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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Declining responsiveness of plasmodium falciparum infections to Artemisinin-Based combination treatments on the Kenyan coast
PLoS ONE, Volume 6, No. 11, Article e26005, Year 2011
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Description
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: Controlled-Trials.com ISRCTN88705995. © 2011 Borrmann et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s001.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s002.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s003.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s004.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s005.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3213089/bin/pone.0026005.s006.doc
Authors & Co-Authors
Borrmann, Steffen
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Sasi, Philip Galula
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Mwai, Leah
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Bashraheil, Mahfudh
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Abdallah, Ahmed M.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Muriithi, Steven
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Frühauf, Henrike
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Schaub, Barbara
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Pfeil, Johannes
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Peshu, Judy
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Hanpithakpong, Warunee
Thailand, Bangkok
Faculty of Tropical Medicine, Mahidol University
Rippert, Anja
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Juma, Elizabeth A.
Kenya, Nairobi
Ministry of Health Nairobi
Tsofa, Benjamin K.
Kenya, Nairobi
Ministry of Health Nairobi
Mosobo, Moses
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Lowe, Brett S.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Osier, Faith Hope Among In
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Fegan, Greg
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Lindegårdh, Niklas
Thailand, Bangkok
Faculty of Tropical Medicine, Mahidol University
Nzila, Alexis M.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Peshu, Norbert M.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
MacKinnon, Margaret J.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
United Kingdom, Oxford
Nuffield Department of Medicine
Marsh, Kevin
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
United Kingdom, Oxford
Nuffield Department of Medicine
Statistics
Citations: 114
Authors: 23
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0026005
e-ISSN:
19326203
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Case-Control Study
Study Approach
Quantitative