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Title: Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: An individual patient data meta-analysis
Authors: 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
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
Keywords: Immunology and Microbiology;Medicine
Issue Date: 22-Sep-2015
Citation: Malaria Journal. Vol.14, No.1 (2015)
Abstract: © 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.
ISSN: 14752875
Appears in Collections:Scopus 2011-2015

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