literature review of immunisation

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• Published: 01 April 2021

Determinants of full childhood immunization among children aged 12–23 months in sub-Saharan Africa: a multilevel analysis using Demographic and Health Survey Data

• Setegn Muche Fenta   ORCID: orcid.org/0000-0003-4006-3455 1 ,
• Hailegebrael Birhan Biresaw 1 ,
• Kenaw Derebe Fentaw 1 &
• Shewayiref Geremew Gebremichael 1  

Tropical Medicine and Health volume  49 , Article number:  29 ( 2021 ) Cite this article

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Sub-Saharan Africa is one of the highest under-five mortality and low childhood immunization region in the world. Children in Sub-Saharan Africa are 15 times more likely to die than children from high-income countries. In sub-Saharan Africa, more than half of under-five deaths are preventable through immunization. Therefore, this study aimed to identify the determinant factors of full childhood immunization among children aged 12–23 months in sub-Saharan Africa.

Data for the study was drawn from the Demographic and Health Survey of nine sub-Saharan African countries. A total of 21,448 children were included. The two-level mixed-effects logistic regression model was used to identify the individual and community-level factors associated with full childhood immunization

The prevalence of full childhood immunization coverage in sub-Saharan Africa countries was 59.40% (95% CI: 58.70, 60.02). The multilevel logistic regression model revealed that secondary and above maternal education (AOR = 1.38; 95% CI: 1.25, 1.53), health facility delivery (AOR = 1.51; 95% CI: 1.41, 1.63), fathers secondary education and above (AOR = 1.28, 95% CI: 1.11, 1.48), four and above ANC visits (AOR = 2.01; 95% CI: 1.17, 2.30), PNC visit(AOR = 1.55; 95% CI: 1.46, 1.65), rich wealth index (AOR = 1.26; 95% CI: 1.18, 1.40), media exposure (AOR = 1.11; 95% CI: 1.04, 1.18), and distance to health facility is not a big problem (AOR = 1.42; 95% CI: 1.28, 1.47) were significantly associated with full childhood immunization.

The full childhood immunization coverage in sub-Saharan Africa was poor with high inequalities. There is a significant variation between SSA countries in full childhood immunization. Therefore, public health programs targeting uneducated mothers and fathers, rural mothers, poor households, and those who have not used maternal health care services to promote full childhood immunization to improve child health. By enhancing institutional delivery, antenatal care visits and maternal tetanus immunization, the government and other stakeholders should work properly to increase child immunization coverage. Furthermore, policies and programs aimed at addressing cluster variations in childhood immunization need to be formulated and their implementation must be strongly pursued.

In 2019, 5.2 million children died, and about 14,000 children still die every day worldwide. Children continue to experience widespread geographic inequalities in their chances of survival. Sub-Saharan Africa is still the region with the highest child mortality rate in the world. The region had an average child mortality rate of 76 deaths per 1000 live births in 2019. Over 80% of the 5.2 million child deaths occurred in sub-Saharan Africa and Central and Southern Asia. More than half of these deaths have occurred in sub-Saharan Africa. Three of the five countries (Ethiopia, Nigeria, and the Democratic Republic of Congo) in which half of the world’s child deaths have occurred are in sub-Saharan Africa [ 1 , 2 , 3 ].

Immunization is one of the most cost-effective measures in public health to reduced child morbidity and mortality worldwide [ 4 ]. An extended program on immunization (EPI) was introduced by the World Health Organization (WHO) in 1974 to develop and expand immunization programs worldwide to reduce child mortality [ 5 ]. The rate of under-five deaths reduced significantly from 12.6 million in 1990 to 5.3 million in 2018, following the implementation of the EPI program. Sub-Saharan Africa remains the region with the highest child and under-five mortality in the world and this may be closely related to taking vaccines [ 2 , 6 ].

Every year, a vaccine prevents an estimated 2.5 million deaths among children under five ages. In 2018, about 116 million (86%) infants received vaccines globally to protect them against polio, diphtheria, tetanus, pertussis, and measles [ 7 ]. Despite this success, more than 1.5 million people worldwide die of vaccine-preventable diseases each year. In 2019, 19.4 million infants did not receive basic vaccines, 60% of who live in Angola, Brazil, Congo, Ethiopia, India, Indonesia, Nigeria, Pakistan, Philippines, and Vietnam [ 7 ]. About 3 million children die from infectious diseases every year in the African region. While many of these deaths could be prevented by prompt immunization, an estimated 20% of children in the country do not receive the vaccinations they need to defend against vaccine-preventable diseases [ 8 , 9 ]. Besides, more children are vulnerable to vaccine-preventable diseases when a high percentage of children in the African region do not receive vaccines on time [ 9 , 10 ]. One in five African children will be without lifesaving vaccines in 2016 [ 11 ].

Previous studies conducted in various sub-Saharan African countries to identify factors related to full childhood immunization have been institutional-based and to consider only individual factors [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Nevertheless, childhood vaccination may be impacted by community-level factors such as media exposure [ 19 , 20 ], distance to health facilities [ 21 , 22 ], residence [ 23 ], country [ 24 ], and cluster (enumeration area) [ 24 ]. Besides, the above studies did not use a multi-country method to identify factors associated with full childhood immunization based on the pooled Demographic and Health Survey (DHS) data. Furthermore, the application of a conventional logistic regression analysis approach to analyzing data in a hierarchical design (i.e., children nested within communities) undermines the assumptions of independence of regression. This study used a multi-level logistic regression analysis to address these gaps and further estimate the major effect of individual and community-level factors in sub-Saharan Africa [ 25 , 26 ]. Therefore, this study aimed to identify the determinants factors of full childhood immunization among children aged 12–23 months in sub-Saharan Africa at the individual and community levels.

Data source

The data used in this study were obtained from the Demographic and Health Survey (DHS) of nine Sub-Saharan-African countries (Ethiopia, Ghana, Democrat Republic of Congo, Senegal, Rwanda, Malawi, Tanzania, Namibia, and Zambia). Countries have been selected on the basis of their related economic growth, contiguity, and availability of data. The DHS collects using similar standard protocol from most of the low- and middle-income countries to facilitate the comparability among countries. It covers a wide range of topics like family planning, maternal, and child health, fertility, gender, malaria, HIV/AIDS, and nutrition. Sample selection in the surveys involved a two-stage stratified sampling method. Each country was divided into clusters. In the first stage, enumeration areas (EAs) were selected in each cluster and a household listing exercise was conducted in all selected enumeration areas. The list of households was used as a basis for household selection. In the second stage, households were selected from each enumeration area. In this study, we used the “latest” or most recent surveys conducted since 2013-2017, and the data used for analysis was taken by pooling the DHS data of the nine countries. The pooled DHS data include 21,148 children aged 12-23 months (Table 1 ).

Outcome variable

Full immunization for children aged 12–23 months was the outcome variable of this study. According to the WHO definition [ 27 , 28 , 29 ], full immunization was defined as having received all eight EPI-recommended doses of vaccine (one dose of Bacille Calmette-Guerin (BCG), three doses of DPT and three doses of polio, and one dose of measles).

Independent variables

The potential variables associated with full childhood immunization were categorized as individual- and community-level variables. These variables have been selected based on different works of literature [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The individual-level variables include the age of mothers, wealth index, mothers employment status, maternal education level, father education level, number of living children, ANC visits during pregnancy, place of delivery, sex of household head, and PNC visit. Besides, residence, distance to the health facility, exposure to mass media, cluster (enumeration area), and country were considered as a community-level variable.

Statistical analysis

The data were weighted using sampling weight (v005), primary sampling unit (v023), and strata (v021) after extracting data using SPSS statistical software version 20 to draw relevant inferences. The data were analyzed using R statistical software version 4.0. Descriptive statistics including percents, bar charts, and frequency tables were used to describe the study respondents. In the DHS data, children and women were nested within a cluster; they may share similar characteristics within the cluster. Since the data had a hierarchical structure, and this violates the independence of observations and equal variance assumption of the traditional logistic regression model. This means that the heterogeneity between clusters needs to be taken into account by the use of advanced models. The two-level mixed-effects logistic regression model was used to identify the individual and community-level factors associated with full childhood immunization. Four consecutive models were fitted in our study. The first is the null model (model I), appropriate for detecting the existence of a possible contextual effect which is fitted without any explanatory variable. The second model fitted by including only individual-level variables (model II), the third model with community-level variables (model III), and the last model (model IV) fitted by including both individual and community-level variables.

The result of the fixed effect reported in terms of adjusted odds ratio with a 95% confidence interval (CI). All variables with p values ≤ 0.05 have been considered statistically significant. The measures of variation (random-effects) were presented using intra-cluster correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV). ICC is a measure of within-cluster variation, the variation between individuals within the same cluster, and it was calculated using the formula: \( ICC=\frac{V_A}{V_A+\raisebox{1ex}{${\pi}^2$}\!\left/ \!\raisebox{-1ex}{$3$}\right.}=\frac{V_A}{V_A+3.29} \) , where V A is the estimated variance in each model [ 30 ]. The total variation attributed to an individual or/and community-level factors at each model was measured by the proportional change in variance (PCV), which was calculated as: \( \mathrm{PCV}=\frac{V_A-{V}_B}{V_A} \) , where V A = variance of the initial model, and V B = variance of the model with more terms [ 30 ]. The MOR is the median odds ratio between the individual of higher propensity and the individual of lower propensity when comparing two individuals from two different randomly chosen clusters and it measures the unexplained cluster heterogeneity, the variation between clusters by comparing two persons from two randomly chosen different clusters. It was computed using the formula:

where V A is the cluster level variance. The MOR measure is always greater than or equal to 1. If the MOR is 1, there is no variation between clusters [ 30 , 31 , 32 , 33 ]. Multicollinearity was tested using the variance inflation factor (VIF) test, suggesting that there was no multicollinearity since all variables had VIF<5 and a tolerance greater than 0.1.

Model comparison

Deviance information criteria (DIC), Akaike’s information criterion (AIC), and Bayesian’s information criterion (BIC) were used to compare the candidate model. The model with the minimum value of the information criterion will be selected as the best model of the analysis [ 34 ].

The pooled prevalence of full immunization coverage

The pooled prevalence of full childhood immunization coverage in the nine SSA countries was 59.40% (95% CI: 58.70, 60.02). Ghana (77.2%), Malawi (77.2%), and Tanzania (74.8%) were the countries with the highest proportions of full immunization coverage. Rwanda (39%), Congo (40.7%), and Ethiopia (48.6%) were the lowest proportions of full immunization coverage (Fig. 1 ).

Prevalence of full immunization in sub-Saharan African countries

Specific immunization coverage in sub-Saharan African countries

The coverage of BCG vaccination in sub-Saharan African countries was nearly three-thirds. The prevalence of polio 1 immunization in sub-Saharan Africa was more than 85%. In contrast, the least coverage of immunization offered to children in the region was measles with approximately 70%. The coverage of vaccinations delivered in the area and nine countries from the chart can be seen for more clarification (Fig. 2 ).

Vaccination specific immunization coverage among children aged 12-23 months in sub-Saharan African countries

Socio-demographic characteristics of respondents

The majority 15,615 (72.8%) of children were born in a rural area and 15,369 (71.7%) of mothers were married. More than three-fourths 16,706 (77.9%) of children were born at health institutions and about 2743 (12.8%) of women did not have visits during pregnancy. One-fourths (25.3%) of mothers were not formally educated and one-thirds (78.1%) of mothers were housewives. Around half 10,344 (48.2%) of children were born from low economic status households and 8440 (39.4%) were from mothers who had PNC checkups. Furthermore, the chi-square test of association showed that maternal education, maternal occupation, maternal age, marital status, father education, sex of household head, media exposure, distance to health facilities, number of ANC visits, postnatal care, place of residence, place of delivery, number of living children, wealth index, and country were significantly correlated with full childhood immunization (Table 2 ).

Factors associated with full immunization in sub-Saharan Africa

The results of the multilevel logistic regressions were summarized in Table 3 . The model with smaller deviance and the largest likelihood (model IV) was the best fit; the data and the interpretation of the fixed effects were based on this model. Maternal education, maternal occupation, maternal age, marital status, father education, sex of household head, media exposure, distance to health facilities, number of ANC visits, postnatal care, place of residence, place of delivery, number of living children, wealth index, and country were significantly associated with full childhood immunization in the sub-Saharan African countries. The odds of being fully immunized among children whose mother attained secondary school and above were 1.38 (AOR = 1.38; 95% CI: 1.25, 1.53) times higher than children whose mother had no education. Children whose mothers’ age 35–49 years were 0.64 (AOR = 0.64; 95% CI: 0.55, 0.74) times lower odds of being fully immunized than those children whose mothers age 15–19 years. Married mothers were 1.41(AOR = 1.41; 95% CI: 1.27, 1.56) times higher likelihood of fully immunizing their children than living alone mothers. Mothers who had four and above ANC visit during pregnancy were 2.01 (AOR = 2.01; 95% CI: 1.17, 2.30) times higher odds of fully immunizing their children than mother who did not have ANC visit during pregnancy. Children from rich households were 1.26 (AOR = 1.26; 95% CI: 1.18, 1.40) times higher probability of fully immunized compared to children in the poor household. A mother who had a PNC visit was 1.55 (AOR = 1.55; 95% CI: 1.46, 1.65) times more likely to have fully immunizing their child compared to a mother who did not have a PNC visit. Children born at a health facility were 1.51 (AOR = 1.51; 95% CI: 1.41, 1.63) times higher odds of being fully immunized than those children born at home. Children born to father who attained secondary education and above were 1.28 (AOR = 1.28, 95% CI: 1.11, 1.48) times higher likelihood of fully immunized than children whose father did not have formal education. Employed mothers were 0.85 (AOR =0.85, 95% CI: 0.80, 0.91) times higher likelihood of fully immunizing their children than those employed women. Children who live in the rural areas were 0.79 (AOR = 0.79; 95% CI: 0.70, 0.89) times lower likelihood of fully immunized compared to children living in the urban areas. The odds of being fully immunized were increased by 42% (AOR = 1.42; 95% CI: 1.28, 1.47) in children living in areas where the distance to a health facility is not a big problem compared to children living in areas where the distance to a health facility is a big problem. Children born to mothers who have media exposure were 1.11 (AOR = 1.11; 95% CI: 1.04, 1.18) times higher likelihood of fully immunizing their children than children born to mothers who did not have media exposure. Children living in Ethiopia (AOR = 1.40; 95% CI: 1.28, 1.62), Ghana (AOR = 5.04; 95% CI: 4.30, 5.90), Malawi (AOR = 5.11; 95% CI: 4.58, 5.71), Namibia (AOR = 3.78; 95% CI: 3.21, 4.44), Rwanda (AOR = 3.78; 95% CI: 3.37, 4.25), Tanzania (AOR = 4.27; 95% CI: 3.75, 4.86), and Zambia (AOR = 3.32; 95% CI: 2.97, 3.71) were more likely to be fully immunized relative to children in the Democratic Republic of Congo. Moreover, children living in Senegal were 0.86 (AOR = 0.86, 95% CI: 0.78, 0.94) times lower odds of full immunization compared to children in the Democratic Republic of Congo (Table 3 ).

Measures of variation (random-effects)

The result of the random effect model was given in Table 4 . The finding indicated that there was a significant variation in the full childhood immunization across the clusters. The intra-class correlation coefficients of the null model showed that 29.40% of the variation in fully childhood immunization was related to community-level factors. After adding individual-level and community-level factors, there is a statistically significant variation in full childhood immunization across communities or clusters. About 71.61% of the full childhood immunization in communities was accounted for in the full model. The MOR for full immunization was 3.04 in the null model which revealed that there was variation between communities (clustering) (3.04 times higher than the reference (MOR = 1)). The unexplained community variation in full immunization was decreased to a MOR of 1.81 when both individual and community factors were added to the model. This showed that in the full model the effects of clustering are still statistically significant when we considered both individual and community factors (Table 2 ).

The full childhood vaccination coverage among 12–35 month children in Sub-Saharan Africa was 59.4%. It was low as compared to the two South Asian countries Bangladesh and Nepal 85% [ 35 ]. The potential explanation for these discrepancies may be due to the presence of health system infrastructure, variations of policies against immunization services, variability in the awareness of immunization services, and socio-cultural differences across countries.

The multilevel multivariable logistic regression model revealed that maternal education, maternal occupation, maternal age, marital status, father education, sex of household head, media exposure, distance to health facilities, number of ANC visits, postnatal care, place of residence, place of delivery, number of living children, wealth index, and country were significantly associated with full childhood immunization in the sub-Saharan African countries.

The study also revealed that maternal education was a significant predictor of full childhood immunization. Educated mothers were more likely to fully immunize their children than uneducated mothers. This is in line with the studies carried out in Ghana [ 12 ], Ethiopia [ 15 , 19 , 21 ], Somalia [ 22 ], the Democratic Republic of Congo [ 36 ], Pakistan [ 37 ], and Zimbabwe [ 38 ]. Likewise, fathers who have attended primary education and higher were more likely to fully vaccinate their children than fathers who did not attend formal education. It was supported by studies reported in Pakistan [ 37 ] and Somalia [ 39 ]. This may be attributed to the fact that educated parents have a greater understanding of the value of childhood immunization and child health than uneducated parents.

Compared to children living in urban areas, children living in rural areas were less likely to be fully immunized. This result is consistent with studies conducted in Ghana [ 12 ], Ethiopia [ 15 , 19 ], and Afghanistan [ 40 ]. Their possible justification might that there is a low level of schooling, low wealth index, long distance to health facilities, and lack of knowledge about childhood immunization among parents in rural areas [ 23 ].

Mothers born at the health facilities were more likely to fully vaccinate their children compared to mothers who were born at home. This finding is supported by a study done in Ethiopia [ 15 , 19 ], Somalia [ 22 ], the Democratic Republic of Congo [ 36 ], Zimbabwe [ 38 ], Indonesia [ 41 ], and Senegal [ 42 ]. The possible justification might be due to a mother who delivered in a health facility is more likely to obtain training on the value of immunization from health professionals. Children born to mothers who attended antenatal care during pregnancy were more likely to be fully immunized. This result is in line with studies done in Ethiopia [ 15 , 19 ], Democratic Republic of Congo [ 36 ], Pakistan [ 37 ], Zimbabwe [ 38 ], Indonesia [ 41 ], Senegal [ 42 ], and India [ 43 ]. Compared with those living alone mothers, the probability of fully vaccinated children among married mothers was higher. This was consistent with studies in rural Somalia [ 39 ]. Relative to children from a poor household, the probability of full childhood immunization among children from the medium and rich household was higher. The previous studies also showed that children with a higher wealth index were more likely to be fully immunized [ 15 , 21 , 36 , 37 , 41 ]. This might be due to the indirect cost needed for travel to health facilities or time spent away from income-generating activity to make it difficult for the poorest households to avail themselves of services that exist in the community [ 20 ].

