The Immunization Agenda 2030 Strategy to reach zero-dose children in low-income and middle-income countries: a scoping review

Abstract

Introduction

Intensified efforts are needed to achieve the Immunization Agenda 2030 (IA2030) target to halve the number of children not reached by routine vaccination (‘zero-dose’ (ZD) children) by 2030. This scoping review maps and synthesises the scientific literature on ZD children in low-income and middle-income countries since the IA2030 launch.

Methods

Our protocol, developed per the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines, was registered on the Open Science Framework prior to execution, and our search strategies were designed by a research librarian. We searched MEDLINE (Ovid), CINAHL Complete (EBSCOhost), EBM Reviews (Ovid), EMBASE (Ovid), LILACS and Google Scholar for peer-reviewed studies with quantitative evidence on ZD children published between January 2020 and January 2024. Using Covidence, we screened citations in a two-stage process by two independent reviewers and conducted data charting using a pretested form. Disagreements were resolved by consensus or consultation with a senior reviewer.

Results

Of the 82 articles included, 73 provided evidence on prevalence, and/or distribution, 24 on barriers to vaccination services and 44 on deprivations faced by ZD children, their households and communities, with the risk of deprivations varying importantly across contexts. The barriers to vaccination most reported related to the intent to vaccinate (n=20), followed by community access (n=10). Deprivations mainly concerned access to health services, such as low utilisation of maternal health services (n=22), and other key development indicators, such as low socioeconomic status (n=29) and poor maternal education/literacy (n=28). We found no studies (n=0) on interventions focused on reaching ZD children with routine immunisation services.

Conclusion

Our findings highlight the imperative to generate evidence on interventions delivering routine immunisation to ZD children and missed communities. Results also underscore the need for transformative approaches that address multiple deprivations using carefully selected, integrated services, tailored to context-specific needs.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

WHAT THIS STUDY ADDS

• The most commonly reported barriers to vaccination services for ZD children concerned the intent to vaccinate, followed by community access, reflecting gaps related to behavioural and social drivers of vaccination, and to the interaction between health systems and communities.

• ZD children, households and communities face multiple deprivations, with the risk of deprivations varying across contexts, suggesting variations in the likelihood of ZD children surviving, thriving or reaching their potential.

• We found no studies on interventions that focused specifically on reaching ZD children with routine immunisation services, highlighting a critical evidence gap.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Our findings emphasise the need for interventions that address the root causes of low uptake of vaccines and other essential services, privileging community-centric approaches.

• To drive transformative change aligned with the Sustainable Development Goals (SDGs) for the children and communities most left behind, context-sensitive and integrated intervention strategies that recognise and address multiple deprivations are required.

• Our review underscores the urgent need to generate evidence on interventions that deliver routine immunisation to ZD children and missed communities, including outcomes, cost-effectiveness and impact.

Introduction

The Immunization Agenda 2030 (IA2030), endorsed by the World Health Assembly (WHA) in May 2020, provides strategic guidance to improve global immunisation coverage and ensure that no one is left behind with immunisation.^{1 2} A key target is to reduce the number of zero-dose (ZD) children—those without any routine vaccines—by 25% by 2025 and by 50% by 2030, compared with the 2019 baseline.^{1 3} Gavi, the Vaccine Alliance, has made reaching ZD children and missed communities the core focus of its fifth strategic period (Gavi 5.0/5.1), hypothesising that ZD children are disproportionally clustered in marginalised communities facing systemic forms of disadvantage, with poor access to healthcare, and other essential services.^{2 4 5} In June 2024, the Gavi Board decided that ZD children and missed communities were to remain a core priority for its next strategic period (Gavi 6.0).⁶ ZD children are operationally defined by Gavi and IA2030 as those aged 12–23 months who have not received their first dose of diphtheria–tetanus–pertussis-containing vaccine (DTP1). According to the latest estimates from the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), there were 14.5 million ZD children worldwide in 2023, an increase from 12.8 million in 2019.⁷ Disruptions to immunisation services caused by the COVID-19 pandemic led to significant setbacks in essential childhood vaccination coverage, with lower income countries most affected.⁸ Intensified efforts are needed to understand how to sustainably reach ZD children and missed communities to achieve the IA2030 ZD target. There is a substantial body of evidence on improving coverage of childhood immunisation in low and middle-income countries (LMICs).⁹,¹² However, before the emphasis on ZD children with IA2030, few studies differentiated ZD children—those who have not received any vaccines—and under-immunised children—those who are partially but not fully vaccinated—although about 70% of underimmunised children in 2019 were ZD children.⁷ A systematic review on reasons related to non-vaccination and undervaccination of children in LMICs, conducted before the IA2030 launch, found that only 11 of the 202 included studies provided evidence specific to unvaccinated children.¹³

