COVID-19 vaccine acceptance among health care workers in Africa: A systematic review and meta-analysis.

INTRODUCTION: Coronavirus Disease (COVID-19) vaccine acceptance, and hesitancy amongst Health Care Workers (HCWs) on the African continent have been examined through observational studies. However, there are currently no comprehensive reviews among these cadre of population in Africa. Hence, we aimed to review the acceptance rate and possible reasons for COVID-19 vaccine non-acceptance/hesitancy amongst HCWs in Africa.
METHODS: We searched Medline/PubMed, Google Scholar, and Africa Journal Online from January, 2020 to September, 2021. The Newcastle-Ottawa Quality Assessment tool adapted for cross-sectional studies was used to assess the quality of the retrieved studies. DerSimonian and Laird random-effects model was used to pool the COVID-19 vaccine acceptance rate. Sub-group and sensitivity analyses were performed. Reasons for COVID-19 vaccine hesitancy were also systematically analyzed.
RESULTS: Twenty-one (21) studies were found to be eligible for review out of the 513 initial records. The estimated pooled COVID-19 vaccine acceptance rate was 46% [95% CI: 37%-54%]. The pooled estimated COVID-19 vaccine acceptance rate was 37% [95% CI: 27%-47%] in North Africa, 28% [95% CI: 20%-36%] in Central Africa, 48% [CI: 38%-58%] in West Africa, 49% [95% CI: 30%-69%] in East Africa, and 90% [CI: 85%-96%] in Southern Africa. The estimated pooled vaccine acceptance was 48% [95% CI:38%-57%] for healthcare workers, and 34% [95% CI:29%-39%] for the healthcare students. Major drivers and reasons were the side effects of the vaccine, vaccine's safety, efficacy and effectiveness, short duration of the clinical trials, COVID-19 infections, limited information, and social trust.
CONCLUSION: The data revealed generally low acceptance of the vaccine amongst HCWs across Africa. The side effects of the vaccine, vaccine's safety, efficacy and effectiveness, short duration of the clinical trials, COVID-19 infections, limited information, and social trust were the major reasons for COVID-19 hesitancy in Africa. The misconceptions and barriers to COVID-19 vaccine acceptance amongst HCWs must be addressed as soon as possible in the continent to boost COVID-19 vaccination rates in Africa.

Introduction

The current Coronavirus Disease (COVID-19) pandemic is a global public health emergency that offers significant challenges to health-care systems [1, 2]. ‘‘Coronaviruses are large, enveloped, positive-strand RNA viruses that can be categorized into genera; alpha, beta, delta and gamma, of which alpha and beta are known to infect humans” [3]. Human Corona Viruses (HCoVs) i.e. HCoV 229E, NL63, OC43 and HKU1 are endemic globally and account for 10%- 30% of upper respiratory tract infections in adults humans [3].

The current basic reproductive number (R0) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS COV-2) is estimated to be three and as a result the threshold of herd immunity for COVID-19 is roughly around 67 percent [4, 5]. This purport that after the population’s acquired immunity reaches 67 percent and above, COVID-19 infection rates will start to decline [6].

Individual and community initiatives such as enhanced hand cleanliness, physical distancing, and the personal protective equipment are currently being used to reduce disease transmission. However, with the world facing an economic downturn and an uncertain future, a COVID-19 vaccine is perhaps the best option for halting the epidemic [7, 8].

The SARS Cov-2 Development and Access Strategy established by Africa Center for Disease Control in 2020 aim to vaccinate at least 60% of African Population by 2022 to develop herd immunity [9]. Africa has received approximately 143 million doses in total as of September, 2021, but only 39 million people, or around 3% of the continent’s population, had been adequately vaccinated. In the United States, 52 percent of people are fully vaccinated, whereas in the European Union, 57 percent are [10]. The willingness of Health Care Workers (HCWs) to be vaccinated against COVID-19 acts as a valuable role model for the general public [11].

As the vaccine becomes more widely available in Africa, Sevidzem et al identified and evaluated some probable link to vaccination acceptability in Africa. The factors included vaccination deployment plans, religious practices, vaccine hesitation, proliferation of misinformation, HCW attitudes towards the vaccine, social effects, and supportive environment [12]. Vaccine aversion among the general public has a direct association to vaccine hesitancy among HCWs [13]. Thus, HCWs role in vaccine acceptability cannot be underestimated as a result of their modeling behavior [13].

A rapid systematic review of global vaccine acceptance among HCWs ranged from approximately 28% to 73% [6]. Similarly, a comprehensive review and meta-analysis of cross-sectional studies of health workers’ intentions to vaccinate against COVID-19 indicated a moderate acceptance rate [i.e., 51 percent]. The authors did admit, however, that the population studied were largely from economically developed countries, which limited the study’s generalizability [14]. Clearly, this cannot be extended to represent HCW intentions to vaccinate against COVID-19 in Africa.

COVID-19 vaccine acceptance, and hesitancy amongst HCWs on the African continent have been examined through observational studies [7, 15]. However, there are currently no comprehensive reviews among these cadre of population in Africa. Hence, we aimed to systematically review the acceptance rate and possible reasons for COVID-19 Vaccine non-acceptance/hesitancy amongst HCWs in Africa. The outcome would enable stakeholders [i.e., policy makers, researchers and government] package effective health promotion measures to boost COVID-19 vaccine uptake in Africa.

