Pairwise and three-country comparisons of high and low COVID-19 vaccination rates in 12 African countries: a mixed-method study protocol

Abstract

Introduction

The COVID-19 pandemic has highlighted significant disparities in vaccine uptake across sub-Saharan Africa, yet research exploring the regional and country-specific factors influencing these rates remains limited. Understanding these factors is crucial for developing targeted regional and global public health interventions to improve vaccination uptake and strengthen pandemic preparedness. This study aims to fill a critical knowledge gap by assessing the factors influencing vaccination rates across sub-Saharan Africa at the operational, systemic and socio-political levels.

Methods and analysis

The study will employ a comparative case study design across 12 African countries to examine context-specific factors influencing pandemic vaccine preparedness. The 12 selected countries (Angola, Botswana, Burundi, Cameroon, Côte d'Ivoire, Malawi, Namibia, Nigeria, Rwanda, Senegal, South Africa and Uganda) will be categorised by vaccination rate (high, moderate or low). The study will integrate quantitative and qualitative data to provide comprehensive insights. Quantitative data, including COVID-19, macroeconomic, health system and governance indicators, will be sourced from reputable online portals, such as the WHO, the World Bank and Our World in Data. Qualitative data will be collected through key informant interviews with experts across participating African countries, except Angola. Due to delays in obtaining ethics approval in Angola, no primary data collection including key informant interviews will be conducted in Angola unless ethics approval is obtained. Angola will therefore be included through a secondary data approach, drawing on publicly available reports, published literature and relevant case studies. All qualitative data will be analysed using thematic analysis, and quantitative data will be analysed using descriptive methods.

Ethics and dissemination

Ethics approval was obtained from Western University’s Health Sciences Research Ethics Board (126398) and relevant bodies in the 11 participating countries. Findings will be shared through reports to public health authorities, policy briefs and presentations at academic conferences and peer-reviewed publications.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The study uses a pairwise and three-country comparison design to explore how operational, systemic and sociopolitical factors differ across countries and how these factors influence vaccination uptake.

• The study uses a mixed-methods approach, combining quantitative data and key informant interviews to provide comprehensive data to understand the factors influencing vaccination uptake in sub-Saharan Africa.

• The sensitive nature of discussions on governance, policy and public sector integrity may influence some participants’ willingness to share their views openly.

• The study includes 12 countries and is limited to anglophone and francophone countries in Africa, which may limit the extent to which the findings reflect the full diversity of contexts across sub-Saharan Africa.

Introduction

Vaccination is widely acknowledged as one of the most effective public health interventions for preventing and controlling infectious diseases. Historical examples include the elimination of smallpox and the control of influenza outbreaks during the Industrial Revolution, when rudimentary approaches were applied. Since then, significant efforts and advancements have been geared towards the reduction of infectious diseases in the world, with the most recent being the deadliest COVID-19 pandemic.¹ In our study, we focus on COVID-19 vaccination as a case study, as it provides a unique context for examining vaccine rollout under emergency conditions that required immediate policy changes, large-scale vaccination programmes and faster vaccine deployment. The fact that COVID-19 vaccines were introduced globally within a relatively short time frame suggests that our study findings will provide deep insight to strengthen pandemic vaccine preparedness and response strategies in sub-Saharan Africa.

The effects of COVID-19 transcended geographical boundaries as the pandemic’s burden was felt across many societies, especially in low- and middle-income countries.² In Africa, estimates of the continent’s preparedness for a mass vaccination campaign indicated that the region was ill-prepared to handle the distribution of COVID-19 vaccines.³ This assessment was based on the COVID-19 Vaccine Introduction Readiness Assessment Tool, developed by the UNICEF and WHO to assess countries’ readiness to introduce the COVID-19 vaccine.⁴ In late 2020, the assessment tool was shared with the ministries of health of all 47 countries in the WHO African Region. By November 2020, self-reported data indicated that the African continent had an average readiness of 33%, far below the WHO-recommended benchmark of 80% for vaccine deployment.^{3 4} Low readiness was observed across four key areas: resource and funding plans, data collection and monitoring, cold chain and logistics and community engagement.⁴ According to the assessment, less than 25% of countries had adequate plans for at least one of those areas, and less than 12% had tools for all.⁴ Despite shortcomings in these areas, other areas showcased better preparation, as about 49% of African countries had identified priority groups for vaccination and 44% had established coordination mechanisms for vaccine rollout.⁴ Prior vaccine implementation programmes in Africa, including meningitis and Human Papillomavirus vaccination initiatives, demonstrate that successful deployment depends on governance, coordination, implementation capacity and community engagement.^{5 6}

