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No Evidence of Plasmodium falciparum k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites
Antimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers, which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over 2 decades...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879256/ https://www.ncbi.nlm.nih.gov/pubmed/31591113 http://dx.doi.org/10.1128/AAC.01067-19 |
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author | Wamae, Kevin Okanda, Dorcas Ndwiga, Leonard Osoti, Victor Kimenyi, Kelvin M. Abdi, Abdirahman I. Bejon, Philip Sutherland, Colin Ochola-Oyier, Lynette Isabella |
author_facet | Wamae, Kevin Okanda, Dorcas Ndwiga, Leonard Osoti, Victor Kimenyi, Kelvin M. Abdi, Abdirahman I. Bejon, Philip Sutherland, Colin Ochola-Oyier, Lynette Isabella |
author_sort | Wamae, Kevin |
collection | PubMed |
description | Antimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers, which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over 2 decades of changing antimalarial drug policy in Kenya. We did not detect any of the validated kelch 13 (k13) artemisinin resistance markers; nonetheless, a single k13 allele, K189T, was maintained at a stable high frequency (>10%) over time. There was a distinct shift from chloroquine-resistant transporter (crt)-76, multidrug-resistant gene 1 (mdr1)-86 and mdr1-1246 chloroquine (CQ) resistance alleles to a 99% prevalence of CQ-sensitive alleles in the population, following the withdrawal of CQ from routine use. In contrast, the dihydropteroate synthetase (dhps) double mutant (437G and 540E) associated with sulfadoxine-pyrimethamine (SP) resistance was maintained at a high frequency (>75%), after a change from SP to artemisinin combination therapies (ACTs). The novel cysteine desulfurase (nfs) K65 allele, implicated in resistance to lumefantrine in a West African study, showed a gradual significant decline in allele frequency pre- and post-ACT introduction (from 38% to 20%), suggesting evidence of directional selection in Kenya, potentially not due to lumefantrine. The high frequency of CQ-sensitive parasites circulating in the population suggests that the reintroduction of CQ in combination therapy for the treatment of malaria can be considered in the future. However, the risk of a reemergence of CQ-resistant parasites circulating below detectable levels or being reintroduced from other regions remains. |
format | Online Article Text |
id | pubmed-6879256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-68792562019-12-03 No Evidence of Plasmodium falciparum k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites Wamae, Kevin Okanda, Dorcas Ndwiga, Leonard Osoti, Victor Kimenyi, Kelvin M. Abdi, Abdirahman I. Bejon, Philip Sutherland, Colin Ochola-Oyier, Lynette Isabella Antimicrob Agents Chemother Epidemiology and Surveillance Antimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers, which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over 2 decades of changing antimalarial drug policy in Kenya. We did not detect any of the validated kelch 13 (k13) artemisinin resistance markers; nonetheless, a single k13 allele, K189T, was maintained at a stable high frequency (>10%) over time. There was a distinct shift from chloroquine-resistant transporter (crt)-76, multidrug-resistant gene 1 (mdr1)-86 and mdr1-1246 chloroquine (CQ) resistance alleles to a 99% prevalence of CQ-sensitive alleles in the population, following the withdrawal of CQ from routine use. In contrast, the dihydropteroate synthetase (dhps) double mutant (437G and 540E) associated with sulfadoxine-pyrimethamine (SP) resistance was maintained at a high frequency (>75%), after a change from SP to artemisinin combination therapies (ACTs). The novel cysteine desulfurase (nfs) K65 allele, implicated in resistance to lumefantrine in a West African study, showed a gradual significant decline in allele frequency pre- and post-ACT introduction (from 38% to 20%), suggesting evidence of directional selection in Kenya, potentially not due to lumefantrine. The high frequency of CQ-sensitive parasites circulating in the population suggests that the reintroduction of CQ in combination therapy for the treatment of malaria can be considered in the future. However, the risk of a reemergence of CQ-resistant parasites circulating below detectable levels or being reintroduced from other regions remains. American Society for Microbiology 2019-11-21 /pmc/articles/PMC6879256/ /pubmed/31591113 http://dx.doi.org/10.1128/AAC.01067-19 Text en Copyright © 2019 Wamae et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Epidemiology and Surveillance Wamae, Kevin Okanda, Dorcas Ndwiga, Leonard Osoti, Victor Kimenyi, Kelvin M. Abdi, Abdirahman I. Bejon, Philip Sutherland, Colin Ochola-Oyier, Lynette Isabella No Evidence of Plasmodium falciparum k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title | No Evidence of Plasmodium falciparum
k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title_full | No Evidence of Plasmodium falciparum
k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title_fullStr | No Evidence of Plasmodium falciparum
k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title_full_unstemmed | No Evidence of Plasmodium falciparum
k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title_short | No Evidence of Plasmodium falciparum
k13 Artemisinin Resistance-Conferring Mutations over a 24-Year Analysis in Coastal Kenya but a Near Complete Reversion to Chloroquine-Sensitive Parasites |
title_sort | no evidence of plasmodium falciparum
k13 artemisinin resistance-conferring mutations over a 24-year analysis in coastal kenya but a near complete reversion to chloroquine-sensitive parasites |
topic | Epidemiology and Surveillance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879256/ https://www.ncbi.nlm.nih.gov/pubmed/31591113 http://dx.doi.org/10.1128/AAC.01067-19 |
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