To determine the level of COVID-19 vaccine acceptance among HCWs in Africa.

To assess the drivers of COVID-19 vaccine non-acceptance/hesitancy among HCWs in Africa.

Methods

Protocol registration and best practice

The Center for Reviews and Dissemination standards were followed in preparing this systematic review and meta-analysis [16]. Also, the current review was conducted and reported according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) [17] [see S1 Table]. The protocol was registered at PROSPERO: [CRD42021275065].

HCWs, and health science students from Africa continent, were included. HCW was operationally defined as; Doctors, Nurses, Pharmacists, allied health professionals, paramedics, and Healthcare students [i.e., medical students, nurse students etc.].

Adults HCWs aged ≥18 years were included.

All primary studies such as longitudinal, cohort, case-control and cross-sectional studies reporting COVID-19 vaccine acceptance and hesitancy among HCWs in Africa were included in the current review.

Original observational studies published in English were included.

General population, other university students, and children were excluded.

Non-COVID-19 vaccine acceptance studies.

COVID-19 studies reporting animal studies, reviews, commentaries, letter to editors were excluded.

COVID-19 vaccine acceptance and hesitancy articles published in other language other than English were excluded

COVID-19 acceptability studies among HCWs outside the Africa continent [i.e., Asia, Europe, America, and Australia continents] were also excluded.

Outcome of interest

The outcome of interest was COVID-19 vaccine acceptance/and hesitancy rate among HCWs in Africa. In addition, the reasons for COVID-19 hesitancy were explored.

Information sources and search strategies

Medline/PubMed, Google Scholar, Africa Journal Online, and MedRxiv (preprint) were searched. The search was restricted to studies published between January,2020 to September, 2021. The search was limited to articles published in English. Reference lists of articles that met the inclusion and exclusion criteria were reviewed manually to identify additional studies.

Medical Sub-Heading (MeSH) terms and free text were used in the search approach. These terms were combined with the Boolean operators ‘OR’ and ‘AND’. The key terms included; COVID-19, Vaccine, Hesitancy, acceptance, Health care worker, Africa, Sub-Saharan Africa. The full search string is shown in S2 Table.

Data screening and selection

The data screening and selection involved the following; Two co-authors independently screened the titles and abstracts against the eligibility criteria. Full texts of the articles were then obtained. A disagreement was then resolved by consensus. To ensure that independent reviewers apply the selection criteria reliably, a screening guide was used [18].

Data extraction and management

Two co-authors extracted the data from the eligible published articles using a pre-tested and standardized excel spreadsheet. Data such as the author’s name, year of publication, country, survey period, study design, sample size, HCWs population, acceptance rate, and, reasons for COVID-19 acceptance/hesitancy rate were extracted. Mendeley was used to managed and remove duplicated articles.

Quality assessment and risk of bias

The Newcastle-Ottawa Quality Assessment tool adapted for cross-sectional studies [19] was used to assess the quality of the retrieved studies. It is graded on 10-point stars. This process was done by two independent reviewers and average was taken as a final score for that particular study. The Newcastle-Ottawa Quality Assessment tool contains three domains. Domain 1 evaluates the methodological quality of each study [5 stars], domain 2 assesses the comparability of the study [2 stars] and domain 3 evaluates the outcome measure and related statistical analysis [3 stars] [19]. Furthermore, the review rated the overall quality of the studies into three; [low risk of bias (7–10), moderate risk of bias (5–6), and high risk of bias (0–4)] [20].

Data synthesis

Extracted data was exported into Stata (version 16; Stata Cooperation, TX, USA) from Microsoft excel 2013 for all analyses. Due to the presence of heterogeneity [I2 = 96%, p≤0.001], a meta-analysis using the random effect model was used to pool the COVID-19 vaccine acceptance rate among the HCWs at 95% confidence interval and presented in a forest plot. The presence of heterogeneity among studies was quantified by estimating the variance using the I2 statistics [21]. The I2 takes values between 0 and 100%, and a value of 0% indicates absence of heterogeneity. I2 was interpreted based on Higgins and Thompson classification, percentages of 25%, 50% and 75% was considered as low, moderate and high heterogeneity, respectively [21]. A sub-group analysis was performed based on sub-region (West Africa vs. East Africa vs. Southern Africa vs. North Africa) and type of participants (Healthcare workers vs. Healthcare students). Leave one out sensitivity analysis was performed to examine the effects of a single study on the overall pooled estimate. Publication bias was checked by the funnel plot and Egger’s test. The drivers/factors for COVID-19 vaccine non-acceptance/hesitancy among HCWs in Africa were systematically reviewed. A factor/driver for COVID-19 vaccine non-acceptance/hesitancy was eligible if it had been assessed and data from at least two studies were available.

