This meta-analysis provides the most comprehensive synthesis of mpox vaccine acceptance and uptake in Africa, covering the period from 1970 to 2024. Framed within both continental and global perspectives, our findings reveal a moderate willingness to vaccinate (53.55%) but low recent uptake (3.4% post-2022). This underscores a persistent gap between intent and action, a gap that threatens outbreak control.

The pooled mpox vaccine acceptance rate across African studies was 53.55%, slightly lower than the global pooled estimates of 56–59.7% reported in recent systematic reviews [73,74]. Despite this relatively small difference, African acceptance exceeded averages reported for certain regions, such as Southeast Asia and the Eastern Mediterranean [13].

Marked inter-country variability was evident, with acceptance ranging from 85% in the DRC to 28.84% in Ethiopia. The higher acceptance in the DRC may be explained by its long-standing experience with mpox outbreaks, its population’s familiarity with orthopoxvirus vaccination from the smallpox eradication era, and targeted immunization programs in endemic zones [32,40,42]. In contrast, Ethiopia’s lower rates may reflect minimal direct exposure to mpox, reduced perceived personal risk, and the influence of competing public health priorities [68,75]. Similar trends have been documented globally, with elevated acceptance observed in countries recently affected by severe outbreaks, such as Nigeria and the United Kingdom during 2022–2023 [76,77].

Subregional analysis revealed the highest vaccine acceptance in Southern Africa (67.43%), with lower rates in Eastern, Central, and Western Africa. By population group, general population acceptance was moderate to high (62.46%), whereas healthcare workers (51.63%) and medical students (46.17%) demonstrated an unexpectedly lower willingness to vaccinate. This finding echoes results from Ebola and COVID-19 vaccination campaigns, where occupational exposure alone did not consistently lead to higher uptake [16,25,63]. Contributing factors may include vaccine safety concerns, limited mpox-specific training, and exclusion from priority vaccination lists [25,78].

Beyond acceptance rates, our analysis reveals significant disparities in actual mpox vaccine coverage across Africa. The most notable temporal pattern was the sharp drop in uptake from 36.0% before 2022 to just 3.4% post-2022. This decline is likely due to multiple factors, including limited vaccine availability, dependence on donor-driven allocations, and the absence of sustained, large-scale vaccination campaigns after the initial outbreak response. The WHO’s 2023 decision to declare mpox no longer a Public Health Emergency of International Concern may have further diminished perceived urgency, contributing to reduced demand and political prioritization [79].

The mpox vaccination coverage in Africa was 20.94% (95% CI: 10.06-38.56). Our findings were non-significantly lower than observed in global pooled estimate of 30.9% (95% CI, 21.0– 41.7%) [13]. This highlight the geographiscal disparity in vaccine delivery across various regions globally. Moreover, The gap between vaccine acceptance and actual uptake was particularly pronounced among healthcare workers (5.5%) and hospital-based populations (1.7%). In Eastern Africa, the only available study reported 0% coverage. This significant mismatch echoes patterns seen with Ebola and COVID-19 vaccination efforts in Africa, where acceptance often exceeded 60%, but coverage lagged due to logistical challenges, inequitable distribution, and inconsistent risk communication [78,80,81]. These persistent barriers highlight the urgent need to strengthen vaccine supply chains, enhance targeted outreach, and embed mpox vaccination into routine immunization programs.

Historically, smallpox vaccination campaigns in Africa achieved coverage exceeding 90%[40]. This underscores the feasibility of high uptake and highlights the extent of the current gaps. Smallpox eradication succeeded due to ample vaccine supply, efficient delivery systems, and a high public threat perception. In contrast, the current mpox landscape is marked by a breakdown of the orthopoxvirus vaccination infrastructure, diminished public familiarity with the disease, and competition from other immunization priorities [40].

This study adds new knowledge by quantifying the magnitude of the acceptance-uptake gap for mpox vaccines in Africa. It identifies greater inter-country variability compared to global trends, documents a sharp decline in uptake post-2022, and reveals unexpectedly low acceptance among healthcare workers. These findings suggest that strategies focused solely on demand generation are insufficient. Instead, a holistic approach addressing both vaccine supply and systemic delivery constraints is required.

The gap between vaccine acceptance and actual uptake was particularly pronounced among healthcare workers (5.5%) and hospital-based populations (1.7%). In Eastern Africa, the only available study reported 0% coverage. This significant mismatch echoes patterns seen with Ebola and COVID-19 vaccination efforts in Africa, where acceptance often exceeded 60%, but coverage lagged due to logistical challenges, inequitable distribution, and inconsistent risk communication [82–84]. These persistent barriers highlight the urgent need to strengthen vaccine supply chains, enhance targeted outreach, and embed mpox vaccination into routine immunization programs in countries facing recurrent outbreaks.

