Chaikitgosiyakul Sethawud, Kuamsab Napaporn, Tia Taweesak, Putaporntip Chaturong, Jongwutiwes Somchai
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand.
Am J Trop Med Hyg. 2024 Nov 19;112(2):266-273. doi: 10.4269/ajtmh.24-0065. Print 2025 Feb 5.
Placental malaria is an important cause of fetomaternal morbidity and mortality among pregnant women infected with Plasmodium falciparum. The pathogenesis involves the binding of VAR2CSA on the surface of infected erythrocytes to chondroitin sulfate proteoglycans on syncytiotrophoblasts in the intervillous space of the placenta. Anti-VAR2CSA antibodies confer protection from adverse pregnancy outcomes in falciparum malaria; therefore, VAR2CSA is a strong vaccine candidate against placental malaria. To date, little is known about transcription of var2csa among isolates from male and nonpregnant patients in low transmission areas. In this study, transcription and copy number variation of var2csa were analyzed in 55 P. falciparum isolates from nonpregnant women, men and children with symptomatic malaria in five endemic provinces of Thailand. Reverse transcription polymerase chain reaction (PCR) detected var2csa transcripts in 43 (78.2%) blood samples. Multiple copies of var2csa were identified in 16 of 55 (29.1%) isolates by quantitative real-time PCR. Copy number variation of var2csa was not associated with the patients' sex, age group, ethnicity, parasite genotypes, parasite density, and geographic origins. These data suggest that P. falciparum carrying multicopy var2csa had a wide geographic distribution in Thailand with a prevalence rate comparable to those observed in high transmission areas of Africa. The high prevalence of isolates from male and nonpregnant patients with var2csa transcription suggests that the transcription of this gene occurs naturally during blood stage infection. Whether VAR2CSA is expressed and immunogenic among nonpregnant falciparum malaria patients requires further study.
胎盘疟疾是感染恶性疟原虫的孕妇发生母婴发病和死亡的重要原因。其发病机制涉及感染红细胞表面的VAR2CSA与胎盘绒毛间隙合体滋养层细胞上的硫酸软骨素蛋白聚糖结合。抗VAR2CSA抗体可预防恶性疟导致的不良妊娠结局；因此，VAR2CSA是预防胎盘疟疾的有力疫苗候选物。迄今为止，对于低传播地区男性和非妊娠患者分离株中var2csa的转录情况知之甚少。在本研究中，对来自泰国五个疟疾流行省份有症状疟疾的非妊娠女性、男性和儿童的55株恶性疟原虫分离株进行了var2csa的转录和拷贝数变异分析。逆转录聚合酶链反应（PCR）在43份（78.2%）血样中检测到var2csa转录本。通过定量实时PCR在55株分离株中的16株（29.1%）中鉴定出多个var2csa拷贝。var2csa的拷贝数变异与患者的性别、年龄组、种族、寄生虫基因型、寄生虫密度和地理来源无关。这些数据表明，携带多拷贝var2csa的恶性疟原虫在泰国具有广泛的地理分布，其流行率与在非洲高传播地区观察到的相当。来自男性和非妊娠患者且有var2csa转录的分离株的高流行率表明，该基因的转录在血液阶段感染期间自然发生。非妊娠恶性疟患者中VAR2CSA是否表达及其免疫原性需要进一步研究。