Results

The electronic search yielded 513 articles; 400 articles remained after the duplicate articles were deleted. After screening the abstracts and titles, 200 articles were removed [i.e., irrelevant to the study]. One hundred and seventy (170) were removed because they were unrelated to the current research. Thirty (30) full-text papers were evaluated for eligibility. Nine papers were removed from the final data synthesis, leaving only 21 articles. The results are displayed in Fig 1.

Fig 1

Preferred Reporting Items for Systematic Review and Meta-Analysis-Adapted flow showing the results of the search.

Characteristics of the studies

Out of the 21 studies included, 7 were conducted in North Africa, 6 in West Africa, 6 in East Africa and an article each from central and southern Africa. The sample size ranged from 182 to 2133, totaling 14132 participants. The participants were mainly doctors, nurses, medical laboratory scientists, pharmacists, and allied health staff. The first survey was performed in March-April 2020, and the most recent was conducted in March-June 2021. The studies were all cross sectional and published between 2020 and 2021. Majority of the included studies had low-moderate risk of bias [20/21]. The findings are summarized in Table 1.

Table 1

Characteristics of the studies [n = 14132].

Author and Year	Country	Participants	Survey period	Male (%)	Age/Years	Sample Size	Acceptance rate n (%)	Reasons for Vaccine Hesitancy	Quality assessment
Nzaji, 2020 [22]	DR Congo	Doctors, Nurses, Midwives, and Laboratory Technicians	March/April, 2020	50.9	40.31±11.67, Majority; 25–40 (63%)	613	27.7	Not stated	Low
Fares, 2021 [23]	Egypt	Doctors, Nurses, Pharmacists, Physiotherapists, and Dentists	Dec, 2020-Jan, 2021	18.7	Majority;17–35 (70.4%)	385	21	Lack of enough clinical trials, and Fear of vaccine’s side effects	Low
El-Sokkary, 2021 [24]	Egypt	Doctors, Dentists, Pharmacist, and others	Jan, 2021	22.4	NA	308	26	Severity of COVID-19 Vaccine safety	Moderate
Agyekum, 2021 [15]	Ghana	Doctors, Nurses/midwives, and Allied health	Jan/Feb, 2021	36.8	Majority; 30–39 (56.0%)	234	39.3	vaccine safety vaccine side effects Acquiring COVID-19 through vaccination	Moderate
Dula, 2021 [7]	Mozambique		March, 2021	NA	NA	566	86.6	Vaccine side effects Made to cause harm Vaccine not effective	Moderate
Adeniyi, 2021 [25]	South Africa	Doctors, Nurses, Pharmacists, Allied Health, Support staff	Nov/Dec, 2020	18.5	Majority; 26–55 (79.2%)	1308	90.1	Not stated	Low
Shehata, 2021 [26]	Egypt	Doctors	March/June, 2021	40.6	Majority: 31–40 (71.5%)	1268	24.3	Vaccine side effects Short duration of Clinical Trial Concerns about safety and efficacy	High
Saied,2021 [27]	Egypt	Healthcare Students	Jan, 2021	34.8	20.2±1.8	2133	34.9	Insufficient information about vaccine side effect Insufficient information about the vaccine Insufficient trust from vaccine source	Moderate
Kanyike, 2021 [28]	Uganda	Healthcare Students	March, 2021	62.8	Majority: <25 (61.2%)	600	37.3	Vaccine side effects Misinformation ineffectiveness	Low
Ngasa, 2021 [29]	Cameroon	Doctor, Nurse, laboratory technician, Pharmacist, Public health, student, Other	Not stated	51.8	29.1±6.6	371	45.4	Efficacy of the vaccine Short duration of clinical trials Adverse effects	Low
Aliae, 2021 [30]	Egypt	Doctor, Nurse, laboratory technician, Pharmacist, student, Other	Dec, 2020-Jan, 2021	34.9	Majority; 18–45 (55.0%)	496	45.9	Not stated	Moderate
Alle,2021 [31]	Ethiopia	Doctor, Anesthetists, Nurses, Midwives, Pharmacists, Laboratory Professional	Not stated	63.6	Majority; 18–25 (55.0%)	327	42.3	Not stated	Low
Guangul, 2021 [32]	Ethiopia	Physicians, health officers, nurses, Lab Technicians, Pharmacist, others	Not stated	69.3	Majority; 18–29 (58.2%)	668	72.2	Concerns about safety, Ineffective Acquiring COVID-19 through vaccination Side effects, Short duration of clinical trial	Low
Ahmed, 2021 [33]	Ethiopia	All Health professionals	Jan-March, 2021	70.2	Majority;30–39 (54.0%)	409	33.2	Not stated	Low
Annan, 2021 [34]	Ghana	Doctors	Not stated	49.2	Majority; 25–30 (83.0%)	305	66.9	Not stated	Low
Adejumo,2021 [35]	Nigeria	Doctors, Nurse, Lab scientist, pharmacist, Physiotherapist, others	Oct, 2020	64.3	40.0±6.0, Majority 18–40 (72.9%)	1470	55.5	Not stated	Low
Robinson,2021 [36]	Nigeria	All Health professionals	Dec, 2020-Jan, 2021	56.7	Majority; 30–49 (66.6%)	1094	48.8	Safety, Ineffectiveness Side effects Fear of the unknown	Moderate
Oriji, 2021 [37]	Nigeria	Nurses, Lab scientist, Pharmacist, others	April, 2021	25.3	Majority; <36 (47.8)	182	27.4	To see what will happen (fear) Short duration of Clinical trial Side effects Safety issues Lack of trust in government/manufacturer	Moderate
Khairy, 2021 [38]	Sudan	Doctors, Nurse, Lab scientist, pharmacist, public health, others	March- April 2021,	46.7	35.3±10.6	576	57	Not stated	Low
Zammit, 2021 [39]	Tunisia	Doctors, Nurses pharmacy, paramedic	Jan, 2021	26.6	37.4 ±9.5, Majority; <41 (66.1%)	493	48.1	Not stated	Low
Mudenda,2021 [40]	Zambia	Pharmacy student	April, 2021	50.3	Majority; 18–29 (81.2%)	326	24.5	Side effects Ineffectiveness Safety issues Short clinical trials	Moderate

