COVID-19 vaccine hesitancy in Latin America and Africa: a scoping review

Abstract: Vaccination has played an important role in the containment of COVID-19 pandemic advances. However, SARS-CoV-2 vaccine hesitancy has caused a global concern. This scoping review aims to map the scientific literature on COVID-19 vaccine hesitancy in Latin America and Africa from a Global Health perspective, observing the particularities of the Global South and using parameters validated by the World Health Organization (WHO). The review reporting observes the recommendations of the PRISMA for Scoping Reviews (PRISMA-ScR) model. Search was conducted in PubMed, Scopus, Web of Science, and Virtual Health Library (VHL) databases, selecting studies published from January 1, 2020 to January 22, 2022. Selected studies indicate that COVID-19 vaccine hesitancy involves factors such as political scenario, spread of misinformation, regional differences in each territory regarding Internet access, lack of access to information, history of vaccination resistance, lack of information about the disease and the vaccine, concern about adverse events, and vaccine efficacy and safety. Regarding the use of conceptual and methodology references from the WHO for vaccine hesitancy, few studies (6/94) use research instruments based on these references. Then, the replication in Global South of conceptual and methodological parameters developed by experts from the Global North contexts has been criticized from the perspective of Global Health because of it may not consider political and sociocultural particularities, the different nuances of vaccine hesitancy, and issues of access to vaccines.


Introduction
The COVID-19 pandemic has exacerbated a complex Global Health scenario with the interaction of the SARS-CoV-2 and noncommunicable diseases, problems of health service access and functioning, socioeconomic inequality, and non-enforcement of social rights, making it a phenomenon of syndemic 1 .
In addition to health measures such as physical distancing and hygiene, vaccination against COV-ID-19 significantly contributed to prevent the spread of the epidemic 2 .A successful vaccine campaign is directly related to the broad acceptance by the population and its effectiveness depends on sustained adoption to maintain the effect of immunity and stop the circulation of the infectious agent 3 .Despite knowledge legitimized by science about the effectiveness and success of mass immunization, social reactions against vaccines are seen in the history of immunization, creating challenges to Public Health 4 .
Considering the importance of understanding and implementing actions to address this phenomenon, the working group on vaccine hesitancy of the Strategic Advisory Group of Experts on Immunization (SAGE), World Health Organization (WHO), defined vaccine hesitancy as the "delay in acceptance or refusal of vaccines despite availability of vaccination services" 5 (p. 7).This definition excludes access issues 5,6 , because "in low uptake situations where lack of available services is the major factor, hesitancy can be present but is not the principle reason for unvaccinated and undervaccinated members of the community" 5 (p.7).
The WHO EURO Vaccine Communications Working Group proposed the 3C model (confidence, complacency, and convenience), based on the European experience with vaccine hesitancy, which was later reformulated into the 5C scale to include "risk calculation" and "collective responsibility" besides the three determinants of vaccine hesitancy present in the 3C model 7 .The Matrix of Vaccine Hesitancy Determinants was created to guide the development of vaccine hesitancy indicators, research questions, diagnosis, and intervention 5,6,8 .The determinants are grouped into contextual, individual, and group influences/vaccine-specific issues 5,6,8 .It is not known whether this matrix was developed from the experiences and aspects of the Global North and South 9 , but it has been recommended for studies at a global level and studies conducted in the Global South.
More recently, the Working Group on Behavioral and Social Drivers of Vaccination (BeSD), also linked with WHO, has developed another tool to understand the drivers and obstacles to vaccine uptake.The extensive document titled Behavioural and Social Drivers of Vaccination: Tools and Practical Guidance for Achieving High Uptake 10 contains surveys to investigate determinants of vaccine hesitancy, both in children and specifically regarding COVID-19 vaccines.
In the case of vaccination against COVID-19, studies conducted in African and Latin American countries showed that hesitancy was linked with religious beliefs, association between vaccination and surveillance of government authorities, lack of information about adverse events, vaccine safety and efficacy, and dissemination of fake news 11,12,13,14,15 .
Previous scoping reviews sought to map COVID-19 vaccine hesitancy worldwide 16 and in highincome countries 17 .The results showed aspects related to hesitancy 16,17 : concerns about vaccine safety and efficacy, adverse events, perception of low risk in relation to COVID-19 infection, religious beliefs, cost of vaccine, rapid development of vaccines, lack of trust in government and health authorities, dissemination of fake information, unavailability of clear information about vaccines, racism and discrimination, preference for alternative treatments to the biomedical paradigm.
