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.

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.

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.

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.

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.

Economic-Related Inequalities in Zero-Dose Children: A Study of Non-Receipt of Diphtheria-Tetanus-Pertussis Immunization Using Household Health Survey Data from 89 Low- and Middle-Income Countries.

Despite advances in scaling up new vaccines in low- and middle-income countries, the global number of unvaccinated children has remained high over the past decade. We used 2000-2019 household survey data from 154 surveys representing 89 low- and middle-income countries to assess within-country, economic-related inequality in the prevalence of one-year-old children with zero doses of diphtheria-tetanus-pertussis (DTP) vaccine. Zero-dose DTP prevalence data were disaggregated by household wealth quintile. Difference, ratio, slope index of inequality, concentration index, and excess change measures were calculated to assess the latest situation and change over time, by country income grouping for 17 countries with high zero-dose DTP numbers and prevalence. Across 89 countries, the median prevalence of zero-dose DTP was 7.6%. Within-country inequalities mostly favored the richest quintile, with 19 of 89 countries reporting a rich-poor gap of ≥20.0 percentage points. Low-income countries had higher inequality than lower-middle-income countries and upper-middle-income countries (difference between the median prevalence in the poorest and richest quintiles: 14.4, 8.9, and 2.7 percentage points, respectively). Zero-dose DTP prevalence among the poorest households of low-income countries declined between 2000 and 2009 and between 2010 and 2019, yet economic-related inequality remained high in many countries. Widespread economic-related inequalities in zero-dose DTP prevalence are particularly pronounced in low-income countries and have remained high over the previous decade.

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.

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries. Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future. Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Zero-dose children and the immunisation cascade: Understanding immunisation pathways in low and middle-income countries.

INTRODUCTION: Zero-dose prevalence refers to children who failed to receive any routine vaccination. Little is known about the "immunisation cascade" in low- and middle-income countries (LMICs), defined as how children move from zero dose to full immunisation. METHODS: Using data from national surveys carried out in 92 LMICs since 2010 and focusing on the four basic vaccines delivered in infancy (BCG, polio, DPT and MCV), we describe zero-dose prevalence and the immunisation cascade in children aged 12 to 23 months. We also describe the most frequent combinations of vaccines (or co-coverage) among children who are partially immunized. Analyses are stratified by country income groups, household wealth quintiles derived from asset indices, sex of the child and area of residence. Results were pooled across countries using child populations as weights. RESULTS: In the 92 countries, 7.7% were in the zero-dose group, and 3.3%, 3.4% and 14.6% received one, two or three vaccines, respectively; 70.9% received the four types and 59.9% of the total were fully immunised with all doses of the four vaccines. Three quarters (76.8%) of children who received the first vaccine received all four types. Among children with a single vaccine, polio was the most common in low- and lower-middle income countries, and BCG in upper-middle income countries. There were sharp inequalities according to household wealth, with zero-dose prevalence ranging from 12.5% in the poorest to 3.4% in the wealthiest quintile across all countries. The cascades were similar for boys and girls. In terms of dropout, 4% of children receiving BCG did not receive DPT1, 14% receiving DPT1 did not receive DPT3, and 9% receiving DPT3 did not progress to receive MCV. INTERPRETATION: Focusing on zero-dose children is particularly important because those who are reached with the first vaccine are highly likely to also receive remaining vaccines.

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.

Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit-risk analysis of health benefits versus excess risk of SARS-CoV-2 infection.

BACKGROUND: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. We aimed to compare the health benefits of sustaining routine childhood immunisation in Africa with the risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through visiting routine vaccination service delivery points. METHODS: We considered a high-impact scenario and a low-impact scenario to approximate the child deaths that could be caused by immunisation coverage reductions during COVID-19 outbreaks. In the high-impact scenario, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, rotavirus, measles, meningitis A, rubella, and yellow fever to approximate the future deaths averted before 5 years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. In the low-impact scenario, we approximated the health benefits of sustaining routine childhood immunisation on only the child deaths averted from measles outbreaks during the COVID-19 risk period. We assumed that contact-reducing interventions flattened the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport, and that upon child infection the whole household will be infected. Country-specific household age structure estimates and age-dependent infection-fatality rates were applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation, with 95% uncertainty intervals (UIs) from a probabilistic sensitivity analysis. FINDINGS: In the high-impact scenario, for every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, 84 (95% UI 14-267) deaths in children could be prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children is 85 000 (4900-546 000), for their siblings (<20 years) is 75 000 (4400-483 000), for their parents or adult carers (aged 20-60 years) is 769 (148-2700), and for older adults (>60 years) is 96 (14-307). In the low-impact scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0-10); if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3000 (182-21 000). INTERPRETATION: The deaths prevented by sustaining routine childhood immunisation in Africa outweigh the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. Routine childhood immunisation should be sustained in Africa as much as possible, while considering other factors such as logistical constraints, staff shortages, and reallocation of resources during the COVID-19 pandemic. FUNDING: Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation.

