Analysis of copy number variation in <italic style="font-style: italic">pfpm</italic>2 gene of <italic style="font-style: italic">Plasmodium falciparum</italic> in 122 imported cases in Changsha from 2016 to 2019

Bin TIAN; Xiaojun SHEN; Yu LIAO; Qingren ZENG

doi:10.16016/j.1000-5404.202005173

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Analysis of copy number variation in pfpm2 gene of Plasmodium falciparum in 122 imported cases in Changsha from 2016 to 2019

Basic Medicine | 更新时间：2026-01-26

- Analysis of copy number variation in pfpm2 gene of Plasmodium falciparum in 122 imported cases in Changsha from 2016 to 2019
- Journal of Third Military Medical University Vol. 42, Issue 20, Pages: 2012-2017(2020)
- 作者机构：
  
  1.410013 长沙，中南大学湘雅医学院医学寄生虫学系
  2.410005 长沙，长沙市疾病预防控制中心
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Hunan Province(2020JJ8042)
- DOI：10.16016/j.1000-5404.202005173
  CLC： R181.81;R372;R382.31
- Received：26 July 2020，
  
  Revised：2020-07-29，
  
  Published：30 October 2020
- 稿件说明：
移动端阅览
Bin TIAN, Xiaojun SHEN, Yu LIAO, et al. Analysis of copy number variation in pfpm2 gene of Plasmodium falciparum in 122 imported cases in Changsha from 2016 to 2019[J]. Journal of Third Military Medical University, 2020, 42(20): 2012-2017.
DOI：

Bin TIAN, Xiaojun SHEN, Yu LIAO, et al. Analysis of copy number variation in pfpm2 gene of Plasmodium falciparum in 122 imported cases in Changsha from 2016 to 2019[J]. Journal of Third Military Medical University, 2020, 42(20): 2012-2017. DOI： 10.16016/j.1000-5404.202005173.

摘要

目的

了解长沙市近4年来输入性恶性疟原虫(

Plasmodium falciparum

P.f

)的血浆蛋白酶基因2(

plasmodium falciparum plasmepsin

pfpm

2)基因拷贝数变异(copy number variations

CNVs)情况，用以预测输入性抗药性虫株出现风险。

方法

收集长沙市输入性疟疾定点医疗机构在2016-2019年收治的单一感染

P.f

患者外周静脉血制作的干血斑样本122份，采用荧光实时定量PCR检测

P.f

的

pfpm

2基因CNVs，以

P.f

的

pfpm

2基因CNVs增加参数来分析抗药虫株在不同输入年份间和不同输出国间产生的可能性。

结果

来自25个输入国122例

P.f

患者的临床虫株

pfpm

2基因CNVs值为1.222±0.422，显著高于标准虫株3D7 CNVs值(1.007±0.023，

0.001)。在122个临床虫株中，有23个

pfpm

2基因的CNVs值

1.5，分别来源于尼日利亚(6/15)、刚果(5/18)、科特迪瓦(2/5)、塞拉利昂(2/8)等12个国家的恶性疟病例。在2016-2019年输入的病例数中，

pfpm

2基因CNVs值

1.5的临床虫株数在各年度输入总数中所占比率分别为13.2% (5/38)、16.0% (4/25)、22.9% (8/35)和25.0% (6/24)，各年度总虫株数的CNVs值分别为1.061±0.323、1.184±0.247、1.292±0.571和1.414±0.360。经

检验，除2017与2018年、2018与2019年之间的差异无统计学意义外，其余年度间比较差异均有统计学意义(

0.05)。来源于尼日利亚、科特迪瓦、坦桑尼亚和布隆迪4个国家的临床

虫株CNVs均值显著高于总体(122个病例来源)均值(

0.05)。

结论

长沙市输入性

P.f

的

pfpm

2基因CNVs值逐年提高，提示抗药性虫株有发展趋势；某些来源于西非国家的临床虫株可能产生了抗药性，提示我国疟疾防控机构要注意现行抗疟药对某些输入性恶性疟患者的治疗效果可能不佳。

Abstract

Objective

To analyze copy number variations (CNVs) of

pfpm

2 gene in 122 imported cases of

Palciparum falciparum

(

P.f

) infection in Changsha from 2016 to 2019 for predicting the risk of imported drug-resistant

P.f

strains in Changsha.

Methods

We collected dried blood spot samples of anticoagulated peripheral venous blood from 122 patients with a single infection of

P.f

who were treated in designated medical facilities for malaria in Changsha in the years of 2016-2019. For each specimen

the CNVs of

pfpm

2 gene were detected in parallel with the standard strain 3D7 using real-time PCR. The CNVs values of the samples were compared across the years and also among different source countries of the cases.