We conducted a preliminary search to identify completed and ongoing reviews on ZD children in LMICs since the IA2030 was endorsed in 2020 (online supplemental appendix 1). We found two reviews on risk factors and interventions for ZD and underimmunised children in limited geographies: one on Nigeria,¹⁴ and another, which was ongoing, on 17 Sub-Saharan African countries.¹⁵ We also identified a narrative review covering the years 2000–2021 on potential interventions for reaching ZD children in LMICs, which relied heavily on grey literature and key informant interviews due to limited published literature on ZD children available during this period.¹⁶ Both completed reviews emphasised the need for evidence on interventions for ZD children.^{14 16} We found no comprehensive synthesis of the empirical evidence focusing on ZD children in all LMICs. To address this gap, we undertook a scoping review to map and synthesise existing scientific literature on ZD children in LMICs since 2020. Specifically, this review intends to identify evidence related to prevalence, distribution, risk factors, deprivations and interventions focusing on ZD children and their outcomes. The findings aim to highlight potential course corrections needed for Gavi 5.0/5.1 and IA2030 and to inform key decisions for the development of Gavi’s next strategy (Gavi 6.0, 2026–2030). We aspire to repeat this scoping review on an annual or bi-annual basis until 2030 for an updated synthesis of the emerging evidence on ZD children, thereby informing the remainder of the IA2030 strategic period.

Methods

Protocol

Our protocol was developed following the latest guidance from the Johanna Briggs Institute^{17 18} and was prospectively registered on the Open Science Framework¹⁹ on 25 January 2024 (https://osf.io/cgfw9/).²⁰ The findings are reported according to PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews)²¹ (online supplemental appendix 2).

Eligibility criteria

To be included, evidence sources needed to provide quantitative evidence on ZD children and include data from LMICs, as defined by the World Bank.²² In addition to the IA2030 operational definition (no-DTP1),³ we considered alternative definitions that can identify children without any routine vaccines, such as those who had not received any of the four basic vaccines from the original WHO Expanded Programme on Immunization (EPI)—Bacille Calmette-Guérin (BCG), polio, DTP and measles-containing vaccine (MCV)—or any vaccine in their national immunisation schedule. We also considered studies providing evidence on ‘unvaccinated’ or ‘unimmunised’ children and other common synonyms for ZD children. We considered studies on supplementary immunisation activities (SIAs) targeting measles-ZD and polio-ZD children, provided they included precampaign coverage data of at least one other routine vaccine. To ensure comprehensiveness, any article containing information on ZD children in LMICs was included, regardless of whether ZD children were the primary focus. For all definitions, we considered studies that included children up to 5 years of age, aligning with the WHO Big Catch-Up strategy.²³ We included primary research studies and reviews and excluded those containing only qualitative information, conference abstracts or grey literature. Only studies published after 1 January 2020 were considered, given the WHA endorsement of the IA2030 in May 2020 and the launch of IA2030 and Gavi 5.0 in 2021.^{1 2} Preprints were also admissible.

Information sources and search strategy

To identify relevant studies, we searched the following databases: MEDLINE (Ovid), CINAHL Complete (EBSCOhost), EBM Reviews (Ovid), EMBASE (Ovid), LILACS as well as Google Scholar. We limited our scope to studies published between 1 January 2020 and 11 January 2024. No language restrictions were applied. The search strategies were designed by a research librarian (DZ) and peer-reviewed by another senior information specialist using the PRESS (Peer Review of Electronic Search Strategies) checklist.²⁴ The reproducible searches are publicly available in Borealis Dataverse²⁵ (online supplemental appendix 3). Final search results were exported into EndNote and deduplicated by the librarian (DZ) using an established method.²⁶ We supplemented the database search with expert recommendations and manual screening of reference lists from included articles. We also screened the reference list from an unpublished systematic review on interventions for ZD and underimmunised children in Sub-Saharan Africa.¹⁵

Study selection

Records were screened in two stages, involving an initial review of titles and abstracts, followed by a full-text review of prioritised articles. Screening and inclusion decisions were made by at least two of four independent reviewers (AB, JD, BCA and CT) using the Covidence platform and a pretested eligibility checklist (online supplemental appendix 4). Bi-weekly meetings were held to resolve disagreements by consensus and ensure consistent application of the eligibility criteria. A senior reviewer (MJ) was consulted as required.

