Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Su Q

PROVIDER: S-EPMC9102636 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rubella vaccines have been used to prevent rubella and congenital rubella syndrome (CRS) in several World Health Organization (WHO) regions. Mathematical modelling studies have simulated introduction of rubella-containing vaccines (RCVs), and their results have been used to inform rubella introduction strategies in several countries. This systematic review aimed to synthesize the evidence from mathematical models regarding the impact of introducing RCVs. We registered the review in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42020192638. Systematic review methods for classical epidemiological studies and reporting guidelines were followed as far as possible. A comprehensive search strategy was used to identify published and unpublished studies with no language restrictions. We included deterministic and stochastic models that simulated RCV introduction into the public sector vaccination schedule, with a time horizon of at least five years. Models focused only on estimating epidemiological parameters were excluded. Outcomes of interest were time to rubella and CRS elimination, trends in incidence of rubella and CRS, number of vaccinated individuals per CRS case averted, and cost-effectiveness of vaccine introduction strategies. The methodological quality of included studies was assessed using a modified risk of bias tool, and a qualitative narrative was provided, given that data synthesis was not feasible. Seven studies were included from a total of 1393 records retrieved. The methodological quality was scored high for six studies and very high for one study. Quantitative data synthesis was not possible, because only one study reported point estimates and uncertainty intervals for the outcomes. All seven included studies presented trends in rubella incidence, six studies reported trends in CRS incidence, two studies reported the number vaccinated individuals per CRS case averted, and two studies reported an economic evaluation measure. Time to CRS elimination and time to rubella elimination were not reported by any of the included studies. Reported trends in CRS incidence showed elimination within five years of RCV introduction with scenarios involving mass vaccination of older children in addition to routine infant vaccination. CRS incidence was higher with RCV introduction than without RCV when public vaccine coverage was lower than 50% or only private sector vaccination was implemented. Although vaccination of children at a given age achieved slower declines in CRS incidence compared to mass campaigns targeting a wide age range, this approach resulted in the lowest number of vaccinated individuals per CRS case averted. We were unable to conduct data synthesis of included studies due to discrepancies in outcome reporting. However, qualitative assessment of results of individual studies suggests that vaccination of infants should be combined with vaccination of older children to achieve rapid elimination of CRS. Better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Guidelines for reporting of outcomes in mathematical modelling studies and the conduct of systematic reviews of mathematical modelling studies are required.