University of Khartoum

Clinical Determinants of Early Parasitological Response to ACTs in African Patients with Uncomplicated Falciparum Malaria: A literature Review and Meta-Analysis of Individual Patie...

Clinical Determinants of Early Parasitological Response to ACTs in African Patients with Uncomplicated Falciparum Malaria: A literature Review and Meta-Analysis of Individual Patie...

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dc.contributor.author Adjuik, Martin
dc.contributor.author Krishna, Sanjeev
dc.contributor.author Zongo, Issaka
dc.contributor.author Alemayehu, Bereket Hailegiorgis
dc.contributor.author Adam, I.
dc.contributor.other Department of Obstetrics and Gynecology en_US
dc.date 2015
dc.date.accessioned 2016-01-10T11:25:18Z
dc.date.available 2016-01-10T11:25:18Z
dc.date.issued 2016-01-10
dc.date.submitted 2016
dc.identifier.uri http://khartoumspace.uofk.edu/handle/123456789/18352
dc.description.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 °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. en_US
dc.language.iso en en_US
dc.publisher BMC MEDICINE en_US
dc.subject Clinical en_US
dc.subject falciparum en_US
dc.subject Malaria en_US
dc.title Clinical Determinants of Early Parasitological Response to ACTs in African Patients with Uncomplicated Falciparum Malaria: A literature Review and Meta-Analysis of Individual Patie... en_US
dc.type Publication en_US
dc.Faculty Medicine en_US

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