Zero-dose children and the extended immunisation cascade: Understanding the path to full immunisation with six childhood vaccines in 43 countries.

Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs). Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles. Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV. Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals.

Exploring the "Urban Advantage" in Access to Immunization Services: A Comparison of Zero-Dose Prevalence Between Rural, and Poor and Non-poor Urban Households Across 97 Low- and Middle-Income Countries.

Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique challenges, living far from health facilities and with lower-quality health services, which can impact their access to life-saving vaccines. Our goal was to compare the prevalence of zero-dose children in poor and non-poor urban and rural areas of low- and middle-income countries (LMICs). Zero-dose children were those who failed to receive any dose of a diphtheria-pertussis-tetanus (DPT) containing vaccine. We used data from nationally representative household surveys of 97 LMICs to investigate 201,283 children aged 12-23 months. The pooled prevalence of zero-dose children was 6.5% among the urban non-poor, 12.6% for the urban poor, and 14.7% for the rural areas. There were significant differences between these areas in 43 countries. In most of these countries, the non-poor urban children were at an advantage compared to the urban poor, who were still better off or similar to rural children. Our results emphasize the inequalities between urban and rural areas, but also within urban areas, highlighting the challenges faced by poor urban and rural children. Outreach programs and community interventions that can reach poor urban and rural communities-along with strengthening of current vaccination programs and services-are important steps to reduce inequalities and ensure that no child is left unvaccinated.

Child immunization status according to number of siblings and birth order in 85 low- and middle-income countries: a cross-sectional study.

Background: Identification of unvaccinated children is important for preventing deaths due to infections. Number of siblings and birth order have been postulated as risk factors for zero-dose prevalence. Methods: We analysed nationally representative cross-sectional surveys from 85 low and middle-income countries (2010-2020) with information on immunisation status of children aged 12-35 months. Zero-dose prevalence was defined as the failure to receive any doses of DPT (diphtheria-pertussis-tetanus) vaccine. We examined associations with birth order and the number of siblings, adjusting for child's sex, maternal age and education, household wealth quintiles and place of residence. Poisson regression was used to calculate zero-dose prevalence ratios. Findings: We studied 375,548 children, of whom 13.7% (n = 51,450) were classified as zero-dose. Prevalence increased monotonically with birth order and with the number of siblings, with prevalence increasing from 11.0% for firstborn children to 17.1% for birth order 5 or higher, and from 10.5% for children with no siblings to 17.2% for those with four or more siblings. Adjustment for confounders attenuated but did not eliminate these associations. The number of siblings remained as a strong risk factor when adjusted for confounders and birth order, but the reverse was not observed. Among children with the same number of siblings, there was no clear pattern in zero-dose prevalence by birth order; for instance, among children with two siblings, the prevalence was 13.0%, 14.7%, and 13.3% for firstborn, second, and third-born, respectively. Similar results were observed for girls and boys. 9513 families had two children aged 12-35 months. When the younger sibling was unvaccinated, 61.9% of the older siblings were also unvaccinated. On the other hand, when the younger sibling was vaccinated, only 5.9% of the older siblings were unvaccinated. Interpretation: The number of siblings is a better predictor than birth order in identifying children to be targeted by immunization campaigns. Zero-dose children tend to be clustered within families. Funding: Gavi, the Vaccine Alliance.

Religious affiliation as a driver of immunization coverage: Analyses of zero-dose vaccine prevalence in 66 low- and middle-income countries.

Background: The literature on the association between religion and immunization coverage is scant, mostly consisting of single-country studies. Analyses in low and middle-income countries (LMICs) to assess whether the proportions of zero-dose children vary according to religion remains necessary to better understand non-socioeconomic immunization barriers and to inform interventions that target zero-dose children. Methods: We included 66 LMICs with standardized national surveys carried out since 2010, with information on religion and vaccination. The proportion of children who failed to receive any doses of a diphtheria-pertussis-tetanus (DPT) containing vaccine - a proxy for no access to routine vaccination or "zero-dose" status - was the outcome. Differences among religious groups were assessed using a test for heterogeneity. Additional analyses were performed controlling for the fixed effect of country, household wealth, maternal education, and urban-rural residence to assess associations between religion and immunization. Findings: In 27 countries there was significant heterogeneity in no-DPT prevalence according to religion. Pooled analyses adjusted for wealth, maternal education, and area of residence showed that Muslim children had 76% higher no-DPT prevalence than Christian children. Children from the majority religion in each country tended to have lower no-DPT prevalence than the rest of the population except in Muslim-majority countries. Interpretation: Analyses of gaps in coverage according to religion are relevant to renewing efforts to reach groups that are being left behind, with an important role in the reduction of zero-dose children.

Exposure of Zero-Dose Children to Multiple Deprivation: Analyses of Data from 80 Low- and Middle-Income Countries.

The concept of multiple deprivation recognizes that the same individuals, households, and communities are often exposed to several forms of scarcity. We assessed whether lack of immunization is also associated with nutritional, environmental, and educational outcomes. We analyzed data from nationally representative surveys from 80 low- and middle-income countries with information on no-DPT (children aged 12-23 months without any doses of a diphtheria, pertussis and tetanus containing vaccine), stunting, wasting, maternal education and use of contraception, improved water and sanitation, and long-lasting insecticidal nets. Analyses of how these characteristics overlap were performed at individual and ecological levels. Principal component analyses (PCA) provided additional information on indicator clustering. In virtually all analyses, no-DPT children were significantly more likely to be exposed to the other markers for deprivation. The strongest, most consistent associations were found with maternal education, water, and sanitation, while the weakest associations were found for wasting and bed nets. No-DPT prevalence reached 46.1% in the most deprived quintile from first PCA component derived from deprivation indicators. All children were immunized in the two least deprived quintiles of the component. Our analyses provide strong support for the hypothesis that unimmunized children are also affected by other forms of deprivation.

