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Abstract：
BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas.
METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source.
RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype.
CONCLUSIONS: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite\'s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.
METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source.
RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype.
CONCLUSIONS: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite\'s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.
摘要：
背景：镰状细胞性状（SCT）是指携带β-珠蛋白基因的一个异常拷贝，HbS等位基因.SCT提供预防疟疾的保护，控制寄生虫密度和防止发展为有症状的疟疾。然而,尚不清楚SCT是否也影响传播阶段和蚊子感染参数.破译SCT对人向蚊子传播疟疾的影响是理解在疟疾流行地区维持该特征的机制的关键。
方法：该研究于2017年6月至7月在生活在Mfou地区的无症状儿童中进行，喀麦隆。从无症状儿童收集血样，通过显微镜进行疟疾诊断，疟原虫通过PCR和血红蛋白通过RFLP分型。使用来自HbAA和HbAS基因型的配子体携带者的血液，通过膜喂养测定法评估配子体对蚊子的传染性。根据配子细胞来源的血红蛋白基因型，拟合了零膨胀模型以预测卵囊在蚊子中的分布。
结果：在参加研究的1557名儿童中，314个(20.16%)为HbAS基因型。儿童恶性疟原虫配子细胞的患病率在HbAS个体中为18.47％，在HbAA中为13.57％，差异有统计学意义(χ2=4.61,P=0.032)。HbAS配子细胞携带者的感染多重性较低（HbAS的中位数=2基因型/携带者，HbAA的中位数=3.5基因型/携带者，Wilcoxon和秩检验=188,P=0.032)。献血者中的配子细胞密度显着影响HbAS和HbAA个体的蚊子感染率。当在喂养测定中使用免疫或初始血清时,HbAS基因型对蚊子感染结果没有显著影响。在AB替代饲喂实验中，与HbAS相比，HbAA血液中蚊子感染的比值比为0.56（95％CI0.29-1.10），表明以含有HbAS基因型配子细胞的血液为食的蚊子感染的风险高两倍。
结论：疟原虫传播阶段在SCT个体中更为普遍。这可能反映了寄生虫在有性阶段的投资增加，以提高无性复制受阻时的存活率。我们的研究结果对公共卫生的影响表明，需要在HbAS流行率高的地区采取强化疟疾控制干预措施。在蚊子从献血者接受原始血清的喂养实验中，类似的感染参数表明，对配子细胞表面蛋白的免疫反应发生在HbAS和HbAA个体中。以消耗免疫因子的HbAS血液为食的蚊子感染的风险较高，这表明HbAS红细胞膜特性的变化可能会影响循环红细胞内配子细胞的成熟过程。
方法：该研究于2017年6月至7月在生活在Mfou地区的无症状儿童中进行，喀麦隆。从无症状儿童收集血样，通过显微镜进行疟疾诊断，疟原虫通过PCR和血红蛋白通过RFLP分型。使用来自HbAA和HbAS基因型的配子体携带者的血液，通过膜喂养测定法评估配子体对蚊子的传染性。根据配子细胞来源的血红蛋白基因型，拟合了零膨胀模型以预测卵囊在蚊子中的分布。
结果：在参加研究的1557名儿童中，314个(20.16%)为HbAS基因型。儿童恶性疟原虫配子细胞的患病率在HbAS个体中为18.47％，在HbAA中为13.57％，差异有统计学意义(χ2=4.61,P=0.032)。HbAS配子细胞携带者的感染多重性较低（HbAS的中位数=2基因型/携带者，HbAA的中位数=3.5基因型/携带者，Wilcoxon和秩检验=188,P=0.032)。献血者中的配子细胞密度显着影响HbAS和HbAA个体的蚊子感染率。当在喂养测定中使用免疫或初始血清时,HbAS基因型对蚊子感染结果没有显著影响。在AB替代饲喂实验中，与HbAS相比，HbAA血液中蚊子感染的比值比为0.56（95％CI0.29-1.10），表明以含有HbAS基因型配子细胞的血液为食的蚊子感染的风险高两倍。
结论：疟原虫传播阶段在SCT个体中更为普遍。这可能反映了寄生虫在有性阶段的投资增加，以提高无性复制受阻时的存活率。我们的研究结果对公共卫生的影响表明，需要在HbAS流行率高的地区采取强化疟疾控制干预措施。在蚊子从献血者接受原始血清的喂养实验中，类似的感染参数表明，对配子细胞表面蛋白的免疫反应发生在HbAS和HbAA个体中。以消耗免疫因子的HbAS血液为食的蚊子感染的风险较高，这表明HbAS红细胞膜特性的变化可能会影响循环红细胞内配子细胞的成熟过程。