Data charting

The four reviewers (AB, JD, BCA, CT) conducted data charting using a pretested tool designed for this review (online supplemental appendix 5) and using Covidence. To ensure preliminary findings were available in time for discussions on the design of Gavi 6.0 in spring 2024, independent double data extraction for all articles was not feasible. To mitigate this, articles with a clear focus on ZD were prioritised for double extraction, with selection made by at least two reviewers. In total, 43% (n=35) of the articles underwent double extraction. Bi-weekly meetings were maintained to enhance accuracy and consistency in data charting, and disagreements were resolved by consensus and in consultation with a senior reviewer (MJ), as required. The data charting form collected data on study characteristics (such as aim, research design, source of funding, authors’ affiliations and geographical scope) and on five themes: (1) prevalence and distribution of ZD children; (2) barriers to vaccination; (3) deprivations faced by ZD children and missed communities; (4) interventions focusing on reaching ZD children with routine immunisation services and (5) integration of routine immunisation services with other Primary Health Care (PHC) services for ZD children and missed communities.

Data analysis

Main analysis

The main analysis was based on data extracted²⁷ with the data charting form. The four reviewers (AB, JD, BCA and CT) performed data analysis, guided by a senior reviewer (MJ). To ensure accuracy and consistency, data preprocessing involved thorough cross-checks, with corrections approved by at least two independent reviewers. We then conducted a descriptive statistical analysis using frequencies and percentages, grouping studies by characteristics, and on the five themes. The studies reporting barriers to the delivery of vaccination services to ZD children were categorised as per the Exemplars in Global Health framework, which includes three main categories: intent to vaccinate, community access and facility readiness.^{28 29} The studies reporting deprivations faced by ZD children, households and communities were mapped against those highlighted by Hogan and Gupta.³⁰ Charts and tables were created to provide visual representations of our findings.

Bibliometric analysis

A bibliometric analysis was conducted by a research librarian (DZ) to provide insights into funding, authorship and coauthorship. This analysis used bibliometric data extracted from the SciVal platform, Scopus and manual search for the funding section and Dimensions AI for the network bibliographic analysis. Findings are reported based on the Guideline for Reporting Bibliometric Reviews of the Biomedical Literature (BIBLIO).³¹

Results

Out of 5216 records identified via database searches, 5097 were excluded based on titles and abstracts and 47 studies were excluded after full-text screening (figure 1). We note a minor deviation from protocol: following data extraction, we removed two articles that were published in a non-indexed journal, as advised by our research librarian (DZ), due to concerns about the journal’s credibility. Of the 82 articles included in the review, 73 articles were found in SciVal and included in the bibliometric analysis (online supplemental appendix 6).

Figure 1. PRISMA flow diagram.

Study characteristics

Of the 82 included articles, 79 were primary research articles and 3 were reviews. A total of 78 articles were published and 4 articles were drafts or preprints. Most primary research studies were cross-sectional and investigated correlates of ZD vaccination status. For the primary research articles, an overview of study characteristics is presented in table 1.

Table 1. Characteristics of sources of evidence—primary research articles (n=79).

Methodology	n (%)
Quantitative	74 (94)
Mixed methods	5 (6)
Data sources	n (%)
Secondary data	57 (72)
Primary data	17 (22)
Primary and secondary data	5 (6)
Research design	n (%)
Cross-sectional	54 (68)
Mathematical modelling	9 (11)
Longitudinal	5 (6)
Ecological	2 (2)
Case study	2 (2)
Quasi-experimental	2 (2)
Other	8 (10)
Antigens used to define ZD	n (%)
No-DTP1	37 (47)
None of the vaccines included in the EPI/national immunisation schedule	20 (25)
None of the four basic vaccines (DTP1, MCV1, Polio1, BCG)	9 (11)
More than one definition	7 (9)
Other/not specified	6 (8)
Study population age
<24 months	50 (63)
>2 years–5 years	21 (27)
Not specified/unclear	8 (10)

40/79 primary research studies used secondary data from Demographic and Health Surveys (DHS), Multiple Indicator Cluster Surveys (MICS) and/or other large-scale surveys.

