Declining genetic polymorphism of the C-terminus Merozoite Surface Protein-1 amidst increased Plasmodium knowlesi transmission in Thailand.

Publisher: BioMed Central Country of Publication: England NLM ID: 101139802 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2875 (Electronic) Linking ISSN: 14752875 NLM ISO Abbreviation: Malar J Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Plasmodium knowlesi*/genetics ; Polymorphism, Genetic* ; Merozoite Surface Protein 1*/genetics ; Malaria*/transmission ; Malaria*/parasitology; Thailand/epidemiology ; Humans ; Haplotypes

Background: Recent reports from Thailand reveal a substantial surge in Plasmodium knowlesi cases over the past decades, with a more than eightfold increase in incidence by 2023 compared to 2018. This study investigates temporal changes in genetic polymorphism associated with the escalating transmission of P. knowlesi malaria in Thailand over time using the prominent vaccine candidate, pkmsp1 as a marker.
Methods: Twenty-five P. knowlesi samples collected in 2018-2023 were sequenced for the 42-kDa region of pkmsp1 and compared with 24 retrieved sequences in 2000-2009, focusing on nucleotide diversity, natural selection, recombination rate, and population differentiation.
Results: Seven unique haplotypes were identified in recent samples, compared to 15 in earlier samples. Nucleotide and haplotype diversity were lower in recent samples (π = 0.016, Hd = 0.817) than in earlier samples (π = 0.018, Hd = 0.942). Significantly higher synonymous substitution rates were observed in both sample sets (d S -d N  = 2.77 and 2.43, p < 0.05), indicating purifying selection and reduced genetic diversity over time. Additionally, 8 out of 17 mutation points were located on predicted B-cell epitopes, suggesting an adaptive response by the parasites to evade immune recognition. Population differentiation analysis using the fixation index (F st ) revealed high genetic differentiation between parasite populations in central and southern Thailand or Malaysia. Conversely, the relatively lower F st value between southern Thailand and Malaysia suggests a closer genetic relationship, possibly reflecting historical gene flow.
Conclusion: This study highlights a decline in genetic diversity and evidence of purifying selection associated with the recently increased incidence of P. knowlesi malaria in Thailand. The minor genetic differentiation between P. knowlesi populations from southern Thailand and Malaysia suggests a shared recent ancestry of these parasites and underscores the need for coordinated efforts between the two countries for the elimination of P. knowlesi.
Competing Interests: Declarations Ethics approval and consent to participate Written informed consent/assent was obtained from all patients, including children and their parents. The use of parasite DNA samples, associated data, and the study protocol, including consent/assent processes, received ethical approval from the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Bangkok (Approval numbers: MUTM2018-016-05 and MUTM2017-078-05). Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)

Update of: bioRxiv. 2024 Jun 27:2024.06.27.600943. doi: 10.1101/2024.06.27.600943. (PMID: 38979329)

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U19 AI089672 United States AI NIAID NIH HHS; FF-123/2567 Mahidol University (Fundamental Fund: fiscal year 2024 by National Science Research and Innovation Fund (NSRF))

Keywords: Plasmodium knowlesi; Gene polymorphism; Genetic diversity; Malaria; Merozoite surface protein-1; Thailand

0 (Merozoite Surface Protein 1)

Date Created: 20241113 Date Completed: 20241114 Latest Revision: 20241119

20250114

PMC11562464

10.1186/s12936-024-05162-z

39538241