Chaorattanakawee Suwanna, Nuchnoi Pornlada, Hananantachai Hathairad, Tumkosit Uranan, Saunders David, Naka Izumi, Ohashi Jun, Patarapotikul Jintana
Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani, Thailand.
Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.
PLoS One. 2018 Jan 17;13(1):e0190418. doi: 10.1371/journal.pone.0190418. eCollection 2018.
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.
疟原虫毒力是导致恶性疟原虫感染严重程度的一个重要因素，在不同的恶性疟原虫菌株中有所不同。关于能够识别导致严重疟疾的菌株的毒力标志物，人们了解得相对较少。我们研究了恶性疟原虫裂殖子表面蛋白2基因（msp2）的基因变异对毒力的影响，因为它之前被假定为一个因素。我们分析了来自无并发症疾病患者以及因严重疟疾入院且伴有或不伴有脑部疾病的患者的单个恶性疟原虫克隆感染的300个msp2序列。研究了msp2变异与疾病严重程度的关联。我们发现，FC27样msp2基因第2区第8密码子处的N等位基因与无脑部并发症的严重疾病显著相关（比值比=2.73，P=0.039），而3D7样msp2基因第4区第17密码子处的K等位基因与脑型疟疾相关（比值比=3.52，P=0.024）。数据表明相关等位基因在寄生虫入侵过程和免疫介导的致病性中可能发挥作用。发现感染复数与无脑部并发症的严重疾病相关，但与脑型疟疾无关。msp2-FC27-第2区-8N和3D7-第4区-17K等位基因的变异似乎是寄生虫毒力标志物，可能有助于确定严重和脑型疟疾的可能性。还应探索它们与严重疾病潜在宿主因素的相互作用。
