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.


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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.
Bmc Medicine
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, Martensson 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
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WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group
1741-7015 (Electronic)
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Publication types: Journal ArticlePublication Status: epublishDocument Type: Review
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.
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05/10/2015 12:26
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30/04/2021 6:16
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