The impact of sub-national heterogeneities in demography and epidemiology on the introduction of rubella vaccination programs in Nigeria

Rubella infection during pregnancy can result in miscarriage or infants with a constellation of birth defects known as congenital rubella syndrome (CRS). When coverage is inadequate, rubella vaccination can increase CRS cases by increasing the average age of infection. Thus, the World Health Organisation recommends that countries introducing rubella vaccine be able to vaccinate at least 80% of each birth cohort. Previous studies have focused on national-level analyses and have overlooked sub-national variation in introduction risk. We characterised the sub-national heterogeneity in rubella transmission within Nigeria and modelled local rubella vaccine introduction under different scenarios to refine the set of conditions and strategies required for safe rubella vaccine use. Across Nigeria, the basic reproduction number ranged from 2.6 to 6.2. Consequently, the conditions for safe vaccination varied across states with low-risk areas requiring coverage levels well below 80%. In high-risk settings, inadequate routine coverage needed to be supplemented by campaigns that allowed for gradual improvements in vaccination coverage over time. Understanding local heterogeneities in both short-term and long-term epidemic dynamics can permit earlier nationwide introduction of rubella vaccination and identify sub-national areas suitable for program monitoring, program improvement and campaign support. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by the U.S. Centers for Disease Control and Prevention. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Declaration of Helsinki, and approved by the National Health Research Ethics Committee of Nigeria (NHREC) (protocol code NHREC/01/01/2007, date of approval: 27 August 2019) and the Human Subjects Review Board at the US Centers for Disease Control and Prevention where it was determined to be non-research as the study involved testing previously collected de-identified specimens. Written informed consent to use specimens to test for diseases other than HIV was obtained from all subjects involved in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Gridded population counts for 2020 in Nigeria at a spatial resolution of 3 arc seconds were obtained from the WorldPop database (, [[34][1]]). The number of births by age group used in the calculation of age-specific fertility rates as well as the state-level MCV1 coverage were made available by the Demographic and Health Surveys (DHS) Program in Nigeria (, [[33][2]]). Age-stratified mortality data for Nigeria was obtained from the United Nations, Department of Economic and Social Affairs, Population Division (, [[32][3]]). Raw seroprevalence data are unavailable due to privacy consideration as datasets include global positioning system coordinates which might enable identification of location of study subjects. Only restricted individuals had access to the datasets for analyses purposes only. [1]: #ref-34 [2]: #ref-33 [3]: #ref-32