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Molecular Detection of Mutations in the Propeller Domain of Kelch 13 and pfmdr1 Copy Number Variation in Plasmodium falciparum Isolates from Thailand Collected from 2002 to 2007

Chaiyaporn Chaisatit Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Piyaporn Sai-ngam Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Sasikanya Thaloengsok Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Sabaithip Sriwichai Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Krisada Jongsakul Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Mark Fukuda Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Michele Spring Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Mariusz Wojnarski Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Norman Waters Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Paphavee Lertsethtakarn Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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Brian A. Vesely Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand;

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DOI:
https://doi.org/10.4269/ajtmh.21-0303
Volume/Issue:
Volume 105: Issue 4
Page(s):
1093–1096
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ABSTRACT.

We determined the prevalence of Kelch 13 mutations and pfmdr1 copy number in samples collected from the Thailand–Myanmar border, the Thailand–Cambodia border, and southern Thailand from 2002 to 2007. C580Y was the most prevalent in Trat (Thailand–Cambodia border) and Ranong (Thailand–Myanmar border) at 42% (24/57) and 13% (6/48), respectively. Less predominant mutations were also identified including R539T (7%, 4/57) and Y493H (2%, 1/57) in Trat, P574L (6%, 3/48) and P553L (2%, 1/48) in Ranong, and N537I and D452E (7%, 1/15) in Sangkhlaburi (Thailand–Myanmar border). Samples from Mae sot (33%, 11/33) harbored the highest percentage of multiple pfmdr1 copies, followed by Trat (18%, 10/57), Chiang Dao in 2003 (13%, 4/30), Phang Nga (5%, 2/44), and Chiang Dao in 2002 (4%, 1/26). This retrospective study provides geographic diversity of K13 and pfmdr1 copies and the emergence of these molecular markers in Thailand, an important background information for future surveillance in the region.

Author Notes

Address correspondence to Brian A. Vesely, Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Rd., Bangkok 10400, Thailand. E-mail: brian.vesely.mil@afrims.org

Financial support: This work was supported by the United States Department of Defense, Armed Forces Health Surveillance Division-Global Emerging Infectious Disease Surveillance (AFHSD-GEIS) Branch and Defense Malaria Assistance Program (DMAP). The funding source had no role in the analysis or interpretation of data, preparation of the manuscript or the decision to publish.

Disclosure: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions containing herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.

Authors’ addresses: Chaiyaporn Chaisatit, Piyaporn Sai-ngam, Sasikanya Thaloengsok, Sabaithip Sriwichai, Krisada Jongsakul, Michele Spring, Mariusz Wojnarski, Norman Waters, Paphavee Lertsethtakarn, and Brian A. Vesely, Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: chaiyapornc.ca@afrims.org, piyaporns.fsn@afrims.org, sasikanyat.ca@afrims.org, sabaithips.fsn@afrims.org, krisadaj.ctr@afrims.org, michele.spring.ctr@afrims.org, mariusz.wojnarski.mil@afrims.org, norman.waters.mil@afrims.org, paphaveel.fsn@afrims.org, and brian.vesely.mil@afrims.org. Mark Fukuda, Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mail: mark.fukuda.mil@afrims.org.

Copyright:
© The American Society of Tropical Medicine and Hygiene 2021
Received:
13 Mar 2021
|
Accepted:
14 May 2021
|
Published Online:
16 Jul 2021
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    Wongsrichanalai C, Sibley CH, 2013. Fighting drug-resistant Plasmodium falciparum: the challenge of artemisinin resistance. Clin Microbiol Infect 19: 908–916.

  • 2.

    Dondorp AM et al., 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.

  • 3.

    Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619–2620.

  • 4.

    Ariey F et al., 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.

  • 5.

    Ménard D et al., 2016. A worldwide map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med 374: 2453–2464.

  • 6.

    Price RN et al., 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438–447.

  • 7.

    Kamau E, Alemayehu S, Feghali KC, Saunders D, Ockenhouse CF, 2013. Multiplex qPCR for detection and absolute quantification of malaria. PLoS One 8: e71539.

  • 8.

    Khammanee T, Sawangjaroen N, Buncherd H, Tun AW, Thanapongpichat S, 2019. Molecular surveillance of Pfkelch13 and Pfmdr1 mutations in Plasmodium falciparum isolates from southern Thailand. Korean J Parasitol 57: 369–377.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Talundzic E et al., 2015. Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign. PLoS Pathog 11: e1004789.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Putaporntip C, Kuamsab N, Kosuwin R, Tantiwattanasub W, Vejakama P, Sueblinvong T, Seethamchai S, Jongwutiwes S, Hughes AL, 2016. Natural selection of K13 mutants of Plasmodium falciparum in response to artemisinin combination therapies in Thailand. Clin Microbiol Infect 22: 285.e1–285.e8.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Imwong M et al., 2020. Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study. Lancet Infect Dis 20: 1470–1480.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Ye R et al., 2016. Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border. Sci Rep 6: 20100.

  • 13.

    Alker AP et al., 2007. Pfmdr1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border. Am J Trop Med Hyg 76: 641–647.

  • 14.

    Phyo AP et al., 2016. Declining efficacy of artemisinin combination therapy against P. falciparum malaria on the Thai-Myanmar border (2003–2013): the role of parasite genetic factors. Clin Infect Dis 63: 784–791.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    van der Pluijm RW et al., 2019. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study. Lancet Infect Dis 19: 952–961.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Department of Disease Control , 2019. Guideline for the Treatment of Malaria in Thailand. Available at: malaria.ddc.moph.go.th. Accessed July 31, 2020.

    • PubMed
    • Export Citation
  • 17.

    Rossi G, De Smet M, Khim N, Kindermans JM, Menard D, 2017. Emergence of Plasmodium falciparum triple mutant in Cambodia. Lancet Infect Dis 17: 1233.

  • 18.

    Mukherjee A et al., 2017. Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16: 195.

  • 19.

    Demas AR, Sharma AI, Wong W, Early AM, Redmond S, Bopp S, Neafsey DE, Volkman SK, Hartl DL, Wirth DF, 2018. Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. Proc Natl Acad Sci USA 115: 12799–12804.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Breglio KF et al., 2018. A single nucleotide polymorphism in the Plasmodium falciparum atg18 gene associates with artemisinin resistance and confers enhanced parasite survival under nutrient deprivation. Malar J 17: 391.

    • PubMed
    • Search Google Scholar
    • Export Citation
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