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.

Out-of-pocket expenditures and financial risks associated with treatment of vaccine-preventable diseases in Ethiopia: A cross-sectional costing analysis.

BACKGROUND: Vaccine-preventable diseases (VPDs) remain major causes of morbidity and mortality in low- and middle-income countries (LMICs). Universal access to vaccination, besides improved health outcomes, would substantially reduce VPD-related out-of-pocket (OOP) expenditures and associated financial risks. This paper aims to estimate the extent of OOP expenditures and the magnitude of the associated catastrophic health expenditures (CHEs) for selected VPDs in Ethiopia. METHODS AND FINDINGS: We conducted a cross-sectional costing analysis, from the household (patient) perspective, of care-seeking for VPDs in children aged under 5 years for pneumonia, diarrhea, measles, and pertussis, and in children aged under 15 years for meningitis. Data on OOP direct medical and nonmedical expenditures (2021 USD) and household consumption expenditures were collected from 995 households (1 child per household) in 54 health facilities nationwide between May 1 and July 31, 2021. We used descriptive statistics to measure the main outcomes: magnitude of OOP expenditures, along with the associated CHE within households. Drivers of CHE were assessed using a logistic regression model. The mean OOP expenditures per disease episode for outpatient care for diarrhea, pneumonia, pertussis, and measles were $5·6 (95% confidence interval (CI): $4·3, 6·8), $7·8 ($5·3, 10·3), $9·0 ($6·4, 11·6), and $7·4 ($3·0, 11·9), respectively. The mean OOP expenditures were higher for inpatient care, ranging from $40·6 (95% CI: $12·9, 68·3) for severe measles to $101·7 ($88·5, 114·8) for meningitis. Direct medical expenditures, particularly drug and supply expenses, were the major cost drivers. Among those who sought inpatient care (345 households), about 13·3% suffered CHE, at a 10% threshold of annual consumption expenditures. The type of facility visited, receiving inpatient care, and wealth were significant predictors of CHE (p-value < 0·001) while adjusting for area of residence (urban/rural), diagnosis, age of respondent, and household family size. Limitations include inadequate number of measles and pertussis cases. CONCLUSIONS: The OOP expenditures induced by VPDs are substantial in Ethiopia and disproportionately impact those with low income and those requiring inpatient care. Expanding equitable access to vaccines cannot be overemphasized, for both health and economic reasons. Such realization requires the government's commitment toward increasing and sustaining vaccine financing in Ethiopia.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

BACKGROUND: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. METHODS AND FINDINGS: We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. CONCLUSIONS: In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

Cost of providing emergency obstetric care in Tanzania's Kigoma region.

BACKGROUND: The provision of Emergency Obstetric and Neonatal Care (EmONC) is critical for reducing maternal mortality, yet little is known about the costs of EmONC services in developing countries. This study estimates these costs at six health facilities in Tanzania's Kigoma region. METHODS: The study took a comprehensive programmatic approach considering all sources of financial and in-kind support over a 1-year period (1 July 2012 to 30 June 2013). Data were collected retrospectively and costs disaggregated by input, sources of support, programmatic activity, and patient type (nonsurgical, surgical patients, and among the latter patients undergoing caesarean sections). RESULTS: The median per-patient cost across the six facilities was $290. Personnel and equipment purchases accounted for the largest proportions of the total costs, representing 32% and 28%, respectively. Average per-patient costs varied by patient type; cost per nonsurgical patient was $80, $258 for surgical patients and $426 for patients undergoing caesarean sections. Per-patient costs also varied substantially by facility type: mean per-patient cost at health centres was $620 compared with $169 at hospitals. CONCLUSIONS: This study provides the first cost estimates of EmONC provision in Kigoma. These estimates could inform programme planning and highlight areas with potential scope for cost reductions.

A Framework for Assessing the Impact of Outbreak Response Immunization Programs.

The impact of outbreak response immunization (ORI) can be estimated by comparing observed outcomes to modelled counterfactual scenarios without ORI, but the most appropriate metrics depend on stakeholder needs and data availability. This study developed a framework for using mathematical models to assess the impact of ORI for vaccine-preventable diseases. Framework development involved (1) the assessment of impact metrics based on stakeholder interviews and literature reviews determining data availability and capacity to capture as model outcomes; (2) mapping investment in ORI elements to model parameters to define scenarios; (3) developing a system for engaging stakeholders and formulating model questions, performing analyses, and interpreting results; and (4) example applications for different settings and pathogens. The metrics identified as most useful were health impacts, economic impacts, and the risk of severe outbreaks. Scenario categories included investment in the response scale, response speed, and vaccine targeting. The framework defines four phases: (1) problem framing and data sourcing (identification of stakeholder needs, metrics, and scenarios); (2) model choice; (3) model implementation; and (4) interpretation and communication. The use of the framework is demonstrated by application to two outbreaks, measles in Papua New Guinea and Ebola in the Democratic Republic of the Congo. The framework is a systematic way to engage with stakeholders and ensure that an analysis is fit for purpose, makes the best use of available data, and uses suitable modelling methodology.

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.

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.

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.

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.