However, the method strategy of both studies only included publications in English 16,17 .Also, both reviews did not analyze the use of conceptual and methodological tools produced in the Global North applied to Global South countries.Then, our review conducted a reflective analysis on the realities of local contexts of the Global South, with a focus on how the frameworks proposed by WHO SAGE have been used in the Global Health in order to understand the phenomenon of COVID-19 vaccine hesitancy and the impact on health policies 18,19,20 .
In this sense, this scoping review intends to promote original contributions to the particularities of social, cultural, and local aspects of COVID-19 vaccine hesitancy in Latin American and African countries from a critical perspective of Global Health 21 , which consider the relations of power, authority, inclusion and exclusion observed in the scientific field, governments, and health institu-Cad.Saúde Pública 2023; 39(8):e00041423 tions in the Global North and Global South.This perspective highlights inequalities among actors who design and actors who receive global health interventions, in order to understand the reproduction of the dichotomy between "the West and the rest" 18 .
Vaccine hesitancy in the Global South must be understood according to the complexity of cultural, social, ethnic, and regional differences 9 , including vaccines against COVID-19.Then, this study aims to identify, map, and systematize scientific evidence of COVID-19 vaccine hesitancy in Latin American and African countries.

Method
This scoping review seeks to understand broader issues in order to synthesize evidence and map the literature about a field of knowledge that has not yet been fully reviewed or has a complex and heterogeneous nature 22,23 .This study is based on the following question: How has the scientific literature addressed COVID-19 vaccine hesitancy in Latin American and African countries?
This scoping review reporting was structured according to the PRISMA for Scoping Reviews (PRISMA-ScR) checklist items 22,23 : title, structured summary, rationale, objectives, methods (review protocol, eligibility criteria, information sources, search, selection of sources of evidence, organization and synthesis of results), results (selection of evidence, characteristics, appraisal, presentation, and synthesis of results), discussion according to critical global health perspective, study limitations, and final considerations.
Studies in English, Portuguese, and Spanish published from January 1st, 2020 (year when COVID-19 was considered a Public Health Emergency of International Concern by the WHO) to January 22, 2022 were included in this review.A search was conducted in PubMed, Scopus, Web of Science, and Virtual Health Library (VHL) databases.Eligibility criteria included complete empirical, qualitative, quantitative, mixed methods research studies that explicitly and implicitly include COVID-19 vaccine hesitancy in their results, indicating outcomes of acceptance or not, performed with any population in Latin American and African countries, regardless of age group, gender, or other criteria of social differentiation.Publications such as comments, editorials, studies on COVID-19 vaccine development, reviews, studies that did not cover countries in Africa or Latin America, and studies that did not include findings on COVID-19 vaccine hesitancy in their results and discussions were not included.
Searches in the databases were performed in January 2022 using descriptors related to COVID-19, vaccine hesitancy, and countries in Latin America and/or Africa (Supplementary Material: https:// cadernos.ensp.fiocruz.br/static//arquivo/suppl-e00041423-en_8375.pdf).Search results were exported to the EndNote (https://endnote.com/)bibliographic reference manager and duplicate studies were excluded.After that, the main author read the titles and abstracts of all studies to exclude those that did not meet the eligibility criteria.In case of any doubt, a second reviewer performed the arbitration by reading the title and abstract, and if doubts persisted, the full study was read.
Three aspects guided the extraction of information in the study reading stage, which were inserted into a Microsoft Excel (https://products.office.com)spreadsheet: (1) General characterization of the studies, including authors, year of publication, journal, country of affiliation, institution of the corresponding author, method aspects (country where the investigation was conducted, study population, objective, and design); (2) Study results regarding acceptance hesitancy, and related reasons; (3) Information of the reference (or not) to the concepts and method references of the WHO SAGE and the context-specific particularities of the Global South reported in the studies.Then, an interpretative analysis of these findings was conducted using the critical perspective in global health regarding vaccine hesitancy 18,21 .

General characteristics of the studies
After the stages of search and study selection, 94 studies were included in this review.Figure 1 shows a flowchart of these stages.