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.

Methods, outcomes, and costs of a 2.5 year comprehensive facility-and community-based HIV testing intervention in Bukoba Municipal Council, Tanzania, 2014-2017.

To diagnose ≥90% HIV-infected residents (diagnostic coverage), the Bukoba Combination Prevention Evaluation (BCPE) implemented provider-initiated (PITC), home- (HBHTC), and venue-based (VBHTC) HIV testing and counseling (HTC) intervention in Bukoba Municipal Council, a mixed urban and rural lake zone community of 150,000 residents in Tanzania. This paper describes the methods, outcomes, and incremental costs of these HTC interventions. PITC was implemented in outpatient department clinics in all eight public and three faith-based health facilities. In clinics, lay counselors routinely screened and referred eligible patients for HIV testing conducted by HTC-dedicated healthcare workers. In all 14 wards, community teams offered HTC to eligible persons encountered at 31,293 home visits and at 79 male- and youth-frequented venues. HTC was recommended for persons who were not in HIV care or had not tested in the prior 90 days. BCPE conducted 133,695 HIV tests during the 2.5 year intervention (PITC: 88,813, 66%; HBHTC: 27,407, 21%; VBHTC: 17,475, 13%). Compared with other strategies, PITC conducted proportionally more tests among females (65%), and VBHTC conducted proportionally more tests among males (69%) and young-adults aged 15-24 years (42%). Of 5,550 (4.2% of all tests) HIV-positive tests, 4,143 (75%) clients were newly HIV diagnosed, including 1,583 males and 881 young adults aged 15-24 years. Of HIV tests conducted 3.7%, 1.8%, and 2.1% of PITC, HBHTC, and VBHTC clients, respectively, were newly HIV diagnosed; PITC accounted for 79% of all new diagnoses. Cost per test (per new diagnosis) was $4.55 ($123.66), $6.45 ($354.44), and $7.98 ($372.67) for PITC, HBHTC, and VBHTC, respectively. In a task-shifting analysis in which lay counselors replaced healthcare workers, estimated costs per test (per new diagnosis) would have been $3.06 ($83.15), $ 4.81 ($264.04), and $5.45 ($254.52), for PITC, HBHTC, and VBHTC, respectively. BCPE models reached different target groups, including men and young adults, two groups with consistently low coverage. Implementation of multiple models is likely necessary to achieve ≥90% diagnostic coverage.

Implementing the package of CDC and WHO recommended linkage services: Methods, outcomes, and costs of the Bukoba Tanzania Combination Prevention Evaluation peer-delivered, linkage case management program, 2014-2017.

