Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

Mapping local variation in educational attainment across Africa.

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

Mapping child growth failure in Africa between 2000 and 2015.

Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.

Learning from the COVID-19 pandemic to strengthen routine immunization systems.

Kate Causey and Jonathan F Mosser discuss what can be learnt from the observed impacts of the COVID-19 pandemic on routine immunisation systems.

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study.

BACKGROUND: The COVID-19 pandemic and efforts to reduce SARS-CoV-2 transmission substantially affected health services worldwide. To better understand the impact of the pandemic on childhood routine immunisation, we estimated disruptions in vaccine coverage associated with the pandemic in 2020, globally and by Global Burden of Disease (GBD) super-region. METHODS: For this analysis we used a two-step hierarchical random spline modelling approach to estimate global and regional disruptions to routine immunisation using administrative data and reports from electronic immunisation systems, with mobility data as a model input. Paired with estimates of vaccine coverage expected in the absence of COVID-19, which were derived from vaccine coverage models from GBD 2020, Release 1 (GBD 2020 R1), we estimated the number of children who missed routinely delivered doses of the third-dose diphtheria-tetanus-pertussis (DTP3) vaccine and first-dose measles-containing vaccine (MCV1) in 2020. FINDINGS: Globally, in 2020, estimated vaccine coverage was 76·7% (95% uncertainty interval 74·3-78·6) for DTP3 and 78·9% (74·8-81·9) for MCV1, representing relative reductions of 7·7% (6·0-10·1) for DTP3 and 7·9% (5·2-11·7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30·0 million (27·6-33·1) children missed doses of DTP3 and 27·2 million (23·4-32·5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8·5 million (6·5-11·6) children not routinely vaccinated with DTP3 and an additional 8·9 million (5·7-13·7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4·6 million (4·0-5·4) children missing doses of DTP3 and 4·4 million (3·7-5·2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020. INTERPRETATION: Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade. FUNDING: Bill & Melinda Gates Foundation.

Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000-2015.

BACKGROUND: Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries. METHODS: We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).

Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000-2016: a spatial and temporal modelling study.

BACKGROUND: Routine childhood vaccination is among the most cost-effective, successful public health interventions available. Amid substantial investments to expand vaccine delivery throughout Africa and strengthen administrative reporting systems, most countries still require robust measures of local routine vaccine coverage and changes in geographical inequalities over time. METHODS: This analysis drew from 183 surveys done between 2000 and 2016, including data from 881 268 children in 49 African countries. We used a Bayesian geostatistical model calibrated to results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, to produce annual estimates with high-spatial resolution (5 ×    5 km) of diphtheria-pertussis-tetanus (DPT) vaccine coverage and dropout for children aged 12-23 months in 52 African countries from 2000 to 2016. FINDINGS: Estimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval [UI] 64·6-80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola. INTERPRETATION: Despite substantial progress in Africa, marked national and subnational inequalities in DPT coverage persist throughout the continent. These results can help identify areas of low coverage and vaccine delivery system vulnerabilities and can ultimately support more precise targeting of resources to improve vaccine coverage and health outcomes for African children. FUNDING: Bill & Melinda Gates Foundation.

Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa.

BACKGROUND: HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50-60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15-49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. METHODS: We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15-49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. RESULTS: We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. CONCLUSIONS: Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa.

Investigating the Spatial Accessibility and Coverage of the Pediatric COVID-19 Vaccine: An Ecologic Study of Regional Health Data.

The COVID-19 pandemic presented the unique challenge of having to deliver novel vaccines during a public health crisis. For pediatric patients, it was further complicated by the delayed timeline for authorizing the vaccine and the differences in dosing/products depending on the patient's age. This paper investigates the relationship between the spatial accessibility and uptake of the COVID-19 vaccine in King County, WA, USA. Public data for COVID-19 vaccine sites were used to calculate spatial accessibility using an enhanced two-step floating catchment area (E2SFCA) technique. Spatial regression analyses were performed to look at the relationship between spatial accessibility and ZIP-code-level vaccination rates. The relationships of these data with other socioeconomic and demographic variables were calculated as well. Higher rates of vaccine accessibility and vaccine coverage were found in adolescent (12- to 17-year-old) individuals relative to school-age (5- to 11-year-old) individuals. Vaccine accessibility was positively associated with coverage in both age groups in the univariable analysis. This relationship was affected by neighborhood educational attainment. This paper demonstrates how measures such as E2SFCA can be used to calculate the accessibility of the COVID-19 vaccine in a region and provides insight into some of the ecological factors that affect COVID-19 vaccination rates.