Regarding the general characteristics of the studies, considering database search was performed in January 2022, most studies were published in 2021 (89), and conducted in African countries (62)  followed by Latin American countries (20).Multicenter studies (12) were the most predominant design.Regarding the countries of affiliation, in African studies, most common countries producing university studies were Ethiopia (14), Nigeria (14), Ghana (7), South Africa (6), and Egypt (6).In Latin America, the Brazilian institutions were more commonly found (6).However, some publications had corresponding authors linked with institutions in the United Arab Emirates (3) and France (2).Multicenter studies had corresponding authors affiliated with institutions from countries in the Global North -the United States (6), Belgium (2), and the United Kingdom (2).Box 1 shows the studies selected for this review.
Regarding the study method, most were quantitative studies (85), followed by mixed methods studies (7) and, finally, qualitative studies (2).As for the study population, most were general population (45), followed by health professionals (24), university students (9), individuals with comorbidities (8), health students and professionals (2), university employees and students (1), parents and/or caregivers of children and/or adolescents (4), and population over 50 years old (1).

COVID-19 vaccine acceptance and hesitancy in a comparative perspective
As the results of studies according to acceptance, hesitancy, and related reasons, most studies presented data of COVID-19 vaccine acceptance (88).
A study conducted across the African continent found population acceptance of 63% 24 .In Nigeria, studies reported the highest acceptance of 88.5% 25 and the lowest acceptance of 22.7% 26 .In South Africa, studies reported acceptance ranging from 81.6% 27 to 55% 28 .In Egypt, the highest acceptance was 32.85% 29 and the lowest, 21% 30 .In Ethiopia, the highest acceptance was 97.9% 25 and the lowest, 45.5% 31 .In Ghana, acceptance ranged from 64.72% 32 to 35% 33 .In Libya, acceptance ranged from 79.6% to 41.2%, depending on the vaccine efficacy 34 .Mozambique reported 71.4% acceptance 35 .In Burkina Faso, acceptance was 79.6% 25 .In the Democratic Republic of the Congo, the highest and lowest acceptance rates were 59.4% and 32.9% 36 .In Somalia, acceptance was 76.8% 37 .In Uganda, depending on the vaccine efficacy, acceptance was 88.8% and 65.4% 36 .Acceptance in Benin was 48.4% and 22.6%, depending on the vaccine efficacy 36 .Malawi had acceptance of 61.7% and 44.4%, depending on the vaccine efficacy 36 .In Mali, it ranged from 74.5% to 45.5%, depending on the vaccine efficacy 36 .
In Latin American countries, the highest and lowest acceptance rates were 94.2% 36 and 66% 38 in Brazil.In Ecuador, vaccine acceptance ranged from 91% to 27%, depending on the vaccine efficacy 14 .In Chile, acceptance was 49% 39 , and in Colombia acceptance ranged from 71.56% to 57.23% 40 .In Peru, vaccine acceptance was 70.4% 41 , and 71.25% in Venezuela 42,43 .
In Latin American countries, the highest vaccine hesitancy rate of 26.1% 38 and the lowest 8.4% 40 were reported in Brazil.In Ecuador, hesitancy ranged from 73% to 9%, depending on the vaccine efficacy 14 .In Chile, 28% were hesitant 39 and 23% refused the vaccine 39 .Peru had 10.1% refusal and 19.5% hesitancy 41 .In Venezuela, vaccine hesitancy was 28.75% 43 .Figure 2 shows a map with the highest percentages of COVID-19 vaccine hesitancy reported in selected studies.

Particularities of vaccine hesitancy in the Global South
Although most studies are focused on quantitative data, some publications describe specificities in the Global South regarding vaccine hesitancy in social, cultural, political, and economic dimensions.
In the study conducted by Andrade 42,43 , religious factors influenced vaccine hesitancy in Venezuela, where belief in conspiracy theories has increased with the country's political instability.Also, non-religious participants were more willing to receive the COVID-19 vaccine than Catholic and Protestant participants, with Venezuelan Pentecostals as the most hesitant religious group regarding COVID-19 vaccines.
