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Title: Declining responsiveness of plasmodium falciparum infections to Artemisinin-Based combination treatments on the Kenyan coast
Authors: Steffen Borrmann
Philip Sasi
Leah Mwai
Mahfudh Bashraheil
Ahmed Abdallah
Steven Muriithi
Henrike Frühauf
Barbara Schaub
Johannes Pfeil
Judy Peshu
Warunee Hanpithakpong
Anja Rippert
Elizabeth Juma
Benjamin Tsofa
Moses Mosobo
Brett Lowe
Faith Osier
Greg Fegan
Niklas Lindegårdh
Alexis Nzila
Norbert Peshu
Margaret Mackinnon
Kevin Marsh
Kenya Medical Research Institute
Universitat Heidelberg
Muhimbili University of Health and Allied Sciences
Mahidol University
Ministry of Health Nairobi
Nuffield Department of Clinical Medicine
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 10-Nov-2011
Citation: PLoS ONE. Vol.6, No.11 (2011)
Abstract: Background: The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies. Methods: On the Kenyan coast we studied the treatment responses in 474 children 6-59 months old with uncomplicated P. falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995) Results: The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005-2006 to 87% in 2007-2008 (odds ratio, 5.4, 95%CI, 2.7-11.1; P < 0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7-9.9; P = 0.002) in the DHA-PPQ and AM-LM groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005-2006 and 2007-2008 (OR body temperature > 37.5°C, 2.8, 1.9-4.1; P < 0.001). Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof. Conclusions: The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better understanding of the mechanisms underlying reduced parasite clearance rates. Trial Registration: ISRCTN88705995. © 2011 Borrmann et al.
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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