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Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast

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 ol...

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Autores principales: Borrmann, Steffen, Sasi, Philip, Mwai, Leah, Bashraheil, Mahfudh, Abdallah, Ahmed, Muriithi, Steven, Frühauf, Henrike, Schaub, Barbara, Pfeil, Johannes, Peshu, Judy, Hanpithakpong, Warunee, Rippert, Anja, Juma, Elizabeth, Tsofa, Benjamin, Mosobo, Moses, Lowe, Brett, Osier, Faith, Fegan, Greg, Lindegårdh, Niklas, Nzila, Alexis, Peshu, Norbert, Mackinnon, Margaret, Marsh, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213089/
https://www.ncbi.nlm.nih.gov/pubmed/22102856
http://dx.doi.org/10.1371/journal.pone.0026005
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author Borrmann, Steffen
Sasi, Philip
Mwai, Leah
Bashraheil, Mahfudh
Abdallah, Ahmed
Muriithi, Steven
Frühauf, Henrike
Schaub, Barbara
Pfeil, Johannes
Peshu, Judy
Hanpithakpong, Warunee
Rippert, Anja
Juma, Elizabeth
Tsofa, Benjamin
Mosobo, Moses
Lowe, Brett
Osier, Faith
Fegan, Greg
Lindegårdh, Niklas
Nzila, Alexis
Peshu, Norbert
Mackinnon, Margaret
Marsh, Kevin
author_facet Borrmann, Steffen
Sasi, Philip
Mwai, Leah
Bashraheil, Mahfudh
Abdallah, Ahmed
Muriithi, Steven
Frühauf, Henrike
Schaub, Barbara
Pfeil, Johannes
Peshu, Judy
Hanpithakpong, Warunee
Rippert, Anja
Juma, Elizabeth
Tsofa, Benjamin
Mosobo, Moses
Lowe, Brett
Osier, Faith
Fegan, Greg
Lindegårdh, Niklas
Nzila, Alexis
Peshu, Norbert
Mackinnon, Margaret
Marsh, Kevin
author_sort Borrmann, Steffen
collection PubMed
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
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spelling pubmed-32130892011-11-18 Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast Borrmann, Steffen Sasi, Philip Mwai, Leah Bashraheil, Mahfudh Abdallah, Ahmed Muriithi, Steven Frühauf, Henrike Schaub, Barbara Pfeil, Johannes Peshu, Judy Hanpithakpong, Warunee Rippert, Anja Juma, Elizabeth Tsofa, Benjamin Mosobo, Moses Lowe, Brett Osier, Faith Fegan, Greg Lindegårdh, Niklas Nzila, Alexis Peshu, Norbert Mackinnon, Margaret Marsh, Kevin PLoS One Research Article 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 Public Library of Science 2011-11-10 /pmc/articles/PMC3213089/ /pubmed/22102856 http://dx.doi.org/10.1371/journal.pone.0026005 Text en Borrmann et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Borrmann, Steffen
Sasi, Philip
Mwai, Leah
Bashraheil, Mahfudh
Abdallah, Ahmed
Muriithi, Steven
Frühauf, Henrike
Schaub, Barbara
Pfeil, Johannes
Peshu, Judy
Hanpithakpong, Warunee
Rippert, Anja
Juma, Elizabeth
Tsofa, Benjamin
Mosobo, Moses
Lowe, Brett
Osier, Faith
Fegan, Greg
Lindegårdh, Niklas
Nzila, Alexis
Peshu, Norbert
Mackinnon, Margaret
Marsh, Kevin
Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title_full Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title_fullStr Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title_full_unstemmed Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title_short Declining Responsiveness of Plasmodium falciparum Infections to Artemisinin-Based Combination Treatments on the Kenyan Coast
title_sort declining responsiveness of plasmodium falciparum infections to artemisinin-based combination treatments on the kenyan coast
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213089/
https://www.ncbi.nlm.nih.gov/pubmed/22102856
http://dx.doi.org/10.1371/journal.pone.0026005
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