High-resolution mapping of essential maternal and child health service coverage in Nigeria: a machine learning approach.

BACKGROUND: National-level coverage estimates of maternal and child health (MCH) services mask district-level and community-level geographical inequities. The purpose of this study is to estimate grid-level coverage of essential MCH services in Nigeria using machine learning techniques. METHODS: Essential MCH services in this study included antenatal care, facility-based delivery, childhood vaccinations and treatments of childhood illnesses. We estimated generalised additive models (GAMs) and gradient boosting regressions (GB) for each essential MCH service using data from five national representative cross-sectional surveys in Nigeria from 2003 to 2018 and geospatial socioeconomic, environmental and physical characteristics. Using the best-performed model for each service, we map predicted coverage at 1 km2 and 5 km2 spatial resolutions in urban and rural areas, respectively. RESULTS: GAMs consistently outperformed GB models across a range of essential MCH services, demonstrating low systematic prediction errors. High-resolution maps revealed stark geographic disparities in MCH service coverage, especially between rural and urban areas and among different states and service types. Temporal trends indicated an overall increase in MCH service coverage from 2003 to 2018, although with variations by service type and location. Priority areas with lower coverage of both maternal and vaccination services were identified, mostly located in the northern parts of Nigeria. CONCLUSION: High-resolution spatial estimates can guide geographic prioritisation and help develop better strategies for implementation plans, allowing limited resources to be targeted to areas with lower coverage of essential MCH services.

Evaluating Scope and Bias of Population-Level Measles Serosurveys: A Systematized Review and Bias Assessment.

BACKGROUND: Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021. METHODS: On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075). RESULTS: We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias. CONCLUSIONS: While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.

Prevalence of clinical forms of Chagas disease: a systematic review and meta-analysis - data from the RAISE study.

Background: There is a lack of up-to-date estimates about the prevalence of Chagas disease (ChD) clinical presentations and, therefore, we aimed to assess the prevalence of clinical forms of ChD among seropositive adults, pooling available data. Methods: A systematic review was conducted in Medline, Embase, Biblioteca Virtual em Saúde and Cochrane databases looking for studies published from 1990 to August 2023, which investigated the prevalence of ChD clinical forms among seropositive adults, including: (i) indeterminate phase, (ii) chronic Chagas cardiomyopathy (CCM), (iii) digestive and (iv) mixed (CCM + digestive) forms. Pooled estimates and 95% confidence intervals (CI) were calculated using random-effects models. Studies quality and risk of bias was assessed with the Leboeuf-Yde and Lauritsen tool. Heterogeneity was assessed with the I2 statistic. The study was registered in the PROSPERO database (CRD42022354237). Findings: 1246 articles were selected for screening and 73 studies were included in the final analysis (17,132 patients, 44% men). Most studies were conducted with outpatients (n = 50), followed by population-based studies (n = 15). The pooled prevalence of the ChD clinical forms was: indeterminate 42.6% (95% CI: 36.9-48.6), CCM 42.7% (95% CI: 37.3-48.3), digestive 17.7% (95% CI: 14.9-20.9), and mixed 10.2% (95% CI: 7.9-13.2). In population-based studies, prevalence was lower for CCM (31.2%, 95% CI: 24.4-38.9) and higher for indeterminate (47.2%, 95% CI: 39.0-55.5) form. In meta-regression, age was inversely associated with the prevalence of indeterminate (ß = -0.05, P < 0.001) form, and directly associated with CCM (ß = 0.06, P < 0.001) and digestive (ß = 0.02, P < 0.001) forms. Heterogeneity was overall high. Interpretation: Compared to previous publications, our pooled estimates show a higher prevalence of CCM among ChD seropositive patients, but similar rates of the digestive form. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

Prevalence of Chagas disease among Latin American immigrants in non-endemic countries: an updated systematic review and meta-analysis.

