Background Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. Methods We tested population-level human immune responses in longitudinal and cross-sectional plasma from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. Results AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Discussion Reactivity to AgSAP and AgTRIO peaked after infection, with no differences between transmission seasons within region or between low and moderate transmission regions. This suggests that reactivity reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

中文翻译：

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两种蚊子唾液抗原有望成为近期暴露于恶性疟原虫感染蚊虫叮咬的生物标志物


背景 使用传统的昆虫学接种率测量疟疾传播强度是困难的。对蚊子唾液蛋白（如 SG6）的抗体反应已被用作暴露于按蚊叮咬的生物标志物。在这里，我们研究了四种蚊子唾液蛋白作为人类暴露于感染恶性疟原虫的蚊子的潜在生物标志物：mosGILT、SAMSP1、AgSAP 和 AgTRIO。方法 我们使用基于多重磁珠的测定法测试了来自塞内加尔低传播和中度传播地区的已知恶性疟原虫感染个体的纵向和横截面血浆中人群水平的人类免疫反应。结果 AgSAP 和 AgTRIO 是近期暴露于受感染蚊子的最佳指标。在中度流行地区对 AgSAP 的抗体反应，以及在低流行和中流行地区对 AgTRIO 的抗体反应，均显著高于健康非流行对照队列的反应 （p 值分别为 = 0.0245、0.0064 和 <0.0001）。在疟疾传播季节期间和外部，低传播区和中度传播区之间或同等群体之间没有抗体反应显著差异。对于 AgSAP 和 AgTRIO，反应性在临床恶性疟原虫感染后 2-4 周达到峰值，并在感染后 3 个月下降。讨论 对 AgSAP 和 AgTRIO 的反应性在感染后达到峰值，区域内或低传播和中度传播区域之间的传播季节之间没有差异。这表明反应性反映了暴露于传染性蚊子或近期叮咬，而不是一般的蚊子暴露。动力学表明反应性相对较短。 AgSAP 和 AgTRIO 是有希望的候选者，可纳入多重检测中，用于对恶性疟原虫感染的蚊子暴露的种群水平变化进行血清监测。