Historically, smallpox vaccination campaigns in Africa achieved coverage exceeding 90% [40]. This underscores the feasibility of high uptake and highlights the extent of the current gaps. Smallpox eradication succeeded due to ample vaccine supply, efficient delivery systems, and a high public threat perception. In contrast, the current mpox landscape is marked by a breakdown of the orthopoxvirus vaccination infrastructure, diminished public familiarity with the disease, and competition from other immunization priorities [40].

This study adds new knowledge by quantifying the magnitude of the acceptance-uptake gap for mpox vaccines in Africa. It identifies greater inter-country variability compared to global trends, documents a sharp decline in uptake post-2022, and reveals unexpectedly low acceptance among healthcare workers. These findings suggest that strategies focused solely on demand generation are insufficient. Instead, a holistic approach addressing both vaccine supply and systemic delivery constraints is required.

Furthermore, this study showed that mpox vaccine acceptance and uptake in Africa are influenced by a complex interplay of sociodemographic, psychosocial, and structural factors. Age and sex emerged as significant determinants. Older individuals were more likely to accept vaccination than younger people [33–35,60,82–84], a finding that corroborates previous COVID-19 vaccine studies where older adults reported higher willingness due to a greater perceived vulnerability [85].

Evidence on gender-based acceptance was mixed. Some studies found higher uptake among men [16], while others identified greater acceptance among women [40,43]. This variability mirrors COVID-19 research in Africa, where male acceptance was sometimes higher due to occupational exposure, while female hesitancy was linked to concerns about fertility and vaccine safety [86,87].

In addition to sociodemographic factors, socioeconomic and educational factors also shaped vaccine acceptance in our review. Higher education consistently predicted willingness to vaccinate [70–72], which corroborates previous studies showing that health literacy enhances vaccine confidence [88]. However, the effects of income were contradictory: higher income was associated with both greater [72] and lower acceptance [26]. These inconsistencies likely reflect contextual differences, as wealth may improve access in some settings but coincide with skepticism of government or donor-driven campaigns in others [89]. Beyond formal education, knowledge about mpox, risk perception, and perceived susceptibility were strongly associated with acceptance [16,63,63,67,70]. This aligns with the Health Belief Model, where perceived risk drives preventive health behavior [90]. Additionally, training interventions [16,66] boosted willingness, echoing evidence from Ebola and COVID-19 vaccination programs in Africa where targeted education improved uptake [91].

Trust and information emerged as central themes. Confidence in health authorities and the healthcare system [25,72,92], and trust in the vaccine’s safety [25,41,92,92,93], were critical drivers, consistent with global evidence that institutional trust underpins vaccine confidence [94]. Conversely, mistrust has repeatedly undermined campaigns during Ebola and and COVID-19 outbreaks [95]. Receiving information from health authorities increased acceptance [24,41,93], while social influences such as peer and family recommendations also shaped decisions [16,93]. A prior vaccination history, including for COVID-19 or influenza, predicted acceptance [26,66,67,92], suggesting that established immunization habits carry over to new vaccines [96]. Structural barriers were equally important: free provision [16,24] and urban residence [25,72] increased uptake, while rural populations faced greater challenges, consistent with long-standing inequities in African immunization programs [97]. Finally, family history of mpox increased both risk perception and acceptance [92], mirroring Ebola outbreaks where personal experience heightened demand [98].

Taken together, these findings show that improving mpox vaccine uptake in Africa requires multi-level interventions that address structural inequities in access, tailor education and communication for different sociodemographic groups, build trust through transparent messaging, and leverage prior vaccination experiences. The complex interplay of individual, social, and systemic factors underscores the need for context-specific strategies to ensure that acceptance translates into equitable uptake across the continent.

Importantly, this study adds new knowledge by quantifying the magnitude of the acceptance–uptake gap for mpox vaccines in Africa, identifying greater inter-country variability compared with global trends, documenting a post-2022 collapse in uptake, and revealing unexpectedly low acceptance among healthcare workers. These findings suggest that strategies focusing solely on demand generation may be insufficient. Instead, holistic approaches that simultaneously address vaccine supply, equitable distribution, and systemic delivery challenges are needed to effectively convert stated willingness into completed vaccinations.