Immunological surveillance using anti-gSG6-P1 IgG biomarker reveals spatio-temporal dynamics of Anopheles exposure and gaps in malaria risk assessment in the Greater Mekong Subregion

Abstract

Entomological parameters such as mosquito biting rates often fail to capture variability in human behavior, thereby limiting its accuracy for assessing the population-level malaria risk. This study investigated the use of previously described Anopheles gambiae-based anti-salivary biomarker, anti-gSG6-P1, as a serological marker for Anopheles exposure, and examined key entomological, human, and environmental risk factors in Sisaket Province, Thailand. Blood samples were collected via finger prick from the same set of 184 participants across three seasons: rainy (August 2022), cool-dry (December 2022), and hot-dry (April 2023). Anti-gSG6-P1 IgG levels were quantified using ELISA. Factor Analysis of Mixed Data revealed that seasonality exerted the strongest influence on anti-gSG6-P1 IgG levels, which was likely driven by human activities, particularly the frequency of rubber tapping activity in the areas where Anopheles dirus is present. A higher frequency of rubber plot entry (5–7 days/week) significantly increased anti-gSG6-P1 IgG responses (1.08 ± 0.36) compared with the lower frequency group (0–4 days/week) (0.96 ± 0.35). Furthermore, our findings revealed the complex interplay between anti-gSG6-P1 IgG levels and the seasonality of human behavioral and vector dynamics. These factors highlight key limitations of the anti-gSG6-P1 IgG biomarker in the Greater Mekong Subregion, particularly the lack of well-characterized anti-gSG6-P1 IgG serological response kinetics in regions where predominant vector species exhibit low salivary peptide homology to An. gambiae. These findings emphasize the need for new serological tools tailored to malaria vector species present in the Subregion to improve malaria risk assessment and strengthen vector control strategies.