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泰国-缅甸边境青蒿素衍生物治疗失败患者中恶性疟原虫的基因型多样性

Plasmodium falciparum genotype diversity in artemisinin derivatives treatment failure patients along the Thai-Myanmar border.

作者信息

Congpuong Kanungnit, Hoonchaiyapoom Thirasak, Inorn Kornnarin

机构信息

Bansomdejchaopraya Rajabhat University, Bangkok 10600, Thailand.

Bureau of Vector Borne Disease, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.

出版信息

Korean J Parasitol. 2014 Dec;52(6):631-7. doi: 10.3347/kjp.2014.52.6.631. Epub 2014 Dec 23.

DOI:10.3347/kjp.2014.52.6.631
PMID:25548414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4277025/
Abstract

Genetic characteristics of Plasmodium falciparum may play a role in the treatment outcome of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1), msp-2, and glutamate-rich protein (glurp) loci and the treatment outcome of uncomplicated falciparum malaria patients along the Thai-Myanmar border who were treated with artemisinin derivatives combination therapy. P. falciparum isolates were collected prior to treatment from 3 groups of patients; 50 cases of treatment failures, 50 recrudescences, and 56 successful treatments. Genotyping of the 3 polymorphic markers was analyzed by nested PCR. The distribution of msp-1 alleles was significantly different among the 3 groups of patients but not the msp-2 and glurp alleles. The allelic frequencies of K1 and MAD20 alleles of msp1 gene were higher while RO33 allele was significantly lower in the successful treatment group. Treatment failure samples had a higher median number of alleles as compared to the successful treatment group. Specific genotypes of msp-1, msp-2, and glurp were significantly associated with the treatment outcomes. Three allelic size variants were significantly higher among the isolates from the treatment failure groups, i.e., K1270-290, 3D7610-630, G650-690, while 2 variants, K1150-170, and 3D7670-690 were significantly lower. In conclusion, the present study reports the differences in multiplicity of infection and distribution of specific alleles of msp-1, msp-2, and glurp genes in P. falciparum isolates obtained from treatment failure and successful treatment patients following artemisinin derivatives combination therapy.

摘要

恶性疟原虫的遗传特征可能在疟疾感染的治疗结果中发挥作用。我们研究了裂殖子表面蛋白-1(msp-1)、msp-2和富含谷氨酸蛋白(glurp)基因座的多样性与泰国-缅甸边境接受青蒿素衍生物联合疗法治疗的非复杂性恶性疟患者治疗结果之间的关联。在治疗前从3组患者中收集恶性疟原虫分离株;50例治疗失败病例、50例复发病例和56例治疗成功病例。通过巢式PCR分析3个多态性标记的基因分型。3组患者中msp-1等位基因的分布存在显著差异,但msp-2和glurp等位基因无显著差异。msp1基因的K1和MAD20等位基因频率在治疗成功组中较高,而RO33等位基因显著较低。与治疗成功组相比,治疗失败样本的等位基因中位数较高。msp-1、msp-2和glurp的特定基因型与治疗结果显著相关。治疗失败组分离株中的3个等位基因大小变体显著更高,即K1270-290、3D7610-630、G650-690,而2个变体K1150-170和3D7670-690显著更低。总之,本研究报告了在接受青蒿素衍生物联合疗法治疗失败和成功的患者中获得的恶性疟原虫分离株中,感染多样性以及msp-1、msp-2和glurp基因特定等位基因分布的差异。

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Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border.全基因组关联分析鉴定出与来自中缅边境的恶性疟原虫对多种抗疟药物的抗性相关的遗传位点。
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本文引用的文献

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Spread of artemisinin resistance in Plasmodium falciparum malaria.疟原虫青蒿素耐药性的传播。
N Engl J Med. 2014 Jul 31;371(5):411-23. doi: 10.1056/NEJMoa1314981.
2
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Malar J. 2013 Nov 9;12:403. doi: 10.1186/1475-2875-12-403.
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Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity.在泰缅边境地区鉴定恶性疟原虫对青蒿琥酯-甲氟喹联合用药的耐药性:临床寄生虫学反应、全身药物暴露和体外寄生虫敏感性的综合分析。
Malar J. 2013 Jul 30;12:263. doi: 10.1186/1475-2875-12-263.
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Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda.乌干达坎帕拉儿童中轻度和重度疟疾中恶性疟原虫感染的遗传多样性。
Parasitol Res. 2013 Apr;112(4):1691-700. doi: 10.1007/s00436-013-3325-3. Epub 2013 Feb 14.
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