Navigating the Road to Immunization Equity: Systematic Review of Challenges in Introducing New Vaccines in Sub-Saharan Africa's Routine Programs

1. Introduction

Vaccination remains one of the most effective strategies for preventing and controlling infectious diseases, offering protection against over 20 potentially life-threatening conditions worldwide [1]. Over the past five decades, vaccination has been estimated to save more than 130 million lives, underscoring its critical role in global health [2]. Recognizing its importance, the World Health Assembly has recommended the introduction of new vaccines into national immunization programs, particularly to address emerging diseases of public health concern [3].

Technical and financial assistance has been pivotal to vaccine introduction for resource-limited settings, such as sub-Saharan Africa. Between 2000 and 2022, Gavi, the Vaccine Alliance, invested over 11 billion US dollars to improve access to vaccines across the African continent [4].

Specific initiatives, including the COVAX mechanism funded by the European Union, have supported the deployment of COVID-19 vaccines in 15 African countries [5]. Similarly, the AMVIRA initiative has facilitated malaria vaccine introduction in 19 African nations [6]. Supporting new vaccine rollout also encompasses research, clinical trials [7], and pilot phase implementation [8]. These efforts have led to measurable successes. In Botswana, for instance, introducing COVID-19 vaccines resulted in more than 50% population coverage [9], while the rollout of cholera vaccines successfully curtailed transmission during an outbreak in Lusaka, Zambia [10]. Despite such achievements, significant challenges have been identified in implementing new vaccines in sub-Saharan Africa [11]. First, many new vaccines require stringent storage and transportation conditions to maintain efficacy, which poses difficulties in keeping the cold chain in remote or resource-constrained regions [12]. Second, affordability and funding sustainability challenges threaten coverage rates, particularly in countries with fragile health systems and economies [13].

Additionally, new vaccine introduction frequently encounters resistance fueled by misinformation, mistrust, or entrenched cultural beliefs [14]. Operational challenges further compound these issues. Evaluations of vaccine introductions have highlighted inadequacies in adverse event monitoring systems and limitations in data infrastructure, impeding the comprehensive assessment of vaccine safety and coverage [15]. Furthermore, new vaccines necessitate additional training for healthcare workers, exacerbating workloads in health systems already strained by human resource shortages [16]. Logistical barriers are another key challenge, particularly in reaching remote and marginalized populations [17]. To better understand these challenges, identify effective solutions, and guide the introduction of new vaccines in sub-Saharan Africa, we systematically reviewed published articles examining barriers to vaccine rollout and their associated mitigation strategies in the region.

2. Materials and Methods

This systematic review followed the PRISMA 2020 Statement guidelines to ensure rigor and transparency in reporting [18]. A comprehensive search strategy, guided by the PICO approach, was developed to identify relevant quantitative and qualitative studies. Five electronic databases—PubMed, Scopus, CINAHL, Web of Science, and Embase—were queried, yielding 796 articles. The search period spanned January 2019 to December 2024. The detailed PubMed search strategy is provided in Appendix A1 (see Table A1). The review protocol was prospectively registered on the PROSPERO platform (registration number: 532857; registered on April 6, 2024) to enhance methodological transparency and reduce the potential for bias.

2.1. Inclusion/Exclusion Criteria

We restricted our search to articles published in English or French between January 2019 and July 2024, focusing on the challenges of introducing new vaccines in sub-Saharan Africa. Articles were excluded if they were: (i) dissertations or theses, (ii) press publications, (iii) editorials, (iv) editorial reports, (v) supplementary articles, (vi) newsletters, or (vii) studies not accessible in the university library.

2.2. Selection of Studies

Articles retrieved were imported into Rayyan software for systematic screening. The selection process followed a stepwise approach based on our research question and inclusion criteria. Initially, articles were screened by title and abstract by the principal investigator and collaborators (SF, WSR, LTB, NMN). Of 796 articles identified, 11 duplicates and 732 articles not meeting the inclusion criteria were excluded. Fifty-three articles underwent full-text review, and 20 were excluded for the following reasons: insufficiently described or missing methodology (n=5), lack of specificity to new vaccines (n=4), not vaccine-related (n=1), not focused on African countries (n=2), prepublication articles not validated (n=2), results based on commentary rather than evidence (n=5), data dated beyond the eligibility window (n=1).

Disagreements on eligibility were resolved through consensus among reviewers, resulting in the inclusion of 33 studies. These comprised 26 quantitative studies, 4 qualitative studies, 2 mixed-methods studies, and 1 clinical trial.