To achieve the 60% vaccination coverage in Africa, it was projected that approximately 1.5 billion doses of the COVID-19 vaccine would be required across the continent, at a cost of US$7 billion to US$10 billion.² These high dose requirements for the African continent exceeded the capacity of successful systems, such as the WHO’s Expanded Programme on Immunization.⁷ In response to the financial burden imposed by the COVID-19 pandemic, the Africa Export-Import Bank developed and signed a vaccine-finance outline in 2021, offering up to US$4 billion in credit to support vaccine procurement in Africa.² By October 2021, the WHO published a report presenting the outcome of all countries aiming to vaccinate 40% of their populations by the end of 2021 and 70% by mid-2022. While most African countries did not meet the latter target, five countries: Botswana, Cape Verde, Mauritius, Rwanda and Seychelles achieved the 40% goal by the end of 2021.⁸ Countries such as Mauritius, Rwanda and Seychelles, which surpassed the 60% coverage by April 2022, benefited from collaborations with national organisations. On the contrary, many countries not only failed to reach the 2021 goal but also had not yet reached 10% coverage.⁸

Despite the challenges, African countries made significant progress in their vaccination efforts throughout 2022 and 2023. By the end of 2022, the vaccination rates in Africa, which is the total number of people who received all prescribed doses of the COVID-19 vaccine, ranged from 0.22% to as high as 85.27%, with an average rate of 31% (SD=19).⁹ These statistics mask significant variations among countries, with some nations achieving high vaccination rates while others struggle to implement widespread vaccination programmes. Several factors contributed to these disparities, including initial vaccine supply issues, distribution challenges, vaccine hesitancy and varying levels of political commitment and healthcare infrastructure.¹⁰

As of 2023, there has been an increased emphasis on integrating COVID-19 vaccination into routine health services and exploring multi-antigen vaccination approaches to enhance overall immunisation coverage in Africa.¹¹ The ongoing efforts reflect a commitment to not only address the immediate challenges posed by the pandemic but also to strengthen long-term health resilience across the continent. Thus, this study aims to conduct pairwise (or three-country) comparisons of countries within sub-Saharan Africa (Central, Eastern, Southern and Western) with different vaccination rates: high, moderate and low. The goal is to identify key operational, systemic and political factors that influence vaccination uptake in Africa.

Conceptual expectations guiding the study

Findings from a prior systematic review on upstream factors influencing COVID-19 vaccination in Africa identified governance, infrastructure and intersectoral coordination as key factors of COVID-19 vaccine uptake.^{12 13} Also, a recent quantitative study examining systemic-level predictors of vaccination uptake in Africa suggests that countries with a higher number of COVID-19 vaccine doses, higher public sector integrity and higher government effectiveness have higher vaccination rates.¹⁴ Drawing on these findings, this study is guided by the following conceptual expectations:

• Vaccine supply: Countries with a higher number of secured COVID-19 doses are expected to have higher vaccination rates.

• Public sector integrity: Countries with higher levels of public sector integrity are expected to have higher vaccination rates.

• Government effectiveness: Countries with higher government effectiveness are expected to have higher vaccination rates.

These expectations are not intended for hypothesis testing. Rather, they will guide the comparative case analysis and help inform the interpretation of qualitative findings from key informant interviews. The study will examine how vaccine supply, public sector integrity and governance shaped COVID-19 vaccination uptake across participating countries.

Methods and analysis

Study design

The study will employ a comparative case study design to examine context-specific factors influencing pandemic vaccine preparedness. Countries will be categorised according to vaccination rate: high, moderate and low. Pairwise comparisons will enable a more detailed, focused analysis of contrasts between two countries within the same region, while a three-country comparison will provide a broader perspective by identifying regional patterns and differences. Together, these approaches will help explore how operational, systemic and sociopolitical factors differ between countries and how these disparities influence vaccination uptake.