Regarding political factors, studies conducted in Brazil and Venezuela mentioned opposition to the vaccine of their respective presidents Jair Bolsonaro and Nicolás Maduro 42,43,47,48,49 .Maduro questioned the safety of the AstraZeneca vaccine, even refusing to buy it, and because his government was not recognized by many nations 42,43 .In Brazil, part of supporters of then President Jair Bolsonaro rejected the COVID-19 vaccine, based on Bolsonaro's speech in relation to the vaccine as an individual choice and the criticism to the Sinovac-CoronaVac vaccine, produced by a Chinese pharmaceutical company 47,48,49 .The negative perception of coping with COVID-19 and the political opposition to the Federal Government were associated with the intention to be vaccinated 49 , in addition to the political context of delay in the acquisition and availability of COVID-19 vaccines and political disputes between federal and state governments 47,49 .
The categories of race and ethnicity also influenced vaccine hesitancy -in Venezuela, marginalized ethnic minorities were more likely to present COVID-19 vaccine hesitancy 42,43 .In South Africa, the black population showed lower vaccine hesitancy (26%) 28 .
Cad. Saúde Pública 2023; 39(8):e00041423   24 ; Khiari et al. 117 Alvarado-Socarras et al. 101 Vaccine cost Adebisi et al. 44 ; Alle & Oumer 100 ; Anjorin et al. 24 ; Bongomin et al. 53 ; Dinga et al. 65 ; Harapan et al. 67 Freedom of choice Alle & Oumer 100 ; Mejri et al. 119 Cad.Saúde Pública 2023; 39(8):e00041423 Regarding differences in vaccine hesitancy between urban and rural areas, findings from studies conducted in Zambia, South Africa, the Democratic Republic of the Congo, and Ghana showed that vaccine hesitancy was higher in urban areas with more access to the Internet and, consequently, to social media and misinformation about COVID-19 vaccines when compared to rural areas 28,32,50,51 .In Nigeria, the population living in the south of the country was more likely to be vaccinated while the population in the north was more likely to refuse it 24 .Then, strategies to reduce vaccine hesitancy must consider regional aspects of each African territory 24 .In Latin America, the intention to be vaccinated in Peru and Brazil was lower in areas of greater social inequality 38,41 .
Some epidemiological studies revealed that women were more likely to hesitate to accept COVID-19 vaccine in African countries 24,25,28,32,36,37,52,53,54 due to possible access to misinformation, such as the rumor that COVID-19 vaccine could make a person sterile 37 .
In Africa, the history of resistance to vaccination and growing misinformation disseminated via social media by leaders and religious groups about vaccines in general, including COVID-19 vaccines, were addressed in some studies 32,36,51,55,56,57 .The lack of clear information about the disease and vaccines were factors that influenced hesitancy in Ethiopia and the Democratic Republic of the Congo -with public distrust in participating in COVID-19 vaccine tests in the Democratic Republic of the Congo 51,58 .Another factor that influenced vaccine hesitancy in African countries was the lower mortality from COVID-19 in these countries, due to the perception that the continent had a reduced risk of COVID-19, as in the case of Ghana and Uganda 36,59,60 .
Two studies conducted in Brazil obtained a low percentage of COVID-19 vaccine hesitancy and a higher percentage of acceptance among respondents 36,61 .According to these studies, the result is influenced by the high transmission and mortality rates of COVID-19 36,61 .However, another publication claims that hesitant participants did not understand or were not informed about the high risk of COVID-19 in Brazil 62 .
The third aspects of this analysis emphasized the influence of the WHO SAGE group as a reference for designing epidemiological studies on vaccine hesitancy.The report produced by the group 5,6 and the publication by Larson et al. 63 presents tools to measure and monitor vaccine hesitancy such as the Vaccine Hesitancy Scale (VHS).Despite this effort, most epidemiological studies (88) did not use references, method designs, and instruments developed by the WHO SAGE.
Regarding the term "vaccine hesitancy", 61 of the 94 studies mention it without referring to the WHO and 26 studies use the WHO definition in the introduction of the study, but do not discuss the results according to the WHO SAGE framework.One exception is the study by Anjorin et al. 24 , conducted across the African continent, and whose corresponding author is affiliated with a research institution in South Africa.It provided the definition of vaccine hesitancy and used the 3C model as a reference to discuss the results.According to this study, the perceived risk of SARS-CoV-2 is significantly related to vaccine hesitancy; therefore, the authors concluded the findings agree with the model of confidence, complacency, and convenience proposed by the WHO SAGE 24 .
