Systematic Review of the Manifestations of Congenital Rubella Syndrome in Infants and Characterization of Disability‐Adjusted Life Years (DALYs)

Abstract

Congenital rubella syndrome (CRS) continues to cause disability among unvaccinated populations in countries with no or insufficient rubella vaccine coverage to prevent transmission. We systematically reviewed the literature on birth outcomes associated with CRS to estimate the duration, severity, and frequency of combinations of morbidities. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English with primary data on the frequency of CRS manifestations for ≥20 cases and identified 65 studies representing 66 study populations that met our inclusion criteria. We abstracted available data on CRS cases with one or more hearing, heart, and/or eye defect following maternal rubella infection during the period of 0-20 weeks since the last menstrual period. We assessed the quality and weight of the available evidence using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Most of the evidence originates from studies in developed countries of cohorts of infants identified with CRS in the 1960s and 1970s, prior to the development of standardized definitions for CRS and widespread use of vaccine. We developed estimates of undiscounted disability-adjusted life years (DALYs) lost per CRS case for countries of different income levels. The estimates ranged from approximately 19 to 39 for high-income countries assuming optimal treatment and from approximately 29 to 39 DALYs lost per CRS case in low- and lower- middle-income countries assuming minimal treatment, with the lower bound based on 2010 general global burden of disease disability weights and the upper bound based on 1990 age-specific and treatment-specific global burden of disease disability weights. Policymakers and analysts should appreciate the significant burden of disability caused by CRS as they evaluate opportunities to manage rubella.

Systematic Review of Health Economic Analyses of Measles and Rubella Immunization Interventions

“…Most of the measles economic studies that characterized DALYs only included mortality with or without consideration of the impacts of acute cases, except for one study that used unspecific disability weights (i.e., slight, moderate, severe disability) and one study for India . Recent efforts to improve the quantification of the pregnancy and birth outcomes associated with rubella infections in early pregnancy should help to further efforts to better capture the full costs associated with rubella, and more efforts are needed to better characterize the DALYs associated with measles.…”

“…Public health concern about rubella arises mainly due to its ability to cause devastating outcomes in the fetus when contracted by susceptible women early in pregnancy . Rubella infection in pregnancy leads to an increased risk of miscarriage, stillbirth, infant mortality, and one or more of the birth defects associated with congenital rubella syndrome (CRS), including hearing impairment, blindness, cardiac defects, and mental retardation, which may lead to life‐long severe disability or premature death …”

The Costs and Valuation of Health Impacts of Measles and Rubella Risk Management Policies

“…Although we focus on global policy, we seek to account for some of the significant variability in the world by stratifying the inputs into the four different World Bank income levels (WBIL): high‐income (HIGH), upper‐middle‐income (UMI), lower‐middle‐income (LMI), and low‐income (LOW), similar to the approach used for polioviruses . Specifically, based on the approach we applied to characterize probabilities of sequelae and disability‐adjusted life years (DALYs) for CRS, we characterize DALYs for all measles and rubella infection and vaccine‐related adverse health outcomes assuming optimal treatment in high‐income countries, minimal treatment in low‐income countries, and different ratios for optimal:minimal treatment in UMI and LMI, respectively.…”

The impact of Measles-Rubella vaccination on the morbidity and mortality from Congenital Rubella Syndrome in 92 countries

“…The number of CRS deaths in year y was calculated by multiplying the number of CRS cases born in year y by the assumed case fatality rate (30%see Table 2). The number of DALYs for cases in year y was calculated by multiplying the number of CRS cases in year y by the corresponding DALY (from 29 ), which was based on the country-specific World Bank Income group for 2017. 30 Both the DALYs and the assigned World Bank income group remained fixed over time.…”