Pooled COVID-19 vaccine acceptance rate among HCWs in Africa

The COVID-19 vaccination acceptance rate was calculated using data from twenty-one (21) studies in Africa. Based on the DerSimonian and Laird random-effects model, meta-analysis revealed a pooled COVID-19 acceptance rate of 46% [95% CI: 37%-54%] (Fig 2). However, there was significant variability among the studies [I2 = 96%, p≤0.001].

Fig 2

COVID -19 vaccine acceptance rate among HCWs in Africa.

Publication bias assessment

No evidence of publication bias was found after symmetrical inspection using the funnel plot (Fig 3) and Egger’s regression test (0.1654).

Fig 3

Assessment of publication bias.

Sub-group and sensitivity analysis for COVID-19 vaccine acceptance rate

Sub-group analysis

As shown in Table 2, sub-group analysis was based on sub-regions (i.e., North Africa vs. Central Africa, East Africa vs. West Africa). The pooled estimated COVID-19 acceptance rate was 37% [95% CI: 27%-47%] in North Africa, 28% [95% CI: 20%-36%] in Central Africa, 48% [CI: 38%-58%] in West Africa, 49% [95% CI: 30%-69%] in East Africa, and 90% [CI: 85%-96%] in Southern Africa.

Table 2

Pooled COVID-19 vaccine acceptance rate stratified by sub-region and type of participants.

Group	Number of datasets	Pooled estimate at 95%CI	I2 [p-value]
Sub-region
Central Africa	1	28% [95% CI: 20%-36%]	-
North Africa	7	37% [CI: 27%-47%]	92.47% [p≤0.001]
West Africa	6	48% [CI: 38%-58%]	87.31% [≤0.001]
South Africa	1	90% [CI: 85%-96%]	-
East Africa	6	49% [95% CI: 30%-69%]	96.50% [≤0.001]
Type of participants
Health workers	18	48% [95% CI: 38%-57%]	96.14% [≤0.001]
Health science student	3	34% [95% CI: 29%-39%]	37.13% [≤0.001]

CI = Confidence Interval

Similarly, further stratification by type of participants (health workers vs. health science students). The estimated pooled COVID-19 vaccine acceptance was 48% [95% CI: 38%-57%] for HCWs, and 34% [95% CI: 29%-39%] for the healthcare students [Table 3].

Table 3

Reasons for COVID-19 vaccine hesitancy among HCWs in Africa.

Reason	Number of studies	References
Side effects of the vaccine	10	[7, 15, 23, 26, 28, 29, 32, 36, 37, 40]
Vaccine’s safety	7	[15, 23, 24, 26, 36, 37, 40]
Efficacy and effectiveness	7	[7, 26, 28, 29, 32, 36, 40]
Short duration of the clinical trials	6	[23, 26, 29, 32, 37, 40]
COVID-19 infections	2	[15, 32]
Limited information	2	[27, 28]
Lack of Social trust	2	[27, 37]

Sensitivity analysis for COVID-19 acceptance rate

Leave one out sensitivity analysis was performed to re-estimate the pooled effect on outcome of the remaining studies on the pooled COVID-19 acceptance rate. The results revealed that, no single study had a signifcant impact on the overall result. The pooled acceptability rate of COVID-19 vaccine ranged from 43% [95% CI: 35%-52%] to 47% [95% CI: 38%-55%] (S3 Table).

Reasons for COVID-19 vaccine non-acceptance among HCWs in Africa

The current systematic review and meta-analysis identified 8 main reasons for COVID-19 vaccine hesitancy among HCWs in Africa. These includes: the side effects of the vaccine [7, 15, 23, 26, 28, 29, 32, 36, 37, 40] the vaccine’s safety [15, 23, 24, 26, 36, 37, 40], efficacy and effectiveness [7, 26, 28, 29, 32, 36, 40], short duration of the clinical trials [23, 26, 29, 32, 37, 40], COVID-19 infections [15, 32], limited information [27, 28], and lack of social trust [insufficient trust in the vaccine’s source, lack of trust from the manufacturers, lack of trust from governments] [27, 37]. The results are summarized in Table 3.

