**3. Reaching Zero-Dose Children to Accelerate Equitable Immunization**

National immunization programs have made impressive gains in the past two decades, as many children, including those in low- and middle-income countries, are now protected against the leading causes of pneumonia, diarrhea, meningitis, and liver disease. Breadth of protection, defined by WHO to be the average coverage across 11 vaccines, doubled from 34% in 2000 to 68% in 2021 [7], meaning an increased number of children in the world are now protected against an array of vaccine-preventable diseases. However, while many life-saving vaccines have been added to national immunization schedules, some children continue to be deprived of the benefits of even the most basic vaccines in almost all countries.

In 2021, there were 25 million underimmunized infants worldwide, as measured by the lack of three doses of the DTP-containing vaccine (DTP3) (Figure 1), which is the standard measure of the strength of routine immunization systems [8]. However, of these 25 million children, 18.2 m (73%) were zero-dose children, highlighting how essential it will be to reach zero-dose children to improve routine immunization coverage. The importance of focusing on zero-dose children is apparent when considering trends over the past decade. Coverage with three doses of the DTP-containing vaccine (DTP3) rose by 11 percentage points between 2000 (72%) and 2010 (83%) but then by only 3 percentage points between 2010 and 2019 (86%) [8]. The modest increase in DTP3 coverage in the decade prior to the COVID-19 pandemic was largely driven by a reduction in the percentage of children who had received their first dose of DTP but failed to receive their second or third doses of DTP; i.e., DTP drop-out decreased by about one-third (6.7% to 4.4%). In comparison, the coverage of DTP1 increased by only 1 percentage point between 2010 (89%) and 2019 (90%), meaning 1 in 10 children were zero-dose children prior to the pandemic [8]. Increasing

DTP3 coverage will therefore be dependent on reaching zero-dose children and ensuring they are fully immunized.

**Figure 1.** Annual number of zero-dose children and non-zero-dose underimmunized children globally, 2010–2021. Data source: WHO/UNICEF Estimates of National Immunization Coverage (WUENIC), July 2022 [8].

There is also evidence that reaching a zero-dose child may catalyze a cascade of further vaccinations. In an analysis of household survey data from 92 LMICs considering four basic vaccines, most children had either received no doses of any vaccines or received doses of three or more different vaccines [6]. This finding suggests that reaching zero-dose children should be a major focus of immunization programs seeking to increase full immunization coverage, as children who receive one dose almost always move on to receive several other vaccinations.

#### **4. Where Are Zero-Dose Children?**

Most zero-dose children live in low- and lower-middle-income countries, accounting for 87% of the global total of 18 million [8]. In 2021, six large-population countries, namely, India (2.7 m), Nigeria (2.2 m), Indonesia (1.1 m), Ethiopia (1.1 m), Philippines (1 m), and the Democratic Republic of the Congo (0.7 m), accounted for half of all zero-dose children. There are also smaller countries that have chronically low coverage and a very high proportion of zero-dose children who are zero-dose even without COVID-related disruptions, for example, Papua New Guinea (56%), South Sudan (49%), Somalia (48%), and Central African Republic (46%) as of 2019 [8]. All of these countries face fragility and conflict, which lead to weaker and less predictable immunization delivery.

High rates of zero-dose children in fragile and conflict settings also play out at the subnational level across countries. An analysis that combined conflict data from the Armed Conflict Location & Event Data Project (ACLED) with subnational coverage estimates from the Institute for Health Metrics and Evaluation (IHME) found that nearly 20% of zero-dose children in 99 LMICs live in conflict-affected settings [9]. The same analysis also concluded that roughly 40% of zero-dose children live in settings highlighted by the Equity Reference Group on Immunization (ERG), namely, urban, remote rural, and conflict-affected settings, with the remaining living in non-urban rural settings. In related work, Utazi et al. found high rates of zero-dose children in conflict-affected and remote rural regions, which are common in parts of the Sahel and the Horn of Africa [10].

More data are needed to quantify the sizes of zero-dose populations in urban slums at the global level, as they are often not captured by household surveys and are geographically too small for vaccine coverage levels to be estimated with geostatistical models. Work that has been conducted suggests that children living in slums may have better access to

services than those in rural areas but still face large inequalities compared to wealthier urban households [10,11].

