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Title: Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis
Authors: Makoto Saito
Rashid Mansoor
Kalynn Kennon
Anupkumar R. Anvikar
Elizabeth A. Ashley
Daniel Chandramohan
Lauren M. Cohee
Umberto D'Alessandro
Blaise Genton
Mary Ellen Gilder
Elizabeth Juma
Linda Kalilani-Phiri
Irene Kuepfer
Miriam K. Laufer
Khin Maung Lwin
Steven R. Meshnick
Dominic Mosha
Victor Mwapasa
Norah Mwebaza
Michael Nambozi
Jean Louis A. Ndiaye
François Nosten
Myaing Nyunt
Bernhards Ogutu
Sunil Parikh
Moo Kho Paw
Aung Pyae Phyo
Mupawjay Pimanpanarak
Patrice Piola
Marcus J. Rijken
Kanlaya Sriprawat
Harry K. Tagbor
Joel Tarning
Halidou Tinto
Innocent Valéa
Neena Valecha
Nicholas J. White
Jacher Wiladphaingern
Kasia Stepniewska
Rose McGready
Philippe J. Guérin
University of Health and Allied Sciences, Ghana
University of Malawi College of Medicine
Medical Research Council Laboratories Gambia
Institut Pasteur du Cambodge
Makerere University
Ifakara Health Institute
Universite Cheikh Anta Diop
Kenya Medical Research Institute
Shoklo Malaria Research Unit
University Medical Center Utrecht
London School of Hygiene & Tropical Medicine
National Institute of Malaria Research India
Universitat Basel
The University of North Carolina System
Mahosot Hospital, Lao
University of Maryland School of Medicine
Nuffield Department of Clinical Medicine
Duke University
Yale University
Université de Lausanne (UNIL)
Infectious Diseases Data Observatory
WorldWide Antimalarial Resistance Network (WWARN)
Tropical Diseases Research Centre
Lower Myanmar
Institut de Recherche en Sciences de la Santé
Keywords: Medicine
Issue Date: 1-Jan-2020
Citation: The Lancet Infectious Diseases. (2020)
Abstract: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. Methods: We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. Findings: Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57–14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14–0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34–0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18–0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29–23·82). Interpretation: Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation. Funding: The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.
ISSN: 14744457
Appears in Collections:Scopus 2020

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