Longitudinal studies include four studies tracing countries over time and one study following individuals over time.

Studies with target ages of ≤24 months that also included other age groups to account for variations in national vaccination schedules in certain countries were still categorised under ≤24 months.

Characteristics for each study are provided in online supplemental appendix 7.

BCG, Bacille Calmette-Guérin; DTP1, diphtheria–tetanus–pertussis-containing vaccine; EPI, Expanded Programme on Immunization; MCV, measles-containing vaccine; ZD, zero dose.

Among the included studies, the five countries most represented were Nigeria (n=40); India (n=34); Ethiopia (n=34); the Democratic Republic of the Congo (DRC) (n=31) and Pakistan (n=30) (figure 2).

Figure 2. Geographical coverage among low and middle-income countries. Articles may cover more than one country; Geographical coverage among World Bank regions and Gavi segments is presented in online supplemental appendix 7.

Among the 69 studies in the bibliometric analysis, the greatest number was funded by two organisations: Gavi, the Vaccine Alliance (n=28), and the Bill and Melinda Gates Foundation (n=27). Moreover, 97% (n=67) were open-access articles. Detailed findings of the bibliometric analysis are available in online supplemental appendix 6.

Thematic coverage

Of the 82 studies included in this review, 73 provided evidence on the prevalence and/or distribution of ZD children in defined contexts, 24 discussed barriers to the delivery of vaccination services to ZD children and 44 reported deprivations experienced by ZD children (and sometimes their households and communities). We found no studies (n=0) on interventions that focused specifically on reaching ZD children with routine immunisation services and, consequently, no studies (n=0) providing evidence on the integration of routine immunisation services with other PHC services (online supplemental appendix 8).

Prevalence and distribution

Of the 73 studies providing evidence on prevalence and distribution, 41 highlighted subnational variations in the prevalence of ZD children within countries, while eight emphasised that clusters of ZD children can also be found within high-performing areas. Twenty-six studies discussed differences in the ZD prevalence between urban and rural settings and five documented concentrations of ZD children in conflict-affected areas.

Factors that impede the delivery of vaccination services to ZD children

Of the 24 articles that discussed factors that hinder the delivery of vaccination services to ZD children, 20 provided findings related to the intent to vaccinate, 10 discussed barriers related to community access and 3 highlighted factors associated with facility readiness (table 2).

Table 2. Factors that impede the delivery of vaccination services to ZD children (immediate drivers).

Immediate drivers of vaccine delivery		Key findings
Intent to vaccinate (n=20)	Awareness/knowledge	Myths, rumours and fears surrounding vaccines/lack of faith in immunisation (n=2) Religious and cultural beliefs (n=2) Unawareness of vaccination services, including catch-up (n=2) Mother/family’s personal choice of not vaccinating child (n=2) Ignoring the need for vaccination/not being able to name any vaccine-preventable disease (VPD) (n=2) Mistrust in public institutions (n=1)
	Attitude/perceptions
	Community norms
	Agency	Women’s lack of autonomy/restricted decision-making power; lower social independence/lower empowerment of women (n=8) Not having one of the biological parents as a guardian (n=1) Children without a parent as the head of the household (n=1) War-related loss of family members (n=1) Family problems, including maternal illness (n=1)
	Prior experiences	This factor was not reported in the studies included in the review.
Community access (n=10)	Accommodation/acceptability	Mothers’ busy schedules during vaccination times/lack of time (n=3) Parents having to pay for a vaccination card or another immunisation-related service (n=2)
	Structural barriers	Long distance/travel time to health facilities (n=6) Insecurity/issues accessing vaccination services due to war (n=2) Unavailability of health facilities within the community (n=1)
Facility readiness (n=3)	Workforce	Staff absenteeism/unavailability (n=2) Under-performance of EPI staff/lack of clarity on job responsibilities (n=1) Lack of monitoring mechanisms and accountability (n=1) Lack of/inadequate incentives for healthcare workers/vaccinators and inadequate incentives/lack of reimbursement for outreach work expenses (n=1) Lack of coordination between community workers and vaccinators (n=1) Low coverage of visits by field workers (n=1)
	Supply	Inadequate outreach vaccination services (n=1) Unreliable and underutilised data, and/or lack of data to plan outreach services (n=1) Vaccines not available (n=1) Schedules of vaccination services (n=1) Long waiting times (n=1)

This framework was adapted with minor modifications from the Exemplars in Global Health framework on vaccine delivery (immediate drivers).^{28 29}

Articles may cover more than one category, and more than one barrier/factor.