Pairwise comparisons are an effective method for assessing the importance of different attributes in shaping a given outcome, enabling the ranking of attributes^{15 16} by allowing individuals to compare them in pairs, covering all possible combinations,¹⁷ rather than ranking them all at once.¹⁸ This approach is more intuitive and can reduce subjectivity when assigning weights to attributes.¹⁷ Previous research has applied pairwise comparisons to identify factors that systematically predict why some countries have successfully scaled up oral rehydration solutions while others have not.¹⁹

Patient and public involvement

Our initial engagement with stakeholders in Africa played a pivotal role in refining our research protocol, particularly the approach to pairwise (or three-country) comparisons. We engaged with four stakeholders: three from the Africa Centres for Disease Control and Prevention (CDC) and one from the WHO AFRO.

During these engagements, we presented an overview of our project, which aims to investigate the factors influencing variations in COVID-19 vaccination rates across sub-Saharan Africa through pairwise (three-country) comparisons of countries with different vaccination rates (high, moderate and low). The feedback from stakeholders helped refine our approach to the pairwise comparisons, focusing on clarifying the comparative value of our study and its contribution to future pandemic preparedness.

One key suggestion was to split our first research objective into two distinct components, including the development of an algorithm to assess COVID-19 vaccine performance across countries. This insight led us to sharpen our focus on identifying operational, systemic, and political factors influencing vaccination rates, ensuring that the comparative design would provide meaningful insights into which factors influence vaccine uptake. By comparing countries within the same sub-region (Central, Eastern, Southern or Western Africa), we aimed to identify regional patterns that could inform both local and global public health strategies.

Stakeholders also raised concerns regarding the initial selection of countries for the pairwise comparisons. It was noted that the selection seemed biased toward Anglophone countries. They suggested including francophone countries, such as Senegal and Côte d'Ivoire, which are geographically close to the selected anglophone countries, to provide more balanced comparisons across linguistic and cultural contexts and to strengthen regional representation. This feedback prompted us to consider a more diverse selection of countries, ensuring that the study captures a wider range of vaccination experiences across different geographical and linguistic contexts.

Additionally, stakeholders emphasised the importance of selecting countries based on regional health organisations (eg, the West African Health Organisation), which could provide valuable contextual insights for the pairwise comparisons. They also highlighted the importance of comparing countries within the same region (eg, West Africa) as this would contextualise findings within shared socio-political and healthcare environments. This recommendation reinforced the need to group countries by region, enabling us to contextualise findings based on differences in socio-political structures, healthcare systems and cultural practices. Another important insight was the issue of cross-border influences on vaccination rates. Stakeholders advised us to consider how populations may seek vaccination in neighbouring countries with stronger health systems. This ‘cross-border influence’ could affect vaccination data, leading to underreporting in the country where individuals get vaccinated elsewhere or overreporting in the country where non-residents are vaccinated. We were encouraged to investigate how such factors might impact the results of our pairwise comparisons.

In response to this feedback, the study design was revised to include francophone countries and incorporate a broader range of countries within each sub-region, ensuring that the study captures a more diverse set of vaccination experiences across different languages and geographical contexts. We also refined our comparative framework to clarify the research aims and focus on identifying significant factors influencing vaccination rates.

Country selection criteria

The study’s country selection criteria are designed to ensure a comparable and comprehensive analysis. First, countries must have a population of at least 10 million to enhance comparability. However, an exception is made for the Southern Africa region, where, aside from South Africa, all countries have populations below 10 million. Including smaller countries in this region is therefore necessary to capture the region’s vaccination dynamics. Second, countries are prioritised based on their COVID-19 vaccination performance: high rate (>70%), moderate rate (30%–69%) and low rate (<30%). This approach allows for a balanced examination of both successful and challenged vaccination efforts. Additionally, both anglophone and francophone countries are included to capture linguistic, cultural and administrative diversity, recognising the influence of these factors on public health strategies. Finally, regional representation is ensured by selecting countries that account for at least 15% of their sub-region’s population, thereby allowing meaningful comparisons and avoiding biases from geographic proximity. This comprehensive selection strategy aims to provide valuable insights into the factors influencing COVID-19 vaccination uptake across sub-Saharan Africa.

