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Title: Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: A literature review and meta-analysis of individual patient data
Authors: Salim Abdulla
Ishag Adam
George O. Adjei
Martin A. Adjuik
Bereket Alemayehu
Richard Allan
Emmanuel Arinaitwe
Elizabeth A. Ashley
Mamadou S. Ba
Hubert Barennes
Karen I. Barnes
Quique Bassat
Elisabeth Baudin
Nicole Berens-Riha
Anders Björkman
François Bompart
Maryline Bonnet
Steffen Borrmann
Teun Bousema
Philippe Brasseur
Hasifa Bukirwa
Francesco Checchi
Prabin Dahal
Umberto D'Alessandro
Meghna Desai
Alassane Dicko
Abdoulaye A. Djimdé
Grant Dorsey
Ogobara K. Doumbo
Chris J. Drakeley
Stephan Duparc
Teferi Eshetu
Emmanuelle Espié
Jean François Etard
Abul M. Faiz
Catherine O. Falade
Caterina I. Fanello
Jean François Faucher
Babacar Faye
Oumar Faye
Scott Filler
Jennifer A. Flegg
Bakary Fofana
Carole Fogg
Nahla B. Gadalla
Oumar Gaye
Blaise Genton
Peter W. Gething
José P. Gil
Raquel González
Francesco Grandesso
Bryan Greenhouse
Brian Greenwood
Anastasia Grivoyannis
Philippe J. Guerin
Jean Paul Guthmann
Kamal Hamed
Sally Hamour
Simon I. Hay
Eva Maria Hodel
Georgina S. Humphreys
Jimee Hwang
Maman L. Ibrahim
Daddi Jima
Joel J. Jones
Vincent Jullien
Elizabeth Juma
Patrick S. Kachur
Piet A. Kager
Erasmus Kamugisha
Moses R. Kamya
Corine Karema
Ifakara Health Institute
University of Khartoum Faculty of Medicine
University of Ghana
International Center for AIDS Care and Treatment Programs
MENTOR Initiative
Infectious Diseases Research Collaboration
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
Ludwig-Maximilians-Universitat Munchen
Karolinska University Hospital
Sanofi S.A.
Kenya Medical Research Institute
Universitat Tubingen
German Centre for Infection Research
London School of Hygiene & Tropical Medicine
Radboud University Nijmegen Medical Centre
Institut de Recherche pour le Developpement Dakar
Uganda Malaria Surveillance Project
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
University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology
University of California, San Francisco
Medicines for Malaria Venture
Jimma University
IRD Centre de Montpellier
Mahidol University
University of Ibadan
IRD Institut de Recherche pour le Developpement
Universite Paris Descartes
Besançon University Medical Center
The Global Fund to Fight AIDS, Tuberculosis and Malaria
Monash University
Portsmouth Hospitals NHS Trust
Tropical Medicine Research Institute Sudan
National Institute of Allergy and Infectious Diseases
Swiss Tropical and Public Health Institute (Swiss TPH)
Centre Hospitalier Universitaire Vaudois
University of Oxford
Karolinska Institutet
Faculdade de Ciencias, Universidade de Lisboa
Binghamton University State University of New York
University of Washington, Seattle
Institut de Veille Sanitaire
Novartis Pharmaceuticals Corporation
Wellcome Trust Centre for Human Genetics
National Institutes of Health, Bethesda
Liverpool School of Tropical Medicine
Centre de Recherche Médicale et Sanitaire
Federal Ministry of Health - Ethiopia
Ministry of Health and Social Welfare
Academic Medical Centre, University of Amsterdam
Catholic University of Health and Allied Sciences
Makerere University
Ministry of Health
Drugs for Neglected Diseases Initiative
Projecto de Saúde de Bandim
Kolding Sygehus
Centre de Recherches Médicales de Lambaréné
University of London
Médecins Sans Frontières
European & Developing Countries Clinical Trials Partnership
Federal Ministry of Health Sudan
Uppsala Universitet
University of Abomey-Calavi
University of Cocody
Institut Pasteur du Cambodge
Royal Tropical Institute - KIT
University of Calabar
Institute of Tropical Diseases Research and Prevention
Mbarara University of Science and Technology
Tropical Diseases Research Centre
Muhimbili University of Health and Allied Sciences
Institut de Recherche en Sciences de la Santé
Universite Marien Ngouabi
Keywords: Medicine
Issue Date: 7-Sep-2015
Citation: BMC Medicine. Vol.13, No.1 (2015)
Abstract: © 2015 WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group. Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29, 493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13, 664), artesunate-amodiaquine (n = 11, 337) and dihydroartemisinin-piperaquine (n = 4, 492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
ISSN: 17417015
Appears in Collections:Scopus 2011-2015

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