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. 2022 Mar 1;50(1):19.
doi: 10.1186/s41182-022-00409-4.

Reduction in Plasmodium falciparum Pfk13 and pfg377 allele diversity through time in southern Vietnam

Nguyen Quang Thieu  1 , Vu Duc Chinh  1 , Truong Van Hanh  1 , Nguyen Van Dung  1 , Hidekazu Takagi  2 , Takeshi Annoura  3 , Satoru Kawai  4 , Gaku Masuda  5   6 , Nguyen Van Tuan  7 , Vu Viet Hung  1 , Shusuke Nakazawa  8 , Richard Culleton  8   9 , Nguyen Thi Huong Binh  1 , Yoshimasa Maeno  10   11
Affiliations

Reduction in Plasmodium falciparum Pfk13 and pfg377 allele diversity through time in southern Vietnam

Nguyen Quang Thieu et al. Trop Med Health. .

Abstract

Background: Plasmodium falciparum has acquired resistance to artemisinin in Southeast Asia, with mutations in the P. falciparum Kelch-13 (Pfk13) gene associated with the resistance phenotype. The widespread use of Artemisinin-based combination therapy (ACT)s in Southeast Asia has led to the selection and spread of parasites carrying mutations in Pfk13. We characterised the allele diversity of Pfk13 and pfg377, an artemisinin-resistance neutral polymorphic gene, in parasite DNA extracted human blood from in southern Vietnam in 2003, 2012, 2015 and 2018.

Method: This study was conducted in Bu Gia Map commune, Binh Phuoc province, Vietnam, from May 2018 to January 2019. Twenty-four samples from 2018 to 2019, 30 from 2003, 24 from 2012 and 32 from 2015 were analysed. Malaria-infected human blood was collected by finger-prick and used for molecular analysis. A nested-PCR targeting the small subunit ribosomal RNA gene was used for Plasmodium species identification, followed by amplification and nucleotide sequencing of Pfk13 and region 3 of pfg377. Archived blood samples collected in the same region in 2012 and 2015 were also analysed as above for comparison.

Results: The genetic diversity of Pfk13 and pfg377 was lower in 2018-2019 compared to 2012 and 2015. The number of distinct Pfk13 mutants decreased from three in 2012 and 2015, P553L, V568G and C580Y, to one, C580Y in 2018-2019. In 2018-2019, the frequency of C580Y mutant strains was 71% (17/24 isolates). All samples were wild type in 2003. In 2012 and 2015, there were single-strain infections as well as co-infections with two mutant strains or with mutant and wild strains, whereas there were no co-infections in 2018. pfg377 allele diversity decreased from five alleles in 2012 to two alleles in 2018-2019.

Conclusion: The genetic diversity of P. falciparum was reduced at the two genetic loci surveyed in this study, Pfk13 and pfg377. In the case of the former gene, we observed an increase in the prevalence of parasites carrying the C580Y gene, known to confer reduced susceptibility to ACTs. The reduction in the diversity of pfg377 may be linked to the clonal expansion of parasite strains carrying the C580Y mutation, leading to an overall reduction in parasite genetic diversity across the population.

Keywords: Artemisinin resistance; Gametocyte; K13-propeller gene; Plasmodium falciparum; Vietnam; pfg377 gene.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Geographical map of Bu Gia Map commune, Binh Phuoc Province as the study area
Fig. 2
Fig. 2
Prevalence of Pfk13 mutations in Plasmodium falciparum in Binh Phuoc province, 2003 to 2019
Fig. 3
Fig. 3
Comparison of the prevalence of Pfk13 mutants and pfg337 alleles between 2012 and 2018–2019
See this image and copyright information in PMC

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