Among the studies that used the scale or developed research instruments based on WHO SAGE publications (6), a study conducted in Ethiopia used a questionnaire to assess vaccine hesitancy of the participants according to the WHO definition 64 .The WHO Matrix of Vaccine Hesitancy Determinants (contextual, individual/group determinants, and specific issues about vaccine/vaccination) was used in three studies -one in Brazil 47 , one in Cameroon 65 , and one in Egypt 30 .Regarding the 5C questionnaire, a multicenter study conducted in Middle Eastern countries used an adapted version for the Arabic language and culture to investigate the psychological antecedents of COVID-19 vaccination 66 .A multicenter study in Asia, Africa, and South America used the VHS to measure the belief in the benefits of vaccination and the perceived risk of new vaccines 67 .All these studies had corresponding authors affiliated with institutions in the Global South.
Cad. Saúde Pública 2023; 39(8):e00041423 Discussion COVID-19 vaccine hesitancy can be an obstacle to reducing the effects of the pandemic.The findings of this review show that concern about possible adverse events, uncertainty about vaccine efficacy and safety, and lack of confidence in clinical trials for the development of COVID-19 vaccines were similar to other studies 16,17,68,69 .Considering the phenomenon of hesitancy is multidimensional, the main justifications for hesitancy involve factors that go beyond biomedical biases to include sociocultural aspects with dichotomies such as medical/scientific view vs. cultural/popular view and universality vs. singularity 70 .This scenario became even more complex with the advent of COVID-19, with the resurgence of movements of disbelief in science, dissemination of fake news about vaccines, ideological polarization, and socioeconomic vulnerability 9 .
The strong association between the political scenario and (non-)acceptance of vaccines is also reflected in COVID-19 vaccines.In this review, political instability, disbelief in the government and the health system, and the feeling of not having a voice or power in the face of structures such as the State itself, have a direct influence on the spread of conspiracy theories 71,72 .On the other hand, it is important to critically analyze the scenario in which these conspiracy theories were created, as many of them have concrete roots in the recent local history of these territories.
Underdeveloped countries were repeatedly used for tests with human beings, which today resulted in vaccine refusal due to the fear of being laboratory subjects 73,74 .The power relationship between the Global North and the Global South, expressed in a past of coloniality and violence still alive in the memory of colonized countries, is reflected in the rejection of practices that supposedly come from the North.Then vaccines are seen by different groups as population control strategies in underdeveloped countries, as "western malevolence", or as a method to extinguish undesirable groups 75,76,77,78 .Therefore, discussions that associate the low level of vaccine acceptance in Africa with the fact that Africa had lower COVID-19 mortality rates or more misinformation may lead to reductionisms 9 .
On the other hand, associating low percentages of vaccine hesitancy with countries that had many COVID-19 cases and deaths may also disregard local contexts.This review, for example, found that many studies highlighted high acceptance of vaccine in Brazil, establishing this association.However, Brazil is internationally recognized for its National Immunization Program, which has built a culture of collective immunization 79,80 .At the same time, like other Latin American countries -as seen in this review -the country had to handle political instability, mismanagement of the COVID-19 pandemic, denial speeches by the president of the republic, and well-grounded direct association between "being opposed to the government" and "intention to be vaccinated" 47,48,49 .
Likewise, as demonstrated in this review, some countries in the Global South still face sanctions from Global North countries, due to the non-recognition of their governments -such as Venezuela 42,43 .Then, the power relations are evident between the Global North and the Global South, requiring discussions on low vaccination coverage in these countries from a broad perspective, which does not reduce (non-)vaccination to vaccine hesitancy or lack of information 9,81 .
Finally, in both Latin America and Africa, religious factors were also relevant in the population's decision to be or not vaccinated.Religion is a driving factor for vaccine hesitancy in general in the Global South 82,83,84 , and this trend was also seen for COVID-19 vaccines 42,43,85 .Then, inserting religious leaders in vaccination campaigns can be beneficial for vaccine adherence 86,87,88 .