Discussion

The systematic review, and meta-analysis was carried out to ascertain the COVID-19 vaccine acceptance rate, and possible reasons for the vaccine’s hesitancy amongst HCWs in Africa. The data revealed generally low acceptance of the vaccine amongst HCWs across Africa, and considerable COVID-19 vaccine reluctance. The possible reasons for the vaccine’s hesitancy were: the side effects of the vaccine, concerns about the vaccine’s safety, efficacy and effectiveness, short duration of the clinical trials, COVID-19 infections, limited information, and social trust.

The overall acceptance rate for the COVID-19 vaccination was 46% [95% CI: 37%-54%]. This is comparable to a previous systematic review and meta-analysis from the western world 51% [14] and higher than a US observational based study of 36% [41]. However, our estimate is lower than prior observational studies conducted in China 86.2% [42], France 76.9% [43], Saudi Arabia 64.9% [44], Canada 80.9% [45], Germany 91.7% [46] and United Kingdom 59% [47]. Low confidence in the vaccine, invasion of media misinformation, conspiracy theories, infodemic, religious beliefs, and possibly past vaccine hesitancy in the continent could all be factors contributing to the low COVID-19 vaccination acceptance rate [48, 49].

The study also revealed an estimated COVID-19 vaccine acceptance rate of 34% [95% CI:29%-39%] by the healthcare students. The estimated value is lower than previous studies in Italy 91.9% [50], US 53% [51], and France 58% [52]. Complacency, exacerbated by low illness risk, and low mortality in the continent since the epidemic began, could be contributing factors in this group of participants [53].

Certain common impediments to the acceptance of the COVID-19 vaccine seemed to be shared by HCWs across the continent. These included, side effects of vaccines, vaccine safety, efficacy and effectiveness of the vaccines, short duration of the clinical trials, the possibility of contracting COVID-19 infection from vaccines, limited information on the vaccines, and lack of social trust (i.e., insufficient trust in the vaccine’s source, lack of trust from the manufacturers, lack of trust from governments). vaccine hesitancy is mostly induced by the dissemination of misleading information, primarily through social media platforms and with the assistance of anti-vaccination organizations [54]. Biswas and colleagues conducted a scoping review analysis of 35 studies and found that HCWs worldwide have a 22.5% COVID-19 acceptance rate on average. Their reasons for refusing the vaccination were identical to those revealed in this study [11].

In general, persuading individuals who are vaccine skeptics to change their beliefs is difficult, especially in a continent where there has been a history of vaccination resistance. Nevertheless, it’s preferable to concentrate on disseminating positive and factual vaccine information while also strengthening healthcare workers’ resistance to fraudulent information. Easy access and mandatory COVID-19 vaccination policies in Africa is a good way to promote COVID-19 immunization uptake. Encouragement of vaccine production within Africa, and comparison of these vaccines with others produced outside the continent, could build more confidence in the safety and efficacy of vaccines among health care workers in the continent. This would involve isolating local strains of the virus to be used in the production of vaccines and the conduction of clinical trials among locals. The outcome of this will be, more tailored interventions to the fight against the pandemic on the continent, and will bring the fight against COVID-19 nearer home. This will also help debunk unfavorable theories about the intents behind the production of vaccines. Finally, the onus is on governments and significant international stakeholders in the pandemic fight to utilize social media to educate the public, especially HCWs, on facts concerning vaccines in order to help debunk some claims made by conspiracy theorists.

This systematic review and meta-analysis have a number of limitations that should be acknowledged. First, the current review considered only English published papers and as a result some relevant articles maybe missed. Secondary, there was significant heterogeneity across the studies. Nevertheless, to the best of the authors’ knowledge, this is the first systematic review and meta-analysis on COVID-19 acceptance and hesitancy rate in Africa. The review used well-validated systematic review and meta-analysis models that are fully compliant with current international standards and recommendations. Sensitivity analyses were performed to determine the robustness of the estimates obtained from the meta-analysis.

Conclusion

The result of this review revealed generally low acceptance of the COVID-19 vaccine amongst HCWs across Africa. Major drivers and reasons were the side effects of the vaccine, vaccine’s safety, efficacy and effectiveness, short duration of the clinical trials, COVID-19 infections, limited information, and social trust. The willingness of HCWs to be vaccinated against COVID-19 acts as a valuable role model for the general public and hence, the misconceptions and barriers to COVID-19 vaccine acceptance amongst these cadre of professionals must be addressed as soon as possible in the continent.

PRISMA checklist.

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Search strategy for the databases.

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Leave one out sensitivity analysis.

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22 Dec 2021

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Reviewer #1: Thank you for your research and manuscript. The content of the manuscript is important and needed in today's context around the COVID-19 pandemic. I would suggest major changes for the manuscript regarding grammar, spelling and some broader points regarding the purpose of the research and implications implications of results. Please find below my detailed comments:

1. Grammar and spelling:

- I would recommend authors to review the grammar of the article. There are some sentences throughout the manuscript that are grammatically incorrect, the verb form does match the pronoun.

- There is also the use of pronouns that could be summarized differently, for example authors refer to MA and LA in the methods section, they could just refer to MA and LA as “two authors” or “two researchers.”

-COVID-19 should be capitalized. In many instances it is not capitalized, please correct.

