학술논문
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
Document Type
Author
Abdulla, Salim; Adam, Ishag; Adjei, George O.; Adjuik, Martin A.; Alemayehu, Bereket; Allan, Richard; Arinaitwe, Emmanuel; Ashley, Elizabeth A.; Ba, Mamadou S.; Barennes, Hubert; Barnes, Karen I.; Bassat, Quique; Baudin, Elisabeth; Berens-Riha, Nicole; Bjoerkman, Anders; Bompart, Francois; Bonnet, Maryline; Borrmann, Steffen; Bousema, Teun; Brasseur, Philippe; Bukirwa, Hasifa; Checchi, Francesco; Dahal, Prabin; D'Alessandro, Umberto; Desai, Meghna; Dicko, Alassane; Djimde, Abdoulaye A.; Dorsey, Grant; Doumbo, Ogobara K.; Drakeley, Chris J.; Duparc, Stephan; Eshetu, Teferi; Espie, Emmanuelle; Etard, Jean-Francois; Faiz, Abul M.; Falade, Catherine O.; Fanello, Caterina I.; Faucher, Jean-Francois; Faye, Babacar; Faye, Oumar; Filler, Scott; Flegg, Jennifer A.; Fofana, Bakary; Fogg, Carole; Gadalla, Nahla B.; Gaye, Oumar; Genton, Blaise; Gething, Peter W.; Gil, Jose P.; Gonzalez, Raquel; Grandesso, Francesco; Greenhouse, Bryan; Greenwood, Brian; Grivoyannis, Anastasia; Guerin, Philippe J.; Guthmann, Jean-Paul; Hamed, Kamal; Hamour, Sally; Hay, Simon I.; Hodel, Eva Maria; Humphreys, Georgina S.; Hwang, Jimee; Ibrahim, Maman L.; Jima, Daddi; Jones, Joel J.; Jullien, Vincent; Juma, Elizabeth; Kachur, Patrick S.; Kager, Piet A.; Kamugisha, Erasmus; Kamya, Moses R.; Karema, Corine; Kayentao, Kassoum; Kiechel, Jean-Rene; Kironde, Fred; Kofoed, Poul-Erik; Kremsner, Peter G.; Krishna, Sanjeev; Lameyre, Valerie; Lell, Bertrand; Lima, Angeles; Makanga, Michael; Malik, ElFatih M.; Marsh, Kevin; Mårtensson, Andreas; Massougbodji, Achille; Menan, Herve; Menard, Didier; Menendez, Clara; Mens, Petra F.; Meremikwu, Martin; Moreira, Clarissa; Nabasumba, Carolyn; Nambozi, Michael; Ndiaye, Jean-Louis; Ngasala, Billy E.; Nikiema, Frederic; Nsanzabana, Christian; Ntoumi, Francine; Oguike, Mary; Ogutu, Bernhards R.; Olliaro, Piero; Omar, Sabah A.; Ouedraogo, Jean-Bosco; Owusu-Agyei, Seth; Penali, Louis K.; Pene, Mbaye; Peshu, Judy; Piola, Patrice; Plowe, Christopher V.; Premji, Zul; Price, Ric N.; Randrianarivelojosia, Milijaona; Rombo, Lars; Roper, Cally; Rosenthal, Philip J.; Sagara, Issaka; Same-Ekobo, Albert; Sawa, Patrick; Schallig, Henk D. F. H.; Schramm, Birgit; Seck, Amadou; Shekalaghe, Seif A.; Sibley, Carol H.; Sinou, Vronique; Sirima, Sodiomon B.; Som, Fabrice A.; Sow, Doudou; Staedke, Sarah G.; Stepniewska, Kasia; Sutherland, Colin J.; Swarthout, Todd D.; Sylla, Khadime; Talisuna, Ambrose O.; Taylor, Walter R. J.; Temu, Emmanuel A.; Thwing, Julie I.; Tine, Roger C. K.; Tinto, Halidou; Tommasini, Silva; Toure, Offianan A.; Ursing, Johan; Vaillant, Michel T.; Valentini, Giovanni; Van den Broek, Ingrid; Van Vugt, Michele; Ward, Stephen A.; Winstanley, Peter A.; Yavo, William; Yeka, Adoke; Zolia, Yah M.; Zongo, Issaka
Source
BMC Medicine. 13
Subject
Language
English
ISSN
1741-7015
Abstract
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 degrees 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.