Estimation of Annual Exposures and Antibody Kinetics Against Norovirus GII.4 Variants from English Serology Data, 2007-2012.

Norovirus in humans is highly contagious, causing diarrhoea and vomiting, and is especially common in young children. Winter incidence varies annually, and previous research indicates that the change of dominant norovirus variant is followed by high incidence, but having a clear mechanism to explain this observation could support better prediction of epidemics. Here we analyse unique norovirus serology blockade data from 656 children in England collected via opportunistic sampling between 2007-2012 using a mathematical model of multi-variant antibody kinetics to infer metrics such as annual attack rates and age-specific infection rates. Analysis reveals that overall infection rates were 204 infections per 1000 person-years (posterior median; 95% credible intervals: 188-221). Infection rates were lowest in children aged under 1 year at 164 infections per 1000 person-years (95% CrI: 121-209) and highest in children aged 5 years and older, at 252 infections per 1000 person-years (95% CrI: 212-288). The annual attack rate was highest in 2002, coincident with transition of the dominant variant to Farmington Hills, and high attack rates are frequently observed with emergence of new variants, but not always. Parameter estimates indicate moderate evidence for the immune imprinting hypothesis: a stronger antibody response to variants encountered earliest in life. Estimates of infection rates estimated here from serology are higher than incidence reported within similar settings based on disease only and is consistent with considerable asymptomatic infection. The combined use of multi-variant antibody data and a mathematical model provide key insights on the natural history of norovirus variants which can inform epidemic planning.