Distance to the health facilities was strongly associated with full childhood immunization. Relative to women who reported distance to a health facility was not a big problem, women who reported distance to the health facility was a big problem that decreases the likelihood of full childhood vaccination. This finding was supported by studies conducted in Ethiopia [ 21 ] and Somalia [ 22 ].

Media exposure is another factor associated with full childhood immunization. Among women who have to expose to the media, the likelihood of full childhood immunization was higher compared to their counterparts. This finding is in line with studies done in Ethiopia [ 19 , 20 ], Zimbabwe [ 38 ], East Africa [ 24 ], and sub-Saharan Africa (SSA) [ 44 ]. Compared to housewife mothers, the odds of full vaccination among women who had employed were low.

As the number of children in the family increases, the odds of full childhood immunization decreases significantly. This finding was supported by studies conducted in Pakistan [ 37 ]. This could be due to the reason that the number of children in a household increases, the family’s available resources may be exhausted, parents may be busy to complete their children’s needs.

Compared to a mother who did not have a PNC visit, a mother who had a PNC visit was more likely to have fully immunized her child. This finding was in line with those of other similar studies in Ethiopia [ 21 ], India [ 43 ], and the Democratic Republic of Congo [ 36 ]. This can be due to the fact that the mother who visited the PNC received guidance and support care on the benefits of child immunization from health professionals.

Relative to the male household head, the odds of full childhood immunization with the female household head were higher. This finding was supported by findings in Ethiopia [ 15 ]. The finding also showed that the probability of full childhood immunization decreases as the age of the mother increases. This finding is consistent with studies in Ethiopia [ 21 ]. This can be attributed to the fact that older mothers do not have enough time to vaccinate their children due to a greater number of children and a workload for caring for their children.

The full childhood immunization coverage in sub-Saharan Africa was poor with high inequalities. The finding found that there is a significant difference between SSA countries in full childhood immunization. Maternal education, maternal occupation, maternal age, marital status, father education, sex of household head, media exposure, distance to health facilities, number of ANC visits, postnatal care, place of residence, place of delivery, number of living children, wealth index, and country were significantly associated with full childhood immunization. Therefore, public health programs targeting uneducated mothers and fathers, rural mothers, poor households, and those who have not used maternal health care services to promote full childhood immunization to improve child health. By enhancing institutional delivery, antenatal care visits and maternal tetanus immunization, the government and other stakeholders should work properly to increase child immunization coverage. Furthermore, policies and programs aimed at addressing cluster variations in childhood immunization need to be formulated and their implementation must be strongly pursued.

Availability of data and materials

Data is available online and you can access it from www.measuredhs.com .

Abbreviations

Akaike’s information criterion

Antenatal care

Adjusted odds ratio

Confidence intervals

Deviance information criterion

Enumeration areas

Demographic and Health Survey

Intra-cluster correlation

Median odds ratio

Proportional change in variance

Postnatal care

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Fenta, S.M., Biresaw, H.B., Fentaw, K.D. et al. Determinants of full childhood immunization among children aged 12–23 months in sub-Saharan Africa: a multilevel analysis using Demographic and Health Survey Data. Trop Med Health 49 , 29 (2021). https://doi.org/10.1186/s41182-021-00319-x

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• Published: 22 August 2022

A systematic literature review to clarify the concept of vaccine hesitancy

• Daphne Bussink-Voorend   ORCID: orcid.org/0000-0002-9873-1404 1 ,
• Jeannine L. A. Hautvast 1 ,
• Lisa Vandeberg   ORCID: orcid.org/0000-0002-7229-2378 2 ,
• Olga Visser 1 &
• Marlies E. J. L. Hulscher   ORCID: orcid.org/0000-0002-2160-4810 3  

Nature Human Behaviour volume  6 ,  pages 1634–1648 ( 2022 ) Cite this article

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• Human behaviour
• Infectious diseases
• Preventive medicine

Vaccine hesitancy (VH) is considered a top-10 global health threat. The concept of VH has been described and applied inconsistently. This systematic review aims to clarify VH by analysing how it is operationalized. We searched PubMed, Embase and PsycINFO databases on 14 January 2022. We selected 422 studies containing operationalizations of VH for inclusion. One limitation is that studies of lower quality were not excluded. Our qualitative analysis reveals that VH is conceptualized as involving (1) cognitions or affect, (2) behaviour and (3) decision making. A wide variety of methods have been used to measure VH. Our findings indicate the varied and confusing use of the term VH, leading to an impracticable concept. We propose that VH should be defined as a state of indecisiveness regarding a vaccination decision.

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In 2019, vaccine hesitancy (VH) was named by the World Health Organization (WHO) as one of the top-10 threats to global health, following a five-fold global increase in measles, a disease that can be prevented by vaccination 1 , 2 . The largest increase was reported in the WHO regions covering Europe and the Americas 2 . The impact of these measles outbreaks is substantial, with rises in morbidity, mortality and costs 3 , 4 , 5 . The increasing incidence of measles and other vaccine-preventable diseases has been attributed to a failure to reach adequate immunization coverage rates 2 , 6 . In the European region, VH has been identified as the main barrier to vaccination coverage 7 , 8 . This is in contrast to other regions, such as sub-Saharan Africa, where immunization coverage rates are challenged by a combination of barriers, including access and availability 9 .

In the past decade, VH has become a key topic of research in various fields, following rises in vaccine-preventable diseases, the introduction of new vaccines, the spread of misinformation and lagging vaccination coverage 10 . Moreover, the COVID-19 pandemic has drawn further attention to the role of VH in limiting the uptake of vaccines and failure to achieve collective immunity 11 , 12 , 13 . This has led to the proliferation of scientific literature on VH in the public health, biomedical and social science research fields 10 .

In 2012, the WHO established a strategic advisory group of experts (SAGE) working group with the mandate of defining VH and suggesting how to monitor and address it. The working group proposed a broad definition, describing a VH continuum from acceptance to refusal of vaccines or as a delay in acceptance or refusal despite the availability of the vaccines. The working group described VH as “A complex behavioural phenomenon specific to vaccines, context, time, and place and influenced by factors of complacency, convenience, and confidence” 14 . This broad definition emphasizes variability by describing that VH may vary between types of vaccines and different contexts, may change over time or between different geographical locations and is influenced by various determinants.

The concept of VH has been described and applied in various ways. When definitions are broad and lack clarity, this can lead to the emergence of different concepts with overlapping domains, with various concepts being used interchangeably by some and recognized as distinct entities by others 15 . Additionally, lack of conceptual clarity can lead to inadequate operationalization and cause confusion among researchers 15 . This is problematic because when studies use similar terminology with a different meaning, their results are incomparable across subgroups, locations or contexts. A clear conceptualization is needed to develop meaningful measures allowing comparison of results 16 .

A lack of conceptual clarity is observed in the literature on VH, where VH is variously conceptualized as a psychological state and as different types of vaccination behaviour 17 , 18 . In addition, the terms ‘vaccine confidence’, ‘low uptake’ and ‘low intention to vaccinate’ are often equated with VH 19 , 20 . Confusion among researchers is then illustrated by inconsistencies in the applied definitions 21 , 22 . It has even been argued that VH is a catch-all category, aggregating many different concepts rather than being one measurable construct; and this is impeding progress in the research field 23 .

A good concept definition consists of characteristics, attributes or features that are unique to that concept and distinguish it from other closely related concepts 15 . Given the importance of VH for predicting and influencing individual vaccination decisions, it is important to explore the uses of VH and propose an optimal operationalization, distinguishing VH from other closely related concepts. Such clarification could enable a universally adopted definition and aid further research in this area.

The purpose of this systematic review was to provide an overview of how VH is operationalized in the literature in terms of conceptualizations, subpopulations and measurements. Following an assessment of the various conceptualizations, we differentiated the common themes, related concepts, research fields and vaccine types. The scope and structure of this systematic review is visualized in Fig. 1 . On the basis of an interpretation of these findings, we suggest a way forward by proposing a renewed definition for VH.

Aiming to give an overview of VH, we recognize three types of operationalizations: conceptualizations (blue), identification of subpopulations (orange) and measurements (green). Conceptualizations of VH are analysed at three levels: (1) common themes, (2) closely related concepts and (3) potential variation in conceptualization between research field and vaccine type. Each type of operationalization and its levels are discussed in separate sections.

Study selection and characteristics

The search strategy yielded 7,427 publications. After screening the titles and abstracts, 919 publications were selected for full-text screening. A total of 420 publications met the inclusion criteria. Seven additional studies were found through citation searching, two of which met the inclusion criteria, adding up to a total of 422 studies. Some studies met the criteria of more than one category, with 36 studies categorized under VH conceptualizations, 63 under VH subpopulations and 373 under VH measurements. The search process is summarized in the PRISMA flow chart (Fig. 2 ) 24 . The characteristics of included studies are described in more detail in Supplementary Table 1 .

Visualization of the process involving identification of records from databases, screening of records, assessing reports for eligibility, inclusion of eligible studies and exclusion of non-eligible reports with reasons for exclusion. The number of records or reports in each step of the process is shown in brackets.

The included studies cover a wide geographical distribution. The limited majority (54%) originated in high-income countries (HIC), mainly the United States, Canada, Italy, Australia and France. A smaller group (43%) originated in low- and middle-income countries (LMICs), primarily China, India and Turkey. The remaining studies (3%) originated in a combination of HIC and LMICs. The majority (60%) were published in 2021 and 2022.

The included studies approach VH in relation to various vaccine types: 51% pertaining to COVID-19, 29% to childhood, 4% to human papillomavirus, 4% to influenza and 2% to miscellaneous vaccines. Additionally, 11% of the studies concern vaccines in general. Various research fields are represented, including public health (43%), biomedical science (30%), paediatrics (15%) and social sciences (12%). Mixed methods appraisal tool (MMAT) scores were calculated for 88% of the included studies, while the others could not be assessed due to their study types. The majority (68%) scored 3 or higher, indicating that 60% of the quality criteria were met.

Vaccine hesitancy conceptualization

From the 36 studies on VH conceptualization, we extracted and analysed 304 excerpts. Supplementary Table 2 shows the extracted text excerpts for each study. Our thematic analysis revealed that 93 excerpts describe an overall characterization of VH. The majority of these (69%) describe the nature of VH as heterogenous 14 , 21 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , complex 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 29 , 33 , 35 , 38 , 39 , 40 , 41 , 42 , 43 or varied, depending on the type of vaccine and the context 14 , 18 , 20 , 21 , 23 , 27 , 28 , 30 , 33 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 .

VH is conceptualized in 208 excerpts. The thematic analysis revealed three predominant conceptualizations in 165 (79%) excerpts: cognitions or affect, behaviour and decision making. These three conceptualizations overlap in the majority of the studies and excerpts. Illustrative excerpts of each conceptualization are presented in Table 1 . The remaining 45 (22%) excerpts represent a fragmented group of conceptualizations, without emerging themes.

Vaccine hesitancy conceptualized as cognitions or affect

From all 36 studies 14 , 17 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 98 excerpts were extracted as conceptualizing VH in terms of cognitions or affect, including questioning, emotions or beliefs regarding vaccination. For this conceptualization, we rank-ordered the most frequently used descriptions of VH, including having or expressing concerns 21 , 25 , 26 , 27 , 29 , 30 , 34 , 35 , 36 , 40 , 42 , 43 , 46 , 51 , 53 , doubts 21 , 28 , 29 , 36 , 43 or questions 21 , 26 , 47 and being reluctant 23 , 27 , 29 , 32 , 36 , 38 , 45 , 49 , 53 , 54 or unsure 14 , 21 , 27 , 29 , 34 . Many authors describe VH as pertaining to beliefs 34 , 49 , attitudes 21 , 26 , 37 , 43 , 51 or both 23 , 29 , 30 , 55 . Furthermore, vaccine-hesitant individuals are described as ambivalent to vaccination or perceiving ambiguity in vaccine-related risks 21 , 36 , 50 , 53 .

Vaccine hesitancy conceptualized as behaviour

From 35 studies 14 , 17 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 94 excerpts were extracted as conceptualizing VH as a behaviour. The majority of the excerpts describe VH in terms of various behaviours 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 29 , 31 , 32 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 44 , 45 , 51 , as illustrated by the following example: “VH refers to a ‘delay’ in acceptance or ‘refusal’ of vaccines” 14 . Other excerpts describe VH as a range or continuum between the extreme ends of accepting all vaccines and refusing all vaccines 21 , 22 , 27 , 28 , 29 , 30 , 31 , 33 , 36 , 38 , 43 . In a minority of the excerpts, VH is described as a specific type of vaccination behaviour, including vaccinating as recommended (despite reluctance, concerns or feeling unsure) 26 , 46 , 47 , 49 , refusing vaccines 28 or delaying vaccines and choosing an alternative schedule 50 . Some studies explicitly state that VH should not be described as a vaccination behaviour 17 , 18 , 36 , 40 . Within articles, there were inconsistencies in the behavioural descriptions of VH 18 , 22 , 26 , 27 , 28 , 29 , 31 , 38 , 41 .

Vaccine hesitancy conceptualized as decision making

From 19 studies 18 , 21 , 23 , 26 , 27 , 30 , 31 , 32 , 36 , 37 , 38 , 40 , 42 , 44 , 45 , 50 , 52 , 53 , 30 excerpts were extracted as conceptualizing VH in terms of vaccine decision-making. Some authors adopt the term VH when describing individuals who are undecided, indecisive or under consideration, and not yet having made a final vaccine decision 21 , 23 , 26 , 31 , 32 , 45 , 50 . Vaccine-hesitant individuals are described as being in various states of indecision 23 , 31 , 32 , 37 or as seeking more information to make ‘the right decision’ about vaccination 21 , 53 . Moreover, some authors describe VH as an approach to 38 or a transient stage in the process of vaccine decision-making itself 21 , 23 , 37 .

Vaccine hesitancy and related concepts

VH is often described in relation to other concepts. We extracted 142 excerpts from 31 studies describing closely related concepts 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 50 , 51 , 52 , 53 . The three most common concepts are confidence or trust, complacency and convenience. Together, these are referred to as ‘the 3 Cs’ 14 and described in 69 of 142 (49%) excerpts. Most often, the 3 Cs are described as having a causal relationship with VH and as representing determinants 14 , 18 , 20 , 29 , 33 , 35 , 38 , 41 , 48 , 56 .

From 25 studies, 46 excerpts were extracted as describing confidence 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 29 , 30 , 33 , 34 , 35 , 36 , 38 , 39 , 41 , 42 , 43 , 44 , 46 , 47 , 48 , 52 . ‘Confidence’ is defined as the trust that people have in the immunizations, the healthcare system itself, and the process leading to decisions on licensing or recommended schedules 14 , 27 , 35 . Few studies describe the (lack of) trust or confidence as a component of VH 23 , 34 , 52 .

From 22 studies 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 29 , 30 , 33 , 35 , 38 , 39 , 40 , 41 , 43 , 44 , 47 , 48 , 50 , 52 , 41 excerpts were extracted on the theme of complacency. ‘Complacency’ is the individual evaluation of the risks and benefits of vaccines and of the need to vaccinate 14 , 18 , 20 , 35 . The concept of complacency in relation to VH is described as the tendency to perceive the risks of vaccination as unknown or disproportionally high and the risks of the vaccine-preventable disease as low 44 , 50 . Vaccine-hesitant individuals are more committed to assessing vaccine risks and seeking ways to minimize them 23 , 40 , 47 , 50 .

From 15 studies 14 , 18 , 20 , 21 , 22 , 25 , 29 , 33 , 35 , 38 , 39 , 41 , 42 , 43 , 48 , 27 excerpts were extracted as describing the theme of convenience. ‘Convenience’ concerns not only physical availability and geographical accessibility of vaccines, but also the user-friendliness of and ability to understand immunization services 14 , 18 , 35 , 42 . In our analysis, we found that many authors refer to convenience by describing VH as the delaying or refusal of vaccines ‘despite availability’ 14 , 18 , 21 , 22 , 23 , 25 , 26 , 29 , 33 , 35 , 38 , 39 , 41 . This description acknowledges that availability of vaccines is related to vaccine uptake, while VH itself is not influenced by availability issues. However, one study adopts inconvenience and difficulty to access vaccines as dimensions of VH 42 .

Variations between research fields and vaccine types

We identified the respective research field and vaccine type of each study in the qualitative analysis to explore related differences in descriptions of VH. We identified 19 public health studies 18 , 21 , 23 , 25 , 26 , 27 , 28 , 29 , 32 , 33 , 36 , 37 , 38 , 41 , 45 , 47 , 50 , 51 , 53 , 6 paediatric studies 14 , 31 , 34 , 35 , 39 , 48 , 8 social science studies 17 , 20 , 22 , 42 , 44 , 46 , 49 , 52 and 3 biomedical studies 30 , 40 , 43 . The primary difference observed was that conceptualizations of VH in terms of decision making emerged predominantly in the public health 18 , 21 , 23 , 32 , 38 , 50 , 54 and social science fields 42 , 44 , 52 . In studies conceptualizing VH in terms of cognitions or affect, the terms ‘beliefs’ and ‘concerns’ were used in all research fields, while ‘reluctance’, ‘doubts’ and ‘questions’ were used almost exclusively in the public health field. The conceptualization of VH as a behaviour occurred in all research fields.

VH was discussed in relation to vaccination in general 14 , 17 , 18 , 22 , 23 , 27 , 28 , 29 , 32 , 33 , 35 , 36 , 38 , 41 , 42 , 43 , 46 , 48 , 49 or specifically with regard to childhood vaccines 21 , 25 , 26 , 30 , 31 , 34 , 37 , 39 , 40 , 47 , 50 , 51 , 53 , in 19 and 13 of the studies, respectively. The remaining 4 studies discussed VH in relation to COVID-19 44 , 45 , 52 and influenza 20 . Our analysis compared the studies on general vaccination and childhood vaccines but found no major differences in their respective conceptualizations.