Results

We analyzed a total of 122

P.f

strains isolated from imported cases from 25 countries. The mean value of CNVs of

pfpm

2 gene in the 122 strains was significantly higher than that of the standard strain 3D7 (1.222±0.422

1.007±0.023

0.001). There were 23 Strains Whose CNVs Values of

pfpm

2 gene were higher than 1.5

which were imported from 12 countries including Nigeria (6/15)

Congo (5/18)

Cote d'Ivoire (2/5) and Sierra Leone (2/8). The percentage of strains with

pfpm

2 CNVs

1.5 was 13.2% (5/38) in 2016

16.0% (4/25) in 2017

22.9% (8/35) in 2018 and 25.0% (6/24) in 2019 respectively. The mean value of

pfpm

2 gene CNVs was 1.061±0.323 in 2016

1.184±0.247 in 2017

1.292±0.571 in 2018 and

1.414±0.360 in 2019

showing significant differences across the years except the years of 2017 and 2018 or 2018 and 2019 (

0.05

0.001). The mean values of

pfpm

2 gene CNVs of the strains from Nigeria

Cote d'Ivoire

Tanzania and Burundi were significantly higher than the overall mean of the 122 strains (

0.05).

Conclusion

The CNVs of

pfpm

2 gene of

P.f

imported from African countries to Changsha are increased year by year

suggesting an increase in the risk of drug-resistant

P.f

strains in Changsha. Some clinical

P.f

strains from West Africa may have developed drug resistance

and thus may show poor response to current antimalarial drugs.

关键词

Keywords

references

ROUT S, MAHAPATRA R K. Plasmodium falciparum : Multidrug resistance[J ] . Chem Biol Drug Des, 2019, 93(5): 737-759. DOI: 10.1111/cbdd.13484.

HALDAR K, BHATTACHARJEE S, SAFEUKUI I. Drug resistance in plasmodium[J]. Nat Rev Microbiol, 2018, 16(3): 156-170. DOI: 10.1038/nrmicro.2017.161.

QIDWAI T. Exploration of copy number variation in genes related to anti-malarial drug resistance in Plasmodium falciparum [J ] . Gene, 2020, 736: 144414. DOI: 10.1016/j.gene.2020.144414.

BEGHAIN J, LANGLOIS A C, LEGRAND E, et al . Plasmodium copy number variation scan: gene copy numbers evaluation in haploid genomes[J ] . Malar J, 2016, 15: 206. DOI: 10.1186/s12936-016-1258-x.

BOPP S, MAGISTRADO P, WONG W, et al . Plasmepsin Ⅱ-Ⅲ copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum [J ] . Nat Commun, 2018, 9(1): 1769. DOI: 10.1038/s41467-018-04104-z..

WITKOWSKI B, DURU V, KHIM N, et al . A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: a phenotype-genotype association study[J ] . Lancet Infect Dis, 2017, 17(2): 174-183. DOI: 10.1016/S1473-3099(16)30415-7..

HUCKABY A C, GRANUM C S, CAREY M A, et al . Complex DNA structures trigger copy number variation across the Plasmodium falciparum genome[J ] . Nucleic Acids Res, 2019, 47(4): 1615-1627. DOI: 10.1093/nar/gky1268..

FOGUIM TSOMBENG F, GENDROT M, ROBERT M G, et al . Are k13 and plasmepsin Ⅱ genes, involved in Plasmodium falciparum resistance to artemisinin derivatives and piperaquine in Southeast Asia, reliable to monitor resistance surveillance in Africa?[J ] . Malar J, 2019, 18(1): 285. DOI: 10.1186/s12936-019-2916-6..

LOESBANLUECHAI D, KOTANAN N, DE COZAR C, et al . Overexpression of plasmepsin Ⅱ and plasmepsin Ⅲ does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine[J ] . Int J Parasitol Drugs Drug Resist, 2019, 9: 16-22. DOI: 10.1016/j.ijpddr.2018.11.004..

LEROY D, MACINTYRE F, ADOKE Y, et al . African isolates show a high proportion of multip le copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker[J ] . Malaria J, 2019, 18(1): 111-126..

AMAMBUA-NGWA A, AMENGA-ETEGO L, KAMAU E, et al . Major subpopulations of Plasmodium falciparum in sub-Saharan Africa[J ] . Science, 2019, 365(6455): 813-816..

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⁰

Analysis of copy number variation in pfpm2 gene of Plasmodium falciparum in 122 imported cases in Changsha from 2016 to 2019

DOI：10.16016/j.1000-5404.202005173

摘要

Abstract

关键词

Keywords

references