Epidemiological profile, trend, seasonality, and factors associated with Yellow fever disease and barriers to vaccination: a retrospective observational study of multi-season national surveillance data in Nigeria, 2017 - 2021

Since its resurgence in 2017, Yellow fever (YF) outbreaks have continued to occur in Nigeria despite routine immunization and implementation of several reactive mass vaccination campaigns, resulting in substantial morbidity and mortality. Nigeria is considered a high-priority country for implementing the WHO EYE strategy, which is targeted at eliminating YF outbreaks by 2026. This retrospective observational study was conducted to describe the epidemiological profile of reported cases, trends, and seasonality of YF incidence; identify factors associated with Yellow fever disease (YFD) and barriers to YF vaccination in Nigeria. Univariate, bivariate and multivariate binary logistic regression analysis was done. Of 13014 suspected YF cases, 7640 (58.7%) had laboratory confirmation for Yellow fever virus (YFV). Predictors of YFD were male sex (aOR 2.36, 95% CI: 1.45-3.91) compared to female; age group being 15-29 years (aOR 4.13, 95% CI: 1.59-13.00) compared to under-five; residing in the Derived Savannah (aOR 30.10, 95% CI: 11.50-104.00), Lowland/Mangrove/Freshwater rainforest (aOR 8.84, 95% CI: 3.24-31.10), Guinea Savannah/Jos Plateau (aOR 6.13, 95% CI: 1.90-23.50) compared to the Sahel/Sudan savannah; working in outdoor settings compared to indoor (aOR 1.76, 95% CI: 0.96-3.22); and vomiting (aOR 2.62, 95% CI: 1.39-4.83). The rainy season was protective against YFD (aOR 0.32, 95% CI: 0.19-0.52) compared to the dry season. Because being unvaccinated emerged as protective factor (aOR:0.51, 95% CI: 0.25-1.00) compared to those with unknown vaccination status, the data was further disaggregated by vaccination status. Predictors with higher odds ratios were found among unvaccinated. Predictors of YFD among the vaccinated were the first quarter compared to the second quarter of the year (aOR 4.04, 95% CI: 1.48-12.95) and residing in the southern region compared to the north (aOR 14.03, 95% CI: 4.09-88.27). Barriers to YF vaccination were the rainy season compared to the dry season (aOR 1.29, 95% CI: 1.05-1.57), being 15 years or older (15-29: aOR 2.06, 95% CI: 1.51-2.83; 30-44: aOR 2.11, 95% CI: 1.45-3.07; 45-59: aOR 2.72, 95% CI: 1.63-4.58; 60+: aOR 6.55, 95% CI: 2.76-17.50), residing in the northern region (aOR 3.71, 95% CI: 3.01-4.58) compared to the south, and occupation being butcher/hunter/farmer (aOR 2.30, 95% CI: 1.52-3.50) compared to home-based/office workers. Being a student was protective against being unvaccinated (aOR 0.62, 95% CI: 0.47-0.83). Several factors were associated with YFD, which were aggravated by lack of vaccination. Although barriers to vaccination were elucidated, inadequate vaccination coverage alone may not account for the recurrent outbreaks of YF in Nigeria. These findings are critical for planning public health interventions and to guide further research that would enable Nigeria end YF epidemics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement SEA received funding in the form of PhD fellowship scholarship from the Japan International Cooperation Agency () for implementation of this research work. NO - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### 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: Approval for this study was sought by submission of the study proposal (see Other supporting material) to the Research Ethics Committee of the Nigeria Centre for Disease Control and Prevention, which was reviewed and approved. 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 The dataset used in our study is a third-party data archived with the NCDC, which is the national public health institute in Nigeria. Access is granted by the NCDC on request for specific dataset. Such request could be directed to dgo{at}ncdc.gov.ng.