Vaccine hesitancy subpopulations

Of the 422 included studies, 63 identified various VH subpopulations. We extracted text excerpts describing the classifications of these subpopulations and the authors’ rationales for the distinctions. The analysis identified themes aligned with the three VH conceptualization categories. Fourteen studies grouped VH subpopulations on the basis of criteria from the conceptualization as cognitions or affect 21 , 23 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 and 3 studies grouped VH on the basis of the conceptualization of decision making 69 , 70 , 71 . VH subpopulations grouped solely on the basis of criteria from the behaviour conceptualization were not found. However, 19 studies grouped hesitant individuals on the basis of criteria from the conceptualizations of both cognitions or affect, and behaviour 26 , 47 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 . The remaining 27 studies did not identify subpopulations in terms of the three conceptualizations. Twelve studies identified subpopulations on the basis of degree of VH 51 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 . Although degree of VH does not directly contribute to understanding of the VH concept, the instruments used to quantify it and determine cut-off values for the subpopulations contain valuable information about the operationalizations. These instruments are discussed in the following section. In addition, a group of 10 studies distinguished a VH subpopulation by asking about willingness to be vaccinated but used different criteria to do so 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 . This method was mainly found in studies on COVID-19 vaccination, published in 2021. This demonstrates the emergence of a conceptual VH category that was not identified from the conceptual studies. The final 5 studies grouped subpopulations according to miscellaneous criteria 45 , 49 , 110 , 111 , 112 . An overview is provided Supplementary Table 3 .

Measurements of vaccine hesitancy

Of the 422 studies included, 373 report a measurement of VH in individuals. An overview is provided in Supplementary Table 4 , grouping the studies according to the instruments used. The most common, albeit highly heterogenous, method used in 210 (56%) studies is a brief VH assessment comprising 1–3 questions 64 , 65 , 66 , 68 , 71 , 74 , 75 , 84 , 85 , 88 , 90 , 96 , 97 , 98 , 100 , 102 , 103 , 105 , 106 , 107 , 108 , 109 , 111 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 . The questions, as well as the criteria or cut-off points used to define hesitancy, vary widely between the studies. The majority of questions used in this method cover operationalizations of VH that did not emerge from our conceptual analysis, including intention and willingness. A group of 124 studies assess VH by asking about vaccination intention. For example, one measurement asks “What would you do if a COVID-19 vaccine were available?”. Respondents answering either “I would eventually get a vaccine, but wait a while first”, “I would not get a vaccine” or “I’m not sure” are all classified as hesitant 169 . A group of 35 studies assess VH by asking about willingness, exemplified by the question: “Are you willing to receive the COVID-19 vaccination?”. Respondents answering “yes, but I choose to delay timing of injection” are considered hesitant 100 . Furthermore, 23 studies assess VH by an explicit verbatim assessment of experienced hesitancy levels. This is exemplified by the question: “Overall, how hesitant about childhood vaccines would you consider yourself to be?”. Respondents answering “not too hesitant”, “not sure”, “somewhat hesitant” or “very hesitant” are considered hesitant 136 . Finally, a minority of 14 studies assess VH with questions covering conceptualizations that did emerge from our conceptual analysis; for example, by asking about previous vaccination behaviour: “Have you ever hesitated, delayed, or refused getting a vaccination for your child or yourself due to reasons other than allergies and sickness?”. Respondents answering “yes” to this question are considered hesitant 122 . The remaining 14 studies use miscellaneous questions to assess VH. Notably, the intention and willingness measures to assess VH are found mainly in studies published in 2021 on COVID-19 vaccination, while the other methods have been used throughout the covered period and in the context of different vaccines.

The second most common method, applied by 132 (35%) studies, is the use of a validated instrument. The most common instrument, used in 70 studies, is the parent attitudes about childhood vaccines (PACV) survey, introduced by Opel et al. 34 . The PACV consists of 15 questions about immunization behaviour, beliefs about vaccine safety and efficacy, attitudes toward vaccine mandates and exemptions, and trust 299 , thereby operationalizing VH as both cognitions or affect, and behaviour. Trust (or confidence) is also included in this instrument. In our conceptual analysis, confidence emerged as a distinct concept, albeit closely related to VH. Clear cut-off points for hesitancy were formulated and applied in the vast majority of the studies using this instrument (shown in Supplementary Table 4 ). The PACV is variously used in its original form 34 , 91 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 , 310 , 311 , 312 , 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 , 328 , 329 , 330 , 331 , 332 , 333 , 334 , 335 , 336 , 337 , 338 , or in adapted 339 , 340 , 341 , 342 , 343 , 344 , 345 , 346 , 347 , 348 , 349 , 350 , 351 , 352 , 353 , 354 , 355 or shorter versions 51 , 62 , 89 , 93 , 95 , 356 , 357 , 358 , 359 , 360 , 361 .

Other studies use a variety of validated and broadly used instruments. The SAGE instrument is applied in 13 of the studies 41 , 362 , 363 , 364 , 365 , 366 , 367 , 368 , 369 , 370 , 371 , 372 , 373 , with questions reflecting the different conceptualizations (cognitions or affect, behaviour and decision making) and related concepts including convenience, complacency and confidence 41 . The vaccine hesitancy scale (VHS), used in 39 studies 83 , 99 , 374 , 375 , 376 , 377 , 378 , 379 , 380 , 381 , 382 , 383 , 384 , 385 , 386 , 387 , 388 , 389 , 390 , 391 , 392 , 393 , 394 , 395 , 396 , 397 , 398 , 399 , 400 , 401 , 402 , 403 , 404 , 405 , 406 , 407 , 408 , 409 , 410 , was derived from a subscale of the SAGE instrument, narrowed to conceptualize VH as cognitions or affect and include the related concept of confidence 69 . The studies using the SAGE instrument and VHS use varying outcomes or cut-off values (or no outcomes or cut-off values at all) to define hesitancy (shown in Supplementary Table 4 ). The Oxford COVID-19 vaccine hesitancy scale was recently designed exclusively for the assessment of VH for COVID-19 vaccination and subsequently applied in 5 studies 44 , 411 , 412 , 413 , 414 . Other instruments described in the context of VH but intended to assess other concepts include the 5C scale 22 of psychological antecedents of vaccine behaviour, the vaccine acceptance scale (which covers the domains cognitions and affects, confidence and legitimacy of government vaccine mandates 46 ) and the multidimensional vaccine hesitancy scale covering perceptions regarding vaccines in general 42 . Instruments assessing confidence have also been applied to assess hesitancy 415 .

The remaining 31 (8%) studies use a variety of unique, self-developed methods to measure hesitancy. These are classified as ‘miscellaneous’ 25 , 50 , 52 , 69 , 73 , 92 , 94 , 416 , 417 , 418 , 419 , 420 , 421 , 422 , 423 , 424 , 425 , 426 , 427 , 428 , 429 , 430 , 431 , 432 , 433 , 434 , 435 , 436 , 437 , 438 , 439 . Examples include measurement of VH based on vaccination rates from medical records 418 and statistical procedures used to group participants according to their patterned responses to a questionnaire 92 , 439 .

Our systematic review reveals that VH is conceptualized in the literature as involving cognitions or affect, behaviour and decision making, representing three distinct but interacting entities. Closely related concepts include confidence or trust, perceptions of the need to vaccinate and of risk (complacency), and convenience. VH subpopulations are grouped according to a variety of criteria, with the majority originating in the three identified conceptualizations. Studies measuring VH have used a wide variety of instruments. The most commonly applied instruments include a brief assessment comprising 1–3 variable questions and the PACV for childhood vaccines. The instruments operationalize hesitancy using one or more of the three identified conceptualizations, but also introduce novel conceptualizations including intention and willingness. When synergizing the findings on different VH operationalizations, we found psychological and behavioural operationalizations, with the psychological operationalizations being cognitions or affect, and decision making.

Our findings illustrate the challenge of operationalizing VH, with studies adopting different conceptualizations, subpopulations and measurements. Dubé et al. acknowledged this challenge of operationalizing the VH concept due to its heterogeneity and the diversity in attitudes and behaviours 29 . Furthermore, our findings align with a recent study demonstrating the many interpretations of VH used across Europe 440 . These inconsistencies in terminology are even evidenced in the Merriam-Webster dictionary, where ‘hesitancy’ is defined as a quality or state of being that involves indecision or reluctance 441 , aligning with VH conceptualized as decision making and cognitions or affect, while ‘vaccine hesitancy’ is defined as the reluctance or refusal to vaccinate 442 , thereby also including a conceptualization of behaviour.

In the introduction, we describe interchangeable use of various terms with VH 19 , 20 . In our review, we also found numerous examples, including ‘confidence’ 443 , ‘low intention’ 444 and ‘unwillingness’ 270 . We identify these concepts as related but not synonymous to VH. For instance, some authors note that confidence or trust are used interchangeably in relation to VH 19 , 22 , suggesting equivalent meanings. Others describe an inverse relationship, meaning that lower levels of confidence are associated with higher levels of VH 19 , 33 , 54 , 56 , 445 . In line with this, VH is described as originating from a lack of confidence 446 and as a possible indicator of declining confidence 56 .

Additionally, in our analysis of subgroups and measurements, we found that VH is frequently operationalized in terms of willingness and intention, which we did not find in our conceptual analysis of VH. Willingness and intention to vaccinate, similar to the ‘vaccine confidence’ concept, are inversely related concepts that are unequivocally linked to VH but are and should not be treated as synonymous. Using these terms interchangeably is not only inappropriate but also contributes to confusion and unclarity of the VH concept. This clarity is needed because unclear concepts give rise to differences in our understanding of its determinants, correlates and consequences, hindering efforts to study and address VH 15 , 23 , 440 . Furthermore, at an operational level, there may be a mismatch between a concept and its measures 15 . This is demonstrated in our review by the highly variable methods we found to measure VH, leading to incomparable results. Particularly during 2021, there has been a plethora of studies reporting VH measurements that, due to divergent definitions and methods, have been of questionable value. As a way forward, we base our reasoning for a renewed definition of VH on the three main identified conceptual categories—behaviour, cognitions or affect, and decision making—as these have proven most promising by their repeated representation in conceptual, subgroup and measurement studies

We argue that conceptualizing VH as vaccination behaviour is untenable, as mere behaviour is insufficiently discriminating between hesitant and non-hesitant individuals. For instance, people may accept vaccines with or without hesitation or reject vaccines with or without hesitation. As concepts are ideally defined by a unique set of features that distinguishes them from other closely related concepts 15 , vaccination behaviour alone is not sufficient to define VH. Furthermore, vaccination behaviour is generally used as the indicator of (non-)acceptance of vaccination. Thus, to use this also to define another concept would create confusion. Authors have commented on the blurred distinction between VH and refusal of vaccines 25 , 39 and criticized behavioural operationalization for its failure to capture VH 17 , 18 , 23 , 25 , 40 . Although we agree that certain types of vaccination behaviour may be manifestations of VH, we argue that including behaviour in the definition and operationalization of VH is neither necessary nor sufficient.

Our analysis shows that VH is furthermore defined by two closely linked conceptualizations that we identify as psychological—cognitions or affect, and decision making. Larson et al. exemplify this stance, arguing that VH is by nature a state of indecision and reluctance 32 . We propose to reject types of vaccination behaviour as a viable conceptualization of VH; this logically results in the proposition that VH should be considered a psychological construct. This is in line with authors who have argued that VH is a psychological state rather than a behaviour 18 , 22 , 26 , 32 , 40 , inspiring our current investigation of what exactly this vaccine-hesitant state entails. In the conceptualization cognitions or affect, VH is mainly described as ‘doubts’, ‘concerns’ and ‘reluctance’ regarding vaccination. Following our analysis, we interpreted these descriptions as different ways of how VH may be affected, experienced or expressed at an individual level, representing a layer surrounding the central element of VH. We therefore interpret cognitions and affect to go hand-in-hand, but not to be at the core of hesitancy. Moreover, we conclude that cognitions or affect are insufficiently distinctive to define VH.

This interpretation does not mean that the identified cognitions or affect are irrelevant to VH. On the contrary, they may prove crucial in shaping VH. However, to arrive at a clear definition of VH, cognitions and affects should be treated as clearly defined entities as well. Only by unravelling and distinguishing them can the exact nature of their relationship with VH be clarified in further research.

In the conceptualization decision making, VH was described as being ‘undecided’, ‘indecisive’, ‘in consideration’ or ‘not yet making a vaccine decision’. All these descriptions include an element of indecision, and this provides a unique and distinctive feature for VH. Additionally, we found that this conceptualization is predominantly discussed in studies in the public health field. This is rather logical, as one would expect this field of research to take a more pragmatic approach, examining the presence of VH at a stage where people have been offered a vaccine or to anticipate public sentiments around willingness to accept a vaccine when it is offered. This probably triggers a decision-making process where VH can emerge and manifest. On the basis of these findings, we argue that VH is a psychological state of being undecided, indecisive or not yet making a decision regarding vaccination.

The study selection was conducted independently by different members of our research team. However, one possible limitation is that we did not attempt to exclude studies of lower quality, as we wanted to maintain a robust selection of studies to enable a broad overview of the relevant literature. Our MMAT assessment, however, indicates that the majority of the studies are of medium quality. A second limitation is that a considerable number of the included conceptual studies (17 of the 36) 14 , 18 , 20 , 21 , 22 , 23 , 25 , 26 , 29 , 35 , 38 , 39 , 40 , 41 , 42 , 43 , 44 quoted the VH definition introduced by the SAGE working group, which may have led to an amplification of the SAGE definition. This may indicate that this definition is well recognized, but potentially overshadows less recognized conceptual definitions of VH. We chose to include all quoted definitions and found that many studies used more than one. We did not look further into conflicting definitions within the articles, but doing so could yield interesting insights.

In conclusion, we propose a definition of VH as a psychological state of indecisiveness that people may experience when making a decision regarding vaccination. We acknowledge that experiencing concerns, doubts or reluctance regarding vaccination may play a vital role in shaping VH. However, we argue that these factors have the highest potential to advance scientific knowledge when treated as relevant constructs integral to shaping VH, rather than treating them as synonymous to VH. Operationalizing VH by measuring or distinguishing subpopulations should ideally be directed at this state of indecision. To avoid confusion, it is important to separate VH from vaccination behaviour, which is already a well-defined concept. This proposal of a renewed definition of a concept that has been used for a decade could be perceived as ‘putting old wine in new bottles’. However, we feel that due to the large amount of highly varied literature, and given the importance of VH research in predicting, explaining and influencing immunization behaviour, it is necessary to take a snapshot of the status quo. The conclusion of this review is that VH is, for now, an impracticable concept, due to the confusing use of multiple, varied operationalizations. To aid further research, the VH concept must be clearly conceptualized and adapted from its broad and inclusive form to a pragmatic and refined alternative. Working on such an alternative, the field should first reach consensus on the definition and then measure VH accordingly. This approach allows for a much-needed comparison between studies to improve our understanding of VH determinants, correlates and consequences on an individual and societal level. Our way forward is to simplify and clarify the operationalization of VH by returning to its root core of indecisiveness.

This systematic review was registered on 11 November 2020 in the PROSPERO database (CRD42020211046). The record and study protocol are available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=211046 .

Relevant publications were searched using the PubMed, Embase and PsycINFO databases to ensure coverage of all relevant research areas in the medical, public health and social science fields. The CINAHL database was also considered, but a pilot search revealed that its unique contributions were limited.

An experienced research librarian used the following keywords to develop a search strategy (Supplementary Methods ): ‘vaccination’, ‘immunization’, ‘vaccination refusal’, ‘vaccination avoidance’, ‘vaccination hesitation’, ‘vaccine hesitancy’, ‘vaccine uptake’, ‘vaccination behaviour’, ‘vaccination attitude’, ‘vaccine confidence’, ‘vaccine acceptance’ and ‘vaccine barriers’. The limitations included a publication date of between 2010 and the date of the search (14 January 2022). Conference abstracts were excluded from the search of the Embase database.

Eligibility criteria

The included studies were all published in peer-reviewed journals and written in English. All study types were eligible, except editorials and commentaries, as we sought to include original studies. Studies on animal vaccines were excluded.

The purpose of this review was to clarify the VH concept by analysing how it is operationalized. We recognized operationalizations at two main levels: conceptual and empirical. This resulted in three main groups: (1) studies describing or defining the VH concept and studies applying the concept by (2) identifying VH subpopulations and (3) measuring VH in individuals. This approach allowed comparison between conceptual and empirical operationalizations of VH.

Study selection

In the first selection round, two members of the research team used RAYYAN software to independently assess the titles and abstracts. Studies were selected when the title or abstract contained the term ‘vaccine hesitancy’. Studies were also selected if the title or abstract indicated that the full text contained further information on VH conceptualization, subpopulations or measurements. Papers without an abstract were selected for full-text screening. After double-screening, the results were de-blinded to allow the researchers to discuss their conflicting judgements until consensus was reached.

In the second selection round, the full texts were screened. The first 30% of studies were double-screened to establish a uniform method. Studies were screened on whether they met the criteria for one or more of the three categories (conceptualization, subpopulations and measurements). The category of ‘conceptualization’ included studies that describe, discuss or explore the VH concept or propose a novel VH measurement instrument. Studies falling into only the second category (subpopulations) were excluded if they merely distinguished between hesitant and non-hesitant groups, since a dichotomous grouping does not contribute to understanding of VH. The references from the included full-text articles were screened to find additional studies matching the selection criteria.

We deviated posthoc from our preregistered study protocol by adjusting the study selection criteria as follows. Initially, we also included studies containing the term ‘vaccine confidence’ (that is, with no mention or operationalization of vaccine hesitancy) as indicated in our study protocol. During the process, we realized that this deviated from our primary aim to clarify the VH concept by differentiating its related concepts. Therefore, we adapted the protocol and excluded 16 studies that were exclusively on vaccine confidence from our analysis

Data collection

The study characteristics were extracted from each of the full-text articles. Data were extracted by one researcher and verified by a second member of the research team. The variables included the first author, year of publication, research field of the first author, type of study, type of participants, number of participants, type of vaccination and country in which the study was conducted (with corresponding economic status) 447 . For the studies that do not include data collection, the country of origin was determined using the affiliation of the first author.

From the studies on VH conceptualization, text excerpts that define or describe VH or describe the relationship of VH to other concepts were extracted. These excerpts were further analysed in the qualitative analysis. From studies that describe different VH subpopulations, information about the categorization of these various subgroups was extracted, including the rationale for the distinguished subpopulations. From studies that describe VH measurements, the instrument(s) and criteria used to define VH were extracted.

