Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 25;11(1):43.
doi: 10.1186/s40249-022-00964-2.

Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008‒2017

Zhensheng Wang  1   2 , Chunyan Wei  1 , Yunchun Pan  3 , Zhihua Wang  4 , Xin Ji  5 , Qianqian Chen  2 , Lianhui Zhang  1 , Zenglei Wang  6 , Heng Wang  7
Affiliations

Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008‒2017

Zhensheng Wang et al. Infect Dis Poverty. .

Abstract

Background: Plasmodium vivax remains the predominant species at the China-Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time.

Methods: A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson's Chi-squared test or Fisher's exact test were applied to determine the statistical frequency differences of mutations between categorical data.

Results: The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12.

Conclusions: Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance.

Keywords: Antimalarial drug; China–Myanmar border; Drug resistance; Molecular marker; Plasmodium vivax.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Geographical prevalence of pvdhfr haplotypes and tandem repeat variants. a The geographical distribution of pvdhfr haplotypes. b Amino-acid sequence alignment of three tandem repeat variants. Bold letters indicate the tandem repeat. c Frequency changes of the tandem repeat variants over time. d The geographical distribution of tandem repeat variants. The size of the pie represents the number of the isolates (n)
Fig. 2
Fig. 2
Geographical prevalence of pvdhps haplotypes and tandem repeat variants. a The geographical distribution of pvdhps haplotypes. b Amino-acid sequence alignment of three tandem repeat variants. c Frequency changes of tandem repeat variants over time. d The geographical distribution of tandem repeat variants. The size of the pie represents the number of the isolates (n)
Fig. 3
Fig. 3
Geographical prevalence of pvmdr1 haplotypes (a) and pvcrt-o haplotypes (b). The size of the pie represents the number of the isolates (n)
See this image and copyright information in PMC

References

    1. World Malaria Report. World Health Organization; 2021. https://www.who.int/publications/i/item/9789240040496.
    1. Huang F, Feng XY, Zhou SS, Tang LH, Xia ZG. Establishing and applying an adaptive strategy and approach to eliminating malaria: practice and lessons learnt from China from 2011 to 2020. Emerg Microbes Infect. 2022;11(1):314–325. doi: 10.1080/22221751.2022.2026740. - DOI - PMC - PubMed
    1. Lai S, Sun J, Ruktanonchai NW, Zhou S, Yu J, Routledge I, et al. Changing epidemiology and challenges of malaria in China towards elimination. Malar J. 2019;18(1):107. doi: 10.1186/s12936-019-2736-8. - DOI - PMC - PubMed
    1. Zaw MT, Thant M, Hlaing TM, Aung NZ, Thu M, Phumchuea K, et al. Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar. Malar J. 2017;16(1):138. doi: 10.1186/s12936-017-1789-9. - DOI - PMC - PubMed
    1. Geng J, Malla P, Zhang J, Xu S, Li C, Zhao Y, et al. Increasing trends of malaria in a border area of the Greater Mekong Subregion. Malar J. 2019;18(1):309. doi: 10.1186/s12936-019-2924-6. - DOI - PMC - PubMed

MeSH terms