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

Malar J. 2024 May 8;23(1):138. doi: 10.1186/s12936-024-04955-6.

Abstract

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.

Keywords: P. falciparum; Artemisinin resistance; Kelch13; Malaria elimination; Mass drug administration.

MeSH terms

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

Substances

  • Artemisinins
  • Antimalarials
  • artemisinin
  • artenimol
  • piperaquine
  • Quinolines
  • Piperazines