Synthesis of results

The text excerpts extracted from the studies conceptualizing VH were thematically coded using ATLAS.ti software. Three research team members developed a coding book of themes and subthemes after independent coding of 30% of the studies. Thereafter, one researcher continued the coding process for the remaining studies. Any emerging new codes were discussed with the other research team members. The results were analysed qualitatively, and the predominant themes were identified by the three team members. When possible, results were grouped by research field and vaccine type to allow for comparison.

The data extracted from the studies describing VH subpopulations were summarized in a table and grouped according to the common themes identified. The data extracted from the studies describing a VH measurement were summarized in a table and grouped according to the instrument or method used. Where multiple measurement instruments are used in one study, the tool used to determine hesitancy was selected as the main instrument.

Quality assessment

The quality of each study was assessed using the MMAT 448 . This tool contains appraisal guidelines for different study types, covering the majority of the included studies. An overall score was calculated (1–5) on the basis of additional communication about the MMAT 2018 version, with higher scores indicating higher quality levels 449 . The first 20% of studies were assessed independently by two members of the research team to ensure consistency. Thereafter, one member of the research team continued the assessment.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability

All data generated or analysed during this study are included in this article and its Supplementary Information . This systematic review is registered in PROSPERO (CRD42020211046).

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Acknowledgements

J.L.A.H. and M.E.J.L.H. received funding from The Netherlands Organisation for Health Research and Development (ZonMw project number 839190002). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank J. van Haren for her valuable contribution in sorting and organizing the data of this systematic review.

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D.B.-V., J.L.A.H., O.V. and M.E.J.L.H. designed the project and analysed the data. D.B.-V., J.L.A.H., L.V., O.V. and M.E.J.L.H. interpreted the data. The manuscript, figures and tables were drafted by D.B.-V. and edited by J.L.A.H., L.V., O.V. and M.E.J.L.H.

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Overview and characteristics of included studies.

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Overview of extracted excerpts.

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Overview of vaccine hesitancy subpopulations.

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Overview of studies describing a measurement of vaccine hesitancy.

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Bussink-Voorend, D., Hautvast, J.L.A., Vandeberg, L. et al. A systematic literature review to clarify the concept of vaccine hesitancy. Nat Hum Behav 6 , 1634–1648 (2022). https://doi.org/10.1038/s41562-022-01431-6

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Assessing the Real-World Effectiveness of Immunizations for Respiratory Syncytial Virus

• 1 Surveillance and Prevention Branch, Coronavirus and Other Respiratory Viruses Division, US Centers for Disease Control and Prevention, Atlanta, Georgia
• Medical News & Perspectives “This Is Our COVID”—What Physicians Need to Know About the Pediatric RSV Surge Jennifer Abbasi JAMA
• Medical News in Brief CDC: RSV Vaccine Recommended for Older People Emily Harris JAMA
• Medical News in Brief FDA Approves Maternal RSV Vaccine Emily Harris JAMA

Immunizations for respiratory syncytial virus (RSV) were newly licensed and recommended for 3 populations in the US in 2023, marking a historic turning point in the prevention of RSV illness in both young children and older adults. First discovered in 1956, RSV has long been recognized as a leading cause of acute respiratory illnesses in young children, resulting in an estimated 58 000 to 80 000 hospitalizations in children younger than 5 years of age each year in the US, with infants at greatest risk of hospitalization. 1 Respiratory syncytial virus has also been increasingly recognized as a cause of severe acute respiratory illness in older adults and is estimated to cause 60 000 to 160 000 hospitalizations and 6000 to 10 000 deaths annually among adults aged 65 years or older in the US. 2 Until 2023, only palivizumab (a monoclonal antibody requiring monthly dosing) was available for RSV prevention for eligible infants and young children with certain underlying conditions that increase risk of severe RSV illness.

The US Centers for Disease Control and Prevention now recommends protecting all infants against RSV-associated lower respiratory tract infection during their first RSV season through either the maternal RSV vaccine (Abrysvo [Pfizer]) given to pregnant people or infant receipt of nirsevimab (a long-acting monoclonal antibody). The maternal RSV vaccine is recommended for pregnant persons at 32 to 36 weeks’ gestation using seasonal administration (ie, September through January in most of the continental US) to protect infants after birth through transplacental transfer of maternal antibodies. Nirsevimab is recommended for infants younger than 8 months of age entering their first RSV season and for some children aged 8 to 19 months with certain high-risk conditions entering their second RSV season. For adults aged 60 years or older, 2 RSV vaccines (Arexvy [GSK] and Abrysvo [Pfizer]) are recommended to prevent RSV lower respiratory tract infection.

All 3 newly licensed RSV immunization products were efficacious in preventing severe RSV illness in prelicensure trials. 1 , 3 - 5 Postlicensure studies are needed to corroborate findings from these trials in real-world settings and in populations underrepresented in the prelicensure trials (eg, adults with immunocompromising conditions or frailty and older age groups among adults aged ≥60 years).

Observational studies of real-world immunization effectiveness typically compare the frequency of the illness outcome among persons who were immunized vs those who were not (cohort design) or the frequency of immunization among persons with the illness outcome vs those without the outcome (case-control or test-negative design). In both approaches, uptake of the immunization in the population must be sufficiently high to allow for an effectiveness evaluation. Immunization and outcome status also must be accurately identified. In addition, differences in the characteristics of immunized and unimmunized persons that might be associated with risk of the illness outcome must be addressed in analyses to optimize validity.

The early introduction phase of newly licensed RSV immunizations in the US poses multiple challenges to the assessment of real-world effectiveness and impact. Low immunization uptake among the recommended groups during the 2023-2024 season may hinder assessments of immunization effectiveness using traditional observational study designs. As of February 2024, uptake of the maternal RSV vaccine among eligible pregnant persons was estimated to be 18%, uptake of nirsevimab among infants younger than 8 months of age was 41%, and uptake of RSV vaccines among adults aged 60 years or older was 22%. 6

In addition, there may be differential uptake within groups recommended for immunization, with some subgroups more likely to be immunized than others. For example, among infants and young children, differential uptake of nirsevimab during the 2023-2024 season may have occurred because of early nirsevimab shortages. Similarly, among adults aged 60 years or older, current recommendations use a shared clinical decision-making framework informed by both the patients’ characteristics, values, and preferences and the health care professionals’ clinical discretion. 2 For both older adults aged 60 years or older and pregnant people, vaccination may also occur more frequently in retail pharmacy settings than for other routine vaccines (eg, because of the cost of stocking vaccines and insurance reimbursement mechanisms). Collectively, factors influencing differential uptake within groups recommended for immunization could lead to increased uptake either among those with poorer health and at greater risk of severe RSV illness (some of whom may be at greater risk of suboptimal immune responses to vaccination) or conversely, among healthier individuals who can more easily seek out vaccination. Both phenomena have been observed in studies of influenza vaccine effectiveness and can lead to bias in effectiveness estimates unless patient differences by immunization status and risk of infection are identified, appropriately measured, and addressed in the analyses.

Accurate identification of RSV immunization status may be hampered by patients’ or caregivers’ recall now that up to 3 respiratory virus immunizations (COVID-19 vaccines, influenza vaccines, and RSV immunizations) are available, and timely verification is likely to be challenging because of varying reporting requirements, jurisdictional immunization information systems, and settings for the administration of vaccines and immunizations. To assess effectiveness in young infants, accurate identification of both maternal RSV vaccination and infant immunization (including receipt of both nirsevimab and palivizumab) is important because all 3 immunizations prevent severe RSV illness. Direct comparison of the effectiveness of maternal RSV vaccination vs infant administration of nirsevimab to prevent severe RSV will require adequate use of both strategies in the same source population, standardized outcomes, and rigorous analytic methods to address differences between infants with maternal RSV vaccination exposure vs infant receipt of nirsevimab.

Interpretation of early real-world estimates of RSV immunization effectiveness during the 2023-2024 season may be affected by both patterns of immunization uptake and RSV circulation. Effectiveness estimates for RSV immunization may only be generalizable to groups that had sufficient uptake to study the effectiveness. For example, if nirsevimab was largely given to infants younger than 6 months of age because of updated prioritization guidance during supply shortages, the estimates may not be generalizable to older children. In addition, protection from immunization is expected to wane, especially in the case of passive immunization of infants through maternal vaccination and immunization in infants and young children with long-acting monoclonal antibodies. Immunization effectiveness is likely to appear higher when estimated early in the season with a shorter interval from vaccination or immunization than when estimated for the full season or over multiple seasons. Two early reports 7 , 8 on nirsevimab from Spain and the US suggest high levels of effectiveness against RSV-associated hospitalization early after receipt (with a median interval of 6 weeks from receipt in the US analysis), but emphasize the need for additional estimates of effectiveness for a complete RSV season.

Despite these anticipated challenges, the advent of immunizations for RSV to protect infants and young children and older adults presents unique opportunities to monitor and measure their public health effectiveness and potential shifts in RSV epidemiology. Real-world studies may answer key questions about immunizations for RSV that could not be fully addressed in prelicensure trials, including (1) the durability of protection from RSV immunization; (2) whether effectiveness varies by vaccine product in older adults, strategy (maternal vaccination or infant immunization) in young infants, and risk groups (eg, those with immunocompromising conditions); and (3) whether RSV immunization protects against a broader range of outcomes than studied in the prelicensure trials.

Newly licensed immunizations for RSV have the potential to prevent substantial numbers of hospitalizations and deaths, and real-world evidence of immunization effectiveness may support eventual introduction in low- and middle-income countries where the public health benefit may be greatest. There are rare moments in public health when decades of effort toward prevention of a specific disease culminate in the introduction of new immunization products with the potential to dramatically reduce morbidity and mortality—for RSV, the real-world evidence will determine if that time is now.

Corresponding Author: Fatimah S. Dawood, MD, Coronavirus and Other Respiratory Viruses Division, US Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30307 ( [email protected] ).

Published Online: April 11, 2024. doi:10.1001/jama.2024.5859

Conflict of Interest Disclosures: None reported.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.

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Dawood FS , Payne AB , McMorrow ML. Assessing the Real-World Effectiveness of Immunizations for Respiratory Syncytial Virus. JAMA. Published online April 11, 2024. doi:10.1001/jama.2024.5859

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• Published: 14 July 2020

Barriers to childhood immunization in sub-Saharan Africa: A systematic review

• Joseph Benjamin Bangura 1 ,
• Shuiyuan Xiao   ORCID: orcid.org/0000-0003-0042-7226 1 , 2 ,
• Dan Qiu 2 ,
• Feiyun Ouyang 1 &
• Lei Chen 3  

BMC Public Health volume  20 , Article number:  1108 ( 2020 ) Cite this article

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Immunization to prevent infectious diseases is a core strategy to improve childhood health as well as survival. It remains a challenge for some African countries to attain the required childhood immunization coverage. We aim at identifying individual barriers confronting parents/caretakers, providers, and health systems that hinder childhood immunization coverage in Sub-Saharan Africa.

This systematic review searched PubMed/MEDLINE, Web of Science and EMBASE. We restricted to published articles in English that focused on childhood immunization barriers in sub-Saharan Africa from January 1988 to December 2019. We excluded studies if: focused on barriers to immunization for children in other regions of the world, studied adult immunization barriers; studies not available on the university library, they were editorial, reports, reviews, supplement, and bulletins. Study designs included were cross-sectional, second-hand data analysis; and case control.

Of the 2652 items identified, 48 met inclusion criteria. Parents/caretakers were the most common subjects. Nine articles were of moderate and 39 were of high methodological quality. Nine studies analyzed secondary data; 36 used cross-sectional designs and three employed case control method. Thirty studies reported national immunization coverage of key vaccines for children under one, eighteen did not. When reported, national immunization coverage of childhood vaccines is reported to be low. Parents/caretaker’ barriers included lack of knowledge of immunization, distance to access point, financial deprivation, lack of partners support, and distrust in vaccines and immunization programs. Other associated factors for low vaccine rates included the number of off-springs, lifestyle, migration, occupation and parent’s forgetfulness, inconvenient time and language barrier. Barriers at health system level cited by healthcare providers included limited human resources and inadequate infrastructures to maintain the cold chain and adequate supply of vaccines.

In this review we identified more thoroughly the parents/caretakers’ barriers than those of providers and health systems. Factors that influenced decisions to get children vaccinated were mainly their gender, beliefs, socio-culture factors in the communities in which they live. Thus it is vital that immunization programs consider these barriers and address the people and societies in their communities across sub-Saharan Africa.

Peer Review reports

Immunization is a protective measure against infectious diseases [ 1 ]. Childhood immunization remains one of the highest impact public health interventions, reducing infectious diseases-related morbidly and mortality of children at a low cost [ 2 ]. It is a core child survival strategy and is demonstrated to avert more than 1·2 million child deaths each year [ 3 , 4 ]. It is a key strategy towards attaining Sustainable Development Goal (SDG) number 3, namely the reduction of under-five mortality to less than 25/1000 live births by 2013 [ 5 ]. Despite these gains, vaccine-preventable diseases remain a major cause of child illnesses and deaths, particularly in low-income countries [ 6 ].

Africa has the highest under-five mortality rate of the entire world and accounts for 40% of the total deaths in this age group. This is mainly due to vaccine-preventable diseases [ 7 ]. Over the past few decades, African immunization programs have made progress, yet coverages remains low for some recommended childhood vaccines. In 2014, it was reported that only Zimbabwe among the Sub-Saharan region was estimated to have met the Global Vaccine Action Plan threshold of 80% or higher coverage of diphtheria–tetanus-pertussis vaccine (DTP3), a benchmark used to measure performance of routine vaccine delivery system [ 8 ]. In 2016, one in five African children goes without lifesaving vaccines [ 9 ]. Most African countries are unable to reach the most vulnerable children populations in remote and rural communities [ 5 , 10 ]. Studies [ 1 , 2 , 3 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] conducted in Africa have attempted to elucidate potential barriers that lead to low uptake and none-completion of immunization series. Previous review [ 55 ] exploring reasons related to non-vaccination and under-vaccination of children in low- and middle-income countries categorized factors into major themes: Immunization systems; communication and information; family characteristics and parental attitudes/knowledge. However, it noted the lack of peer reviewed literature in Central Africa. Another review [ 56 ] investigated factors associated with incomplete or delayed vaccination across countries. Despite its potential importance, it did not categorize findings into major domains, as policy implication for each might be different.

This systematic review aims at identifying relevant studies and summarizing major barriers confronting health systems, providers, and caregivers that hinder immunization coverage in sub-Saharan Africa. The results of this review will add to existing knowledge of the problem, and guide policy makers to improve immunization programs in sub-Saharan Africa, especially in those countries where the included studies had been conducted; and also to provide useful information for further research on these problems.

Search strategy and study selection

The study employed Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRSMA) guidelines [ 57 ]. We performed electronic searches of articles included in this systematic review from the Web of Science, PubMed/Medline and EMBASE from January, 1988 to December, 2019. We combined the following terms: (child or children or childhood or infant or baby or newborn), and (immunization or immunisation or vaccination or vaccine or immunity), and (barrier or hesitant or refuse or refusal or delay or denial or denier or denied or concern or reason or doubt “non-acceptance” or incomplete or obstacle or constraint), and (“Sub Saharan Africa” or 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 “Cote d’Ivoire” or “Equatorial Guinea” or Eritrea 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 Senegal or Sierra Leone or Somalia or “South Africa” or “South Sudan” or Sudan or Tanzania or Togo or Uganda or Zambia or Zimbabwe) [See supplementary materials 1 ].

We restricted to published articles in English that focused on childhood immunization barriers, conducted in Sub-Saharan Africa from January 1988 to December 2019. Articles were excluded if: (i) focused on barriers to immunization for children in other regions of the world, (ii) studied adult immunization barriers (iii) published before December, 1988 and beyond December, 2019; (iv) they were editorials, (v) reports, (vi) review articles, (vii) supplement articles, (vii) bulletins and (ix) studies not available on the university library. We included only observational studies in this systematic review.

Data analysis

Search result items were uploaded into EndNote X7 library. Duplicates were removed. JBB and DQ did the initial screening (title and abstract) and full texts of articles based on the inclusion and exclusion criteria. We resolved disagreements with third review (FO). The study employed narrative synthesis. The author uses the following approaches: tabulation and thematic analysis. The analysis focus on thematically grouping the barriers identified in the included studies. Researchers formulated table to capture descriptive information and data for each include study. This includes author, year, geographical location and number of countries included in a study; participants and demographic; study design; reported national immunization coverage, data source, date; study quality; and key reported barriers. JBB synthesized data and created table with input from LC and SX. JBB and LC classified reported barriers into three major categories: barriers confronting the parents/caretakers, those specific to the health system, and those linked to the providers. Discrepancies were resolved by consensus after discussions.

Study methodological quality

JBB and DQ assessed articles for methodological quality independently based on modified tool designed to assess quantitative and qualitative studies used in a similar study published elsewhere [ 58 ]. [See supplementary materials 2 ] It included a range of items from 1 to 14. Each item scores one point. Based on the scores, we grouped articles into three: low, moderate and high; articles scored 12 points and above were considered high methodological quality, moderate 8 to11 points,7 points and below were low. If ratings differed, we discussed the article in an effort to arrive at a consensus (Fig. 1 ).

Study selection

Our database searches yielded 2652 records. 2250 records were screened by title and abstract after duplicates removed; 76 full-text articles assessed for eligibility. Forty-eight articles met all inclusion criteria for this study; 28 articles were excluded for various reasons. [See supplementary materials 3 ] Nine articles employed second-hand data analysis [ 7 , 12 , 18 , 27 , 37 , 40 , 41 , 42 , 47 ]; thirty-six used cross-sectional design [ 1 , 2 , 3 , 11 , 13 , 14 , 15 , 16 , 17 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 38 , 39 , 42 , 45 , 46 , 48 , 49 , 50 , 51 , 53 , 54 ] and three used case-control study [ 20 , 43 , 44 ]. All described studies were conducted on Africa populations (103,655 adults and 76,327 children). Forty-seven articles focus on identifying barriers to general childhood vaccination 0–59 months [ 1 , 2 , 3 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] in the following countries: Uganda, Ethiopia, Kenya, Sudan, Nigeria, Gabon, Cameroon, South Africa, Tanzania, Burkina Faso, Togo, Ghana, Malawi and few unspecified countries in Sub-Saharan. One critically examined barriers specific to vaccination doses at birth 0 – 1 day [ 18 ] in the Gambia. Thirty articles reported national immunization coverage [ 1 , 2 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 20 , 21 , 22 , 23 , 24 , 25 , 28 , 29 , 32 , 34 , 35 , 38 , 39 , 40 , 43 , 44 , 45 , 46 , 49 , 50 , 52 , 53 , 54 ], eighteen did not [ 3 , 17 , 18 , 19 , 22 , 24 , 26 , 27 , 30 , 31 , 33 , 36 , 37 , 41 , 42 , 47 , 48 , 51 ]. 39 articles were classed as high and 9 were moderate methodological quality. We split results into three sections – parental barriers, health system barriers, and providers’ barriers. 8 studies examined all – parental/caretakers, health systems and providers’ barriers [ 3 , 11 , 13 , 16 , 43 , 45 , 48 , 52 ]; 21 studies examined parental/caretakers and health system barriers [ 1 , 2 , 14 , 15 , 18 , 19 , 22 , 23 , 25 , 29 , 31 , 32 , 33 , 35 , 38 , 44 , 47 , 49 , 50 , 51 , 53 ]; 18 studies only looked at parental//caretakers barriers [ 7 , 12 , 17 , 20 , 21 , 24 , 26 , 27 , 28 , 34 , 36 , 37 , 39 , 42 , 46 , 54 ] and one study examined parental and providers’ barriers. Several Sub-Saharan countries were reported to have low childhood immunization coverage with variations across the region. Nigeria reported lowest with 12·7% in 2013 and Ethiopia highest with 88% in 2013. See summary table for studies’ characteristics and key findings (Table 1 ).

