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Genetic markers of artemisinin resistance in Plasmodium spp. parasites

The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino aryl-alcohol or quinoline families. Ther...

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Autor principal: Sutherland, Colin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288991/
https://www.ncbi.nlm.nih.gov/pubmed/33525848
http://dx.doi.org/10.1042/ETLS20170100
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author Sutherland, Colin J.
author_facet Sutherland, Colin J.
author_sort Sutherland, Colin J.
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description The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino aryl-alcohol or quinoline families. There is now a widely perceived threat to treatment efficacy, as reduced susceptibility to rapid artemisinin clearance in vivo has become prevalent among populations of Plasmodium falciparum in the Greater Mekong subregion since 2008. In vitro and in vivo drug selection studies, heterologous cell expression experiments and genetic epidemiology have identified many candidate markers of reduced ring-stage susceptibility to artemisinin. Certain variants of the P. falciparum pfk13 gene, which encodes a kelch domain protein implicated in the unfolded protein response, are strongly associated with slow parasite clearance by artemisinin in the Mekong subregion. However, anomalies in the epidemiological association of pfk13 variants with true treatment failure in vivo and the curious cell-cycle stage specificity of this phenotype in vitro warrant exploration in some depth. Taken together, available data suggest that the emergence of P. falciparum expressing K13 variants has not yet precipitated a public health emergency. Alternative candidate markers of artemisinin susceptibility are also described, as K13-independent treatment failure has been observed in African P. falciparum and in the rodent malaria parasite Plasmodium chabaudi.
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spelling pubmed-72889912020-06-18 Genetic markers of artemisinin resistance in Plasmodium spp. parasites Sutherland, Colin J. Emerg Top Life Sci Review Articles The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino aryl-alcohol or quinoline families. There is now a widely perceived threat to treatment efficacy, as reduced susceptibility to rapid artemisinin clearance in vivo has become prevalent among populations of Plasmodium falciparum in the Greater Mekong subregion since 2008. In vitro and in vivo drug selection studies, heterologous cell expression experiments and genetic epidemiology have identified many candidate markers of reduced ring-stage susceptibility to artemisinin. Certain variants of the P. falciparum pfk13 gene, which encodes a kelch domain protein implicated in the unfolded protein response, are strongly associated with slow parasite clearance by artemisinin in the Mekong subregion. However, anomalies in the epidemiological association of pfk13 variants with true treatment failure in vivo and the curious cell-cycle stage specificity of this phenotype in vitro warrant exploration in some depth. Taken together, available data suggest that the emergence of P. falciparum expressing K13 variants has not yet precipitated a public health emergency. Alternative candidate markers of artemisinin susceptibility are also described, as K13-independent treatment failure has been observed in African P. falciparum and in the rodent malaria parasite Plasmodium chabaudi. Portland Press Ltd. 2017-12-22 2017-12-22 /pmc/articles/PMC7288991/ /pubmed/33525848 http://dx.doi.org/10.1042/ETLS20170100 Text en © 2017 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Review Articles
Sutherland, Colin J.
Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title_full Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title_fullStr Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title_full_unstemmed Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title_short Genetic markers of artemisinin resistance in Plasmodium spp. parasites
title_sort genetic markers of artemisinin resistance in plasmodium spp. parasites
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288991/
https://www.ncbi.nlm.nih.gov/pubmed/33525848
http://dx.doi.org/10.1042/ETLS20170100
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