Country selection process

To systematically select countries for this study, all sub-Saharan African nations were initially listed in a table according to their COVID-19 vaccination rates. Data on population size and geographic areas were also included. The countries were then grouped by subregion and categorised by vaccination rate. Vaccination rate was defined as the total number of people who received all doses prescribed by the initial vaccination protocol, divided by the country’s total population.²⁰ For consistency, countries with populations below 10 million were excluded across all sub-regions, except Southern Africa. Within each subregion, COVID-19 vaccination rates were categorised into three groups: high rate (>70%), moderate rate (30%–69%) and low rate (<30%). The thresholds for these categories were informed by the CDC.²¹ This allowed for the identification of countries with varying levels of vaccination success.

The next step was to select countries within each sub-region of sub-Saharan Africa. Countries were selected based on similar population sizes but differing vaccination rates. In sub-regions with over 10 countries, a three-country comparison was applied, selecting one country from each vaccination rate category (high, moderate, low). Countries with populations of at least 10 million were prioritised, except in Southern Africa, where Botswana and Namibia were included alongside South Africa due to their contrasting vaccination rates. However, because South Africa has a larger population, it could not be grouped with Botswana and Namibia. Instead, Malawi was selected to be paired with South Africa due to its geographical proximity, differing vaccination rate and more comparable population size (table 1).

Table 1. List of selected countries for pairwise and three-country comparisons.

Comparison	Country	Region	COVID-19 vaccination rate (%) as of 31 December 202224	Population size as of 2022 (millions)25
Pairwise comparison	Angola	Central Africa	23.31	35.6
	Cameroon	Central Africa	9.88	27.6
Three-country comparison	Rwanda	Eastern Africa	72.51	13.6
	Burundi	Eastern Africa	0.22	13.2
	Uganda	Eastern Africa	27.40	47.3
Pairwise comparison	Botswana	Southern Africa	58.52	2.4
	Namibia	Southern Africa	18.27	2.9
Three-country comparison	Côte d’Ivoire	Western Africa	38.36	30.4
	Nigeria	Western Africa	28.66	223.1
	Senegal	Western Africa	8.09	17.7
Pairwise comparison	Malawi	Southern Africa	15.04	20.6
	South Africa	Southern Africa	33.73	62.4

Mixed-methods approach

This study will employ a mixed-methods approach to examine regional and country-specific factors influencing COVID-19 vaccination rates in Africa. By integrating qualitative and quantitative data, this approach will provide a more comprehensive understanding of factors influencing vaccination uptake.

Quantitative approach

The quantitative component of this study will focus on descriptive analysis to summarise COVID-19 vaccination uptake and key country-level indicators across the 12 participating African countries. Vaccination uptake will be categorised into three categories: high (>70%), moderate (30%–69%) or low (<30%). The macroeconomic, health system and policy indicators selected are informed by findings from a prior systematic review^{12 13} and a recent quantitative study that examined systemic-level predictors of vaccination uptake in Africa.¹⁴ The indicators that will be analysed include COVID-19 doses secured, COVID-19 doses administered, population size, GDP per capita, Global Health Security Index, Health Access and Quality Index, Corruption Perceptions Index, Economic Support Index, Stringency Index, Global Peace Index, Government Effectiveness Index and Human Development Index. These indicators will be sourced from curated online portals such as Our World in Data²² and World Bank.²³

Descriptive analysis will be employed to summarise vaccination uptake categories and compare country-level indicators. Summary tables will present the distribution of vaccination rates and the corresponding macroeconomic, health system and policy indicators for each country. To enhance comprehension, data will be visualised using charts. We will use RStudio Cloud (V.2024.12.01) for all descriptive analyses. The ggplot2 package will be used to visualise data and graphical summaries that simply and effectively show the results.

Qualitative approach

To collect comprehensive insights, we will conduct key informant interviews in 11 of the participating countries for which ethics approval has been obtained. The interview questions are open-ended, designed to capture the operational, systemic and socio-political factors influencing vaccination rates in Africa. We will conduct 10 key informant interviews per country, thus a total of 110 interviews.

