1. Introduction
Vaccination is often regarded as one of the most successful and cost-effective public health interventions, saving millions of lives each year and guaranteeing global well-being and development [
1]. Despite this, many children, especially those living in low- and middle-income countries, continue to miss out on life-saving vaccines even though there have been increased efforts globally to improve vaccination coverage and reduce zero-dose prevalence [
2]. Before the pandemic in 2019, 18.4 million children did not receive all three recommended doses of the diphtheria-tetanus-pertussis containing vaccine (DTP), and of those, 70% (12.9 million) were zero-dose children who did not receive any doses of the DTP vaccine [
2]. In 2020, these figures increased to 22 million children and 73% (16 million), respectively, due to the disruptions to immunization services caused by the coronavirus disease 2019 (COVID-19) pandemic [
2,
3,
4]. These disruptions continued in 2021, resulting in 24 million being under-vaccinated and about 18 million being zero dose, with about 62% [
5,
6] of the estimated zero-dose children found to be living in 10 low- and middle-income countries (LMICs), including Nigeria. However, in 2022, a partial recovery in global DTP vaccination coverage was recorded, with the number of zero-dose children decreasing to 14.3 million, evidencing concerted efforts within countries to reach zero-dose children [
2].
Zero-dose children often live in marginalized or underserved communities characterised by poverty, lack of access to basic health services, overcrowding, poor sanitation practices and conflict [
7,
8,
9,
10]. These characteristics, combined with other health-related, socioeconomic, demographic and gender-related factors, cause substantial disparities in the distribution of zero-dose children within countries [
8]. Reaching these at-risk populations, therefore, requires timely and accurate evidence base regarding their sizes, geographic distribution, and other characteristics to support country-tailored strategies and interventions. Also, with recovery from the pandemic being uneven and much slower in LMICs [
11], understanding any changes in vulnerabilities due to disruptions to both routine immunization and vaccination campaigns can help with planning effective mitigation strategies and strengthening immunization services to reach zero-dose children. Administrative data are regularly collected in many LMICs through platforms such as the District Health Information System version 2 (DHIS2) [
12,
13]. However, due to limitations such as numerator and denominator errors, these often have coverage values that cannot reliably inform spatially detailed heterogeneities in coverage and identification of zero-dose children. Household surveys, on the other hand, tend to produce more reliable estimates of coverage, but these are usually designed to be representative at coarse spatial scales, necessitating the use of geospatial modelling approaches to produce coverage estimates at fine spatial scales and for operationally relevant areas, e.g., districts, which are then integrated with population data to assess zero-dose prevalence [
14,
15,
16]. Moreover, survey questionnaires include several modules that assess different characteristics of participants, making the data ideal for evaluating correlates of non-vaccination. Addressing zero-dose prevalence is critical to achieving the WHO’s Immunisation Agenda 2030 target of a 50% reduction in zero-dose children by 2030 and promises to “leave no one behind”, as well as targets within the Sustainable Development Goals [
7,
17] and Gavi, the Vaccine Alliance’s 2021–2025 Strategy [
7,
18].
Nigeria has one of the largest cohorts of un- and under-vaccinated children globally, with 2.3 million and 3 million children estimated to not have received any dose of the DTP and MCV vaccines, respectively, in 2022 [
2]. Before the pandemic in 2019, routine coverage of essential vaccines such as DTP1 and MCV1 were estimated to be 72% and 58%, respectively. In 2022, although global coverage levels showed some recovery following the pandemic, routine coverage remained suboptimal in Nigeria standing at 70% and 60%, respectively, for both basic vaccines [
2]. As a result, Nigeria has continued to experience measles outbreaks, with a resurgence of diphtheria outbreaks in 2023 [
19,
20]. Utazi et al. [
21] found that despite repeated measles vaccination campaigns, measles incidence was related to RI coverage. Over the years, there has been a persistent north-south divide in vaccination coverage in Nigeria, with the northern regions having poorer coverage levels and often higher rates of disease incidence [
21,
22]. Many studies have also identified several demand- and supply-side factors such as maternal education, religion, maternal access to and utilization of health services, poor attitude of health workers, staff shortages, poor conditions at health facilities and vaccine stockouts [
23,
24,
25,
26], as being responsible for poor vaccine uptake and heterogeneities in the distribution of vaccination coverage within the country. The first case of the SARS-CoV-2 virus was recorded on 27 February 2020 [
27] in Lagos state, Nigeria, following which the government launched a response to the pandemic, including a lockdown from March 30 to May 15, 2020 [
28]. COVID-19 vaccination began on March 5, 2021, which saw significant shifts of priorities and resources from vaccination services to COVID-19 response [
29]. These and other interventions are also thought to have further impacted immunization services negatively in the form of reduced access to vaccination, decreases in vaccine demand and uptake, cessation of outreach services and postponement of vaccination campaigns [
3,
21,
30,
31,
32]. These challenges call for innovative approaches and intensified efforts to identify and reach zero-dose children in Nigeria.
