In May 2024, Pennsylvania State University shared that their research, published in Vaccine, reveals the importance of considering “nuances at the local level” when creating vaccination programme policies. The team’s analysis suggests that national level recommendations might prevent some countries from “realising the benefits of vaccination”. The study examines data from Nigeria, 1 of 19 countries that hasn’t yet introduced rubella vaccination.
Rubella vaccination
Rubella is a childhood viral infection that is transmitted by respiratory droplets. After infection, characterised by a mild fever and a rash, the patient develops life-long immunity. However, infection during the first trimester of pregnancy can result in miscarriage or infants with “severe congenital malformations”, known as congenital rubella syndrome (CRS). Thanks to the development of the “highly efficacious” combined measles-rubella (MR) and measles-mumps-rubella (MMR) vaccines and the “widespread introduction” of rubella-containing-vaccine (RCV) in national childhood immunisation programmes, reported rubella cases decreased from 670,894 in 2000 to 10,194 in 2020.
By 2020, 173 (89%) of 194 WHO Member States had introduced routine rubella immunisation, with around 70% of all infants vaccinated.
“The introduction of rubella vaccine is consistently estimated as cost-effective across both developed and developing countries.”
The introduction of the rubella vaccination “usually builds upon existing measles immunisation efforts” as the rubella is delivered as an MR combination vaccine. However, the authors suggest that a “central programmatic concern” is that low or intermediate RCV coverage can increase the mean age of infection, which increases the risk of CRS through infection during pregnancy. However, if coverage is high enough, incidence of rubella decreases across all age groups.
Thus, WHO recommends that at least 80% coverage should be achieved and sustained for each birth cohort through a combination of routine immunisation and campaigns for safe RCV introduction. It is also recommended that introduction should be preceded by a catch-up campaign and followed by follow-up campaigns. By the end of 2023, 19 countries had yet to introduce the MR vaccine into routine immunisation programmes. Therefore, the incidence of CRS “remains high”; in Africa there are an estimated 116 cases per 100,000 live births.
“Understanding the risks and possible strategies for introducing rubella vaccination in these remaining countries, many of which are classified as low-income, is critical towards regional and global rubella elimination goals.”
National vs sub-national
The authors state that “much” of the analysis on RCV introduction has been at national level, which does not account for sub-national variation, and WHO has called for “locally tailored, sub-national solutions”. The paper presents an analysis of sub-national CRS incidence in Nigeria under “various scenarios” of RCV introduction. As Nigeria has not yet introduced routine rubella vaccination, it provides an “ideal” case study; it has a “highly heterogeneous demographic and epidemiological conditions”. A nationally representative serological survey from Nigeria offers a “unique opportunity” to quantify and model local variation in rubella transmission.
The study
The researchers estimated local age-specific seroprevalence and force of infection in each of the 36 states of Nigeria and the Federal Capital Territory (FCT) and incorporated the estimates into a dynamic transmission model. They then simulated the cumulative rates of CRS over 30 years as a function of coverage assuming routine vaccination only to quantify local variability in introduction risk. Next, they considered how future risk might be mitigated by strengthening routine coverage over time and deploying the recommended supplemental immunisation activities (SIAs) at the time of RCV introduction after introduction.
The case study highlights:
- The spatial heterogeneity in transmission risk across Nigeria
- The impact of sub-national variation on CRS risk following RCV introduction
- The potential for programmatic improvements to mitigate this risk and accelerate safe introduction of RCV
“The integration of sub-national epidemiology, dynamic epidemic modelling, and targeted interventions provides a roadmap for the safe introduction of RCV into Nigeria and other countries without existing rubella immunisation programmes.”
Findings
“Rubella vaccination is a highly cost-effective public health intervention that has the potential to greatly reduce the incidence and the associated social and economic costs of severe birth defects.”
The study identifies “substantial differences” in transmission rates among states in Nigeria. The results show that the basic reproduction number of rubella was spatially heterogenous across Nigeria, with higher estimates in the north than the south and spatial patterns of transmission that are “not discernible at the national level”. Simulation-based analyses suggested local differences in the relative risk of RCV introduction. States where R0 and birth rates were low could safely introduce rubella vaccination at coverage levels “well below” that of states with higher R0 and birth rates.
States with the highest estimated current CRS burden were predicted to benefit most from the introduction of rubella vaccination, even at coverage lower than 80%. Higher coverage levels were needed for states with lower estimated current CRS incidence.
“Thus, the criteria for safe RCV introduction across Nigeria was not uniform and was found to depend on sub-national epidemiological and demographic conditions.”
The researchers conclude that the “relative risks of RCV introduction are heterogenous across space”, which means that national-level coverage targets informed by studies on static vaccination strategies at equilibrium can be “overly conservative” and “prolong the time until introduction”.
“An evaluation of the transient dynamics prior to equilibrium can facilitate earlier introduction and help identify the investments in programme monitoring, routine coverage improvement, and continued supplemental campaigns that are necessary to ensure that vaccination efforts are safe and sustainable.”
Elimination is “feasible”
Dr Matthew Ferrari, professor of biology and director of the Centre for Infectious Disease Dynamics at the Huck Institutes of Life Sciences at Penn State, reflects that “all of the policy” around rubella vaccination has been guided by the risk in adults, which has “been holding back the benefit of rubella vaccination in some countries”.
“We grounded the current infection risk and potential pregnancies at risk in strong empirical data and real-world phenomena. Parts of the country can already vaccinate more than 80% of kids, based on their current rate of measles vaccination, but low vaccination coverage in the north is a barrier to introduction across the whole country under the current recommendation.”
Furthermore, the concern about increased CRS cases might not be as bad as is believed. While “some states” could see CRS risk increase by “hundreds of cases”, the increased risk would “not come to fruition until 10 years down the road”.
“Strengthening and improving routine immunisation programmes and advancing them everywhere in the world is a benefit to everyone in the world. The more we do this, the elimination of rubella as a virus on this planet is entirely feasible.”
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