Parental/caretaker barriers

In this systematic review, several cited parental/caretaker’ barriers were modifiable (knowledge, misconception, trust, delivery at home, long waiting time, providers’ hostility, parent’s forgetfulness, inconvenient time and language barrier). Parental/caretaker barriers are factors that impede mothers/caretakers progress in the process of their child accessing and utilizing vaccine services. It was revealed that parent perception influenced immunization of their children [ 1 , 12 , 13 , 14 , 21 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 48 , 49 ]. Parents not being knowledgeable of immunization was the most frequently and consistently reported barrier to childhood immunization [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 44 , 45 , 47 , 48 , 49 , 50 , 52 ]. Wiysonge et al. (2012) stated that “low parental knowledge of immunization and/or lack of access to information about childhood immunization could be an important contributor to the high burden of unimmunized children in sub-Saharan Africa”. Four studies [ 3 , 13 , 25 , 26 ], noted that a child born to a mother with little or no knowledge of vaccination may not complete the required vaccine series. Two articles reported that delay on vaccine birth doses is associated with maternal education [ 18 , 20 ]. Misconceptions about childhood immunization were recorded as major hindrance to effective utilization of immunization services in this review [ 1 , 2 , 11 , 12 , 13 , 14 , 21 , 22 , 29 , 31 , 32 , 48 , 49 ] One article [ 17 ] reported that some parents believed that the immunity induced by vaccines is less effective than that of the natural disease, and they prefer to endure the diseases than immunization. Some caregivers were reported to believe in the efficacy of traditional medicines as an alternative to immunization and concomitant treatment by traditional healers [ 31 , 35 ].

Lack of trust towards vaccines was a major reported barrier. Some community members were reported to refuse immunization services due to the belief that vaccines were ‘harmful’, ‘expired’ and could cause ‘physical disability’ and/or ‘death’ among their children [ 2 , 17 , 21 , 22 , 30 , 32 , 33 , 35 , 38 , 45 , 48 , 53 ]. The place of delivery of a baby was reported as determinants of full immunization of a child. Delivery at health facility enhances full immunization [ 18 , 20 , 22 , 27 , 28 , 40 , 48 ]. Long waiting time at health facilities was frequently and consistency noted [ 11 , 12 , 31 , 35 , 36 , 45 ]. Two articles [ 35 , 53 ], noted that parents sometimes forgot the appointment date for the next immunization visit of their children. Others reported place/time for vaccination being unknown [ 11 ]. Inconvenient immunization time such as on weekend/public holidays was reported as a barrier [ 43 , 54 ]. One study [ 3 ], indicated language as a barrier to childhood immunization.

On the other hand, we also recorded non-modifiable childhood immunization barriers of parents/caretakers. Those categorized as unmodifiable are factors that are extrinsic to the parent / provider dyad. These include occupation, financial limitations, place of residence of mother/caretaker, religion, ethnicity, family size, male partners’ support, and migration; seasonal farm work, feeling ashamed of poverty-associated reasons, and being a single mother. The role of male partners in the decision for childhood vaccination was an important barrier noted. Male partners were often cited as being against vaccinating the children. The decision for immunization was generally a joint decision between the mother and father of the child. But it was noted with strong emphasis that women were in charge of taking children for immunization and sometimes the husbands opposed immunization and stopped their wives from immunizing their children by denying them the social and financial support necessary [ 3 , 16 , 17 , 22 , 33 , 38 ]. The nature of occupation of the mother/caretaker was reported as a major determinant to childhood immunization [ 1 , 11 , 14 , 15 , 21 , 22 , 25 , 30 ]. Housewives were reported to have complied with higher coverage of full immunization status than other occupations such as merchants or public/private employees [ 11 ]. Also, mothers/caretakers were reported to be affected by seasonal factors. One study [ 1 ] stated that, “usually in the first quarter of the year in which most mothers engaged in coffee-collection and processing in coffee processing industries often did not bring their children to the next immunization schedule”. Financial limitation was a major barrier cited that hinder childhood immunization [ 7 , 11 , 13 , 15 , 17 , 24 , 27 , 34 , 36 , 38 , 40 , 42 , 45 , 47 , 50 , 52 ]. The place of residence of the mother was reported as determinants of full immunization of a child [ 37 , 39 , 41 ]. One study noted that the likelihood of vaccination of a child by day 7 is higher among children residing in rural areas than those in urban and pre-urban settings [ 18 ]. Socio-cultural factors and religion were noted to have negatively impacted immunization uptake [ 12 , 18 , 19 , 22 , 23 , 37 , 48 ]. Ethnicity and cultural beliefs were reported barriers to vaccine utilization and coverage; certain ethnic groups within the same country were identified with low coverage. Family size was associated with the probability of a child being fully immunized. It was revealed that children from large families have low vaccine uptakes, considering the burden of other children at home in taking up immunization services [ 11 , 13 , 25 , 46 , 50 ]. Migration was also cited as a hindrance to childhood immunization coverage [ 30 , 35 , 44 , 48 ]. Feeling ashamed of poverty-associated reasons was reported as barrier. Schwarz et al. (2009) indicated that “mothers who felt that they could not dress smartly enough for the approval of other women at the clinic were less likely to attend” [ 24 ]. Babirye et al. (2011) further revealed that “poor mothers often felt stigmatized and bullied from other women and health workers if they did not show up in good clothing” [ 17 ] Being a single mother was also a cited barrier to childhood immunization in this review [ 37 ].

Health system barriers

We noted health system barriers in this review. We describe health system barriers as inherent factors that obstruct the process of delivering vaccine and vaccine related services to it beneficiaries. These includes broken cold chain, irregular supplies and distribution of vaccines; limited human resource and infrastructures, and long distances separating health facilities from families [ 1 , 2 , 3 , 11 , 13 , 14 , 15 , 16 , 19 , 22 , 23 , 25 , 29 , 32 , 35 , 43 , 44 , 47 , 48 , 49 , 50 , 51 , 52 ]. Vaccine shortages at health facility level and difficulties of transporting vaccines were commonly reported to significantly hinder immunization services [1–174 3,11,14,16,19,22,23,25,33,43,47,48,52,51]. Some facilities were reported to have utilized vaccine refrigerators from nearby health centers due to poor working condition of theirs [ 1 , 3 , 32 ]. It was noted that due to staff limitation, only one staff often conducted immunization sessions in the catchment population [ 2 , 3 , 11 , 25 ]. Studies [ 11 , 13 , 45 , 47 , 48 , 49 , 50 , 52 , 53 ] also revealed that some hard-to-reach areas do not have health facilities nearby to provide childhood immunization. Health workers were reported to covers long distances on outreach services due to inadequate health centers [ 11 , 13 , 15 , 43 ]. It was also reported that, caretakers covered long distances to reach immunization centers resulted to non-completion of vaccination series [ 2 , 3 , 13 , 18 , 21 , 22 , 23 , 24 , 25 , 26 , 31 , 36 , 38 , 40 , 41 , 42 , 43 , 46 ]. Some studies [ 11 , 13 , 18 , 26 ] attempted to analyze the associations of distance with immunization outcomes. Tefera et al. (2018) indicated that “families whose home was at least an hour from the vaccination site were less likely to be fully vaccinated (56%) than families whose home was between 30 and 59 min away (67%)”. According to Miyahara et al. 2016, “the longer the distance from vaccination site, the lower the chances of vaccination by day 7 (of life) of a child”. Poor arrangement and coordination of immunization seasons at health center level were identified as barrier [ 16 , 38 , 43 , 45 ].

Providers barriers

In addition to the parental and health system barriers mentioned above, providers were identified as possessing barriers to immunization. Providers’ barriers are those factors that limit the process of health service providers to fully provide vaccine services to it beneficiaries. These factors include the lack of knowledge of vaccine indications and contraindications and the lack of counseling skills [ 3 , 16 , 43 , 52 ]. The restricted vaccine opening policy (use of multi-dose vials and the limited time for their use) was noted as a barrier specifically for the BCG vaccine [ 18 , 30 , 43 ]. It was also cited that reminders were not sent on time about routine immunization or outreach days [ 48 ] Providers’ hostility and rude attitudes to mothers were also a reported immunization barriers in this review [ 15 , 16 , 24 , 30 , 31 , 32 , 33 , 36 , 45 , 52 , 53 ].

Our review aims at identifying major childhood immunization barriers confronting health systems, providers, and parents across sub-Saharan Africa. Understanding of these barriers will help inform decision-makers and other relevant players involved in immunization programs, and to guide health interventions aim at improving immunization coverage. The study revealed childhood immunization barriers affecting utilization and coverage in the region. We grouped these barriers under three separate domains: barriers inherent in the parents/caretakers, those specific to the health system, and those related to the providers. We acknowledge that the categorisation of barriers may be different in this review than in others. Parental barriers were more and consistently identified than providers and health systems. Several of the cited parental/caretakers’ barriers were unmodifiable. Parents/caretakers reported barriers include lack of knowledge, misconceptions, financial deprivation, lack of partners’ support, and distrust of the medical systems. Other associated factors include the number of offspring, life style, migration, place of residence, long waiting time, parent’s forgetfulness; inconvenient time, being a single mother, occupation, language barrier, seasonal farm work, and feeling ashamed of poverty-associated reasons. Health system barriers include inadequate infrastructures and cold chain maintenance; distance and poor coordination. Providers’ constraints include limited human resources, hostile attitude and knowledge.

Knowledge of vaccines is very important for effective vaccine acceptance and utilization by parents. Low vaccination coverage in children is largely a result on the lack of knowledge of vaccines of healthcare providers and parents. Parents with low education and low socioeconomic status attainment showed more uncertainty towards immunization [ 3 , 11 , 13 , 15 , 16 , 17 , 18 , 22 , 24 , 25 , 27 , 28 , 30 , 34 , 35 , 36 , 40 , 42 , 44 , 45 , 48 , 49 ]. This result was also mirrored in another systematic review conducted in middle and low income countries which revealed that, most often, strong tie exist between low socioeconomic status and low level educational; with potential to lower vaccine coverage. However, investigations to understand the dynamics of these relationships are not sufficient [ 55 ]. Thus health education programs targeting these groups are critical in increasing vaccines acceptance, utilization and coverage. Further studies to unearth the dynamics of these relationships are vital. We noted that parents held reservations towards the associated side effects of vaccines. Other expressed a total distrust of immunization programs and vaccines [ 2 , 17 , 21 , 22 , 30 , 32 , 33 , 35 , 38 , 45 , 47 , 48 ]. This is in line with previous review of Influenza Vaccine hesitancy, which pointed out that, a lack of confidence due to low perceived effectiveness of the vaccine was a hindrance to vaccine uptake [ 56 ]. Another review outlined similar beliefs, including concerns about side effects, uncertainty toward vaccine safety, and belief in anti-vaccine theories [ 59 ]. To overcome this, immunization programs should intensify public sensitization on vaccines safety and promote effective mechanisms of addressing parents’ concerns. Healthcare workers should develop approaches that acknowledge parental concerns and respectfully try to correct their misconceptions. The attitude of male partners against immunization is often noted in this review. A study carried out in Cambodia suggested that women’s decision-making power and autonomy were relevant to maternal and child health outcomes [ 60 ] It is important to carefully consider the social contexts during program design and implementation for child immunization. We need to effectively address socio-cultural contexts by involving the entire community, and not only target mothers and female caregivers. The review also raised the pressing need for women to be empowered to overcome their financial challenges in taking their children to vaccination centers.

Equally challenging is overcoming health system barriers identified, including staff shortage, the cost of maintaining the cold chain, storage and transportation of vaccines and consumables. The long distances between health centers and the families they serve are barrier that require systemic policy changes to address. The data suggest that countries should increase government financial gross domestic product (GDP) allocation to their health sector, consistent with the recommendation in the Abuja declaration [ 61 ]. Increased financial resources would enable countries to equip and upgrade existing health facilities and to increase their numbers. Targeted resources may motivate and enable staff deployed in remote areas for effective outreach activities to maximize coverage of immunization. Poor arrangement and coordination of immunization seasons at health-center level was noted [ 16 , 38 , 43 , 45 ] this findings reflect a review (conducted in sub-Saharan countries) focus on children and youth which noted that poorly organized services can cause delays and increase costs for beneficiaries [ 62 ]. A coordinated National Immunization Program can rationalize services, thus improve immunization uptake and regulating healthcare providers.

In this review of barriers to childhood immunization, the parental/caretaker’ barriers were mostly identified, followed by health systems and providers’ barriers. It corroborates a systematic review (studies undertaken across countries) which noted that, family characteristics, parents’ understanding about vaccines and attitude were marked factors to non-immunization of their children. These pose a challenge to immunization programs due to its complexity and require strategic interventions [ 63 ]. A published article exploring vaccine hesitancy stated that various attitudes seems to result into specific categories; for instance, vaccine refusal attitude could be as a result of having little or no knowledge about vaccine, lack of trust on the vaccine or it could as well linked to financial limitations [ 64 ]. This finding disagreed with previous systematic review conducted in middle- and low -income countries. It indicated that the main factors that impede vaccination uptake and coverage were associated with healthcare system [ 55 ]. Some of the barriers cited may be modifiable within the constraints of overstretched health systems. Others may require systemic policy changes to address. Some healthcare system related factors can be realistic to design strategies that can be implemented in a range of settings, such as training of health workers to reduce missed opportunities, improve communication, and remove barriers by enhancing outreach services.

Study limitations

Our study acknowledged and outlined few limitations. As most literatures cited are observational in nature, this study cannot confirm causation nor completely rule out confounding. A few studies also relied on survey data [ 7 , 12 , 18 , 27 , 37 , 40 , 41 ] with the potential for selection or nonresponse bias. Population-based data studies may be liable to misclassification or measurement error, leading to information biases. Retrospective studies of caretakers/parents beliefs are subject to recall bias. Lack of protocol registration of this review may limit the evidence to demonstrate that, components of the research plan have been fully addressed. The review also lack grey literature/unpublished literature searching with potential for publication bias. Majority of the studies were conducted in East Africa [ 1 , 3 , 11 , 12 , 13 , 16 , 17 , 19 , 20 , 21 , 25 , 27 , 28 , 32 , 34 , 38 , 43 , 44 ] and West Africa [ 1 , 15 , 18 , 22 , 23 , 24 , 29 , 30 , 31 , 33 , 36 , 37 , 39 , 40 , 41 , 42 , 45 , 46 ] limiting generalizability to the rest of the continent. A quantitative meta-analysis from these studies may have been useful for analyzing quantitative trends, although the heterogeneity of the studies precluded such analyses.

Although various methods of improving vaccination coverage in sub-Saharan Africa have been identified, achieving the desired levels for the realization of the fullest benefits of immunization is still a major challenge. This can be achieved through combined efforts of healthcare systems and providers; and address people, the communities and societies in which they live. Aggregation of known immunization barriers and the evidence on effective interventions to address these barriers should be core component of immunization programs in Sub-Saharan Africa and elsewhere.

Availability of data and materials

Not applicable.

Abbreviations

Diphtheria–tetanus-pertussis vaccine third dose

Bacillus calmette–guérin

Preferred reporting items for systematic reviews and meta- analysis

Gross domestic product

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Acknowledgements

We would like to thank Emmanuel Osman Kamara from the Language Art Department, Earnest Bai Koroma University of Science and Technology, Sierra Leone for his assistance with English Language editing.

China Medical Board funded the study. Grant number [CMB-14-188]; the funding agency did not play any role in the preparation of this study; study design, data collection, analysis, writing and decision to submission.

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Joseph Benjamin Bangura, Shuiyuan Xiao & Feiyun Ouyang

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JBB and SX conceived the review protocol. JBB, DQ, FO were involved in the data extraction and quality assessment. JBB, LC, SX involved in data synthesis and creation of table; JBB drafted the manuscript with input from all authors. All authors read and approved the final manuscript and submission.

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Additional file 1..

Database search terms and history. Methodological Quality Assessment tool for Qualitative and Quantitative studies. Full-text articles excluded with reasons.

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Bangura, J.B., Xiao, S., Qiu, D. et al. Barriers to childhood immunization in sub-Saharan Africa: A systematic review. BMC Public Health 20 , 1108 (2020). https://doi.org/10.1186/s12889-020-09169-4

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• Volume 14, Issue 2
• Effective interventions for improving routine childhood immunisation in low and middle-income countries: a systematic review of systematic reviews
• Article Text
• Article info
• Citation Tools
• Rapid Responses
• Article metrics

• http://orcid.org/0000-0001-5428-377X Monica Jain 1 ,
• Maren Duvendack 2 ,
• Shannon Shisler 3 ,
• http://orcid.org/0000-0002-8824-9198 Shradha S Parsekar 1 ,
• Maria Daniela Anda Leon 3
• 1 International Initiative for Impact Evaluation , New Delhi , Delhi , India
• 2 University of East Anglia , Norwich , UK
• 3 International Initiative for Impact Evaluation , Washington , DC , USA
• Correspondence to Dr Monica Jain; mjain{at}3ieimpact.org

Objective An umbrella review providing a comprehensive synthesis of the interventions that are effective in providing routine immunisation outcomes for children in low and middle-income countries (L&MICs).

Design A systematic review of systematic reviews, or an umbrella review.

