Genetic diversity of Plasmodium falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon
Genetic diversity of Plasmodium falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon
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DOI：
10.1186/s12936-020-03161-4
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发表时间：
2020-03-18
期刊：
影响因子：
3
通讯作者：
Zhou, Xiao-Nong
中科院分区：
文献类型：
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作者：
Metoh, Theresia Njua;Chen, Jun-Hu;Zhou, Xiao-Nong
疟疾是喀麦隆的一个主要公共卫生问题。研究疟原虫种群内的遗传多样性对于了解疟疾病理机制和确定感染时的疟原虫克隆特征，制定适当的疟疾控制策略至关重要。本研究的目的是对喀麦隆恶性疟原虫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，对研究喀麦隆疟疾传播动态有价值。方法采用巢式PCR和DNA测序对2012 - 2013年350例恶性疟原虫临床分离株进行msp-1片段2、msp-2片段3和glurp基因II区基因分型。结果GLURP共有5个不同的基因型，片段大小在597 ~ 817 bp之间。总共鉴定出16种MSP-1基因型，包括K1、MAD20和RO33，范围从153 ~ 335 bp。本研究的一个特点是在Pfmsp-1等位基因型中发现RO33单态模式。同样，本研究确定了27个不同的Pfmsp-2基因型，大小从140到568 bp不等，其中15个属于3d7型，12个属于FC27等位基因家族。对MSP-1和MSP-2肽的分析表明，msp1和MSP2分支中对应K1多态性的比对区域相似性最高，其次是MAD20，同源性为93% ~ 100%。因此，恶性疟原虫分离株的种群结构与非洲其他地区的相同，这表明用Pfmsp1等位基因变体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。Pfmsp-2基因座的感染多重性（MOI）（3.82）显著高于Pfmsp-1基因座（2.51）（P < 0.05），杂合子数在0.55 ~ 0.96之间。结论恶性疟原虫分离株具有较高的遗传多样性和等位基因频率，表明该地区存在持续的高传播水平。这项研究提倡加强喀麦隆的疟疾控制战略。本研究已获得喀麦隆国家伦理委员会批准。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ClinicalTrials.gov上回顾性注册，注册号为NCT02974348
Background 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. Methods 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. Results 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. Conclusion 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 with the registration number NCT02974348