Against this backdrop, our study aimed to estimate changes in the spatial distribution of zero-dose children and associated risk factors before and during the COVID-19 pandemic in Nigeria, with a view to assessing the impact of the pandemic on immunization service delivery in the country, which can help consolidate mitigation and other strategies required to boost coverage beyond pre-pandemic levels. We analyzed three outcomes/indicators using data from two household surveys implemented before and during the COVID-19 pandemic in Nigeria. We defined a zero-dose child for each outcome as a child aged 12-23 months who had not received the first dose of the diphtheria–tetanus–pertussis-containing vaccine (i.e., DTP or PENTA zero dose) or the first dose of the measles-containing vaccine (MCV zero dose) or any dose of the four basic vaccines—bacilli Calmette-Guerin (BCG) vaccine, oral polio vaccine (OPV), DTP and MCV—(Composite zero dose indicator). Due to data availability, our study considered only demand-side factors or reasons for non-vaccination.
4. Discussion
By evaluating recent spatial and temporal trends in the distribution of zero-dose children in the context of the COVID-19 pandemic, our study further strengthens the scientific evidence base for improving childhood immunization in Nigeria.
Our study provided estimates of numbers of unvaccinated children for DTP, MCV and a composite coverage indicator at different spatial scales during the pre-pandemic and pandemic periods in Nigeria. Interestingly, our 2018 national level DTP and MCV zero-dose estimates of 2.4 million and 3.1 million are in very good agreement with (WHO and UNICEF estimates of national immunization coverage) WUENIC zero-dose estimates of 2.2 million and 3.1 million respectively. Also, our 2021 national level DTP and MCV zero-dose estimates of 2.1 million and 2.8 million in 2021 are very close to corresponding WUENIC zero-dose estimates of 2.2 million and 2.9 million children, respectively (WUENIC zero-dose estimates were calculated using 2022 WUENIC coverage estimates and UNPD estimates 2022 revision). Clearly, the pandemic did not result in any dramatic increases in zero-dose prevalence at the national level, but the persistence of large numbers of unvaccinated children in both time periods means that renewed efforts and novel strategies are needed to reach zero-dose and missed communities in the country. At the district level, no dramatic increases in zero-dose prevalence were found during the pandemic relative to the pre-pandemic era. However, there were some areas with elevated zero-dose estimates (> 3000 children) during the pandemic, as highlighted previously. Some of these districts were located in Kano and Lagos states where either relatively higher COVID-19 cases or deaths [
49] were recorded during the study period, which could have also occurred as a result of the larger population sizes of both states [
38]. Subnational variation in the effect of the pandemic on zero-dose prevalence in Nigeria has also been reported at the state level in a previous study [
31] which focused on Kano and Kaduna states. We note that the lack of substantial increases in zero-dose prevalence at the national level and in many subnational areas in our study, contrary to expectations, might have been due to a quick recovery from the disruptions caused by the pandemic [
50]. Additionally, our study revealed strong geographical disparities and a clear north-south divide in zero-dose prevalence in both time periods and across all three indicators, with districts with higher numbers of zero-dose children concentrated in the northern areas, as corroborated by previous studies [
14,
15,
21,
36,
51]. However, there were also some districts in the south (e.g., in Lagos state) with higher numbers of zero-dose children. This recurring spatial pattern in the distribution of zero-dose children is a strong indication that targeted RI and campaign strategies, focusing on the most problematic areas, will be needed to achieve substantial reductions in zero-dose prevalence within the country. Previous studies [
21,
22] also revealed higher measles case counts in the north and high correlations between measles case counts and MCV zero-dose estimates, further strengthening the evidence for targeted interventions.