Intent to vaccinate refers to the demand for vaccines by primary caregivers, and facility readiness relates to the supply of vaccine services by the health system, while community access includes the barriers and facilitators at the interface between the intent to vaccinate and facility readiness.^{28 29 79}

This table is available with article references in online supplemental appendix 9.

EPI, Expanded Programme on Immunization; VPD, vaccine-preventable disease; ZD, zero dose.

The most frequently reported barriers linked to the intent to vaccinate were myths, rumours and fears surrounding vaccines and lack of faith in immunisation (n=8), as well as restricted decision-making power for women, and other primary caregivers (n=8). Four articles specifically focused on gender inequality and its association with ZD vaccination status. A smaller, yet significant proportion of articles identified barriers associated with community access, long distances and travel time to health facilities being the most commonly cited (n=6). Two articles highlighted issues accessing vaccination services due to war.

Deprivations faced by ZD children/households/communities

A total of 44 articles discussed deprivations experienced by ZD children, their households and communities, concerning: (1) access to immunisation services (n=11); (2) access to other health services and commodities (n=23); access to other non-health services and commodities (n=7) and (3) other important indicators of development³⁰ (n=41) (table 3).

Table 3. Deprivations/forms of disadvantage faced by ZD children, their households and communities.

Deprivations/forms of disadvantage	Measured on:
Related to access to immunisation services (n=11)
Low coverage of maternal tetanus toxoid vaccination (n=7)	Mother
Lack of delivery of other basic EPI vaccines (n=3)	ZD child
Missed opportunities for vaccination (n=3)	ZD child
Related to access to other health services and commodities (n=23)
Low coverage of skilled birth attendance/institutional deliveries (n=17)	Mother
Low coverage of ANC (n=17)	Mother
Lack of care-seeking for childhood illnesses, for example, pneumonia/diarrhoea (n=4)	ZD child
Low coverage of PNC (n=3)	Mother
Non-use of modern contraception (n=3)	Mother
Lack of insecticide-treated nets (ITN) (n=2)	Household
Low coverage of pregnancy registrations during the first trimester (n=1)	Mother
Unsatisfied family planning needs (n=1)	Mother
Low coverage of Vitamin A supplementation (n=1)	ZD child
Low coverage of visits by field workers (n=1)	Household
Related to access to other non-health services and commodities (n=7)
Lack of health insurance (n=2)	Household
Lack of access to a bank account (n=6)	Household
Related to deficits in important indicators of development (n=41)
Poverty/low socioeconomic status (n=29)	Household
Poor maternal education/literacy (n=28)	Mother
Low maternal empowerment (n=8)	Mother
Malnutrition—stunting/stunting/underweight (n=4)	ZD child
Lack of improved WASH (n=2)	Household
Poor learning attainment in preadolescence (n=1)	ZD child

This framework was inspired by Hogan and Gupta.³⁰

Articles may cover more than one category and more than one deprivation/form of disadvantage.

‘Non-use of modern contraception’ refers to women who never used modern contraception (DHS/MICS data), there is no indication of whether this was requested by the women (ie,demand for family planning not satisfied/unmet need).

‘Lack of delivery of other basic EPI vaccines’ refers to the lack of delivery of other basic EPI vaccines for ZD (no-DTP1) children.

This table is available with article references in online supplemental appendix 9.

ANC, antenatal care; DHS, Demographic and Health Surveys; DTP1, diphtheria–tetanus–pertussis-containing vaccine; EPI, Expanded Programme on Immunization; MICS, Multiple Indicator Cluster Surveys; PNC, post-natal care; WASH, water, sanitation, and hygiene; ZD, zero dose.

Among the deprivations related to access to other health services and commodities, those related to the lack of maternal utilisation of health services (n=22) were most frequently reported.

