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Genetic diversity of Plasmodium falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon
Malaria Journal ( IF 2.4 ) Pub Date : 2020-03-18 , DOI: 10.1186/s12936-020-03161-4
Theresia Njuabe Metoh 1, 2, 3 , Jun-Hu Chen 2, 3 , Philip Fon-Gah 4, 5 , Xia Zhou 2, 3 , Roger Moyou-Somo 6, 7 , Xiao-Nong Zhou 2, 3
Affiliation  

Malaria is a major public health problem in Cameroon. The study of the genetic diversity within parasite population is essential for understanding the mechanism underlying malaria pathology and to determine parasite clones profile in an infection, for proper malaria control strategies. The objective of this study was to perform a molecular characterization of highly polymorphic genetic markers of Plasmodium falciparum, and to determine allelic distribution with their influencing factors valuable to investigate malaria transmission dynamics in Cameroon. A total of 350 P. falciparum clinical isolates were characterized by genotyping block 2 of msp-1, block 3 of msp-2, and region II of glurp gene using nested PCR and DNA sequencing between 2012 and 2013. A total of 5 different genotypes with fragment sizes ranging from 597 to 817 bp were recorded for GLURP. Overall, 16 MSP-1 genotypes, including K1, MAD20 and RO33 were identified, ranging from 153 to 335 bp. A peculiarity about this study is the RO33 monomorphic pattern revealed among the Pfmsp-1 allelic type. Again, this study identified 27 different Pfmsp-2 genotypes, ranging from 140 to 568 bp in size, including 15 belonging to the 3D7-type and 12 to the FC27 allelic families. The analysis of the MSP-1 and MSP-2 peptides indicates that the region of the alignment corresponding K1 polymorphism had the highest similarity in the MSP1and MSP2 clade followed by MAD20 with 93% to 100% homology. Therefore, population structure of P. falciparum isolates is identical to that of other areas in Africa, suggesting that vaccine developed with K1 and MAD20 of Pfmsp1 allelic variant could be protective for Africa children but these findings requires further genetic and immunological investigations. The multiplicity of infection (MOI) was significantly higher (P < 0.05) for Pfmsp-2 loci (3.82), as compare with Pfmsp-1 (2.51) and heterozygotes ranged from 0.55 for Pfmsp-1 to 0.96 for Pfmsp-2. High genetic diversity and allelic frequencies in P. falciparum isolates indicate a persisting high level of transmission. This study advocate for an intensification of the malaria control strategies in Cameroon. Trial registration This study was approved by Cameroon National Ethics Committee. It is a randomized controlled trial retrospectively registered in NIH U.S. National Library of Medicine, ClinicalTrials.gov on the 28/11/2016 at https://clinicaltrials.gov/ct2/show/NCT02974348 with the registration number NCT02974348

中文翻译:


喀麦隆受单纯性疟疾影响的儿童中恶性疟原虫的遗传多样性和遗传谱



疟疾是喀麦隆的一个主要公共卫生问题。对寄生虫种群内遗传多样性的研究对于了解疟疾病理学的机制和确定感染中的寄生虫克隆概况以及制定适当的疟疾控制策略至关重要。本研究的目的是对恶性疟原虫的高度多态性遗传标记进行分子表征,并确定等位基因分布及其影响因素,这对研究喀麦隆的疟疾传播动态有价值。 2012年至2013年期间,使用巢式PCR和DNA测序对总共350个恶性疟原虫临床分离株进行了msp-1区块2、msp-2区块3和glurp基因区域II的基因分型。总共5种不同的基因型GLURP 记录的片段大小范围为 597 至 817 bp。总体而言,鉴定出 16 个 MSP-1 基因型,包括 K1、MAD20 和 RO33,范围为 153 至 335 bp。这项研究的一个特点是 Pfmsp-1 等位基因类型中揭示的 RO33 单态模式。该研究再次鉴定了 27 种不同的 Pfmsp-2 基因型,大小范围为 140 至 568 bp,其中 15 种属于 3D7 型,12 种属于 FC27 等位基因家族。 MSP-1和MSP-2肽的分析表明,对应于K1多态性的比对区域在MSP1和MSP2进化枝中具有最高的相似性,其次是MAD20,具有93%至100%的同源性。因此,恶性疟原虫分离株的种群结构与非洲其他地区的种群结构相同,这表明用 Pfmsp1 等位基因变体的 K1 和 MAD20 开发的疫苗可能对非洲儿童具有保护作用,但这些发现需要进一步的遗传和免疫学研究。 与 Pfmsp-1 (2.51) 相比,Pfmsp-2 位点 (3.82) 的感染复数 (MOI) 显着更高 (P < 0.05),杂合子范围从 Pfmsp-1 的 0.55 到 Pfmsp-2 的 0.96。恶性疟原虫分离株的高遗传多样性和等位基因频率表明持续的高水平传播。这项研究主张在喀麦隆加强疟疾控制策略。试验注册本研究得到了喀麦隆国家伦理委员会的批准。这是一项随机对照试验,于 2016 年 11 月 28 日在 NIH 美国国家医学图书馆的 ClinicalTrials.gov 上回顾性注册,网址为 https://clinicaltrials。gov/ct2/show/NCT02974348,注册号为 NCT02974348
更新日期:2020-04-22
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