VIMC modellers recently carried out important work which was influential in changing global rubella vaccination policy and which could, potentially, lead to the eventual elimination of rubella.
Since 2000, the World Health Organization (WHO) has recommended a minimum level of 80% coverage for rubella vaccination (1). Whilst rubella is a mild infection, infection during pregnancy carries a risk that the child is born with Congenital Rubella Syndrome (CRS), which is associated with severe disability, including development delay, heart defects, cataracts and deafness. The WHO guidelines in place were designed to prevent potential increases in the burden of CRS which might occur if the vaccine coverage is too low. For example, rubella vaccination prevents infection, and the reduced transmission in a population that occurs after vaccination is introduced leads to an increased average age at infection. If the vaccination coverage in the population is too low, a so-called “paradoxical effect” might occur, with increases in the number of infections among unvaccinated women of child-bearing age and potentially, an increase in the burden of CRS.
With high levels of rubella vaccine coverage, the global burden of CRS decreased from approximately 100,000 in 2010 to 32,000 by 2019 (2) and by early 2024, only 19 countries had not yet introduced rubella vaccination. Further decreases in the burden of CRS, and perhaps, the eventual elimination of rubella could occur if rubella vaccination could be introduced in these countries. However, attaining 80% rubella vaccination coverage, as required by WHO guidelines, is not straightforward for these countries, since rubella containing vaccine is typically given with the first dose of measles vaccine (MCV1), and the MCV1 coverage for these countries was not always 80%. On the other hand, introduction of rubella vaccine could be possible in these countries if the 80% coverage threshold could be relaxed.
In collaboration with colleagues from the US Centers for Disease Control (CDC), WHO and with additional funding from Gavi, in the summer of 2024, VIMC modelling teams explored whether the guidelines could be relaxed for the countries which had not yet introduced rubella vaccination by 2024. Some suggestion that the WHO guidelines could be relaxed had come from evidence on the transmissibility (R0) of rubella, which has emerged since 2000. The 80% coverage threshold in WHO recommendations assumed high values (>8) for R0. Since those guidelines were written, estimates – including those from VIMC modellers (3,4) - have indicated that R0 was much lower in settings that had not yet introduced rubella vaccination by 2024 than was previously thought.
Building on these findings, two modelling groups (Amy Winter at University of Georgia and Emilia Vynnycky and Timos Papadopoulos at UK Health Security Agency) generated predictions of the CRS incidence for the next 30 years from their models for each of the 19 countries for 18 vaccination scenarios. The scenarios included combinations of wide and narrow age introductory and follow-up campaigns, and routine coverage, and different levels of coverage. The models took account of differences in the epidemiology and plausible R0 values for rubella in each country and included importations. The huge volume of output was processed by VIMC modeller at Penn State (Matt Ferrari) and Kurt Frey at Institute of Disease Modelling. The findings from both modelling groups were compelling: all introduction scenarios were projected to lead to significant reductions in the CRS incidence over 10-15 years and net reductions over 30 years.
In the final stage of the work, the modelling findings were presented to the Strategic Advisory Group of Experts on Immunization (SAGE) at WHO on 24th September 2024. This group comprises 12-15 international experts who are tasked with advising WHO on overall global policies and strategies for all vaccine-preventable diseases. After reviewing the modelling evidence and hearing talks from CDC and WHO regional representatives on the feasibility of rubella vaccine introduction, SAGE reached their landmark recommendation: to remove the 80% coverage threshold for the remaining countries yet to introduce rubella vaccination. At the same time, they reinforced the importance of existing policy for follow-up campaigns, an introductory wide age range campaign and ongoing monitoring. This historic decision paves the way for future reductions in the CRS burden and, once all countries have introduced rubella vaccination and have sufficiently high sustained coverage, the elimination of rubella could one day be possible.
References
World Health Organization. Rubella vaccines. Weekly Epidemiological Record. 2000, 20, 161-169
Vynnycky E, et al. Estimates of the global burden of Congenital Rubella Syndrome, 1996-2019. Int J Infect Dis. 2023 Dec;137:149-156
Nakase T et al. The impact of sub-national heterogeneities in demography and epidemiology on the introduction of rubella vaccination programs in Nigeria. 2024 Aug 13;42(20):125982.
Papadopoulos T and Vynnycky E. Estimates of the basic reproduction number for rubella using seroprevalence data and indicator-based approaches. PLoS Comput Biol. 2022 Mar 3;18(3):e1008858.