Data sources We comprehensively searched 11 academic databases and 23 grey literature sources. The search was adopted from an evidence gap map on routine child immunisation sector in L&MICs, which was done on 5 May 2020. We updated the search in October 2021.

Eligibility criteria We included systematic reviews assessing the effectiveness of any intervention on routine childhood immunisation outcomes in L&MICs.

Data extraction and synthesis Search results were screened by two reviewers independently applying predefined inclusion and exclusion criteria. Data were extracted by two researchers independently. The Specialist Unit for Review Evidence checklist was used to assess review quality. A mixed-methods synthesis was employed focusing on meta-analytical and narrative elements to accommodate both the quantitative and qualitative information available from the included reviews.

Results 62 systematic reviews are included in this umbrella review. We find caregiver-oriented interventions have large positive and statistically significant effects, especially those focusing on short-term sensitisation and education campaigns as well as written messages to caregivers. For health system-oriented interventions the evidence base is thin and derived from narrative synthesis suggesting positive effects for home visits, mixed effects for pay-for-performance schemes and inconclusive effects for contracting out services to non-governmental providers. For all other interventions under this category, the evidence is either limited or not available. For community-oriented interventions, a recent high-quality mixed-methods review suggests positive but small effects. Overall, the evidence base is highly heterogenous in terms of scope, intervention types and outcomes.

Conclusion Interventions oriented towards caregivers and communities are effective in improving routine child immunisation outcomes. The evidence base on health system-oriented interventions is scant not allowing us to reach firm conclusions, except for home visits. Large evidence gaps exist and need to be addressed. For example, more high-quality evidence is needed for specific caregiver-oriented interventions (eg, monetary incentives) as well as health system-oriented (eg, health workers and data systems) and community-oriented interventions. We also need to better understand complementarity of different intervention types.

• Community child health
• Paediatric infectious disease & immunisation
• Health policy
• Systematic Review

Data availability statement

Data are available upon reasonable request. The systematic reviews and other documents included in this study are public and available. The data extracted from these studies are available from the corresponding author upon request.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/bmjopen-2023-074370

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STRENGTHS AND LIMITATIONS OF THIS STUDY

This review synthesises the evidence base on routine child immunisation interventions in low and middle-income countries at a higher level of abstraction (ie, at the systematic review of systematic reviews level), thus filling a gap in the literature.

Our review uses an intervention taxonomy that was developed and refined based on existing literature, extensive discussion, pilot testing and expert feedback allowing an assessment of interventions oriented towards caregivers, health systems, communities as well as those outside the health realm separately.

Our review synthesises the evidence both quantitatively through meta-analysis and qualitatively, therefore providing insights into where evidence exists and point out critical evidence synthesis gaps.

The review cautions on the interpretation of our findings because of methodological challenges, including mixed quality of the included systematic reviews and of the primary studies that have included in their synthesis as well as small sample bias.

Introduction

In 2019, close to 20 million children in low and middle-income countries (L&MICs) did not receive the three recommended doses of diphtheria, pertussis and tetanus (DPT) vaccines, often used as an indicator to assess countries’ performance on routine immunisation. 1 Ten countries, in particular Nigeria, India, the Democratic Republic of Congo and Pakistan, account for two out of five unvaccinated children globally. 2 Many L&MICs struggle to achieve high immunisation coverage due to challenges on both the supply and demand side. Examples of supply side constraints include limited availability of health personnel and difficulties in building up their capacity and skills as well as lack of reliable monitoring and surveillance systems to identify and monitor unvaccinated and undervaccinated children. 3 Demand side issues linked to behavioural, social and practical constraints faced by caregivers also play a role, including concerns about vaccine safety, lack of knowledge of when and where to vaccinate their children, fears about vaccination side effects and difficulties in accessing health services. 4 Governments in L&MICs have strengthened national-level immunisation interventions to address supply side constraints and are increasingly focusing on addressing constraints faced by caregivers and communities. To support policymakers and practitioners in making evidence-informed decisions on the interventions that have been effective in addressing the barriers to routine vaccination uptake, it is imperative to provide systematically synthesised evidence.

Several methodologically robust impact evaluations and systematic reviews evaluating the effectiveness of these approaches have been published in the past decade. 5–12 However, there has been no attempt yet to synthesise this extensive evidence base at the meta-level with the exception of Heneghan et al 13 and Besnier et al . 14 First, Heneghan et al qualitatively synthesise child and adult immunisation interventions in both L&MICs and high-income countries (HICs) finding inconclusive results for L&MICs due to the small number of reviews for these countries, inadequate definitions of interventions and suboptimal reporting of interventions in the reviews. Second, Besnier et al examine interventions focusing on improving child health using narrative synthesis tools; they find positive effects of interventions improving immunisation communication, education and social mobilisation on vaccine uptake. While the evidence base on this topic is growing rapidly, Engelbert et al 15 demonstrate that there are clear evidence gaps preventing us from fully understanding what type of immunisation intervention works best, for whom, how and where. This is the first systematic review of systematic reviews with the primary goal to provide more clarity on the type of interventions that are effective in improving routine immunisation outcomes for children in L&MICs. Establishing what is and is not known about the effectiveness of such interventions is crucially important to inform policymakers and practitioners.

Search strategy and selection criteria

This is a systematic review of systematic reviews adopting a mixed-methods approach including a meta-analysis and narrative elements. It draws on the intervention-outcome framework ( online supplemental appendix 1 ) developed by Engelbert et al 15 which distinguishes interventions by different levels, that is, 1st, 2nd and 3rd tiers focusing on the supply side (health system oriented) as well as the demand side (caregiver oriented). It also allows for the identification of community-oriented interventions as well as for those which are non-health policy oriented. This framework guides the presentation of our results. In terms of study design, we included systematic reviews with and without meta-analyses. The population of interest included children below the age of 5 living in L&MICs, but we occasionally included other populations, for example, caregivers and health workers, especially when these were relevant to understanding the impact of immunisation programmes on intermediate outcomes such as attitudes about vaccination, and access to immunisation services. We included studies examining the impact of any intervention on at least one outcome in relation to routine child immunisation. These outcomes are coverage rates or timeliness of full immunisation, third dose of DPT or pentavalent, or measles; additional antigen-specific immunisation coverage outcomes; and intermediate outcomes that precede them in the theoretical causal chain (eg, attitudes about vaccination and access to immunisation services). The detailed eligibility criteria can be found in online supplemental appendix 2 . There were no inclusion restrictions by publication status or language, but studies were excluded when they did not meet our definition of systematic reviews, when they were not effectiveness or intervention reviews, or when they only focused on HICs ( online supplemental appendix 3 ).

Supplemental material

We adopted a comprehensive search strategy that was initially designed for an evidence gap map (EGM) 15 examining the routine child immunisation sector in L&MICs. The search strategy included electronic searches of academic databases and the grey literature, that is, institutional websites ( online supplemental appendix 4 ). The search was completed in October 2021. All search results were screened on title/abstract by a team of trained reviewers. Two reviewers independently screened each abstract. During title and abstract screening, weekly reconciliation meetings were held to discuss and resolve disagreements. Full text screening followed the same approach.

Data analysis

Data were extracted by two researchers independently with reconciliation by others in the review team. Any disagreements were resolved by discussion. We extracted data on context, type of intervention, type of review, design and methods used, outcome measures, quality assessment, study results and findings ( online supplemental appendix 5 ). We have only extracted information at the systematic review level.

Non-independence of reviews (or overlap)

Non-independence of reviews (or overlap) is an issue unique to systematic reviews of systematic reviews. Overlap explores to what extent the primary studies included in the pool of systematic reviews are the same or different. We assessed overlap by compiling a citation matrix which includes all the primary studies (one per row) included in the individual systematic reviews (one per column). Primary studies were sorted alphabetically, and duplicates removed. The primary studies that were the same across reviews were ticked with a check mark. This allowed us to calculate the corrected covered area (CCA) index that describes the extent of overlap in per cent terms 16 17 :

where N is the total number of primary studies included in the systematic reviews (the sum of ticked boxes in the citation matrix), r is the number of rows (the primary studies) and c is the number of columns (included systematic reviews). Pieper et al 17 provide criteria for the interpretation of CCA, where 0–5% suggests slight overlap, 6–10% moderate overlap, 11–15% high overlap and >15% very high overlap. Hennessy and Johnson 16 recommend further overlap investigations in case of a heterogenous evidence base, hence we compare subclusters of reviews examining similar outcomes as well.

Assessment of risk of bias in included studies

The quality of systematic reviews is assessed differently compared with assessing the quality of the primary studies included in systematic reviews; this is due to the unique methodological features of systematic reviews. The quality of the included reviews was assessed independently by two researchers using the checklist developed by the Specialist Unit for Review Evidence (SURE) to allow a critical appraisal to ensure that minimum levels of methodological rigour are met. The SURE 18 checklist was slightly adapted ( online supplemental appendix 6 ).

We also extracted information on the quality assessment tools reported in each included review which have been used to assess the quality of the underlying primary evidence base by the reviews. Nevertheless, risk of bias of primary or supplementary primary studies was not assessed.

Data synthesis

We adopted a mixed-methods synthesis approach to best accommodate both the quantitative and qualitative information available. To synthesise the quantitative data, we implemented a robust variance estimation (RVE) meta-regression approach 19 as this performs well even when study numbers are as low as 10. 20

When an RVE meta-regression approach was not possible, we fitted a random-effects model to the data. In this case, the amount of heterogeneity (ie, τ 2 ), was estimated using the DerSimonian-Laird estimator. 21 In addition, we also reported the Q-test for heterogeneity 22 and the I 2 statistic. 23 Studentised residuals and Cook’s distances were used to examine whether studies may be outliers and/or influential in the context of the model. 24 Studies with a studentised residual larger than the 100×(1–0.05/(2×k)) th percentile of a standard normal distribution were considered potential outliers (ie, using a Bonferroni correction with two-sided α=0.05 for k studies included in the meta-analysis). Studies with a Cook’s distance larger than the median plus six times the IQR of the Cook’s distances were considered to be influential. The rank correlation test 25 and the regression test, 26 using the SE of the observed outcomes as predictor, were used to check for funnel plot asymmetry but only when we had more than 10 studies. 27

Risk ratios (RRs) were the most commonly reported effect size, and thus our metric of choice. ORs were converted to RRs using the following formula 28 :

where p is the risk in the control group implying that ORs can only be converted to RRs when the risk in the control group is known. As this is not always the case, we established a range of plausible risks for the control group (Grant 28 ) drawing on data from Jain et al 29 30 on baseline full immunisation rates to find the mean (0.48) and SD (0.22) of the data to be able to convert ORs to RRs. We did these conversions three times as a sensitivity analysis. First, we used 1 SD below the mean to establish the control group rate (0.26—the least conservative model); second, we used the mean as the control group rate (0.48—the baseline model); and finally, we used 1 SD above the mean (0.70—the conservative model) as the control group rate.

Patient and public involvement

No patients have been involved in this study as it is a review article, hence no patient consent for publication was required.

Our search builds on Engelbert et al 15 who had included 58 systematic reviews in their EGM, which we screened against our inclusion criteria. Six of these reviews did not meet our criteria for inclusion and were thus excluded leaving us with 52 studies. We ran additional searches ( online supplemental appendix 4 ); the electronic search led to 1687 records of which 818 were duplicates leaving 869 for screening. We excluded 823 records based on title and abstract screening. The remaining 46 studies were screened by full text, 39 were excluded, leaving seven new studies for inclusion derived from the electronic search. We identified a further seven records searching the grey literature which all required full text screening. Four were subsequently excluded leaving three new studies for inclusion ( figure 1 ). This two-pronged search strategy led to 10 new systematic reviews to be included. Overall, we included a total of 62 systematic reviews—52 studies from the EGM by Engelbert et al 15 and 10 new studies from the updated search. A summary of the included systematic reviews can be found in online supplemental appendix 7 .

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Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. From: Page et al 32 and Haddaway et al. 33 EGM, evidence gap map; L&MICs, low and middle-income countries.

We test overlap by compiling a citation matrix listing all primary studies which is used to calculate the CCA. Table 1 suggests limited overlap of 0.5% confirming our initial investigations. This is confirmed by Pieper et al 17 who provide guidance on the interpretation of CCA values, for example, with values between 0% and 5% indicating slight overlap.

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We compare subclusters of reviews examining similar outcomes as well finding limited overlap for most outcomes, for example, for measles, full routine immunisation for children, DPT3 and vaccination coverage, the CCA values range from 0.7% to 2.7%. Vaccination timeliness has the highest CCA value (6.9%) indicating moderate levels of overlap. 17

Risk of bias

Using the SURE checklist, we find that of the 62 included reviews, 18 are categorised as high confidence, 6 are of medium confidence and 38 are of low confidence ( online supplemental appendix 8 ).

Effectiveness of interventions

Overall, the evidence base is highly heterogenous in terms of scope, intervention types and outcomes. Table 2 (and online supplemental appendix 9 ) summarises the key findings across all high and medium confidence reviews across all intervention categories. Most of the evidence we uncovered is centred on caregiver-oriented interventions (A) that have positive and statistically significant effects at the first and second tier analysis level ( online supplemental appendices 10 and 11 for findings with details on intervention coding and level of analysis in table 2 — online supplemental appendix 9 ). At the third tier level, our analysis confirms the favourable trends emerging from the first and second tier analyses. For short-term sensitisation and education campaigns (AA2— figure 2 ), we find that the average RR was 1.38 (95% CI 1.33 to 1.44), suggesting that the average outcome differed significantly from zero (z=47.37, p<0.001). As for written or pictorial messages (short message service (SMS), stickers, flyers, etc) to caregivers (AB4— figure 3 ), we find that the average RR of the baseline model stands at 1.24 (95% CI 1.11 to 1.36, p<0.001). Overall, third tier intervention categories are reporting positive and statistically significant effects, which suggest that treated children are more likely to be vaccinated than untreated children. Another intervention category at the third tier for which there is a large evidence base is monetary incentives (AB1) (The evidence on monetary incentive (AB1) interventions is dominated by qualitative narrative methods. There are only two reviews with quantitative evidence, but we could not use them for quantitative synthesis as we were not able to convert effect sizes from standardised mean difference (SMD) to RR) and the evidence is mixed.

Summary of findings

Random-effects (RE) model of short-term sensitisation and education campaigns (AA2). Intervention and outcome codes are taken from online supplemental appendix 1 . DPT, diphtheria, pertussis and tetanus.

Robust variance estimation (RVE) of interventions of written or pictorial messages to caregivers (AB4), mean baseline coverage values. Intervention and outcome codes are taken from online supplemental appendix 1 . DPT, diphtheria, pertussis and tetanus.

For the health system-oriented interventions (B) we had no quantitative evidence, thus we could only rely on narrative synthesis and the results are mixed ( online supplemental appendix 12 ). Depending on the exact nature of the intervention, the contextual background and the specific outcome, the findings range from favourable to inconclusive effects. Among these interventions, the only intervention category at the third tier for which we find positive effects is home visits (BB7). We find mixed results for pay-for-performance schemes (BD5) which have a large evidence base both at the primary study and review level. Additionally, we find inconclusive results based on a thin evidence base for health systems financing (BF4) interventions in which health services are contracted out to non-governmental providers and they are compensated for it. For a third tier category like health system strategic planning (BF1), though the evidence base is large when it occurs in combination with other interventions, that is, as multicomponent interventions, the evidence base for single interventions is rather limited and inconclusive.

As for community-oriented interventions (C and D), the evidence base is very limited, focused on narrative synthesis and finding inconclusive results ( online supplemental appendix 13 ). However, a recent review 29 30 on single and multicomponent community engagement interventions (F) uses a nuanced framework to classify them based on the process of engaging communities and finds them to be effective using meta-analytical methods. We found no evidence on interventions related to non-health-related policies and institutions (E).

This review also assessed the interventions aiming to improve zero dose outcomes through DPT1 and BCG vaccine uptake. We find four reviews suggesting inconclusive evidence for interventions improving DPT1 outcomes. However, for BCG vaccine uptake we find pay-for-performance schemes (BD5—one qualitative review) and community engagement interventions (C and D—one quantitative review) to be effective.

Through this review we have demonstrated that a wealth of systematic reviews on interventions impacting routine child immunisation outcomes exists, but many are very broad in their scope, and hence may not provide a clear answer on all the different types of interventions that may or may not work best for improving immunisation outcomes of children in L&MICs.

For caregiver-oriented interventions (A) the evidence base is of reasonable quality and sufficiently large compared with that on health systems (B) and community-oriented (C and D) interventions. We also find that caregiver-oriented interventions, like those focusing on short-term sensitisation and education campaigns (AA2) as well as written messages to caregivers (AB4), are effective with most findings suggesting positive and statistically significant results. On the other hand, for health system-oriented interventions the evidence base is thin with narrative synthesis approaches dominating and suggesting inconclusive results. For community-oriented interventions the evidence base is limited, but a recent review 29 30 provides high-quality evidence on the effectiveness of community engagement interventions with mostly positive and statistically significant results. Overall, the evidence base provides clearer answers on the effectiveness of caregiver-oriented interventions and to a certain degree of community-oriented interventions than of health system-oriented interventions.

Strengths and weaknesses

We have contributed to the literature by synthesising the evidence base on routine child immunisation interventions in L&MICs at a higher level of abstraction (ie, at the systematic review of systematic reviews level) and this brings about a number of methodological challenges. For example, the validity of this review depends on the coverage and quality of the underlying evidence base and thus using the SURE checklist we drew attention to the mixed quality of the primary evidence base that informed the findings of our included systematic reviews. Consequently, caution must be exercised in the interpretation of the systematic review evidence, especially as no mitigating actions were taken to deal with potential biases. One of the ways to ensure robustness of evidence is to provide subgroup analysis that disaggregates by levels of confidence. However, the majority of the included systematic reviews did not provide subgroup analysis because their analyses were mostly based on small study samples that were not sufficient for credible subgroup analyses. In addition, we were faced with high levels of heterogeneity and a wide range of synthesis approaches limiting our pool of studies for meta-analysis. We addressed these limitations to a certain extent by also considering qualitative evidence. Generally, we have dealt with these methodological challenges as much as possible following guidance provided by the Cochrane and Campbell Collaborations. Finally, most of the included studies did not pay sufficient attention to unpacking causal mechanisms which limited our ability to firmly conclude how and for whom routine child immunisation interventions are working.

Implications for policy and practice

Implications for caregiver-oriented interventions.