The underlying coverage levels also had similar patterns, revealing persistent areas of low coverage, mostly concentrated in the northeast and northwest regions across all three indicators and for both time periods. There were also persistent pockets of low coverage areas in the south, e.g., some areas in Cross River state and some areas near the coastline. However, we note that there were differences in the problematic areas when examining coverage and the zero-dose estimates at the district level. For example, there were some districts in Lagos and Ogun states with moderate coverage levels, but which had higher zero-dose estimates. Also, some of the low coverage districts in Cross River state did not have higher zero-dose estimates, likely due to these areas having lower population densities. Hence, efforts aimed at reducing zero-dose prevalence should target areas where higher zero-dose estimates were estimated, whereas strategies to improve equity in coverage should focus on the low coverage areas. When comparing maps of DTP1 and MCV1 coverage, we observed very similar patterns, with DTP1 coverage being higher in many places, due to the dropouts that often occur between both vaccine doses (and perhaps, the result of the suspension of MCV campaigns during the pandemic in 2021). This is a strong indication that frequent campaigns conducted in Nigeria for MCV, though an effective temporary measure, have not been successful in boosting coverage beyond RI levels. The targeted strategies advocated earlier should, therefore, focus more on strengthening the country’s RI program, as we have also argued elsewhere [
21]. Furthermore, when examining maps of the composite coverage indicator, the low coverage areas occurring mostly in the northeast and northwest and overlapping considerably with low coverage areas for MCV1 and DTP1, are strongly indicative of non-availability of vaccination services and/or vaccine hesitancy. Different strategies would be required in these areas to unravel and address the barriers to vaccination.
When examining the risk factors associated with zero dose, we found that while there were strong similarities between the pre-pandemic and pandemic periods, there were also some minor differences which appeared more pronounced at the subnational/regional level. These similarities and differences are important for characterising the inequities that exist in vaccination coverage in both time periods. At the national level, our study revealed consistent associations between each of socioeconomic status (e.g., maternal literacy, household wealth and access to a bank account) and maternal access to and utilization of health services (e.g., skilled birth attendance) and the odds of zero dose in both time periods. We also found evidence of consistency in the effect of demographic factors (e.g., ethnicity, religion, and mother’s age) and seasonality of vaccination (e.g., birth quarter) on the odds of zero dose in both time periods. At the regional level (based on a reduced set of risk factors), we found additional evidence supporting the results obtained at the national level. Also, these regional level analyses revealed the risk factors most relevant to reaching zero-dose and missed communities in each region. These were: maternal access to and utilization of health services (all regions), communication (northwest), socioeconomic status (northwest, northcentral and south), religion (northeast and, to a great extent, north central), cross-border migration (northwest and northcentral) and remoteness (south). Furthermore, at the national level, we did not find any remarkable differences in the associations between the risk factors and the odds of zero dose between both time periods. However, we found that there were changes in the variables characterizing the effect of remoteness on zero dose in both time periods. For example, travel time to the nearest health facility was associated with all three zero-dose indicators before the pandemic, while distance to coastline was associated with all three zero-dose indicators during the pandemic. Also, there was a pronounced positive effect of communication on the odds of vaccination before the pandemic, suggesting reduced communication regarding vaccination services during the pandemic. We did not explore the differences between both time periods at the regional level further due to smaller sample sizes at this level.
To facilitate the operationalization of these findings, our study produced interactive web-based maps online (link1; link2) to further assist with the identification of towns, communities and, potentially, settlements in the problematic areas. Additional analyses can also be undertaken through triangulation with other data sets, e.g., data on public health facilities offering vaccination services, to better understand the costs and/or efforts needed to reach zero-dose children within each district. Furthermore, the multi-temporal analyses presented here are highly relevant to planning effective outbreak response strategies or catch-up vaccination activities. Nigeria is currently experiencing a diphtheria outbreak which, according to reports [
20], has been more pronounced in Kano, Katsina, Yobe, Bauchi, Kaduna, Borno and Jigawa states as of the beginning of October 2023. Interestingly, these states were among the states where we had estimated the highest prevalence of DTP zero-dose children in both 2018 (mostly between 120 000 and 215 000 DTP zero-dose children per state—see
Supplementary Figure S6) and 2021 (mostly between 80 000 and 240 000 DTP zero-dose children per state), further corroborating the findings from our study. Also, the occurrence of a considerable proportion (one-third) of the confirmed cases of the disease in children aged between 5 and 9 years (as of October 2023), which includes the birth cohort for which we produced zero-dose estimates in 2018 in our study, further evidences the programmatic and operational relevance of our analyses. Specifically, our maps of DTP zero-dose children for both years can be used to determine areas where interventions are needed to fill immunity gaps in both older birth and younger birth cohorts throughout the country. We also note that our district/LGA level zero-dose estimates can be further disaggregated to the ward level to enhance field operations if need be.
