Individual-Level Antibody Dynamics Reveal Potential Drivers of Influenza A Seasonality in Wild Pig Populations

Swine are important in the ecology of influenza A virus (IAV) globally. Understanding the ecological role of wild pigs in IAV ecology has been limited because surveillance in wild pigs is often for antibodies (serosurveillance) rather than IAVs, as in humans and domestic swine. As IAV antibodies can persist long after an infection, serosurveillance data are not necessarily indicative of current infection risk. However, antibody responses to IAV infections cause a predictable antibody response, thus time of infection can be inferred from antibody levels in serological samples, enabling identification of risk factors of infection at estimated times of infection. Recent work demonstrates that these quantitative antibody methods (QAMs) can accurately recover infection dates, even when individual-level variation in antibody curves is moderately high. Also, the methodology can be implemented in a survival analysis (SA) framework to reduce bias from opportunistic sampling. Here we integrated QAMs and SA and applied this novel QAM-SA framework to understand the dynamics of IAV infection risk in wild pigs seasonally and spatially, and identify risk factors. We used national-scale IAV serosurveillance data from 15 US states. We found that infection risk was highest during January-March (54% of 61 estimated peaks), with 24% of estimated peaks occurring from May to July, and some low-level of infection risk occurring year-round. Time-varying IAV infection risk in wild pigs was positively correlated with humidity and IAV infection trends in domestic swine and humans, and did not show wave-like spatial spread of infection among states, nor more similar levels of infection risk among states with more similar meteorological conditions. Effects of host sex on IAV infection risk in wild pigs were generally not significant. Because most of the variation in infection risk was explained by state-level factors or infection risk at long-distances, our results suggested that predicting IAV infection risk in wild pigs is complicated by local ecological factors and potentially long-distance translocation of infection. In addition to revealing factors of IAV infection risk in wild pigs, our framework is broadly applicable for quantifying risk factors of disease transmission using opportunistic serosurveillance sampling, a common methodology in wildlife disease surveillance. Future research on the factors that determine individual-level antibody kinetics will facilitate the design of serosurveillance systems that can extract more accurate estimates of time-varying disease risk from quantitative antibody data.