Due to delays in obtaining ethics approval in Angola, no key informant interviews will be conducted in Angola unless ethics approval is obtained. Instead, a secondary data collection approach will be employed, drawing on publicly available reports, peer-reviewed literature and case studies to examine the operational, systemic and socio-political factors influencing COVID-19 vaccination uptake. This approach will ensure that Angola is still included in the study while ensuring compliance with ethical requirements.

Participant selection criteria

To ensure that participants have the depth of experience necessary to provide meaningful and actionable insights, recruitment in the 11 countries where key informant interviews will be conducted will be based on the following criteria:

1. Individuals who have been in leadership positions between 2020 and 2022 in national organisations or government agencies involved in COVID-19 vaccination efforts in any of these countries: Botswana, Burundi, Cameroon, Côte d'Ivoire, Malawi, Namibia, Nigeria, Rwanda, Senegal, South Africa and Uganda

2. These individuals may have either:

• been directly involved in the planning, implementation or evaluation of COVID-19 vaccination efforts in any of these countries.

• significantly contributed to policy development, resource allocation or vaccine distribution strategies in any of these countries

• been directly engaged in vaccine supply, logistics, distribution or campaigns in any of these countries

• 3 1Individuals must be able to share insights and real-life experiences of successes or challenges encountered during vaccination programmes.

Sampling strategy

A purposive sampling strategy will be employed to identify participants. Potential participants will include individuals from ministries of health, regional vaccination centres and vaccine implementers. Recruitment of participants began on 1 March 2026 and will continue until 30 October 2026. To identify eligible participants, we will use the following approaches:

1. Literature and online search: We will conduct searches of published literature and organisation websites to identify individuals with expertise relevant to the study who meet the eligibility criteria.

2. Referrals: We will ask field experts and eligible study participants if they know any individuals who might be eligible to participate in the study. They will help share the recruitment invitation with potential participants, including the study team’s contact information. Should others be interested in participating, they will contact the study team directly.

Data collection

Qualitative data will be collected through key informant interviews with eligible individuals. The interview will be conducted either in person or virtually via Zoom by one or two members of the research team. The interviews will be designed to encourage participants to share their experiences and insights regarding factors influencing vaccine uptake in their respective contexts. This will allow flexibility in responses while covering critical topics such as vaccine supply, public-sector integrity and government effectiveness. The interview guide is provided as online supplemental file 1. This approach is essential for capturing nuanced insights that inform our understanding of vaccination preparedness. The interview will be up to 60 min. The interviews will also be audio-recorded and transcribed verbatim for analysis.

Data analysis

Qualitative data will be analysed using a thematic analysis approach: (a) interviews will be audio-recorded and transcribed verbatim; (b) transcripts will be checked and edited, as necessary, for accuracy and completeness and to remove possible identifiers; (c) interview transcripts will be analysed using NVivo V.15 Plus; (d) two team members will independently code the interview transcripts for barriers and facilitators, meeting periodically to adjudicate coding differences and create a consensus template; (e) as an additional reliability check, a third reviewer will code a subset of interviews and help resolve coding discrepancies; (f) team members will review transcripts to identify preliminary themes and (g) team members will collectively review preliminary themes, resolve any mislabelling or duplication and agree on a final list of themes and subthemes.

Data integration

We will integrate findings from the quantitative, qualitative and secondary data components to obtain a comprehensive understanding of the factors influencing vaccination rates in the 12 selected African countries. One way we will achieve this is by creating a conceptual framework that maps quantitative data to qualitative insights, facilitating the visualisation of relationships between key indicators in the quantitative analysis and themes emerging from qualitative interviews. Insights from these comparisons will be synthesised to create a framework outlining critical components of pandemic preparedness. The pairwise and three-country comparison approach ensures that the framework is robust, adaptable and able to address diverse conditions across countries, helping governments prepare for future pandemics. The framework’s significance lies in its ability to guide future public health efforts, enabling countries to strengthen their readiness for pandemics by addressing identified gaps and leveraging best practices.

We will also perform thematic alignment, where we will cross-reference the quantitative data with qualitative themes related to barriers and facilitators of vaccination uptake identified through interviews. Another data integration approach will be comparative analysis, which will help us identify similarities and differences between quantitative and qualitative data. For example, if quantitative data indicates that a country with high vaccination rates also has a strong healthcare system, qualitative data from that country will be used to provide context on how the healthcare system was optimised and effectively used. Conversely, if a country has low vaccination rates despite strong government policies, qualitative insights may reveal underlying issues that quantitative measures miss.