Although several studies have evaluated one or more linkage services to improve early enrollment in HIV care in Tanzania, none have evaluated the package of linkage services recommended by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). We describe the uptake of each component of the CDC/WHO recommended package of linkage services, and early enrollment in HIV care and antiretroviral therapy (ART) initiation among persons with HIV who participated in a peer-delivered, linkage case management (LCM) program implemented in Bukoba, Tanzania, October 2014 -May 2017. Of 4206 participants (88% newly HIV diagnosed), most received recommended services including counseling on the importance of early enrollment in care and ART (100%); escort by foot or car to an HIV care and treatment clinic (CTC) (83%); treatment navigation at a CTC (94%); telephone support and appointment reminders (77% among clients with cellphones); and counseling on HIV-status disclosure and partner/family testing (77%), and on barriers to care (69%). During three periods with different ART-eligibility thresholds [CD4<350 (Oct 2014 -Dec 2015, n = 2233), CD4≤500 (Jan 2016 -Sept 2016, n = 1221), and Test & Start (Oct 2016 -May 2017, n = 752)], 90%, 96%, and 97% of clients enrolled in HIV care, and 47%, 67%, and 86% of clients initiated ART, respectively, within three months of diagnosis. Of 463 LCM clients who participated in the last three months of the rollout of Test & Start, 91% initiated ART. Estimated per-client cost was $44 United States dollars (USD) for delivering LCM services in communities and facilities overall, and $18 USD for a facility-only model with task shifting. Well accepted by persons with HIV, peer-delivered LCM services recommended by CDC and WHO can achieve near universal early ART initiation in the Test & Start era at modest cost and should be considered for implementation in facilities and communities experiencing <90% early enrollment in ART care.

Improving Care for Chronic Conditions: Current Practices and Future Trends in Health Plan Programs.

The need for better management of chronic conditions is urgent. About 141 million people in the United States were living with one or more chronic conditions in 2010, and this number is projected to increase to 171 million by 2030. To address this challenge, many health plans have piloted and rolled out innovative approaches to improving care for their members with chronic conditions. This article documents the current range of chronic care management services, identifies best practices and industry trends, and examines factors in the plans' operating environment that limit their ability to optimize chronic care programs. The authors conducted telephone surveys with a representative sample of health plans and made in-depth case studies of six plans. All plans in the sample provide a wide range of products and services around chronic care, including wellness/lifestyle management programs for healthy members, disease management for members with common chronic conditions, and case management for high-risk members regardless of their underlying condition. Health plans view these programs as a "win-win" situation and believe that they improve care for their most vulnerable members and reduce cost of coverage. Plans are making their existing programs more patient-centric and are integrating disease and case management, and sometimes lifestyle management and behavioral health, into a consolidated chronic care management program, believing that this will increase patient engagement and prevent duplication of services and missed opportunities.

Medicines as a Service: A New Commercial Model for Big Pharma in the Postblockbuster World.

The past decade has not been kind to large pharmaceutical companies. Their share prices have been lagging the market after many years of outperforming it. Many had to undergo painful restructuring and workforce reductions because their traditional blockbuster model is becoming extinct. More and more top-selling drugs are being replaced by cheap generics, and developing new drugs is more difficult because fewer opportunities exist and more-costly research and development (R&D) productivity has declined. Although this diagnosis is not disputed, the best course of treatment is not clear. Companies have tried to stop the bleeding with the help of mergers and reorganizations and infused new blood by acquiring biotech companies or their innovative products or by diversifying into products other than prescription drugs. In this article, the authors propose that the pharmaceutical industry can reconfigure its considerable resources to develop innovative and meaningful business models that are based on services that improve access and adherence to prescription drugs for chronic conditions. They argue that such innovation beyond drug development is consistent with the core capabilities of large pharmaceutical companies and has the potential to achieve profit levels similar to those of its traditional models. Their argument is based on the fact that, although effective medicines for most chronic conditions exist, access and adherence to medicines is far from what would be needed to achieve full treatment efficacy. Therefore, value can be created by getting and keeping more patients on their drugs, and innovative business models would allow pharmaceutical companies to capture that value.

Improving Access to Medicines for Non-Communicable Diseases in the Developing World.

Non-communicable diseases (NCDs) now account for the majority of global morbidity and mortality and are increasingly affecting developing countries whose under-resourced health care systems also have to handle a high burden of infectious disease. To counter the global devastation caused by NCDs, the United Nations General Assembly decided to "set a new global agenda" and convened a high-level meeting on NCDs in September 2011. In connection with this meeting, the authors of this article took a first step toward developing a policy research agenda for improving access to NCD medicines in developing countries, a step that the research-based pharmaceutical industry, in particular, can carry forward as part of broader global efforts to combat NCD. The authors provide a framework for understanding the obstacles to access for NCD medicines, review specific issues to be confronted within each obstacle in the developing world, identify promising ideas for improving access to NCD medicines, and point to several highly promising areas for the research-based pharmaceutical industry to focus on as it develops its NCD policy research program in close collaboration with other key stakeholders.