Only one study included in our review examined developmental outcomes for ZD children over the life course. Johri et al³² found that ZD children living in contexts of very low socioeconomic development were at elevated risk of being developmentally behind in learning attainment at ages 8–11 years.

Other risk factors and forms of disadvantage

Of the 82 studies included in this review, a total of 45 articles highlighted associations between demographic and socioeconomic characteristics and ZD vaccination status, the most reported being: low socioeconomic status (n=29); poor maternal education/literacy (n=28); younger maternal age (n=9); religion (n=9); ethnicity/caste (n=9); higher birth order/larger family size (n=6). Factors such as low socioeconomic status, poor maternal education/literacy and low maternal empowerment are usually reported as risk factors and can also be considered as deprivations. While most studies focused on aggregate associations at the country level, seven studies emphasised the need to prioritise subnational high-need geographies, highlighting contexts where ZD children are most likely to face overlapping risks and deprivations.

Finally, we found only one study (n=1) reporting on the relationship between child ZD status and mortality. Karlsson et al³³ identified an association between the national postneonatal and child (28 days to 59 months) mortality rate and the national ZD vaccination prevalence.

Interventions and integration of PHC services for ZD children

We found no studies (n=0) about interventions that focused specifically on reaching ZD children with routine immunisation services and consequently, no studies (n=0) reporting on the integration of immunisation services with other PHC services for ZD children, their families and their communities. Four studies on interventions to reach underimmunised children reported evidence separately for underimmunised and ZD children. Evidence on the cost-effectiveness of reaching ZD children was reported in one of these four studies.³⁴

Discussion

To our knowledge, this scoping review offers the first comprehensive synthesis of the scientific literature on ZD children in LMICs since the launch of IA2030. Our review highlights three overarching findings.

First, the most frequently reported barriers to the delivery of vaccination services to ZD children were related to the intent to vaccinate, addressed by 83% of studies, followed by community access (42%). Facility readiness factors were mentioned in only 13% of studies. In line with the WHO framework on behavioural and social drivers of vaccination (BeSD),^{35 36} our findings suggest that the fundamental gaps in reaching ZD children and missed communities lie in the understanding, motivation, experiences and agency of caregivers as well as in the interaction between health systems and communities. One study in our review, by Ishoso et al, used the WHO BeSD framework to analyse the reasons for non-vaccination and undervaccination in the DRC and found that non-vaccination among ZD children was primarily due to a lack of caregiver motivation to have their children vaccinated, while reasons among undervaccinated children mostly pertained to practical issues. Hence, while facility readiness is a critical precondition for success, reaching ZD and missed communities cannot be achieved uniquely through supply-side strengthening. Engaging with communities is also required to address the factors related to intent to vaccinate and community access, which are highly community-specific and context-specific. Two studies in our review highlighted associations between religious affiliation and no-DTP1 prevalence in specific contexts,³⁷ and ethnic disparities in ZD prevalence,³⁸ two dimensions that may be closely tied to the intent to vaccinate and community access. Engaging with religious leaders and other community members may help understand how these and other contextual factors may influence the beliefs, behaviours and experiences regarding vaccination services. The fact that half of the studies in our review relied on secondary data from large-scale household surveys, such as Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), may explain the under-representation of factors related to facility readiness, as household surveys tend to focus on factors more closely associated with the intent to vaccinate and community access. The use of these data sources enhances the generalisability of the results, given they are nationally representative and use rigorous analytic methods. However, vaccination data from household surveys suffer from potential information biases due to the fact that data are collected from diverse information sources of differing reliability, notably facility-based records, home-based records and caregiver recall.³⁹ Moreover, DHS and MICS surveys do not include all variables related to risk factors and barriers to vaccination that may be of interest for understanding ZD vaccination status. Primary research conducted at the local level can contribute to understanding a wider range of barriers in specific contexts.

