The roles of pre-season immunity, age, viral shedding, and community exposures in shaping influenza household transmission dynamics.

Protective immunity against influenza transmission remains poorly understood due to the high prevalence of undetected asymptomatic infections. To address this, we analyze 1518 individuals and 623 infection episodes from a three-year, rural and urban, South African household cohort study that combines pre-season serum collection with twice-weekly virological testing regardless of symptoms. By developing a subtype/lineage-specific household transmission model and incorporating time-resolved viral shedding kinetics for all observed infections, we disentangle household and community exposure, pre-season immunity, and age effects. After adjusting for exposure intensity, pre-season hemagglutination inhibition (HAI) titers ≥1:40 are associated with a reduced infection risk for A(H1N1)pdm09, A(H3N2), and B/Victoria, but not B/Yamagata. However, children exhibit higher susceptibility and longer viral shedding durations than adults across all subtypes/lineages, even after accounting for pre-season HAI titers. Here, we show persistent age-related effects on influenza susceptibility and viral shedding, underscoring the need to explore immune mechanisms beyond HAI-based correlates of protection.