2. Page 5, first paragraph:

I suggest authors to review the way they reference other studies. For example, on page 5, first paragraph; authors cite a study by Sevidzem Wirsty and colleagues. It is common to cite as “Sevidzem Wirsty et al.” I would also suggest to summarize information from other studies instead of adding the exact quote. For example in the same paragraph, the phrase “Vaccine hesitancy, attitude and uptake by health care workers….” In the same paragraph the sentence “Vaccine aversion among the general public has a direct association to vaccine hesitancy among HCWs” does not have a reference, please provide reference.

3. Please complete the protocol at PROSPERO. The protocol that is published does not match the one described in the submitted paper:

- Participants are different in the submitted manuscript and the PROSPERO protocol

4. In the section “Information Sources and search strategies” on page 8: Please include the exact dates of the search (e.g. from January 2020 to Month/year).

5. Figures and tables.

-The resolution of the figures is not high. I can see pixels in all figures, it would be desirable for the image to be clearer.

- All figures are named “Figure 1” please fix the numbers of the figures to match the text.

6. Comments in the discussion section:

- Page 16, 3rd paragraph: The authors claim the estimated value of acceptance rate they found is lower than those in Italy, US and France. I would suggest authors to write what the acceptance rates were in those country to have figures to compare to the African countries they included in the study.

- The manuscript could be improved by providing more information about the implications of the study regarding policy. The authors discuss policies such as easier access to vaccination and mandatory vaccination policies. They could provide information about what works for high vaccination acceptance in Africa, for example in Table 2, the acceptance of vaccination rate is 90%, significantly higher than other African countries. Authors could take the example of South Africa to discuss what works there versus other countries in Africa.

Reviewer #2: The paper is poorly written; specific issues are directly annotated to the pdf of the paper in the attached file. Moreover, the majority of the considered (statistical) approaches, such as the DerSimonian and Laird random-effects model (REM), the I^2 statistic, the funnel plot and the Egger test, are not adequately explained for non-expert readers. Instead, the leave-one-out meta-analysis is well-done enough.

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Reviewer #2: No

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Submitted filename: Specific Comments.pdf

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24 Jan 2022

Response to reviewers’ comments

I sincerely express my warmest greetings to you and your prestigious journal for your comments and feedback. I write on behalf of my co-authors to submit our reply to your astute experienced reviewers' insightful comments. The methodology used follows a point-by-point approach to responding to all comments. Please see below for our response.

Reviewer 1

Comment: Grammar and spelling:

I would recommend authors to review the grammar of the article. There are some sentences throughout the manuscript that are grammatically incorrect, the verb form does match the pronoun. There is also the use of pronouns that could be summarized differently, for example authors refer to MA and LA in the methods section, they could just refer to MA and LA as “two authors” or “two researchers. -COVID-19 should be capitalized. In many instances it is not capitalized, please correct.

Response: As recommended by the reviewer, the entire manuscript has been thoroughly read once again by all authors and a third independent editor to correct all grammatical errors which has improved the manuscript. Also, the authors have replaced the phrase ‘MA and LA’ with ‘’two authors’ ‘as suggested by the reviewer. Additionally, covid-19 is now capitalized

Comment: Page 5, first paragraph: I suggest authors to review the way they reference other studies. For example, on page 5, first paragraph; authors cite a study by Sevidzem Wirsty and colleagues. It is common to cite as “Sevidzem Wirsty et al.” I would also suggest to summarize information from other studies instead of adding the exact quote. For example, in the same paragraph, the phrase “Vaccine hesitancy, attitude and uptake by health care workers….” In the same paragraph the sentence “Vaccine aversion among the general public has a direct association to vaccine hesitancy among HCWs” does not have a reference, please provide reference.

Response: Authors have taken the reviewer’s comment into consideration and accordingly paraphrased and summarized the sentence. It now reads ‘’ Sevidzem et al identified and evaluated some probable link to vaccination acceptability in Africa. The factors included vaccination deployment plans, religious practices, vaccine hesitation, proliferation of misinformation, HCW attitudes towards the vaccine, social effects, and supportive environment (12)’. Additionally, ‘’Vaccine aversion among the general public has a direct association to vaccine hesitancy among HCWs’’ has now been referenced.

Comment: Please complete the protocol at PROSPERO. The protocol that is published does not match the one described in the submitted paper: Participants are different in the submitted manuscript and the PROSPERO protocol.

Response: Thanks for the comment. The PROSPERO protocol has been amended now.

comment: In the section “Information Sources and search strategies” on page 8: Please include the exact dates of the search (e.g., from January 2020 to Month/year).

Response: Thanks for the comment. The exact dates for the search have now been included i.e., January, 2020 September, 2021

comment: Figures and tables. The resolution of the figures is not high. I can see pixels in all figures, it would be desirable for the image to be clearer. All figures are named “Figure 1” please fix the numbers of the figures to match the text

Response; The authors thank the reviewer for these observations. The figures and table re-done for higher resolutions. All figures named ‘’Figure 1’’ were software and editorial issues. This will be rectified at the editorial level

comment: Comments in the discussion section: Page 16, 3rd paragraph: The authors claim the estimated value of acceptance rate they found is lower than those in Italy, US and France. I would suggest authors to write what the acceptance rates were in those country to have figures to compare to the African countries they included in the study.