Second, our review underscores that ZD children, along with their households and communities, often face multiple deprivations, with the risk of these deprivations varying importantly across contexts. The studies in our review provided rich evidence on individual, household, community and country-level factors correlated with ZD vaccination status. The most commonly reported factors were low socioeconomic status, low maternal education and low maternal use of health services, reflecting substantial deficits in opportunities for human development and service utilisation. Evidence on the consequences of ZD vaccination status was scant. Although mortality is anticipated to be an important consequence of non-vaccination, we found only one study reporting an association between ZD vaccination status and under-5 child mortality, based on an aggregate association at the country level.³³ The lack of individual-level data linking non-vaccination to mortality may partly be attributed to the fact that half of the studies relied on secondary data from large-scale household surveys, such as the DHS and MICS. These surveys do not include information on the vaccination status of deceased children,^{40 41} thus limiting the ability to assess this association at the individual level. Furthermore, although the systematic disadvantages faced by ZD children in early childhood are expected to limit their ability to thrive and flourish, we found only one study reporting child development outcomes for ZD children (no-DTP1). Johri et al⁴² examined vaccination status in early childhood and compared the ability to read, write and perform simple mathematics at ages 8–11 years for ZD and vaccinated children. They found that ZD children had lower learning attainment than their vaccinated counterparts; however, the relationship held only for those living in highly deprived contexts.

Several studies in our review highlighted that the risk of deprivations varies importantly across contexts, suggesting differences in the likelihood of ZD children surviving, thriving or reaching their potential. The earlier studies that were conducted at the outset of the IA2030 strategy period found that ZD children and their families faced more deprivations and had less access to services compared with vaccinated children, based on average comparisons between these two groups, often at the country level.⁴³,⁴⁵ The more recent studies explored the prevalence and correlates of ZD status at a more granular level, using geospatial data to examine subnational patterns. These analyses revealed spatial variations in risks and how the geographic concentration of intersecting forms of disadvantage—such as greater poverty, limited access to health services, low maternal literacy, ethnicity, religion and long travel times—shapes the prevalence and experiences of some ZD children, households and communities.⁴⁶,⁵⁰ Emerging data sources, such as electronic immunisation registries, can be leveraged to explore patterns in ZD prevalence and correlates. For instance, one study in our review, by Mehmood et al,⁵¹ used data from the electronic immunisation registry of Sindh province, Pakistan, to analyse inequity in ZD prevalence at a microgeographic level and provide insights into associated sociodemographic characteristics and risk factors. We found studies reporting that ZD children and their caregivers engage with the health system to some extent, suggesting missed opportunities to provide immunisation and other PHC services.^{4445 51},⁵³ As part of its next strategy, Gavi aims to enhance partnerships to ensure ZD investments are a foundation for delivering other PHC services, contributing to universal health coverage.^{54 55} For the ZD strategy to be transformative, innovative partnerships are needed, such as strengthening the maternal-child care continuum or linking immunisation services with early childhood development programmes for ZD children and missed communities. ZD children in high-needs areas are particularly vulnerable to falling behind, highlighting the need for responsive intervention strategies, sensitive to context and integrated where needed. Engaging with communities is required to comprehend the context-specific barriers to vaccination and to determine locally appropriate solutions.

Third, despite a substantial body of evidence on interventions to boost vaccine demand and supply in LMICs,⁹ we found no studies on interventions that focused specifically on reaching ZD children with routine immunisation services, highlighting a critical evidence gap. This suggests that while the current scientific literature supports the importance of prioritising ZD children, the ‘how’ is not yet supported by empirical evidence. Addressing this evidence gap is critical, not only considering the multiple deprivations faced by ZD children and missed communities but also because these communities—marked by high numbers of ZD and undervaccinated children—may constitute subnational pockets of vulnerability contributing to disease outbreaks.⁵⁰ The existing body of evidence on interventions to improve childhood immunisation coverage in LMICs focuses on children completing their full vaccination, rather than on reaching unvaccinated children,^{9 10} while the current body of evidence on interventions for ZD children is campaign-centric.¹⁴⁵⁶,⁶¹ In their mapping of pro-equity, health system and immunisation-strengthening interventions funded under Gavi 4.0, Dadari et al,⁶² Ivanova et al⁶³ and Ducharme et al⁶⁴ provided a comprehensive overview of potential interventions for delivering routine immunisation to ZD children and missed communities. However, the implementation of such interventions is not yet documented in the scientific literature, possibly due to the relatively recent launch of IA2030.