Through its Zero-dose Reduction Operational Plan (Z-DROP) programme, Nigeria is continuing to intensify efforts to reach its zero-dose and missed communities. Fundamentally, the Z-DROP programme is one of the strategies for achieving the country’s vision of integrated primary health care service delivery [
52]. Through a rigorous prioritization exercise led by the National Primary Health Care Development Agency, Gavi, the Vaccine Alliance, and University of Southampton in August 2022, about 100 LGAs were identified as priority areas where (RI) interventions were urgently needed to reach zero-dose and under-immunized children. About 60 of these LGAs, spread across 8 states, are being targeted in the current phase of the Z-DROP programme. The programme employs a bottom-up approach to design and implement interventions in these areas through engagement with local health workers. These interventions include initial catch-up immunization activities planned as part of the 2023 measles campaigns, aiming to administer recommended routine vaccines to identified zero-dose children and then follow up RI activities to sustain the gains made and to ensure the completion of the immunization schedule. The process of identifying zero-dose children in these LGAs additionally involve the triangulation of coverage survey/zero-dose, surveillance and outreach services data at the ward and health facility levels to identify, geolocate and classify (unreached, far-to-reach, hard-to-reach and never reached) high-priority settlements. These additional analyses also include estimating the target populations and the cost of implementing the required interventions in the identified high-priority settlements to guide resource allocation. The programme also provides a mechanism to document all operational activities for effective supervision and timely tracking of progress.
Our study is subject to some limitations. Our vaccination coverage estimates were produced using information obtained from both home-based records and maternal/caregiver recall, with the latter being subject to recall bias. The sampling frames used in both the 2018 DHS and 2021 MICS-NICS may have missed important vulnerable populations such as those living in conflict areas in Borno state as highlighted previously. This may have led to an underestimation of the zero-dose prevalence in some areas. Our analyses included comparisons of vaccination coverage and zero-dose estimates between the 2018 NDHS and 2021 MICS-NICS to assess the impact of the COVID-19 pandemic on immunization services in Nigeria. Since these surveys were implemented independently and not as repeated or rolling surveys, differences in the survey instruments (e.g., questionnaires), sampling designs and implementation could have affected the differences seen in the comparisons. Our analyses utilized displaced cluster level geographical coordinates to predict coverage levels at 1x1 km resolution. While this may not matter for coverage and zero-dose estimation at the district level using the 2018 DHS data since the DHS program often retains the displaced clusters within their original districts [
53], the displacement may have affected the district level estimates produced using the 2021 MICS-NICS as the initial displacement conducted by the MICS Team which was used in our work only preserved the state boundaries. Since completing our analyses, the displacement of the geographical coordinates from the 2021 MICS-NICS has been updated to preserve the district level boundaries. We carried out some sensitivity analyses (results not presented here) using the updated coordinates, which revealed very minor differences from the results (coverage maps) presented in this work. Furthermore, we did not quantify the uncertainties associated with the zero-dose estimates presented in our work. When uncertainty estimates are available for the population estimates [
54,
55], these can be combined with the uncertainties from vaccination coverage in a statistical framework to produce uncertainties for the zero-dose estimates. Our analysis of the risk factors associated with zero-dose included mainly demand-side factors due to data limitations. The inclusion of supply-side factors in future work will likely yield more programmable insights. Lastly, our exploration of the differences in the risk factors associated with zero dose at the regional level in the pre-pandemic and pandemic periods was limited by smaller sample sizes. This challenge can be overcome in future work through a pooled data analysis.
As immunization programs around the world continue to recover from the disruptions to immunization services caused by the COVID-19 pandemic and getting back on track to achieving the goals and targets set out in the Immunization Agenda 2030, our study has provided programmatically-important insights that can aid policy makers to plan and implement effective strategies to reach zero-dose and missed communities in Nigeria.
Author Contributions
Conceptualization, C.E.U., A.J.T. and J.M.K.A.; methodology, C.E.U. and J.M.K.A.; software, C.E.U. and J.M.K.A.; validation, C.E.U. and J.M.K.A.; formal analysis, C.E.U., J.M.K.A. and H.M.T.C.; investigation, C.E.U., J.M.K.A., H.M.T.C., and I.O.; resources, C.E.U.; data curation, C.E.U., J.M.K.A., H.M.T.C., and I.O; writing—original draft preparation, C.E.U. and J.M.K.A.; writing—review and editing, C.E.U., J.M.K.A., A.J.T., I.O., H.M.T.C., A.E., B.D., B.F., H.S., B.A., and J.C.; visualization, C.E.U., J.M.K.A., I.O., and H.M.T.C.; supervision, C.E.U. and A.J.T.; project administration, C.E.U.; funding acquisition, C.E.U.;. All authors have read and agreed to the published version of the manuscript.