Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study.

BACKGROUND:A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome. METHODS:We analysed residual samples from the national serological survey done in 2014, data from monthly rubella surveillance reports from 2005 and 2016, and additional publications through a systematic review. Using an age-structured population model with provincial strata, we calculated the reproduction numbers and evaluated the gradient of the metapopulation effective reproduction number with respect to potential supplemental immunisation rates. We corroborated these analytical results and estimated times-to-elimination by simulating SIAs among adolescents (ages 10-19 years) and young adults (ages 20-29 years) using a model with regional strata. We estimated the incidence of rubella and burden of congenital rubella syndrome by simulating transmission in a relatively small population lacking only spatial structure. FINDINGS:By 2014, childhood immunisation had reduced rubella's reproduction number from 7·6 to 1·2 and SIAs among adolescents were the optimal elimination strategy. We found that less than 10% of rubella infections were reported; that although some women with symptomatic first-trimester infections might have elected to terminate their pregnancies, 700 children could have been born with congenital rubella syndrome during 2014; and that timely SIAs would avert outbreaks that, as susceptible adolescents reached reproductive age, could greatly increase the burden of this syndrome. INTERPRETATION:Our findings suggest that SIAs among adolescents would most effectively reduce congenital rubella syndrome as well as eliminate rubella, owing both to fewer infections in the immunised population and absence of infections that those immunised would otherwise have caused. Metapopulation models with realistic mixing are uniquely capable of assessing such indirect effects. FUNDING:WHO and National Science Foundation.