There is an urgent need for evidence not only on the implementation outcomes and impact of interventions delivering routine immunisation to ZD children, but also on the integration of services for ZD children and missed communities as well as on the costs and cost-effectiveness of reaching them. This would complement the existing body of evidence on the delivery of integrated services via routine childhood immunisation platforms⁶⁵,⁶⁹ and via vaccination campaigns,⁷⁰ which currently focuses on underimmunised children and SIAs. While there is existing guidance for economic evidence to support policy decisions related to ZD interventions, there is an evidence gap in the scientific literature on the costs of providing immunisation and other essential services to these communities.⁷¹ Efforts are currently underway to generate evidence on the economics of reaching ZD children,⁷² which we hope to capture in potential future updates of this review. Given the higher level of unmet needs, reaching ZD children and missed communities may be more resource-intensive yet more impactful—potentially making these investments equally or even more cost-effective.⁷³ Future research on interventions for ZD children and missed communities could build on lessons from studies on interventions for underimmunised children that leverage community engagement in designing and implementing solutions, as done by Kaduru et al⁷⁴ through the use of a community theatre intervention to improve demand for vaccination services in Nigeria. At this juncture, due to the paucity of primary evidence, addressing the evidence gap on interventions focusing on ZD children and missed communities requires community-driven primary research. Suitable methods may include those that examine the contextual factors influencing implementation outcomes—such as, but not limited to, implementation research and realist evaluations.^{75 76} While such studies may not yield widely generalisable findings, they can generate rich and transferable insights that are adaptable to similar contexts.

Limitations

Our scoping review had at least three key limitations. First, although our search strategies were comprehensive and our screening process rigorous, with all citations screened by two independent reviewers, and frequent discussions to ensure a common understanding of inclusion and exclusion criteria, we may nonetheless have missed relevant articles. However, as we intend to repeat this scoping review on an annual or bi-annual basis until 2030, studies missed in this round may be captured in future updates. Second, independent double data extraction was not feasible for all studies, as we aimed to provide preliminary findings in time for discussions on the design of Gavi 6.0 in spring 2024. To mitigate this, we set a target of 10% double extraction but ultimately completed double extraction for 43% of the articles (n=35), ensuring all articles with a clear focus on ZD children underwent double extraction. Third, we did not appraise study quality, as quality assessment is optional for scoping reviews. Our goal was to provide a comprehensive overview of the existing scientific literature on ZD children. While we reported findings related to ZD vaccination status, we did not assess the strength of evidence nor the degree of association between variables. However, focusing on literature published in indexed journals served as a first-stage filter for higher quality studies. Finally, we highlight several decisions related to the review scope, which should be borne in mind when interpreting and generalising from these results. As we aimed to provide preliminary findings for the spring of 2024, we chose to focus on studies containing quantitative data, assuming a high number of such studies would be available and that including those with only qualitative data might not be feasible. By excluding studies with only qualitative information, we may have missed relevant evidence, and their inclusion may be considered for future updates. Additionally, our decision to only include articles published since January 2020 restricted the range of evidence considered. Finally, due to our focus on the scientific literature, we did not capture evidence currently only documented in the grey literature, such as findings emerging from Gavi’s novel Country ZD Learning Hubs in Bangladesh, Mali, Uganda and Nigeria.⁷⁷ A separate synthesis is being undertaken to learn from these experiences.

Conclusion

Based on our findings, we propose three key orientations for IA2030 partners at global and country levels to accelerate progress towards the IA2030 ZD target. First, while strengthening immunisation services remains critical, success will require partnering with communities to understand and address the root causes of low uptake of vaccines and other essential services. Second, for ZD children and missed communities facing substantial adversity, strategy design should consider how to recognise and address multiple deprivations, using carefully selected, feasible and integrated services, tailored to context-specific needs. Third, our review highlights the urgent need to generate evidence on interventions focusing on reaching ZD children and missed communities with routine immunisation services, including their outcomes, costs, cost-effectiveness and impact. As lessons concerning strategies, implementation and results will be anchored in specific contexts, a wide range of evidence is needed. Reaching ZD children and ensuring their progress towards full immunisation must remain a global priority, considering the well-documented life-saving impact of vaccination. Indeed, a recent modelling study estimated that immunisation has averted approximately 146 million deaths in children under 5 since the launch of the EPI in 1974.⁷⁸ Beyond providing vaccination services, a comprehensive and transformative ZD strategy should leverage innovative partnerships to address co-deprivations and their root causes, fostering sustainable progress in health equity and social justice for children and communities most left behind.

Data availability statement

Data are available in a public, open access repository.