The caregiver-oriented interventions are effective. Sensitisation and education campaigns (AA2) mostly address the knowledge gaps of caregivers on the importance of vaccinations, importance of maintaining a schedule and potential misconceptions around vaccinations. This information is delivered by either frontline health workers or trained facilitators at the health facility, at caregiver homes or in community groups. The SMS reminders (AB4) delivered to the mobile phones of caregivers address the practical barriers that they face regarding when and where to take their child for a vaccine or follow-up doses. Thus, these interventions can be effective in improving vaccine uptake in communities where such barriers are prevalent.

In the last decade, a lot of the attention of researchers, programme implementers and policymakers has been on how to motivate caregivers to vaccinate their children through monetary incentives and there have been a substantial number of experiments involving conditional and/or unconditional cash transfer schemes to assess their effectiveness in improving immunisation outcomes. 15 However, the evidence does not provide a clear answer on their effectiveness and there is a need for an updated review with a more inclusive search strategy for identifying relevant articles published in non-health journals.

Implications for health system-oriented interventions

Among the health system-oriented interventions, home visits (BB7) are worth considering for improvement in vaccine uptake as we find them to be effective. For pay-for-performance schemes (BD5) we find mixed evidence. As a recent review 7 of this intervention category is available and of high quality, there is no need for an update and policymakers can consult it for more details.

Two intervention categories which are of specific policy relevance and would benefit from a stronger evidence base are: (a) interventions focusing on building skills, capacity and motivation of formal health workers (BA1, BA2, BD1, BD2) and (b) new Health Management Information System (HMIS)/dashboard systems (BG1), that is, interventions leveraging digital technologies, which are increasingly being adopted and expanded across L&MICs. For both these intervention categories, Engelbert et al 15 found a substantial number of primary studies, though most were not single but multicomponent interventions.

While the evidence on health system-oriented interventions in the context of immunisation is limited, policymakers seeking to strengthen health systems for the purpose of improving immunisation outcomes can consult the broader literature on health system strengthening for guidance. In fact, there is a systematic review of reviews available, 31 which synthesised evidence that assessed the effects of health systems strengthening interventions on health status and health system outcomes (service utilisation, quality service provision, uptake of healthy behaviours and financial protection) in L&MICs, which may be helpful depending on its quality.

Implications for community-oriented interventions

For guidance on effectiveness of community-oriented interventions, the recent review by Jain et al 29 30 can be consulted as it is comprehensive, provides quantitative evidence and uses a nuanced framework to classify community-oriented interventions based on the process of engaging communities.

Implications for research

Besides addressing critical evidence gaps as described in the section above, we also need to better understand complementarity of interventions, for example, some reviews analysed combinations of caregiver and health system-oriented intervention types (bridging the demand and supply side gaps) finding favourable but also inconclusive effects. We do not yet know which intervention combinations work best in terms of improving immunisation outcomes. Further theory development may be a starting point for contributing to a better understanding of the enablers and barriers of interventions as well as unpacking underlying causal mechanisms and thus improving the selection and targeting of immunisation programmes.

In addition, future research needs to engage more with cost-effectiveness of interventions as we need to learn about what works and at what cost to enable selection of the most impactful and most cost-effective interventions to improve routine child immunisation outcomes. Further work is also needed in improving the quality of both systematic reviews and primary studies. At the review level future research should attempt more subgroup analyses by levels of confidence in primary studies to instil more trust in the results. At the primary study level, researchers should use more robust evaluation methods to minimise the potential biases in the measurement of effects. More work is required to develop user-friendly quality assessment tools for systematic reviewers that minimise the scope for subjective judgements.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

The ethical approval was not required for this umbrella review as all the data were generated from published systematic reviews.

Acknowledgments

This research has been undertaken as a part of 3ie’s immunisation evidence programme, supported by the Bill and Melinda Gates Foundation, Seattle, USA. We thank Sohail Agha, previous Senior Program Officer, Gates Foundation, Seattle, for his support in conceptualisation as well as engagement on the review. Special thanks to Tove Ryman, Senior Program Officer, Gates Foundation, Seattle, whose guidance helped shape the analysis and dissemination of this review. We thank Mark Engelbert who was instrumental in guiding the search process and Avantika Bagai who provided support in the initial phase of the review. We also thank Birte Sniltsveit at 3ie for her comments on this review and Sebastian Martinez at 3ie for his overall support of the review.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1

Twitter @ParsekarShrads

Contributors MJ conceived the review. MJ, SS and MD wrote the protocol. SSP and DA did the systematic search. SSP and MDAL screened and identified studies and MJ and MD made the final decisions regarding study inclusion. SSP and MDAL did the data extraction and critical appraisal. SS, MDAL and MD did the statistical analysis. MD and SSP did the qualitative analysis. MD and MJ wrote the manuscript. MJ provided critical inputs on the whole analysis, checked the data, coordinated the review and had full access to all materials and results. All authors critically reviewed and revised the manuscript and approved the final document for submission. MJ is responsible for the overall content and is the guarantor of this review.

Funding This research was funded through a grant from the Bill & Melinda Gates Foundation (INV-008461) to the International Initiative for Impact Evaluation (3ie). Through this grant the following work has been commissioned: (a) 3ie provided funding and technical assistance for seven impact evaluations of community engagement interventions for immunisation; (b) 3ie conducted a systematic review of community engagement interventions to assess their effectiveness in improving routine child immunisation in L&MICs; and (c) 3ie conducted an evidence gap map on routine child immunisation in L&MICs.

Disclaimer The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Competing interests As members of 3ie staff, MJ had been involved in reviewing deliverables for the evaluations funded by 3ie and providing research teams with technical assistance. MJ, SS, MDAL and SSP have also worked as authors on the systematic review and MJ and SSP have been coauthors of the EGM report. Among these, only the work on the systematic review could pose a potential conflict of interest. However, several procedural safeguards and transparency measures were put in place to mitigate the risk this conflict of interest imposed. All candidate systematic reviews, including the one carried out by 3ie, have undergone a rigorous screening and critical appraisal process by two independent screeners. The authors have no financial interest in this area. MD has authored systematic reviews and systematic reviews of reviews but largely on issues related to financial inclusion. MD is also an editor of the International Development Coordinating Group at the Campbell Collaboration, but this will not pose any conflicts of interest.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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Immunizations and autism: a review of the literature

Affiliation.

• 1 Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
• PMID: 17168158
• DOI: 10.1017/s031716710000528x

Because of a temporal correlation between the first notable signs and symptoms of autism and the routine childhood vaccination schedule, many parents have become increasingly concerned regarding the possible etiologic role vaccines may play in the development of autism. In particular, some have suggested an association between the Measles-Mumps-Rubella vaccine and autism. Our literature review found very few studies supporting this theory, with the overwhelming majority showing no causal association between the Measles-Mumps-Rubella vaccine and autism. The vaccine preservative thimerosal has alternatively been hypothesized to have a possible causal role in autism. Again, no convincing evidence was found to support this claim, nor for the use of chelation therapy in autism. With decreasing uptake of immunizations in children and the inevitable occurrence of measles outbreaks, it is important that clinicians be aware of the literature concerning vaccinations and autism so that they may have informed discussions with parents and caregivers.

Publication types

• Autistic Disorder / etiology*
• Preservatives, Pharmaceutical / adverse effects
• Thimerosal / adverse effects
• Vaccination / adverse effects*
• Vaccines / adverse effects*
• Preservatives, Pharmaceutical

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• Hum Vaccin Immunother
• v.19(2); 2023
• PMC10619519

Challenges of vaccination information system implementation: A systematic literature review

Muhamad adhytia wana putra rahmadhan.

Faculty of Computer Science, Universitas Indonesia, Depok, Indonesia

Putu Wuri Handayani

Globally, healthcare services have begun to show interest in switching from paper-based to electronic-based vaccination records through Vaccination Information Systems (VIS). VIS have been implemented in various countries, but the study on the challenges of implementing VIS in these countries is still limited. The challenges of implementing VIS need to be understood to become a subject of discussion and anticipation by other countries that are just starting to implement VIS. We analyzed 32 selected publications from 634 initially retrieved. Fourteen challenges were successfully identified when implementing VIS, including interoperability, data quality, security and privacy, standardization, usability, internet connectivity, infrastructure, workflow, funding, government regulations, awareness, skeptical response, computer literacy, and staff-related challenges. The challenges of interoperability and data quality were found to be the most widely discussed by previous studies. In addition to identifying the challenges, this study includes a series of solutions that can be applied to overcome each challenge.

Introduction

According to the definition of the World Health Organization (WHO), immunization is the process of making oneself immune to a contagious disease, which is usually done through vaccination. 1 , 2 On the other hand, the definition of immunization, according to the Center for Disease Prevention and Control (CDC), is a process where a person becomes protected from disease through vaccination. 1 , 3 The term immunization is often used interchangeably with vaccination. 3 Therefore, the use of the terms immunization and vaccination in this study will have the same meaning, which is the administration of a vaccine into the body to gain immunity against a contagious disease.

Vaccination plays an important role in public health by reducing the morbidity and mortality rate, reducing healthcare costs, and reducing the use of healthcare facility resources. 4–6 In addition, vaccination has also been recognized as one of the most impactful public health interventions, preventing 4–5 million deaths worldwide each year. 7 If vaccination coverage can be increased globally, vaccination can prevent more than 1.5 million deaths from infectious diseases. 7 Meanwhile, in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and COVID-19 vaccination, COVID-19 vaccination has been predicted to prevent 14.4 million deaths, representing a global reduction of 79% of deaths (14.4 million out of 18.1 million) in the first year of COVID-19 vaccination implementation. 8 Therefore, in most countries in Europe, vaccination is actively recommended by public health authorities. 9

Historically, data related to vaccination, especially in developing countries, was recorded manually using paper-based records. 10 This data is then summarized monthly and entered into an electronic database for reporting purposes. 10 However, such data recording methods often face problems. The impracticality of using paper-based records to calculate vaccination coverage often leads to problems such as inaccurate data caused by recording errors, lack of data completeness, or delay in reporting data. 11–13

As technology advances, global health services have begun to show interest in switching from paper-based vaccination records to electronic records through Immunization or Vaccination Information Systems (VIS). 14 VIS are a confidential, population-based and computerized information system that aims to record, store and provide access to consolidated individual vaccination information. 15 VIS are comprehensive and covers a wide community, including individuals in different geographical areas and health service providers. 16–18

Vaccination records through VIS have been proven to bring many benefits. The benefits of electronic vaccination records through VIS include 1) systematic recording and collection of immunization data, 2) easy access and retrieval of vaccination data, and 3) analysis, reporting, and facilitation of the use of vaccination data for public health decision making in the future. 19–21 The transition from paper to electronic records through VIS will support the use of vaccination data in reducing the morbidity and mortality rate attributed to the vaccine preventable disease. 14 In addition, VIS has been further developed to address the fragmented record-keeping problem by combining an individual’s vaccination information with a particular geographic area. 22

In general, effective implementation of VIS can increase the public’s decision to vaccination and increase access to vaccination, ultimately increasing vaccination uptake rates. 23 A Study in the United States has also shown that electronic vaccination records through VIS provide more complete records than medical records made on paper or reports given by parents. 10 The various benefits provided by VIS make the implementation of VIS worth considering.

Previous studies have discussed the determinants of vaccination acceptance, 24 acceptance or intention to use health information systems, 25–27 and studies on the use of vaccination applications. 23 , 28 A previous study has also conducted a literature review to determine the effectiveness of VIS in increasing vaccination rates and reducing the number of diseases that can be prevented by vaccination, 23 a literature review to determine the benefits produced by the functionality of VIS in overcoming doubts in the public to accept vaccination, 29 and a literature review to determine the vision for the development of VIS, particularly in the context of middle-to-high-income countries. 30

VIS has been implemented in various countries, however, the literature review studies that focus on the challenges of implementing VIS in these countries are still limited. Thus, it is important to understand the challenges of implementing VIS so that it can be discussed and anticipated by other countries that are just starting to implement VIS. This study aims to conduct a literature review to understand the challenges that occur in the implementation of VIS in various countries. This study will present the implementation of VIS in various countries, the challenges that arise in implementing VIS, and what can be done to overcome these challenges.

This systematic review follows the guidelines set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). 31 Using the PRISMA guidelines has been widely adopted by previous researchers in various fields, such as Valverde-Berrocoso et al. 32 in the field of e-learning, Kautsarina and Kusumawati 33 in the field of the Internet of Things (IoT), and Handayani et al. (2018) 34 and Harahap et al. 35 in the field of health. PRISMA is suitable for studies related to healthcare interventions, producing a transparent and comprehensive systematic review. 36

Search strategy

This study’s articles search was done using online databases Scopus, Science Direct, IEEE Xplore, and PubMed. The keywords used to search for relevant articles were: “(“immunization information system” OR “vaccination information system” OR “immunization registry” OR “vaccination registry”) AND (“issue” OR “challenge” OR “implementation”).” The search was carried out to find journal articles or conference proceedings published in the last five years, from January 2017 to December 2022. The authors also reviewed the reference lists included in the articles to make sure that the review was more comprehensive.

Eligibility criteria

The authors established the inclusion criteria as a guideline in selecting the articles to be used. The articles used in this study must be available in full text, written in English, be a primary research article, focus on the implementation of VIS, and discuss the challenges in implementing VIS. In this study, the VIS discussed includes an VIS that records vaccination activities that encompass a wide range of diseases that can be prevented with vaccines. In addition, the subjects recorded in the VIS are not limited to a particular age group, so it covers all ages.

Study selection

The selection of articles used in this study consists of several steps as follows:

Keywords or search strings are used to search for articles in each online database mentioned previously. Duplicate articles are then checked and removed.

Articles are selected based on the compatibility of their title and abstract with the eligibility criteria previously explained. Articles that do not meet the inclusion criteria are then eliminated.

Articles not eliminated in the previous stage are then read in full text to determine if the articles are eligible to be included in the final synthesis based on the eligibility criteria. The reference list from the included articles is also checked to identify the possibility of additional relevant articles.

Data extraction and synthesis

Data extraction was done manually using Microsoft Excel software. The information extracted from the selected articles includes: article title, year, journal source, research object country, vaccination target, name of VIS, research method, and challenges of VIS implementation. The author then used this extracted data to synthesize and group the challenges explicitly and implicitly discussed in the selected articles into several major themes: people, process, technology, and external environment. The technology theme was then further divided into smaller categories, including data, software, or hardware. Subsequently, recommendations for handling these challenges were synthesized so readers and stakeholders could anticipate similar problems when implementing VIS.

The search for articles from online databases successfully identified 634 articles published between 2017 and 2022. From these 634 articles, duplicates were removed and 574 unique articles without duplicates were obtained. The process was then continued with the selection of titles and abstracts, which eliminated 442 articles because they were not related to VIS and were not primary research. Of the 132 articles that passed the title and abstract selection, 132 were selected based on the full text in accordance with the eligibility criteria outlined earlier. Full-text selection successfully eliminated 102 articles, leaving 30 articles that would be further analyzed. Subsequently, two more articles were added based on the results of the reference list examination. The flow diagram of the articles search process can be seen in Figure 1 . In total, 32 articles were included in this study.

Flow diagram of the article selection process.

Study characteristics

The included article in the review comprises articles published from 2017 to 2022. Out of the final selection of articles, 2 were published in 2017, 6 in 2018, 3 in 2019, 9 in 2020, 7 in 2021, and 5 in 2022. When categorized based on the type of articles, 29 were journal articles, and 3 were conference proceedings. Of the 29 journal articles, most of them were published in the journal Vaccine (8 articles) and the Journal of the American Pharmacists Association (5 articles). Classification of articles based on the source of publication can be seen in Figure 2 .

Classification of articles based on journal sources.

The majority of the reviewed articles indicates that study related to VIS is still centered on developed countries such as the United States (US). The selected articles come from various countries, including the US (15 articles), Nigeria (2 articles), Tanzania (2 articles), India (2 articles), Zambia (2 articles), Italy (1 article), Pakistan (1 article), Brazil (1 article), Sweden (1 article), Kenya (1 article), Mexico (1 article), Peru (1 article), United Arab Emirates (1 article), Sierra Leone (1 article), Bangladesh (1 article), European Union (1 article), and Vietnam (1 article). A representation of these countries can be seen in Error! Reference source not found .. It should be noted that some of the research studies were conducted in more than one country, so if the numbers in Figure 3 are summed, the total will be more than 32 articles.

Countries involved in VIS study.

Various countries around the world are known to have great interest from both the community and health officials to develop and implement VIS. 15 Although the interest of various countries in implementing VIS is increasing, this of course is not free from various challenges that arise during the development and implementation of VIS. Some of these challenges include interoperability, data quality, security, and privacy, etc. These challenges are then grouped into several major themes, namely people, process, technology, and external environment. The technology theme is then divided into smaller categories consisting of challenges in the fields of data, software, or hardware. A summary of these challenges can be seen in Table 1 .

Challenges in VIS implementation.

Interoperability

Interoperability in the context of health information systems is the ability of a system to work together and share information effectively and efficiently, with the aim of improving the delivery of effective health services to individuals and communities. 56 Meanwhile, according to ECDC (2018), 15 interoperability in the context of eHealth refers to the ability of two or more systems to exchange data. Interoperability can be seen through three aspects: legal interoperability, semantic interoperability, and technical interoperability. 15

In the studies included in this review, interoperability was one of the most frequently mentioned challenges. Interoperability between VIS and other health systems, such as electronic health records (EHRs) and electronic medical records (EMRs), is a common challenge experienced from the use of VIS. 40 , 44 , 49 , 50 , 53 , 54 VIS users even stated that they would use VIS voluntarily if VIS could be integrated into the government’s health care system. 44

Conventional data exchange mechanisms occur centrally, creating many vulnerabilities such as data breaches, access control, and the potential for single point failures. 48 Critical health information is not shared freely globally due to concerns about privacy and security. 48 However, this limited data exchange causes various obstacles, 45 ranging from vaccination records that cannot be accessed when someone moves from one location to another, 43 , 53 to the possibility of data duplication, 43 , 56

Challenges related to interoperability arise for several reasons, one of which is due to the lack of a nationally recognized ID used to support interoperability with other health information systems. 37 This is due to the lack of specific standards related to vaccination and the data elements needed by vaccination applications. 14 The interoperability challenge is further exacerbated by limited supporting policies and varying information systems. 46

Enabling automatic data exchange between VIS and other health information systems will overcome many challenges faced by healthcare workers. 45 Data standards are one way to produce data that is easily exchangeable and of high quality. 15 Data standards are documented agreements on the representation, format, and definition of data, as well as agreements on the rules for how data is recorded to ensure consistency across sources. 15 Without data standards, the future of interoperability becomes difficult to achieve.