Response: Authors have taken the reviewer’s comment into consideration and accordingly added the COVID-19 vaccine acceptance rate to those countries compared. The paragraph now reads’’ This is comparable to a previous systematic review and meta-analysis from the western world 51% (14) and higher than a US observational based study 36% (40). However, our estimate is lower than prior observational studies conducted in China 86.2% (41), France 76.9% (42), Saudi Arabia 64.9% (43), Canada 80.9% (44), Germany 91.7% (45) and United Kingdom 59% (46)’’……. The study also revealed an estimated COVID-19 vaccine acceptance rate of 34% [95% CI:29%-39%] by the healthcare students. The estimated value is lower than previous studies in Italy 91.9% (47), US 53% (48), and France 58% (49)

Comment: The manuscript could be improved by providing more information about the implications of the study regarding policy. The authors discuss policies such as easier access to vaccination and mandatory vaccination policies. They could provide information about what works for high vaccination acceptance in Africa, for example in Table 2, the acceptance of vaccination rate is 90%, significantly higher than other African countries. Authors could take the example of South Africa to discuss what works there versus other countries in Africa.

Response: Thanks for the comment. While there is no clear policy driving the high vaccination rate in south African on Policy implication, the authors have now discussed policy implication that could drive high vaccination acceptance in Africa, and probably other low- and middle-income countries and the global as a whole. it reads ‘’ it's preferable to concentrate on disseminating positive and factual vaccine information while also strengthening healthcare workers' resistance to fraudulent information. Easy access and mandatory COVID-19 vaccination policies in Africa is a good way to promote covid-19 immunization uptake. Encouragement of vaccine production within Africa, and comparison of these vaccines with others produced outside the continent, could build more confidence in the safety and efficacy of vaccines among health care workers in the continent. This would involve isolating local strains of the virus to be used in the production of vaccines and the conduction of clinical trials among locals. The outcome of this will be, more tailored interventions to the fight against the pandemic on the continent and will bring the fight against COVID-19 nearer home. This will also help debunk unfavorable theories about the intents behind the production of vaccines. Finally, the onus is on governments and significant international stakeholders in the pandemic fight to utilize social media to educate the public, especially HCWs, on facts concerning vaccines in order to help debunk some claims made by conspiracy theorist

Reviewer 2:

Comment: The paper is poorly written; specific issues are directly annotated to the pdf of the paper in the attached file. Moreover, the majority of the considered (statistical) approaches, such as the DerSimonian and Laird random-effects model (REM), the I^2 statistic, the funnel plot and the Egger test, are not adequately explained for non-expert readers. Instead, the leave-one-out meta-analysis is well-done enough.

Response: The authors would like to thank the reviewer for the annotated corrections. The grammatical errors, spacing, referencing, others have been duly corrected as highlighted in the current manuscript. Additionally, the considered statistical approaches have further been explained. It reads ‘’ Due to the presence of heterogeneity [ I2=96%, p≤0.001], a meta-analysis using the random effect model was used to pooled the vaccine acceptance rate among the HCWs at 95% confidence interval and presented in a forest plot. The presence of heterogeneity among studies was quantified by estimating the variance using the I2 statistics (21). The I2 takes values between 0 and 100%, and a value of 0% indicates absence of heterogeneity. I2 was interpreted based on Higgins and Thompson classification, percentages of 25%, 50% and 75% was considered as low, moderate and high heterogeneity, respectively’’

Submitted filename: Response to reviewers.docx

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15 Mar 2022

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Shahzad Aslam, Ph.D.,M.Phil., Pharm-D

Academic Editor

PLOS ONE

Additional Editor Comments:

Please check the language of the manuscript and request proofreading the paper.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I thank the authors for their efforts in answering to comments. Some comments were partially addressed. For example, authors have not edited the word COVID throughout the manuscript (either in upper or lower case), some sentences still include grammatical mistakes throughout the manuscript. Re-reviewing the manuscript, I also realized that the inclusion and exclusion criteria for the manuscripts included in the review is poorly detailed.

Overall, I consider the research and results very important, but the manuscript lacks clarity in detailing methods and results and in other sections of the manuscript. The manuscript can improve enormously with a thorough review of grammar and reflection on the order of reporting methods and results.

Reviewer #2: (No Response)

**********

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Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

18 Mar 2022

Response to reviewers’ comments

I sincerely express my warmest greetings to you and your prestigious journal for your comments and feedback. I write on behalf of my co-authors to submit our reply to your astute experienced reviewers' insightful comments. The methodology used follows a point-by-point approach to responding to all comments. Please see below for our response.

Reviewer 1

Comments: I thank the authors for their efforts in answering to comments. Some comments were partially addressed. For example, authors have not edited the word COVID throughout the manuscript (either in upper or lower case), some sentences still include grammatical mistakes throughout the manuscript. Re-reviewing the manuscript, I also realized that the inclusion and exclusion criteria for the manuscripts included in the review is poorly detailed.