Overall, zero-dose children live in every country in the world. In many countries, the prevalence of zero-dose children can vary substantially across subnational areas. For example, geospatial modeling of subnational DTP1 coverage in Africa found that Angola, Chad, the Democratic Republic of the Congo, Ethiopia, Kenya, Mali, and Nigeria all had mean disparities in DTP1 coverage of 50% or more at the second administrative level [12]. The geographic targeting of resources to support the expansion of routine immunization services to reach missed communities is therefore critical. However, while geographic information can help target resources to reach chronically missed children, in many countries, other factors may be more important than just the geographic setting in determining why children are unvaccinated [10]. As zero-dose children often face multiple barriers to immunization, understanding the social, political, and economic contexts of zero-dose children and their families is key for program design.

#### **5. Who Are Zero-Dose Children and What Barriers Do They Face?**

Recent empirical studies by the International Center for Equity in Health and others have confirmed what most public health practitioners have long known: zero-dose children and their families face multiple barriers to obtaining immunization, and their presence in a community is often an indicator of compounded inequities. Moreover, stigma and discrimination are likely factors in determining whether a child benefits from vaccines.

Gender-related barriers to immunization are a key driver of children missing out on vaccinations. Children with empowered mothers, as defined by the Survey-based Women's emPowERment (SWPER) index, are much less likely to be zero-dose. In particular, in the domain of social independence, children whose mothers were measured to have low or medium levels of social independence were 3.3 times more likely to be zero-dose than children of mothers with high levels of social independence [13]. Although the analysis was not causal, the suggested effect sizes are enormous; theoretically, if barriers to immunization related to women's empowerment could be overcome, there would be 4.7 million fewer zero-dose children globally.

Consistent with the literature on inequalities in access to various health services [14,15], children from poorer households are more likely to be zero-dose than children from wealthier households. Unfortunately, there appears to have been little progress in reducing this gap over the past ten years, and the greatest absolute inequalities occur in the poorest countries, with low-income countries having a 14 percentage point difference in median zero-dose prevalence when comparing the poorest to wealthiest household quintiles [16]. Zero-dose children are often poor, with roughly two-thirds living below the poverty line of USD 1.90 per day [4].

Recent studies suggest that ethnicity and religion may contribute to disparities in immunization in some countries. In a study of 64 LIMCs, the median gap in the prevalence of zero-dose children between ethnic groups with the lowest vs. highest prevalence was 10 percentage points (pp), and gaps of 50 pp were observed in five countries [17]. Importantly, differences in zero-dose prevalence by ethnicity persisted even after controlling for wealth, maternal education, and area of residence, suggesting that other factors linked to ethnicity are key drivers of immunization inequalities in some countries. It is concerning that children from smaller ethnic groups in a country are more likely to be zero-dose than children in the dominant ethnic group [17]. The relationship between religion and immunization status appears to be significant in some countries but not consistently across countries [18]. In 27 of 66 countries studied, zero-dose prevalence varied by religious group, with children from the majority religion tending to be less likely to be zero-dose than children from minority religions, with the exception of countries where Muslims were the majority religion.

One significant gap in the evidence base about zero-dose children is in understanding patterns among refugee, migrant, and nomadic populations. A recent review by the World Health Organization cited 26.4 million refugees in 2020 and 41.3 million internally displaced people due to violence and conflict in 2021, and while some of these populations experience lower immunization rates, it is context-specific with unclear patterns overall [19]. The size of nomadic, displaced, and migrant populations is dynamic and can be exacerbated by conflicts, climate shocks, food shortages, natural calamities, and loss of income. This in turn can increase the number of children who are missed by immunization services as well as household surveys designed to measure immunization coverage [20].

In addition to inequalities associated with accessing immunization, zero-dose children and their families face multiple deprivations related to health and development. Considering other child and maternal health services, zero-dose children and their mothers are roughly two times as likely to miss out on antenatal care and access to an institutional delivery, although interestingly, only about 20% less likely to access care for childhood illnesses or symptoms [21]. In an expanded analysis considering broader development indicators at the individual level, a lack of vaccination was strongly associated with lower access to improved water (prevalence ratio (PR) = 2.60) and sanitation (PR = 1.35), higher rates of childhood stunting (PR = 1.32), lower levels of maternal education (PR = 2.27), and lower levels of maternal demand for family planning satisfied with modern methods (PR = 1.42) [22]. Similar patterns were also observed in ecological analyses looking across countries and across subnational regions within countries, and a principal component analysis looking at these deprivation variables found that nearly all zero-dose children are in the highest deprivation quintile: i.e., if a zero-dose child is found, it is highly likely that they are facing multiple deprivations [22]. A geospatial analysis of time trends in zero-dose children in India from 1992 through 2016 found similar results, with zero-dose children more likely to be poor, have mothers with no education, suffer from severe stunting, and live in less developed states and districts [23].