2.3. Data Extraction and Analysis

Search results were uploaded to Rayyan for organization and deduplication. Initial selection by three reviewers (title and abstract) was followed by a full-text review based on the inclusion and exclusion criteria. A fourth reviewer resolved disagreements. Narrative synthesis was employed to thematically group challenges to introducing new vaccines. Extracted data included author and year of publication, study setting, participants and demographics, study design, vaccine type, study quality, main challenges reported

Challenges were categorized into four domains: acceptability, logistical challenges, service delivery, and coordination/financing.

2.4. Quality Assessment of Studies

The quality of the included studies was assessed using the Mixed Methods Appraisal Tool (MMAT), 2018 version. The MMAT was selected for its applicability to reviews involving qualitative, quantitative, and mixed-methods studies [19]. Each article was evaluated against five criteria, with a score of two points for "Yes" responses and zero for "No" or "Unknown" responses. Total scores were converted into percentages, ranging from 60% to 100%. Of the 33 studies, 12 scored 60%, 14 scored 80%, and 7 achieved 100%.

3. Results

The results of 33 articles concerned the introduction of eight (8) new vaccines. These vaccines include the malaria vaccine (MV), COVID-19 vaccine, human papillomavirus (HPV) vaccine, Ebola virus vaccine, cholera vaccine, hepatitis B vaccine (HBV), rotavirus vaccine and typhoid vaccine. The introduction of these vaccines has essentially revealed four types of challenges. These challenges are grouped into (1) acceptability, (2) immunization service logistics capacity, (3) quality service delivery, and (4) the challenges of coordinating and financing new vaccines.

Figure 1. PRISMA flow diagram (PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only).

Figure 1. PRISMA flow diagram (PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only).

3.1. Acceptability of New Vaccines

Challenges related to the acceptability of new vaccines were reported in 18 of the 33 studies and involved the introduction of five vaccines—against malaria, COVID-19, human papillomavirus (HPV), hepatitis B, and Ebola—in 10 African countries. Acceptability varied by vaccine type and country, ranging from strong adherence to marked reluctance (Table 1).

High vaccine acceptance rates (>90%) were noted for five vaccines across four countries. Key factors driving acceptance included perceived risks of target diseases, such as the Ebola virus in the Democratic Republic of Congo (DRC) [20], the severity of COVID-19 infection in Nigeria [21], the perceived sensitivity of hepatitis B (p<0.05) in Ghana [22], experiential attitudes toward HPV vaccination (p<0.01) in Nigeria [23] and population confidence in malaria vaccine in Sierra Leone [24].

Conversely, vaccine hesitancy emerged in at least eight countries. For COVID-19 vaccines, reluctance was driven by fear of adverse events following immunization (AEFI) in Ethiopia [25] and the DRC [26], lack of information in Senegal [27] and in Sudan [28], low awareness of vaccination in Ethiopia [29], concerns about safety in the DRC [30], religious considerations in Ghana [31] and perceived susceptibility (p<0.001) in Nigeria [32].

For HPV vaccines, barriers to acceptance included parental education level in Ethiopia [33], infodemics in Senegal [34] and in South Africa [35] and trust in regulatory measures in Uganda [36]. Reluctance toward the Ebola vaccine in Guinea stemmed from stigma [7].

3.2. Logistic Challenges

Logistical barriers were reported in seven studies concerning introduction of malaria and HPV vaccines in six countries (Table 2). Challenges included vaccine availability, cold chain infrastructure gaps, and district and facility-level logistics shortfalls.

For the HPV vaccine, specific barriers were global vaccine shortages, delayed rollout in Senegal [34], vaccine unavailability at designated sites in Nigeria [37] and in public programs in South Africa [35], and inadequate cold chain storage in Uganda [36].

For the malaria vaccine, challenges included vaccine supply shortages and resulting community disinterest in Sierra Leone [38] and vaccine stock-outs and inadequate mobile logistics in Ghana [39] [40].

Corrective measures adopted included revising logistics plans to address cold chain gaps in Ghana [39], procuring vaccines through Gavi collaborations in Nigeria [37], and integrating HPV vaccination within school programs in South Africa [35].

3.3. Challenges to Quality Service Delivery

Five studies identified immunization service delivery challenges for hepatitis B, malaria, and HPV vaccines across 13 countries (Table 3). Key issues included inadequate vaccination delivery strategies and healthcare workforce barriers.

