Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisi...

Full description

Bibliographic Details
Main Authors: Thu, AM, Phyo, AP, Pateekhum, C, Rae, JD, Landier, J, Parker, DM, Delmas, G, Watthanaworawit, W, McLean, ARD, Arya, A, Reyes, A, Li, X, Miotto, O, Soe, K, Ashley, EA, Dondorp, A, White, NJ, Day, NP, Anderson, TJC, Imwong, M, Nosten, F, Smithuis, F
Format: Journal article
Language:English
Published: BioMed Central 2024
_version_ 1826314842509672448
author Thu, AM
Phyo, AP
Pateekhum, C
Rae, JD
Landier, J
Parker, DM
Delmas, G
Watthanaworawit, W
McLean, ARD
Arya, A
Reyes, A
Li, X
Miotto, O
Soe, K
Ashley, EA
Dondorp, A
White, NJ
Day, NP
Anderson, TJC
Imwong, M
Nosten, F
Smithuis, F
author_facet Thu, AM
Phyo, AP
Pateekhum, C
Rae, JD
Landier, J
Parker, DM
Delmas, G
Watthanaworawit, W
McLean, ARD
Arya, A
Reyes, A
Li, X
Miotto, O
Soe, K
Ashley, EA
Dondorp, A
White, NJ
Day, NP
Anderson, TJC
Imwong, M
Nosten, F
Smithuis, F
author_sort Thu, AM
collection OXFORD
description Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. Conclusion: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.
first_indexed 2024-09-25T04:16:43Z
format Journal article
id oxford-uuid:32be5457-fff8-4000-9383-c38ff1f56c7f
institution University of Oxford
language English
last_indexed 2024-12-09T03:14:32Z
publishDate 2024
publisher BioMed Central
record_format dspace
spelling oxford-uuid:32be5457-fff8-4000-9383-c38ff1f56c7f2024-10-16T09:39:42ZMolecular markers of artemisinin resistance during falciparum malaria elimination in Eastern MyanmarJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:32be5457-fff8-4000-9383-c38ff1f56c7fEnglishJisc Publications RouterBioMed Central2024Thu, AMPhyo, APPateekhum, CRae, JDLandier, JParker, DMDelmas, GWatthanaworawit, WMcLean, ARDArya, AReyes, ALi, XMiotto, OSoe, KAshley, EADondorp, AWhite, NJDay, NPAnderson, TJCImwong, MNosten, FSmithuis, FBackground: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. Conclusion: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.
spellingShingle Thu, AM
Phyo, AP
Pateekhum, C
Rae, JD
Landier, J
Parker, DM
Delmas, G
Watthanaworawit, W
McLean, ARD
Arya, A
Reyes, A
Li, X
Miotto, O
Soe, K
Ashley, EA
Dondorp, A
White, NJ
Day, NP
Anderson, TJC
Imwong, M
Nosten, F
Smithuis, F
Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title_full Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title_fullStr Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title_full_unstemmed Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title_short Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar
title_sort molecular markers of artemisinin resistance during falciparum malaria elimination in eastern myanmar
work_keys_str_mv AT thuam molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT phyoap molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT pateekhumc molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT raejd molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT landierj molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT parkerdm molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT delmasg molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT watthanaworawitw molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT mcleanard molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT aryaa molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT reyesa molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT lix molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT miottoo molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT soek molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT ashleyea molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT dondorpa molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT whitenj molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT daynp molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT andersontjc molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT imwongm molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT nostenf molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar
AT smithuisf molecularmarkersofartemisininresistanceduringfalciparummalariaeliminationineasternmyanmar