Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum-infected mosquito bites

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 Anopheles mosquito bites. Here, we investigate
four mosquito salivary proteins as potential biomarkers of human exposure
to mosquitoes infected with P. falciparum: mosGILT, SAMPSP1, AgSAP, and
AgTRIO. We tested population-level human immune responses in
longitudinal and cross-sectional plasma samples from subjects 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,
with antibody responses to AgSAP in a moderate endemic area, and to AgTRIO
in both low and moderate endemic areas, significantly higher than 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. 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 due to
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 P.
falciparum-infected mosquito exposure.