For hepatitis B vaccination, inadequate provision of services contributed to a 32% non-vaccination rate across 12 countries [41]. Long waiting times and overburdened staff during malaria vaccine delivery were similarly noted in Ghana [42]. Furthermore, facility managers criticized extended malaria vaccination schedules for contributing to dropouts [40]. Ineffective HPV vaccine delivery strategies included difficulty tracking school-aged children transferred to other districts in Senegal [34] and in Uganda [36]. Challenges were exacerbated by workforce capacity deficits, particularly in Ghana for malaria vaccines [40] and in Senegal for HPV vaccines [34]. Recommendations included phased program scaling [39], stakeholder engagement [34], comprehensive training of healthcare providers [36], and sharing best practices to improve service delivery [40].

3.4. Challenges Associated with Coordinating and Financing New Vaccines

Fourteen studies reported coordination and financing challenges related to six vaccines—malaria, influenza, HPV, rotavirus, typhoid, and hepatitis B—across 17 African countries (Table 4).

Coordination issues included pilot site selection, eligibility criteria for target populations, and implementation planning. In Ghana, the exclusion of districts during malaria vaccine piloting led to dissatisfaction among health officials [40].

Implementation delays were similarly noted. In Senegal, the HPV vaccine rollout was postponed due to vaccine unavailability, insufficient funding, and an incomplete communication plan [43]. Financial resource mobilization challenges impacted the malaria vaccine rollout in Ghana [42].

Financing barriers centered on the high costs of vaccine introduction relative to WHO-recommended affordability thresholds, as observed with influenza vaccines in Kenya [44] and typhoid vaccines in Malawi [45].

Partner co-financing mitigated some costs, enabling HPV introduction in Senegal [46] and Zimbabwe [47] and rotavirus vaccine deployment in Niger [48]. However, cost variations persisted and were linked to differing proportions of co-financing [35].

Several countries adopted alternative strategies. Niger prioritized lower-cost rotavirus vaccines [48], Mozambique reduced HPV vaccine dosing regimens [49], and Malawi cut ancillary program costs [45]. Without subsidies, financial burdens fell to health services and vaccine beneficiaries, as documented with hepatitis B vaccines in 12 countries [41], HPV programs in Nigeria [35], HPV vaccine in Nigeria [37], and in Sierra Leone, where only 56% of respondents were willing to pay $0.69 for the HPV vaccine [38].

This review provides critical insights into the challenges of introducing new vaccines within sub-Saharan Africa’s national immunization programs. By categorizing these challenges into acceptability, logistical capacity, service delivery quality, and coordination and financing, the study identifies cross-cutting barriers that are context-dependent and vaccine-specific. These findings are pivotal for informing policymakers, program managers, and stakeholders to optimize vaccine introduction strategies and strengthen regional health interventions.

Our analysis underscores that vaccine acceptability is variable and context-specific, influenced by vaccine type, perceived risk, and sociocultural factors. High acceptance levels (>90%) were documented for Ebola and hepatitis B vaccines among healthcare workers and target populations in the DRC [20] and Ghana [50], respectively. This acceptance included heightened disease risk perceptions, community trust, and provider advocacy.

Conversely, vaccine hesitancy remains a significant barrier, particularly for COVID-19 and HPV vaccines. For COVID-19 vaccines, fear of adverse events following immunization (AEFI), limited information, and religious concerns contributed to reluctance in Ethiopia [51] and Senegal [27]. Similarly, parental education levels and infodemics drove HPV vaccine hesitancy in Uganda [52] and Senegal [34]. These findings mirror those from Latin America, where vaccine acceptability varied widely by country and target group: 95% among healthcare workers in Mexico but as low as 40% in Peru [53]. Such disparities emphasize the critical role of tailored communication strategies, trust-building interventions, and community engagement to mitigate misinformation and address population-specific barriers. Lessons from successful campaigns—such as Ebola vaccination in the DRC—highlight the importance of integrating risk communication and leveraging trusted local actors.

