Cargando…
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...
Autor principal: | |
---|---|
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 |
_version_ | 1783545381674549248 |
---|---|
author | Sutherland, Colin J. |
author_facet | Sutherland, Colin J. |
author_sort | Sutherland, Colin J. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7288991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sutherlandcolinj geneticmarkersofartemisininresistanceinplasmodiumsppparasites |