One commonly used international standard or framework for interoperability is Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR). 67 HL7 FHIR standard defines how health information can be exchanged between different systems. 68 In FHIR, each part of the care record can be divided into several parts called resources, so that the required parts can be extracted and reused. 69 The use of FHIR does not require a specific language as it can be represented with UML and written in JSON/XML/RDF. 70 FHIR is an ideal standard for internet-based technology implementation and the use of smartphones. 69 , 70 In addition, the implementation of HL7 between VIS and other health systems is known to improve the quality of recorded immunization data 52 and make the process more efficient. 45

Data quality

The quality of immunization data is an important component in the management of the immunization program. 71 The concept of data quality has been widely discussed and defined, as data that represents the reality of what is expected to be described. 72 Data quality has three main criteria: (1) completeness, which states that data is fully stored, (2) timeliness, which states that data is stored in a timely manner according to the established deadline, and (3) accuracy, which states that stored data does not contain errors. 72

In addition to interoperability, data quality is also one of the challenges mentioned in previous study. This challenge includes the lack of validation and data quality control processes that are entered into the system, 58 health service providers who do not report vaccination, 40–42 , 45 duplicate or incomplete vaccination records, 14 , 43 , 46 , 56 , 60 , 61 untimely recording processes, 39 , 42 , 52 , 53 and stored data that is not accurate. 53 , 62 This data quality condition is found to be worse especially for patients who have become adults. This is because the recording and reporting of vaccination for adults in VIS is generally not mandatory, resulting in incomplete adult vaccination history. 40 , 42 , 59 Another challenge from the quality of data stored by VIS is to maintain up-to-date contact information. 62 Inaccurate and outdated contact information can result in vaccination reminders not being received by patients, which can decrease vaccination coverage rates. 62

The issue of data quality has different handling methods based on the desired criteria for data quality. To ensure the completeness of data, the ideal VIS application should be used and input with data from all vaccination locations (both public and private healthcare providers). 58 The data stored in the VIS must cover the entire population and store information about all vaccination recommended by health authorities. 58 To ensure timeliness and reduce the occurrence of non-reporting due to forgetfulness, the time between vaccination and information input into the VIS must be minimized so that information can be real-time. This is particularly relevant during emergency situations 73 or during outbreaks where quick and accurate identification of unvaccinated individuals is important. 74 To improve accuracy and minimize errors, manual input of detailed vaccination information should be avoided. Some countries in the world have avoided manual data entry using several approaches: (1) the VIS in Spain inputs data using information from barcodes, (2) the VIS in 15 countries uses a dropdown menu so that vaccine information can be selected from a predetermined list, (3) the VIS in Finland and Hungary links VIS vaccination data to the product database, and (4) the VIS in Belgium uploads data from electronic medical records (EMRs) through a web service. 58

Security and privacy

Storing vaccination records digitally through an VIS provides a level of security protection that cannot be provided by paper-based storage, especially when the paper used as a recording medium is lost. 75 The VIS must be hosted on secure hardware and software that meet the standards set for protected personal health information. 15 The security required by the VIS covers encryption mechanisms, disaster recovery, confidentiality and privacy practices, and policies based on related laws or regulations to protect individuals whose data is stored in the VIS. 15

In previous studies, there have been several challenges that arise related to user data security and privacy. Examples of these challenges include the proof or certificate of vaccination stored in the system, which is vulnerable to counterfeiting. 47 Then, the data stored in the system is also vulnerable to abuse by irresponsible parties by sharing the patient’s personal information without consent. 47 , 50 , 76 In addition, there is a concern that too many health workers can access a patient’s complete vaccination history stored in the VIS. 15

The vulnerability to abuse of patient information can be minimized by only granting credentials and passwords to selected health staff. 57 In Denmark, a law was announced in 2015 that determined who could access the data and what data needed to be recorded on the VIS. 15 Furthermore, patients can also determine their data usage in detail, that is, determining which information in their health history can be viewed by health staff. 15 In Tanzania, the government policy of the country requires that all patient data must be hosted locally, not on cloud-based servers, so the security and privacy of the stored data is better protected. 57 In Norway, pseudo-anonymization techniques are applied, where patients are identified through an 11-digit national personal identification number. 15 This identification number is then stored in a separate database but still can be linked to the VIS with a unique message ID. 15

Standardization

Standardization has a close relationship with interoperability. To facilitate the occurrence of interoperability between systems, standardization at the data element level is crucial to consider. 75 Keeping the standardization data requirements simple and practical needs to be the top priority. 75 One form of standardization is the use of standardized terminology and uniformity between one system and another system so that they can communicate with each other. 15

Challenges in standardization can be caused by various reasons, one of which is the multitude of systems being developed or used. 46 , 57 In Italy, the variation in systems is due to the high heterogeneity between regions, making it impossible to use a single software for the national scale VIS. 39 Furthermore, the development of open-source and open-access VIS will result in many versions of the same software, where different institutions will modify the software according to their preferences. 50

The challenges in standardization are also caused by a lack of references used in developing the system. 58 The standardization problems during system development include: (1) incomplete definition of the data elements to be stored by the VIS, 37 , 61 (2) use of non-compatible programming language, 56 (3) errors in defining the functions and information required by the system, 58 and (4) non-systematic documentation of the system. 55

In developing VIS, developers have the option to develop their own standards if desired. However, the development of these standards must be regularly updated, and the management of standards requires specific human, organizational, financial, and technical resources. 15 Another option is for developers to use external reference standards developed and maintained by standards development organizations (SDOs). ECDC (2018) 15 recommends that developers use these SDO-established reference standards as optimally as possible instead of creating their own standards.

The challenges and issues related to the usability of VIS have been successfully identified in the selected studies, which include user difficulties in operating the VIS, 49 , 51 , 56 suboptimal access to VIS, with some VIS not accepting adult vaccination records, 40 , 49 , 59 a lack of active support from developers to continuously improve the quality of VIS, 43 the inability of VIS to adapt to different user information needs, 50 the inability of VIS to input old vaccination data previously carried out, 14 the inability of VIS to produce required vaccination reports, 14 the inability of VIS to track vaccine accountability, 65 the separate operation of VIS from other health care systems, providing an unsatisfactory experience, 42 , 60 manual data input processes without providing automatic mechanisms, 53 , 55 slow and sometimes unusable web interfaces, 53 , 66 and the failure of VIS to perform a certain function. 56

Developers of the VIS system need to involve and consider the needs of users when designing, developing, updating, or improving the functionality of the VIS. The VIS should be designed with a high level of acceptance and user-friendliness in mind. 37 The VIS should also meet the requirements of users and operate smoothly without significant barriers. 37 To maintain the acceptance of the VIS and ensure its smooth operation, a mechanism to monitor VIS operations is necessary so that any issues can be promptly resolved. Additionally, the VIS needs to be updated regularly and adapted to keep up with constantly evolving needs.

Internet connectivity

Connectivity is one of the challenges in implementing an online information system. Many countries have started, as part of their national eHealth strategy, efforts to expand connectivity in the health sector through various policies. 72 In the studies retrieved, there are several challenges related to internet connectivity, such as slow, inadequate, or even unavailable internet, 14 , 56 , 57 , 64–66 the inability of the internet to send relatively large data, 37 and problems with data transmission. 37 Some health workers in Nigeria even use internet from cafes and work at night to get good internet connectivity. 65

The solutions to the internet connectivity challenges include several ways. Firstly, active role from government is needed to expand internet connection coverage to various areas across the country. An example is the Brazilian government, which initiated the “National Broadband Program” aimed at providing broadband internet access to all primary healthcare units, resulting in better healthcare speed and quality, ensuring the safety of healthcare data transmission, and providing real-time access to information. 56 Secondly, the use of VIS can be adjusted to the presence of internet connection. Depending on the limitations in the environment regarding the availability of internet connection in the area of VIS implementation, it is important to determine whether VIS should provide the necessary flexibility for online or offline implementation or a combination of both, utilizing synchronization. 72 Different scenarios should be considered to maintain the quality of stored vaccination data.

Infrastructure

VIS requires some basic infrastructure in its implementation, such as adequate physical space for data entry, availability of electrical resources, temperature control, etc. 72 However, these conditions are often difficult to achieve. Previous study mentions several challenges that arise in the implementation of VIS, such as lack of availability of electrical resources, 43 , 57 problems with storage media due to large data, 37 and lack of supporting hardware (computers, tablets, fingerprint devices, etc.). 43 , 53 , 57

The implementation of a health information system like VIS must include the necessary conditions for proper operation and utilization by users. The necessary infrastructure, as previously explained, must be taken into account and provided. Health information systems increasingly require electrical resources due to the use of internet connectivity for remote access, data entry, and online data storage, meaning technical infrastructure is a critical aspect when considering the implementation of VIS. 77 Additionally, upgrading the server as a data storage medium is also worth considering to address previously mentioned challenges. 37

Double reporting system, through paper media and through VIS, is a challenge in the workflow that has been frequently mentioned in previous study. 14 , 37 , 43 , 50 This causes the vaccination data recording process to be considered inconsistent and inefficient. 43 This problem is further compounded by the data entry process that takes a lot of time because it must be done manually without providing an option for automatic entry. 14 , 45 , 49 , 52 , 53 , 78 In addition, in some regions of the United States, recording vaccination data into the VIS requires individual patient consent, which further complicates the workflow of health workers. 49 In some cases, the process of entering vaccination data into the VIS also does not run optimally because the VIS application is separate from the main workflow of the health service information system and requires health workers to enter the VIS separately. 42 , 60

Modifications to the workflow are needed to address the challenges outlined previously. In Tanzania, the Ministry of Health stated its intention to eliminate the requirement for dual reporting by abolishing paper-based reporting in order to focus on improving VIS implementation. 57 Regular education on the use of VIS in the workflow of healthcare workers as a standard practice also needs to be emphasized. 49 Furthermore, the data entry process for vaccination should also use the Health Level-7 (HL7) approach to allow vaccination data to be automatically uploaded to VIS after the vaccination is carried out and to make the workflow of healthcare workers lighter and reduce the time required. 45 , 52

When developing and implementing an VIS, further consideration should be given to the cost and funding process. For example, there will be costs for developers to make adjustments and maintain the system on a regular basis, as well as costs for public health professionals to monitor the system, including evaluation and identification of further adjustments. 15 Additionally, there may be other technical costs, such as data hosting costs, that need to be considered to ensure the smooth maintenance of the system. 15 To ensure that the VIS does not become an abandoned system, it is important to plan the IIS development project with adequate budgeting for improvement, monitoring, and sustained system maintenance.

The problems identified related to funding and costs from previous study are the lack of financial assistance for healthcare facilities implementing VIS. 46 , 50 , 57 , 58 , 65 This makes some healthcare facilities reluctant to implement VIS because they have to pay for its operational costs independently. 45 Additionally, the costs required for the operationalization of VIS, including training activities, monitoring, and periodic system improvement, are often not anticipated and require relatively high costs. 37 , 49 , 56

Several solutions have been attempted to address the financial challenges. Firstly, predictable funding is required before implementing VIS. 50 Countries lacking funding can delay the implementation of VIS until the resources are available and ideally protected by a long-termstrategy with a clear governance structure and budget guaranteed by law. 50 The country can consider innovative funding models, such as the economic incentives used in Peru. 50 Meanwhile, in the United States, some VIS are part of the CDC’s sentinel sites program which provides funding for VIS projects. 62 In Croatia, financial replacement through health insurance funds has been directly shown to enhance the complete recording of vaccination data given. 15

Government regulations

In the ECDC survey, 58 government is defined as a national or regional body responsible for the daily management of the VIS and the data contained within the system. From the perspective of the European Medicines Agency (EMA) regulation of medicines, VIS are critical in producing timely data to monitor and support vaccination benefit and risk assessment. 79 It is important to have regulations in place to regulate the VIS before implementation begins. The challenges identified from previous study related to government regulations on the VIS include challenges related to VIS ownership, 58 as well as a lack of support from the government or superiors in the implementation of the VIS. 45 , 49 , 50 , 56 , 65

The role of the government in the implementation of VIS is very important and can influence the quality of collected immunization data. Countries with low health service provider participation in using VIS can consider legislation to mandate the participation of health service providers in recording immunizations in VIS. 45 The existence of regulations related to recording vaccination using VIS is known to increase the number of documented vaccination records. 59 , 61

VIS should be under the supervision of the competent government, as shown by a survey conducted by ECDC in 2016 which indicated that the majority of VIS in European countries are owned by the government. 58 With the ownership of VIS by the government, the government can encourage the use of the same VIS application in different health services. In addition, information about someone’s immunization that needs to be recorded consistently and available throughout their life is also better ensured as the immunization data is owned by the government, not by a third-party organization.

Previous study has noted several challenges and issues related to the awareness of healthcare providers or health workers regarding the implementation of VIS. Some healthcare providers are known to be unaware that there is an VIS in their area used to record vaccination records, including adult vaccination. 38 , 49 , 60 This indicates that awareness and access to VIS among some healthcare providers is still relatively low. 45 , 51 In addition, some healthcare providers are also known not to provide reminders to patients who miss vaccination schedules despite having been instructed and trained to do so. 43 In addition to the healthcare side, low awareness of VIS also comes from the public as patients. In some areas in the United States, recording vaccination data into the VIS requires individual patient consent and adult patients are known to refuse to give such consent. 49

Solutions related to awareness have been long been promoted. The first European eHealth action plan was developed in 2004. 15 The action plan aimed to increase awareness of the importance of making eHealth an integral part of the health system. 80 In addition, efforts to increase awareness of VIS can also be done by giving a sense of ownership to vaccination recipients over their records and allowing them to have online access to information about certain vaccination. 58 This sense of ownership of vaccination data is expected to increase vaccination recipients’ awareness of VIS. VIS can also provide opportunities for use as an educational tool for both providers and vaccination recipients. 58 This can be done by creating an easily accessible platform that provides clear information and data visualization, for example using a dashboard. 58

Skeptical response

The various benefits possessed by VIS do not necessarily make this system immediately accepted by its users. Previous study has shown that there are some skeptical responses to the implementation of VIS. These responses include the perception that VIS does not provide benefits to either the vaccinated patients or healthcare providers, 45 , 49 the use of VIS is not mandatory by law and not a clinical practice standard, therefore it is not necessary, 49 more time is spent using VIS than serving patients, 49 , 50 VIS use that provides a bad experience, 53 , 57 , 59 , 60 and current record keeping without using VIS functions well, so VIS are not needed. 53 VIS are said to cause various problems related to practicality, efficiency, and workflow. 81 Furthermore, one of the main obstacles in carrying out vaccinations and having an impact on the use of VIS is due to vaccine hesitancy from the community. 82

Overcoming skeptical responses to the use of VIS can be done by effectively communicating the benefits of VIS to users, national authorities, and the public. 50 In addition, after developing VIS and implementing VIS in healthcare facilities, the government must anticipate resistance from these facilities. 50 The solution to this is by conducting progressive training and education activities in healthcare facilities. 50 Education and training sessions are needed to counter resistance from healthcare workers.

Computer literacy

Healthcare workers and the general public are the main users who interact directly with the VIS application. Therefore, computer literacy and user understanding of how to operate the VIS will affect their acceptance of the application. Some of the challenges that have arisen in previous study related to computer literacy are a lack of trained healthcare workers to use VIS, 37 , 43 , 45 , 49 , 56 limited training given to users, 56 , 57 , 60 knowledge gaps among users, 14 some healthcare workers lack confidence in technology, slow learners, or have technophobia. 57

In essence, low computer literacy challenges among VIS users can be addressed by conducting training before the VIS are used. 58 When training activities are carried out, it must be ensured that all training participants are aware of and well-trained in using the VIS. 60 Additionally, the scheduling process of the training activity needs to be planned well so that all training participants can attend and understand how to correctly operate the VIS.

Staff availability

One of the core elements of the implementation of VIS is the empowerment and commitment of human resources which must have a sufficient number and be skilled at every level where the system will operate later on. 72 At every stage of development or implementation of VIS, problems can always arise, such as a shortage of staff. 14 , 46 , 52 , 58 The shortage of staff can be triggered by various things, one of which is the high turnover of health workers and the difficulty in securing and maintaining staff. 37 , 50 , 65 , 66 Some things can cause health workers to resign and leave the health facility, such as low wages for health workers 50 and excessive workload due to the transition from conventional record keeping to record keeping through IIS. 14 , 57 The limited number of staff makes the mentoring and training process for IIS usage not run smoothly. 57 However, there must always be some staff who have the same level of knowledge and expertise in VIS to ensure that work can continue if someone leaves the team. 15

The solution to this problem is by using a cascading training-of-trainers approach to ensure a sustainable peer-to-peer training system for new staff. 37 In addition, in Vietnam, an e-learning training option is also available to train new staff. 37 This reduces the workload of experienced health staff and allows them to focus on other things that require more attention.

This study utilizes data from previous studies to understand the challenges encountered during the implementation of the VIS. This study was conducted in the form of a systematic literature review following the guidelines set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). The literature review successfully identified 14 challenges that arose during the implementation of the VIS, namely interoperability, data quality, security and privacy, standardization, usability, internet connectivity, infrastructure, workflow, funding, government regulations, awareness, skeptical response, computer literacy, and staff availability challenges. Interoperability and data quality challenges were found to be the most discussed challenges in previous studies. In addition to identifying the challenges that arose, this study also includes a series of solutions that can be applied to overcome each challenge. The identification of challenges and solutions can be used to develop policies for implementing the VIS. For example, security and privacy were identified as a challenge, then VIS implementers need to develop policies that regulate user access control to the VIS application. The findings of this study can also be translated into functional or nonfunctional requirements for the development of the IIS application.

The limitations of this review should be taken into consideration. The challenges identified in this study primarily reflect the challenges faced by healthcare workers and healthcare facilities. However, it is essential to note that other users, such as citizens, also play a crucial role in ensuring the effectiveness of the VIS. In addition, it is known that most of the vaccinations recorded in the VIS are for children, and few systems record adult vaccinations. Therefore, further research is needed to better understand the challenges faced by citizens in utilizing the VIS, especially regarding adult vaccination records.

Funding Statement

The work was supported by the Universitas Indonesia [PUTI Q2 Number NKB-570/UN2.RST/HKP.05.00/2023].

Disclosure statement

No potential conflict of interest was reported by the author(s).