Logistical challenges emerged as central barriers, particularly the limitations of cold chain infrastructure and vaccine supply shortages. Insufficient cold chain capacity hampered HPV vaccine delivery in Uganda [52] and malaria vaccination in Ghana [55], consistent with observations from Latin America, where gaps in cold chain availability similarly undermined vaccine introduction efforts [56]. In addition to infrastructure gaps, recurrent vaccine shortages, notably for HPV [43] and malaria vaccines [38], disrupted program continuity and undermined population confidence. Comparable vaccine shortages in Asia and the Pacific highlight the global nature of organizational and funding constraints for vaccine distribution [57]. Cold chain strengthening and innovative logistical solutions, such as mobile storage units, must be prioritized to ensure vaccine potency and access in remote settings. Global partnerships, including Gavi and WHO support, remain critical to addressing supply disruptions and bridging logistical inequities across resource-limited contexts.

Shortcomings in immunization service delivery were widespread and included insufficient workforce capacity, poor customer care, and organizational inefficiencies. Long waiting times and provider negligence were reported during malaria vaccine delivery in Ghana [42] and hepatitis B vaccination across 12 countries [41]. Such findings align with studies on COVID-19 vaccination services in Egypt, where site overcrowding and disorganization were predominant challenges [54].

These barriers underscore the need to streamline service delivery processes, optimize workforce distribution, and strengthen training programs. Strategies to address inefficiencies include phased vaccine rollout approaches, stakeholder involvement, and monitoring frameworks to evaluate provider performance and client satisfaction.

Financing challenges remain a cornerstone barrier to vaccine introduction across Africa, where vaccine and operational costs often surpass available health budgets. For instance, the typhoid vaccine in Malawi [45] and influenza vaccines in Kenya [44] exceeded WHO-defined cost thresholds for health interventions. Unlike resource-constrained regions in Asia, such as Afghanistan, where HPV vaccination costs represented just 0.7% of GDP due to streamlined target cohorts [58], African countries contend with broader target populations and weaker financing mechanisms.

Co-financing agreements, such as Gavi-supported HPV vaccine programs in Senegal [46] and Zimbabwe [47], offer critical opportunities to offset costs. However, sustained government commitments, innovative financing strategies, and cost-effective program adaptations (e.g., reducing HPV vaccine doses [49]) are imperative to overcome long-term financial barriers and ensure equitable vaccine access.

This review is a comprehensive repository of challenges encountered in recent vaccine introductions across the African region. It highlights opportunities for strengthening health systems, aligning resources, and tailoring program interventions to overcome contextual barriers.

By addressing these interrelated challenges, countries can improve the efficiency, equity, and success of future vaccine introduction efforts, particularly in emerging diseases and global immunization goals.

Strengths and Limitations

This review offers a critical overview of vaccine introduction challenges across diverse African settings, providing practical insights to guide immunization program planning and execution. However, limitations must be acknowledged. First, while significant data were synthesized, insufficient evidence on political commitment—an essential determinant of vaccine program success—was available. Second, the exclusion of meta-analytical methods limited the quantitative exploration of results. Finally, contextual heterogeneity across countries warrants cautious interpretation when comparing findings. Variations in socio-economic, cultural, and health system factors may differentially influence vaccine-related challenges and solutions.

5. Conclusions

The successful introduction of new vaccines in sub-Saharan Africa is crucial for advancing immunization goals, but key challenges remain, including issues with coordination, financing, vaccine acceptability, service delivery quality, and logistical constraints. Overcoming these barriers requires evidence-driven approaches tailored to local contexts. Addressing financing gaps through political commitment, innovative funding, and global partnerships is essential, as is enhancing public awareness to combat misinformation and build vaccine trust. Investing in healthcare workforce capacity and strengthening cold and supply chain systems is also critical. By implementing these measures, resilient immunization systems can be built, enabling the introduction of new vaccines, reinforcing health systems, and ensuring equitable healthcare outcomes across Africa.

Appendix A.1

Table A1. PubMed Search Strategy.