We will also use a mixed-method approach to interpret findings collectively, rather than in isolation. This will be done by discussing how qualitative insights enrich our understanding of quantitative data.

Throughout the analysis, we will maintain an iterative feedback loop. As we analyse one data type, we will revisit the other for additional insights or context. This dynamic process will ensure the datasets are complementary to one another. Overall, these strategies will ensure our analysis provides a holistic understanding of the factors influencing vaccination rates by leveraging the strengths of quantitative and qualitative data to inform public health strategies.

Study timeline

Recruitment of eligible participants began on 1 March 2026 and will continue until 30 October 2026. Data collection is expected to be completed by 30 December 2026, with results expected by 30 June 2027. Recruitment and data collection will be conducted in phases and only in countries where ethics approval has been obtained. No recruitment or data collection will occur in any country before the required ethics approval has been obtained.

Ethics and dissemination

As the study involves human participants, we have received ethics approval from Western University’s Health Sciences Research Ethics Board (126 398). Local ethics approvals have also been obtained from ethics committees and relevant approving bodies in the following 11 participating countries: Ministry of Health Research and Development Committee, Botswana (HPRD:6/14/1); National Ethics Committee for the Protection of Human Subjects in Biomedical and Behavioural Research, Burundi (CNE/06/2026); Cameroon National Ethics Committee for Research on Human Health (1885/CE/CNERSH/SP/SPA); National Ethics Committee on Life and Health Sciences, Côte d’Ivoire (00 192–25/MSHPCMU/CNESVS-km); National Health Sciences Research Committee, Malawi (4746); Ministry of Health and Social Services Ethics Committee, Namibia (22/4/2/3); National Health Research Ethics Committee of Nigeria (HREC/01/01/2007); University of Rwanda, College of Medicine and Health Sciences Institutional Review Board (716/CMHS IRB/2025); National Ethics Committee for Health Research, Senegal (SEN25/137); University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (759/2025); and Makerere University School of Health Sciences Research Ethics Committee (MAKSHSREC-2025-972).

Participant recruitment and primary data collection will be conducted only in the 11 countries where ethics approval has been obtained. No primary data collection, including key informant interviews, will be conducted in Angola unless ethics approval is obtained. Participants will be contacted via email or telephone with an introduction to who we are, the purpose of the study, and what participation entails. Participants contacted via email will receive a link to the Letter of Information and Consent (LOI/C) form for their review. Also, for participants contacted via telephone, if participants express further interest, an email with the link to the LOI/C will be sent. All eligible participants interested in participating in the study must sign the consent form either on paper or electronically (via Western University Qualtrics) before they are allowed to participate. The LOI/C forms will provide details on the study objectives, participants’ roles, time commitment, the importance of audio recording, confidentiality, potential benefits and risks, and the procedure for withdrawing from the study. Participants will be informed of their rights to take a break or stop participating at any point during data collection. Prior to participants’ involvement in the study, the research team member will inform participants of their right to withdraw at any point during the interview without consequences. All study materials will be accessible only to research members involved in this study.

The study findings will be disseminated through three primary channels. First, country-specific reports will be prepared and shared with national public health authorities, including ministries of health and key implementing partners in each participating country. Second, policy briefs and presentations will be developed for health policymakers and partner organisations to support evidence-informed decision-making. Third, the study findings will be presented at academic conferences and published as peer-reviewed journal articles. Collectively, these dissemination activities will facilitate knowledge exchange and contribute to regional and global efforts to strengthen equitable pandemic vaccine preparedness.

Expected benefits of the study

The study aims to provide a deeper understanding of the factors influencing vaccination rollout in sub-Saharan Africa using the COVID-19 vaccine as a case study. These findings will address the need for localised evidence to inform public health strategies at both regional and global levels. By identifying operational, health system, governance and socio-political factors affecting vaccine rollout, the study will generate practical insights from the COVID-19 pandemic to guide the development of a framework for strengthening pandemic vaccine preparedness in Africa. This framework will help guide policymakers and public health practitioners in improving vaccination rollout across sub-Saharan Africa.