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

Artemisinins / pharmacology Myanmar Malaria, Falciparum / parasitology Antimalarials / pharmacology Drug Resistance / genetics Plasmodium falciparum / drug effects Humans Cross-Sectional Studies Female Male Adolescent Adult Mass Drug Administration Young Adult Mutation Child Child, Preschool Middle Aged Quinolines / pharmacology Disease Eradication / statistics & numerical data Piperazines

P. falciparum Artemisinin resistance Kelch13 Malaria elimination Mass drug administration

Journal

Malaria journal

ISSN: 1475-2875

Titre abrégé: Malar J

Pays: England

ID NLM: 101139802

Informations de publication

Date de publication:
08 May 2024

Historique:

received: 29 01 2024

accepted: 06 04 2024

medline: 9 5 2024

pubmed: 9 5 2024

entrez: 9 5 2024

Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND BACKGROUND

METHODS 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 RESULTS

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 CONCLUSIONS

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.

Identifiants

DOI: 10.1186/s12936-024-04955-6 PMID: 38720269

pubmed: 38720269

doi: 10.1186/s12936-024-04955-6

pii: 10.1186/s12936-024-04955-6

doi:

Substances chimiques

Artemisinins 0

Antimalarials 0

artemisinin 9RMU91N5K2

artenimol 6A9O50735X

piperaquine A0HV2Q956Y

Quinolines 0

Piperazines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

138

Subventions

Organisme : Wellcome Trust

ID : 214208/Z/18/Z

Pays : United Kingdom

Organisme : Wellcome Trust

ID : 220211

Pays : United Kingdom

Organisme : NIAID NIH HHS

ID : R01 AI048071

Pays : United States

Informations de copyright

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