Search terms	Key-words
Health workers, physicians, nurses, Decision makers, drug industry,	"Decision-makers “OR "Health Personnel"[Mesh] OR "Community Health Workers"[Mesh] OR "Allied Health Personnel"[Mesh] OR "Physicians"[Mesh] OR "nurses"[Mesh] OR "Societies, Pharmaceutical"[Mesh] OR "Drug Industry"[Mesh] OR "Drug and Narcotic Control"[Mesh]
New vaccines	"New vaccines" OR "Ebola Vaccines"[Mesh] OR "West Nile Virus Vaccines"[Mesh] OR "AIDS Vaccines"[Mesh] OR "Cholera Vaccines"[Mesh] OR "Herpes Simplex Virus Vaccines"[Mesh] OR "Dengue Vaccines"[Mesh] OR "Cancer Vaccines"[Mesh] OR "Papillomavirus Vaccines"[Mesh] OR "Vaccines"[Mesh] OR "Rubella Vaccine"[Mesh] OR "Malaria Vaccines"[Mesh] OR "ChAdOx1 nCoV-19"[Mesh] OR "Poliovirus Vaccine, Inactivated"[Mesh]
Challenges, Costs, impact	"Risk-Taking"[Mesh] OR "Challenge" OR "Health Impact Assessment"[Mesh] OR "Cost-Benefit Analysis"[Mesh] OR "Costs and Cost Analysis"[Mesh] OR "Costs"
Low-and-middle income countries	"Angola" OR "Benin" OR "Botswana" OR "Burkina Faso" OR "Burundi" OR "Cabo Verde" OR "Cameroon" OR "Central African Republic" OR "Chad" OR "Comoros" OR "Congo" OR "Democratic Republic of Congo" OR "Cote d'Ivoire" OR "Equatorial Guinea" OR "Eritrea" OR "Eswatini" OR "Swaziland" OR "Ethiopia" OR "Gabon" OR "Gambia" OR "Ghana" OR "Guinea" OR "Guinea-Bissau" OR "Kenya" OR "Lesotho" OR "Liberia" OR "Madagascar" OR "Malawi" OR "Mali " OR "Mauritania" OR "Mauritius" OR "Mozambique" OR "Namibia" OR "Niger" OR "Nigeria" OR "Rwanda" OR "Sao Tome and Principe" OR "Senegal" OR "Seychelles" OR "Sierra Leone" OR "Somalia" OR "South Africa" OR "South Sudan" OR "Sudan" OR "Tanzania" OR "Togo" OR "Uganda" OR "Zambia" OR "Zimbabwe"

Table A1. PubMed Search Strategy.

Search terms	Key-words
Health workers, physicians, nurses, Decision makers, drug industry,	"Decision-makers “OR "Health Personnel"[Mesh] OR "Community Health Workers"[Mesh] OR "Allied Health Personnel"[Mesh] OR "Physicians"[Mesh] OR "nurses"[Mesh] OR "Societies, Pharmaceutical"[Mesh] OR "Drug Industry"[Mesh] OR "Drug and Narcotic Control"[Mesh]
New vaccines	"New vaccines" OR "Ebola Vaccines"[Mesh] OR "West Nile Virus Vaccines"[Mesh] OR "AIDS Vaccines"[Mesh] OR "Cholera Vaccines"[Mesh] OR "Herpes Simplex Virus Vaccines"[Mesh] OR "Dengue Vaccines"[Mesh] OR "Cancer Vaccines"[Mesh] OR "Papillomavirus Vaccines"[Mesh] OR "Vaccines"[Mesh] OR "Rubella Vaccine"[Mesh] OR "Malaria Vaccines"[Mesh] OR "ChAdOx1 nCoV-19"[Mesh] OR "Poliovirus Vaccine, Inactivated"[Mesh]
Challenges, Costs, impact	"Risk-Taking"[Mesh] OR "Challenge" OR "Health Impact Assessment"[Mesh] OR "Cost-Benefit Analysis"[Mesh] OR "Costs and Cost Analysis"[Mesh] OR "Costs"
Low-and-middle income countries	"Angola" OR "Benin" OR "Botswana" OR "Burkina Faso" OR "Burundi" OR "Cabo Verde" OR "Cameroon" OR "Central African Republic" OR "Chad" OR "Comoros" OR "Congo" OR "Democratic Republic of Congo" OR "Cote d'Ivoire" OR "Equatorial Guinea" OR "Eritrea" OR "Eswatini" OR "Swaziland" OR "Ethiopia" OR "Gabon" OR "Gambia" OR "Ghana" OR "Guinea" OR "Guinea-Bissau" OR "Kenya" OR "Lesotho" OR "Liberia" OR "Madagascar" OR "Malawi" OR "Mali " OR "Mauritania" OR "Mauritius" OR "Mozambique" OR "Namibia" OR "Niger" OR "Nigeria" OR "Rwanda" OR "Sao Tome and Principe" OR "Senegal" OR "Seychelles" OR "Sierra Leone" OR "Somalia" OR "South Africa" OR "South Sudan" OR "Sudan" OR "Tanzania" OR "Togo" OR "Uganda" OR "Zambia" OR "Zimbabwe"