Another important aspect in this review is the relationship between the studies and the publications of the WHO SAGE working group.Although WHO SAGE has establishes a definition for vaccine hesitancy, this term has been used in different ways in studies and this lack of conceptual clarity can lead to mistaken interpretations and generate confusion among researchers 89,90,91 .Of note, the concept originally established for "vaccine hesitancy" has already been altered because of the resulting criticisms and reflections.In 2022, the BeSD working group proposed a new definition for vaccine hesitancy as a "motivational state of being conflicted about, or opposed to, getting vaccinated; includes intentions and willingness" 10

(p. VII).
Vaccine hesitancy can be used to explain concerns and questions about vaccination, the interval between the continuum between accepting and refusing all vaccines, used as a synonym for nonvaccination 89,90  studies with different population profiles, contexts, and explanatory factors, vaccine hesitancy can be considered a comprehensive category, and not an empirical concept 92 .
Regarding the use of method designs and research instruments based on WHO SAGE publications, only 6 of all 94 studies in this review used these instruments.However, it should be noted that this review was conducted in January 2022, i.e., before the release of BeSD working group document.Even so, considering that other tools issued by the WHO were well established and validated, such as the Matrix of Determinants and the 5C scale, it is interesting that few studies have used them.
In the perspective of the Global Health, initiatives for the formulation of "global" policies and documents, based on the perspective and expertise of Global North countries and constantly defended by the WHO to be replicated in different contexts, have been criticized 18,93 .Local specificities, for not allowing large-scale comparisons and implementation of policy and models and for requiring unique and adaptable responses, tend to be ignored 93 .Top-down "one-size-fits-all" initiatives do not take into account living conditions and characteristics of the communities where they will be applied 94 .Considering the above, the application of the vaccine hesitancy concept and instruments validated by the WHO may not be adequate to analyze issues of access to vaccines and cost in countries where vaccination is not universal.

Study limitations
The limitations of this scoping review are related to the methodological stages of this type of study.Although a comprehensive search strategy was adopted, some relevant studies may not have been selected, such as technical studies and studies published in French, considering this language is spoken in some African countries.This review did not analyze how each study addressed hesitancy and acceptance in the questions of surveys and scripts of qualitative studies.In addition, the selected studies were not evaluated in terms of evidence quality, as the objective was to map studies on COVID-19 vaccine hesitancy in African and Latin American countries.

Final considerations
The discussion about vaccine hesitancy and, more specifically, COVID-19 vaccine hesitancy, has been the subject of global discussion.The issues presented in this scoping review show that COVID-19 vaccine hesitancy in countries of the Global South is a complex phenomenon.
The use of instruments produced by the Global North can lead to a failure to understand the different social, cultural, and regional aspects involved in COVID-19 vaccine hesitancy, but these aspects are essential for further studies and implementation of health actions 9 .
This scoping review showed that vaccine acceptance and hesitancy rates significantly ranged in different locations, which also indicates that particularities of these locations must be considered as different reasons for vaccine hesitancy.Also, most studies selected in this review are quantitative/ epidemiological studies, which may also limit the understanding of vaccine hesitancy complexity in regional, local, and cultural aspects of African and Latin American countries.Then, qualitative studies in social sciences allow the analysis of thick description to understand the beliefs and attitudes that involve the phenomenon of COVID-19 vaccine hesitancy 70 .In this sense, and based on the understanding of the Global South particularities, effective responses should be developed to address each particularity.

Figure 2
Figure 2Highest percentages of COVID-19 vaccine hesitancy in studies in African and Latin American countries according to the nomenclatures used by the respective authors.
COVID-19 Vaccine Hesitancy among Healthcare Workers and Its Socio-Demographic Determinants in Abia State, Southeastern Nigeria: A Cross-(Umuahia, Nigeria) Vaccine Hesitancy and Religiosity in a Sample of University Students in Venezuela Andrade 103 2021 Venezuela College of Medicine, Ajman University (Ajman, United Arab Emirates) COVID-19 Vaccine Hesitancy, Conspiracist Beliefs, Paranoid Ideation and Perceived Ethnic Discrimination in a Sample of University Students in Venezuela 'Why Should I Take the COVID-19 Vaccine after Recovering from the Disease?' A Mixed-Methods Study of Correlates of COVID-19 Vaccine "They Have Produced a Vaccine, but We Doubt if COVID-19 Exists": Correlates of COVID-19 Vaccine Acceptability among Adults in Kano, Nigeria