Ethnic disparities in immunisation: analyses of zero-dose prevalence in 64 countries.

BACKGROUND: The Sustainable Development Goals (SDGs) recommend stratification of health indicators by ethnic group, yet there are few studies that have assessed if there are ethnic disparities in childhood immunisation in low-income and middle-income countries (LMICs). METHODS: We identified 64 LMICs with standardised national surveys carried out since 2010, which provided information on ethnicity or a proxy variable and on vaccine coverage; 339 ethnic groups were identified after excluding those with fewer than 50 children in the sample and countries with a single ethnic group. Lack of vaccination with diphtheria-pertussis-tetanus vaccine-a proxy for no access to routine vaccination or 'zero-dose' status-was the outcome of interest. Differences among ethnic groups were assessed using a χ2 test for heterogeneity. Additional analyses controlled for household wealth, maternal education and urban-rural residence. FINDINGS: The median gap between the highest and lowest zero-dose prevalence ethnic groups in all countries was equal to 10 percentage points (pp) (IQR 4-22), and the median ratio was 3.3 (IQR 1.8-6.7). In 35 of the 64 countries, there was significant heterogeneity in zero-dose prevalence among the ethnic groups. In most countries, adjustment for wealth, education and residence made little difference to the ethnic gaps, but in four countries (Angola, Benin, Nigeria and Philippines), the high-low ethnic gap decreased by over 15 pp after adjustment. Children belonging to a majority group had 29% lower prevalence of zero-dose compared with the rest of the sample. INTERPRETATION: Statistically significant ethnic disparities in child immunisation were present in over half of the countries studied. Such inequalities have been seldom described in the published literature. Regular analyses of ethnic disparities are essential for monitoring trends, targeting resources and assessing the impact of health interventions to ensure zero-dose children are not left behind in the SDG era.

Children of more empowered women are less likely to be left without vaccination in low- and middle-income countries: A global analysis of 50 DHS surveys.

Background: To help provide a global understanding of the role of gender-related barriers to vaccination, we have used a broad measure of women's empowerment and explored its association with the prevalence of zero-dose children aged 12-23 months across many low- and middle-income countries, using data from standardized national household surveys. Methods: We used data from Demographic and Health Surveys (DHS) of 50 countries with information on both women's empowerment and child immunisation. Zero-dose was operationally defined as the proportion of children who failed to receive any doses of the diphtheria, pertussis, and tetanus containing vaccines (DPT). We measured women's empowerment using the SWPER Global, an individual-level indicator estimated for women aged 15-49 years who are married or in union and with three domains: social independence, decision-making and attitude towards violence. We estimated two summary measures of inequality, the slope index of inequality (SII) and the concentration index (CIX). Results were presented for individual and pooled countries. Results: In the country-level (ecological) analyses we found that the higher the proportion of women with high empowerment, the lower the zero-dose prevalence. In the individual level analyses, overall, children with highly-empowered mothers presented lower prevalence of zero-dose than those with less-empowered mothers. The social independence domain presented more consistent associations with zero-dose. In 42 countries, the lowest zero-dose prevalence was found in the high empowerment groups, with the slope index of inequality showing significant results in 28 countries. When we pooled all countries using a multilevel Poisson model, children from mothers in the low and medium levels of the social independence domain had respectively 3.3 (95% confidence interval (CI) = 2.3, 4.7) and 1.8 (95% CI = 1.5, 2.1) times higher prevalence of zero-dose compared to those in the high level. Conclusions: Our country-level and individual-level analyses support the importance of women's empowerment for child vaccination, especially in countries with weaker routine immunisation programs.

Assessing the overlap between immunisation and other essential health interventions in 92 low- and middle-income countries using household surveys: opportunities for expanding immunisation and primary health care.

BACKGROUND: Unvaccinated children may live in households with limited access to other primary health care (PHC) services, and routine vaccination services may provide the opportunity to bring caregivers into contact with the health system. We aimed to investigate the overlap between not being vaccinated and failing to receive other PHC services in low- and middle-income countries (LMICs). METHODS: Using Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) data between 2010-2019 from 92 LMICs, we analysed six vaccination indicators based on the bacille Calmette-Guérin (BCG), polio, diphtheria-pertussis-tetanus (DPT) and measles vaccines and their overlap with four other PHC indicators - at least four antenatal care (ANC) visits, institutional delivery, careseeking for common childhood illnesses or symptoms and place for handwashing in the home - in 211,141 children aged 12-23 months. Analyses were stratified according to wealth quintiles and World Bank income levels. FINDINGS: Unvaccinated children and their mothers were systematically less likely to receive the other PHC interventions. These associations were particularly marked for 4+ ANC visits and institutional delivery and modest for careseeking behaviour. Our stratified analyses confirm a systematic disadvantage of unvaccinated children and their families with respect to obtaining other health services in all levels of household wealth and country income. INTERPRETATION: We suggested that lack of vaccination goes hand in hand with missing out on other health interventions. This represents an opportunity for integrated delivery strategies that may more efficiently reduce inequalities in health service coverage. FUNDING: Bill & Melinda Gates Foundation, Gavi, the Vaccine Alliance, The Wellcome Trust, Associação Brasileira de Saúde Coletiva and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.