BACKGROUND Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information. METHODS Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species. RESULTS Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38. CONCLUSIONS Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

中文翻译：

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一组来自人类感染性疟原虫物种的重组蛋白，用于血清学监测。

背景疟疾仍然是一个全球性的健康问题，需要对引起这种疾病的疟原虫进行准确监测以指导控制措施的最有效分配。血清学监测在低传播或周期性传播的地区尤为重要，因为患者抗体反应可以提供历史暴露的衡量标准。虽然检测对恶性疟原虫和间日疟原虫的宿主抗体反应的方法已经很好地建立，但由于基因组信息的有限可用性，缺乏免疫诊断候选物，抑制了诺氏疟原虫、卵形疟原虫和疟原虫血清学检测的发展。方法使用最近完成的来自疟原虫、卵形疟原虫和诺氏疟原虫的基因组序列，选择了一组 33 个候选细胞表面和分泌的血液阶段抗原，并使用哺乳动物表达系统以重组形式表达。将这些蛋白质添加到来自恶性疟原虫和间日疟原虫的现有抗原组中，并且通过 ELISA 评估了来自被诊断患有感染的个体的 IgG、IgM 和 IgA 免疫球蛋白对五种不同疟原虫物种的免疫反应性。逻辑回归模型用于量化反应的能力，以确定先前接触不同疟原虫物种的能力。结果 使用来自确诊为疟原虫感染的欧洲旅行者的血清，鉴定了显示物种特异性免疫反应性的抗原，以从五种疟原虫物种中选择一组 22 种蛋白质进行血清学分析。对来自旅行者和生活在疟疾流行地区的确诊感染者的血清中抗原的免疫反应性显示出预测每个物种感染的中等能力，包括卵形疟原虫、疟疾疟原虫和诺氏疟原虫。使用更大的患者样本集和逻辑回归模型显示，使用由 MSP10、P12 和 P38 的诺氏假单胞菌直向同源物组成的抗原组可以准确地检测到诺氏假单胞菌的暴露（AUC = 91%）。结论 利用最近对所有人类感染性疟原虫的基因组序列的可用性。寄生虫和以分泌功能形式表达疟原虫蛋白的方法，已经编制了一个抗原面板，可用于确定暴露于这些寄生虫的情况。