Overall, I consider the research and results very important, but the manuscript lacks clarity in detailing methods and results and in other sections of the manuscript. The manuscript can improve enormously with a thorough review of grammar and reflection on the order of reporting methods and results

Authors’ response: The authors would like to use this opportunity to thank the reviewer for these vital observations. Authors have taken the reviewer’s comment into consideration and accordingly edited the word COVID in upper case throughout the manuscript. Moreover, the entire manuscript has been thoroughly read once again by all authors and a third independent editor to correct all grammatical errors which addresses the grammatical concerns raised by the reviewer. Also, the inclusion and exclusion criteria sections has been reviewed. Finally, the order of reporting methods and results follow a standard guidelines as reported in other reviews.

Submitted filename: Response to reviewer.docx

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22 Apr 2022

26 Apr 2022

Response to reviewers’ comments

I sincerely express my warmest greetings to you and your prestigious journal for your comments and feedback. I write on behalf of my co-authors to submit our reply to your astute experienced reviewers' insightful comments. The methodology used follows a point-by-point approach to responding to all comments. Please see below for our response.

Reviewer 1

There are several points to address in the manuscript including grammatical changes, please see below:

Comments regarding Introduction:

Comment: In the Introduction, page 4, paragraph 3. Please correct the grammatical mistake from “…. with the world facing an economic downturn and the future uncertain,” to “…with the world facing an economic downturn and an uncertain future….”

Response: Thanks for the comment and suggestion. The grammatical error is now rectified as suggested.

Comments regarding Methods:

Comment: Authors list inclusion criteria for studies, the third criterion is “The total number of workers surveyed” but authors do not specify the total number that they considered appropriate for the inclusion criterion.

Response: Thanks for the comment. The third criterion is now deleted to prevent further ambiguity. It is very important to note that the removal of this criterion does not affect the included studies in this review in anyway.

Comment: In the section “Exclusion criteria”, authors mention they exclude studies focused on the general population twice, in exclusion criterion 1 and in exclusion criterion 2, please remove redundancy.

Response: Thanks for the comment and observation. Redundancy is checked and removed as suggested.

Comment: In section “Information sources and search strategies”, please correct the sentence “Reference lists of articles that met the inclusion and exclusion were manually checked to identify extra studies….” to “Reference lists of articles that met the inclusion and exclusion criteria were reviewed manually to identify additional studies……”

Response: Thanks for the comment and suggestion. The sentence is now rectified as suggested.

Comment: The study has two objectives: to determine the level of COVID-19 vaccine acceptance and to assess the drivers of COVID-19 vaccine non-acceptance/hesitancy. However, authors do not specify how they systematically assessed drivers of COVID-19 vaccine non-acceptance.

Response: Thanks for the comment and the observation. We have made a statement to that effect under the data synthesis section. It reads ‘’ The drivers/factors for COVID-19 vaccine non-acceptance/hesitancy among HCWs in Africa were systematically reviewed. A factor/driver for COVID-19 vaccine non-acceptance/hesitancy was eligible if it had been assessed and data from at least two studies were available’’.

Comments regarding the Results section:

Comment: Additionally, authors should clarify what is social trust, how is social trust defined in the studies they reviewed. Reasons for hesitancy are pretty clear (e.g. safety, effectiveness, duration of clinical trials), except for the concept of social trust. Please clarify in results and discussion.

Response: Thanks for the comment. Concept of social trust is now defined and clarified in the results and discussion. It’s defined as ‘’ insufficient trust in the vaccine’s source, lack of trust from the manufacturers, lack of trust from governments’’.

comment: In the results section, a subtitle needs to be changed from “Characteristics of included study” to “Characteristics of the studies”.

Response: Thanks for the comment and suggestion. The subtitle is now rectified as suggested.

Comment: Table 2 needs a proper legend. The legend does not specify what the pooled estimate is. A table needs to be able to stand by itself, here the readers do not know if the pooled estimate is the percentage of acceptance or the percentage of hesitancy.

Response: Thanks for the comment. The Table 2 legend is rectified elaboratively.

Comments regarding the Discussion section:

Comment: In the discussion section, second paragraph, authors mention factors that contribute to vaccine hesitancy (media misinformation, conspiracy theories etc). Authors do not have a reference for these factors. Did they find these factors in the studies they analyzed? Please add reference or clarify.

Response: Thanks for the comment. The authors have referenced the statement appropriately.

Comment: In the discussion section, third paragraph, authors also make a conjecture about why healthcare students show low acceptance rates, but authors do not cite where this information comes from. Was this found in the studies they analyzed? Did they do a review of media articles to make these conjectures? Please add appropriate reference

Response: Thanks for the comment. The authors have referenced the statement appropriately.

Submitted filename: Response to reviewer.docx

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6 May 2022

COVID-19 Vaccine Acceptance among Health care workers in Africa: A Systematic Review and Meta-analysis

PONE-D-21-31691R3

Dear,

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Muhammad Shahzad Aslam, Ph.D.,M.Phil., Pharm-D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

10 May 2022

PONE-D-21-31691R3

COVID-19 vaccine acceptance among health care workers in Africa: A systematic review and meta-analysis

Dear Dr. Ackah:

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