Random effects regression models accounting for study and site heterogeneity were used to explore factors affecting PC1/2 and risk of recrudescence within areas with reported delayed parasite clearance (western Cambodia, western Thailand after 2000, southern Vietnam, southern Myanmar) and in all other areas where parasite populations are artemisinin sensitive. Results: PC1/2 was estimated in 6975 patients, 3288 of whom also had treatment outcomes evaluate d during 28-63 days follow-up, with 93 (2.8 %) PCR-confirmed recrudescences. In areas with artemisinin-sensitive parasites, the median PC1/2 following three-day artesunate treatment (4 mg/kg/day) ranged from 1.8 to 3.0 h and the proportion of patients with PC1/2 >5 h from 0 to 10 %. Artesunate doses of 4 mg/kg/day decreased PC1/2 by 8.1 % (95 % CI 3.2-12.6) compared to 2 mg/kg/day, except in populations with delayed parasite clearance. PC1/2 was longer in children and in patients with fever or anaemia at enrolment. Long PC1/2 (HR = 2.91, 95 % CI 1.95-4.34 for twofold increase, p < 0.001) and high initial parasitaemia (HR = 2.23, 95 % CI 1.44-3.45 for tenfold increase, p < 0.001) were associated independently with an increased risk of recrudescence. In western Cambodia, the region with the highest prevalence of artemisinin resistance, there was no evidence for increasing PC1/2 since 2007. Conclusions: Several factors affect PC1/2. As substantial heterogeneity in parasite clearance exists between locations, early detection of artemisinin resistance requires reference PC1/2 data. Studies with frequent parasite count measurements to characterize PC1/2 should be encouraged. In western Cambodia, where PC1/2 values are longest, there is no evidence for recent emergence of higher levels of artemisinin resistance.
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    The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data
    (2015-03-31) Martin A. Adjuik; Richard Allan; Anupkumar R. Anvikar; Elizabeth A. Ashley; Mamadou S. Ba; Hubert Barennes; Karen I. Barnes; Quique Bassat; Elisabeth Baudin; Anders Björkman; François Bompart; Maryline Bonnet; Steffen Borrmann; Philippe Brasseur; Hasifa Bukirwa; Francesco Checchi; Michel Cot; Prabin Dahal; Umberto D'Alessandro; Philippe Deloron; Meghna Desai; Graciela Diap; Abdoulaye A. Djimde; Grant Dorsey; Ogobara K. Doumbo; Emmanuelle Espié; Jean Francois Etard; Caterina I. Fanello; Jean François Faucher; Babacar Faye; Jennifer A. Flegg; Oumar Gaye; Peter W. Gething; Raquel González; Francesco Grandesso; Philippe J. Guerin; Jean Paul Guthmann; Sally Hamour; Armedy Ronny Hasugian; Simon I. Hay; Georgina S. Humphreys; Vincent Jullien; Elizabeth Juma; Moses R. Kamya; Corine Karema; Jean R. Kiechel; Peter G. Kremsner; Sanjeev Krishna; Valérie Lameyre; Laminou M. Ibrahim; Sue J. Lee; Bertrand Lell; Andreas Martensson; Achille Massougbodji; Hervé Menan; Didier Ménard; Clara Menéndez; Martin Meremikwu; Clarissa Moreira; Carolyn Nabasumba; Michael Nambozi; Jean Louis Ndiaye; Frederic Nikiema; Christian Nsanzabana; Francine Ntoumi; Bernhards R. Ogutu; Piero Olliaro; Lyda Osorio; Jean Bosco Ouédraogo; Louis K. Penali; Mbaye Pene; INDEPTH Network; MENTOR Initiative; National Institute of Malaria Research India; Epicentre; Universite Cheikh Anta Diop; Centre MURAZ; French Foreign Affairs; WorldWide Antimalarial Resistance Network; University of Cape Town; Centro de Investigação em Saúde de Manhiça; Instituto de Salud Global de Barcelona; Karolinska Institutet; Sanofi S.A.; Universitat Tubingen; German Centre for Infection Research; Institut de Recherche pour le Developpement Dakar; Uganda Malaria Surveillance Project; IRD Institut de Recherche pour le Developpement; Universite Paris Descartes; WorldWide Antimalarial Resistance Network (WWARN); Nuffield Department of Clinical Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; Medical Research Council Unit; Centers for Disease Control and Prevention; Drugs for Neglected Diseases Initiative; University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology; University of California, San Francisco; Institut Pasteur de Dakar; IRD Centre de Montpellier; Mahidol University; Besançon University Medical Center; Monash University; University of Oxford; UCL; Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia; Kenya Medical Research Institute; Makerere University; Ministry of Health; Centre de Recherches Médicales de Lambaréné; University of London; Centre de Recherche Médicale et Sanitaire; Uppsala Universitet; University of Abomey-Calavi; University of Cocody; Institut Pasteur du Cambodge; University of Calabar; Mbarara University of Science and Technology; Tropical Diseases Research Centre; Institut de Recherche en Sciences de la Santé; Universite Marien Ngouabi; United States Army; Organisation Mondiale de la Sante; Centro Internacional de Entrenamiento e Investigaciones Medicas; WorldWide Antimalarial Resistance Network (WWARN)-West Africa Regional Centre; Institut Pasteur de Madagascar; Menzies School of Health Research; London School of Hygiene & Tropical Medicine; UNICEF; Centre Hospitalier et Universitaire de Yaounde; Drugs for Neglected Diseases initiative; University of Washington, Seattle; Universite de la Mediterranee Aix-Marseille II; Centre National de Recherche et de Formation sur le Paludisme (CNRFP); World Wide Antimalarial Resistance Network (WWARN)-Asia Regional Centre; University of Maryland School of Medicine; Médecins sans Frontières/Holland; Medical Action Myanmar; Infectious Diseases Research Collaboration; Médecins Sans Frontières; East Africa Regional Office; Hopitaux universitaires de Geneve; Swiss Tropical and Public Health Institute (Swiss TPH); Universitat Basel
    © The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group; licensee BioMed Central. Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.