preprint · medRxiv
Standard entomological approaches for measuring human exposure to malaria-carrying mosquitoes are technically difficult and often inaccurate in areas with low disease transmission. Measuring antibody responses to mosquito salivary antigens offers an alternative method to track exposure to vector bites. This investigation evaluated two candidate salivary antigens from Anopheles gambiae, termed AgSAP and SAMSP1, alongside the established biomarker gSG6-P1. Tests in mice demonstrated increased antibody levels for all three antigens following repeated weekly mosquito bites. In human trials involving residents in coastal Tanzania and direct skin feeding assays, gSG6-P1 and AgSAP antibody levels decreased four weeks after exposure. In contrast, SAMSP1 generated a significantly elevated antibody response during the rainy season. This seasonal variation indicates that SAMSP1 could provide a more dependable biomarker for assessing vector contact where several Anopheles species exist, though human immune response dynamics require more research.
Evaluating human contact with malaria vectors is critical for disease surveillance, but current bug-catching techniques are difficult to run reliably when transmission is low. Using blood tests to detect antibodies against mosquito saliva offers a simpler way to track exposure. Validating reliable markers like SAMSP1 helps public health teams accurately monitor mosquito contact and assess the success of malaria control interventions.
This research could support the development of serological surveillance tools and diagnostic assays for public health organisations and malaria control programmes tracking vector exposure. The technology is at an early research stage, having been evaluated in animal models and small-scale human cohorts, with further investigation needed into antibody dynamics before practical deployment as an epidemiological tool.
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ABSTRACT Background Current methods to determine exposure to malaria-infected mosquitoes via entomologic investigations are technically challenging and can be inaccurate in low transmission settings. Antibody responses to mosquito salivary antigens (MSA) like gSG6-P1 have been used as biomarkers of exposure to Anopheles mosquito bites. Methods This study investigates two novel Anopheles gambiae salivary antigens, AgSAP and SAMSP1, as potential biomarkers of vector exposure. We evaluated the humoral response to gSG6-P1, SAMSP1, and AgSAP in a murine model and in malaria-exposed individuals with submicroscopic parasitemia across different malaria endemicity areas, seasons, and infection statuses in coastal Tanzania. We also analyzed antibody kinetics following direct skin feeding assays carried out using uninfected colony-reared An. gambiae . Results GSG6-P1, AgSAP, and SAMSP1 levels increased in mice at eight weeks after weekly mosquito feedings. However, human gSG6-P1 and AgSAP levels were paradoxically lower four weeks after direct skin feeding assays. SAMSP1 was the only MSA that induced a significantly higher humoral response during the rainy season, suggesting that it may be a more reliable biomarker for vector exposure in regions with multiple Anopheles species. Conclusions Mosquito salivary antigens associated with Plasmodium infection like AgSAP and SAMSP1 show promise as biomarkers of malaria vector exposure. However, the dynamics of IgG response against AgSAP and SAMSP1 after mosquito bites requires further study.
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DOI: 10.1101/2025.07.14.25331506
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