Two Mosquito Salivary Antigens Demonstrate Promise as Biomarkers of Recent Exposure to Plasmodium falciparum-Infected Mosquito Bites.

Abstract

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 4 mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with Plasmodium falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. 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. AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate-endemicity area, and to AgTRIO in both low- and moderate-endemicity areas, were significantly higher than nonendemic controls. No antibody responses significantly differed between low- and moderate-transmission areas, or between equivalent groups during and outside the malaria transmission seasons. AgSAP and AgTRIO reactivity peaked 2-4 weeks after clinical P falciparum infection and declined 3 months after infection. Reactivity to AgSAP and AgTRIO reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure, highlighting their promise for incorporation into multiplexed assays for serosurveillance of population-level changes in P falciparum-infected mosquito exposure.