Shedding light on influenza: viral kinetics, transmission dynamics, and antibody titers of seasonal influenza in two South African community cohorts (PHIRST), 2016-2018

Abstract

Seasonal influenza disproportionately burdens healthcare systems in tropical and low-income regions, yet these areas are overlooked in the literature. This study explored seasonal influenza in South Africa by analyzing the serology and longitudinal infection data collected in both a rural and an urban community in the PHIRST cohort study from 2016 to 2018. We modeled the viral RNA shedding trajectory, a measure of the amount of virus expelled by an infected individual, for each recorded infection episode. These estimates informed a robust household transmission model that evaluated the determinants of risk of infection acquisition. Our results highlight that the hemagglutination inhibition (HAI) antibody titer, a widely accepted correlate of protection, was associated with a reduced risk of infection for A(H1N1)pdm09, A(H3N2), and B/Victoria strains, but only a reduction in the duration of viral shedding for A(H3N2). Moreover, age displayed a strong residual relationship in both analyses, as children demonstrated longer shedding and a higher risk of infection regardless of the HAI titer level and presence of other individual or household risk factors. These findings have important implications for the use of HAI titers as a correlate of protection in studies of seasonal influenza and vaccine production, as there could be unmeasured antibody- or cell-mediated immunity at play. This model methodology can also inform future vaccine distribution policies and non-pharmaceutical intervention strategies in South Africa.