Molecular Parasitology and Entomology Unit, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
Centre for Genomic Research, University of Liverpool, Liverpool, United Kingdom.
Infect Genet Evol. 2023 Jul;111:105416. doi: 10.1016/j.meegid.2023.105416. Epub 2023 Mar 6.
Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P < 0.0001 for POC-CCA; P = 0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p = 0.009) and recessive model (p = 0.01) while the allele C of SNP rs1800871 of IL10 was protective (p = 0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P = 0.04) and IL-10 (P = 0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines.
要在 2030 年前消除血吸虫病这一公共卫生问题，需要更好地了解疾病传播，特别是了解生活在同一环境中的个体的虫荷的不对称分布。正是出于这一考虑，本研究旨在确定与曼氏血吸虫高负荷以及喀麦隆两个血吸虫病流行区儿童的 IgE 和四种细胞因子的血浆浓度相关的人类遗传决定因素。在喀麦隆曼凯内和诺姆坎迪两个血吸虫病流行区的学龄儿童中，分别使用即时循环抗原检测（POC-CCA）和加藤氏厚涂片法（KK）检测尿液和粪便样本中的曼氏血吸虫感染及其感染强度。然后，在携带高负荷血吸虫感染的儿童及其父母和兄弟姐妹中采集血样。从血液中提取 DNA 提取物和血浆。使用 PCR 限制性片段长度多态性和扩增反应突变系统评估五个基因 14 个基因座的多态性。ELISA 检测可确定 IgE、IL-13、IL-10、IL-4 和 IFN-γ 的血浆浓度。曼氏血吸虫感染的流行率在 Makenene（POC-CCA 为 48.6%，KK 为 7.9%）显著高于 Nom-Kandi（POC-CCA 为 31%，KK 为 4.3%）（P < 0.0001）。Makenene 地区儿童的感染强度也高于 Nom-Kandi 地区（POC-CCA 为 P < 0.0001，KK 为 P = 0.001）。STAT6 基因的 SNP rs3024974 的 C 等位基因与携带曼氏血吸虫高负荷的风险增加相关，无论是在加性模型（p = 0.009）还是隐性模型（p = 0.01）中，而 IL10 基因的 SNP rs1800871 的 C 等位基因对曼氏血吸虫高负荷具有保护作用（p = 0.0009）。IL13 基因的 SNP rs2069739 的 A 等位基因和 IL4 基因的 SNP rs2243283 的 G 等位基因与 IL-13（P = 0.04）和 IL-10（P = 0.04）的低血浆浓度相关。本研究表明，宿主遗传多态性可能影响曼氏血吸虫感染的结果（高或低虫荷）以及某些细胞因子的血浆浓度。
