Lapidus Sarah, Goheen Morgan M, Sy Mouhamad, Deme Awa B, Ndiaye Ibrahima Mbaye, Diedhiou Younous, Mbaye Amadou Moctar, Hagadorn Kelly A, Sene Seynabou Diouf, Pouye Mariama Nicole, Thiam Laty Gaye, Ba Aboubacar, Guerra Noemi, Mbengue Alassane, Raduwan Hamidah, Vigan-Womas Inés, Parikh Sunil, Ko Albert I, Ndiaye Daouda, Fikrig Erol, Chuang Yu-Min, Bei Amy K
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Division of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA.
medRxiv. 2024 Apr 22:2024.04.20.24305430. doi: 10.1101/2024.04.20.24305430.
Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with : mosGILT, SAMSP1, AgSAP, and AgTRIO.
We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with known infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay.
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 infection and declined 3 months after infection.
Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting 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 -infected mosquito exposure.
使用传统的昆虫学接种率来测量疟疾传播强度很困难。此前,针对蚊子唾液蛋白(如SG6)的抗体反应已被用作接触蚊虫叮咬的生物标志物。在此,我们研究四种蚊子唾液蛋白,即mosGILT、SAMSP1、AgSAP和AgTRIO,作为人类接触感染疟原虫蚊子的潜在生物标志物。
我们使用基于磁珠的多重检测法,对来自塞内加尔低传播和中传播地区已知疟原虫感染个体的纵向和横断面血浆样本中的人群水平免疫反应进行了检测。
AgSAP和AgTRIO是近期接触感染蚊子的最佳指标。在中度流行地区,对AgSAP的抗体反应,以及在低流行和中度流行地区对AgTRIO的抗体反应,均显著高于健康非流行对照队列中的反应(p值分别为0.0245、0.0064和<0.0001)。低传播地区和中传播地区之间,或疟疾传播季节期间和之外的同等组之间,抗体反应没有显著差异。对于AgSAP和AgTRIO,反应性在临床感染后2 - 4周达到峰值,并在感染后3个月下降。
对AgSAP和AgTRIO的反应性在感染后达到峰值,且在季节上或低传播和中传播地区之间没有差异,这表明反应性可能反映了接触感染性蚊子或近期叮咬,而非一般的蚊子接触。动力学表明反应性持续时间相对较短。AgSAP和AgTRIO有望纳入多重检测,用于血清学监测人群水平上接触感染疟原虫蚊子的变化情况。