Background: Chagas disease (CD), endemic in 21 Latin American countries, has gradually spread beyond its traditional borders due to migratory movements and emerging as a global health concern. We conducted a systematic review and meta-analysis of available data to establish updated prevalence estimates of CD in Latin American migrants residing in non-endemic countries. Methods: A systematic search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Web of Science, and LILACS via Virtual Health Library (Biblioteca Virtual em Saúde - BVS), including references published until November 1st, 2023. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated using random effect models. Heterogeneity was assessed by the chi-square test and the I2 statistic. Subgroup analyses were performed to explore potential sources of heterogeneity among studies. The study was registered in the PROSPERO database (CRD42022354237). Findings: From a total of 1474 articles screened, 51 studies were included. Studies were conducted in eight non-endemic countries (most in Spain), between 2006 and 2023, and involving 82,369 screened individuals. The estimated pooled prevalence of CD in Latin American migrants living in non-endemic countries was 3.5% (95% CI: 2.5-4.7; I2: 97.7%), considering studies in which screening was indicated simply because the person was Latin American. Per subgroups, the pooled CD prevalence was 11.0% (95% CI: 7.7-15.5) in non-targeted screening (unselected population in reference centers) (27 studies); in blood donors (4 studies), the pooled prevalence was 0.8% (95% CI: 0.2-3.4); among people living with HIV Latin American immigrants (4 studies) 2.4% (95% CI: 1.4-4.3) and for Latin American pregnant and postpartum women (14 studies) 3.7% (95 CI: 2.4-5.6). The pooled proportion of congenital transmission was 4.4% (95% CI: 3.3-5.8). Regarding the participants' country of origin, 7964 were from Bolivia, of which 1715 (21,5%) were diagnosed with CD, and 21,304 were from other Latin American countries of which 154 (0,72%) were affected. Interpretation: CD poses a significant burden of disease in Latin American immigrants in non-endemic countries, suggesting that CD is no longer a problem limited to the American continent and must be considered as a global health challenge. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

The Burden of Chagas Disease in the Contemporary World: The RAISE Study.

Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.

Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Assessing Geographic Overlap between Zero-Dose Diphtheria-Tetanus-Pertussis Vaccination Prevalence and Other Health Indicators.

The integration of immunization with other essential health services is among the strategic priorities of the Immunization Agenda 2030 and has the potential to improve the effectiveness, efficiency, and equity of health service delivery. This study aims to evaluate the degree of spatial overlap between the prevalence of children who have never received a dose of the diphtheria-tetanus-pertussis-containing vaccine (no-DTP) and other health-related indicators, to provide insight into the potential for joint geographic targeting of integrated service delivery efforts. Using geospatially modeled estimates of vaccine coverage and comparator indicators, we develop a framework to delineate and compare areas of high overlap across indicators, both within and between countries, and based upon both counts and prevalence. We derive summary metrics of spatial overlap to facilitate comparison between countries and indicators and over time. As an example, we apply this suite of analyses to five countries-Nigeria, Democratic Republic of the Congo (DRC), Indonesia, Ethiopia, and Angola-and five comparator indicators-children with stunting, under-5 mortality, children missing doses of oral rehydration therapy, prevalence of lymphatic filariasis, and insecticide-treated bed net coverage. Our results demonstrate substantial heterogeneity in the geographic overlap both within and between countries. These results provide a framework to assess the potential for joint geographic targeting of interventions, supporting efforts to ensure that all people, regardless of location, can benefit from vaccines and other essential health services.

Estimating national-level measles case-fatality ratios in low-income and middle-income countries: an updated systematic review and modelling study.

BACKGROUND: To understand the current measles mortality burden, and to mitigate the future burden, it is crucial to have robust estimates of measles case fatalities. Estimates of measles case-fatality ratios (CFRs) that are specific to age, location, and time are essential to capture variations in underlying population-level factors, such as vaccination coverage and measles incidence, which contribute to increases or decreases in CFRs. In this study, we updated estimates of measles CFRs by expanding upon previous systematic reviews and implementing a meta-regression model. Our objective was to use all information available to estimate measles CFRs in low-income and middle-income countries (LMICs) by country, age, and year. METHODS: For this systematic review and meta-regression modelling study, we searched PubMed on Dec 31, 2020 for all available primary data published from Jan 1, 1980 to Dec 31, 2020, on measles cases and fatalities occurring up to Dec 31, 2019 in LMICs. We included studies that previous systematic reviews had included or which contained primary data on measles cases and deaths from hospital-based, community-based, or surveillance-based reports, including outbreak investigations. We excluded studies that were not in humans, or reported only data that were only non-primary, or on restricted populations (eg, people living with HIV), or on long-term measles mortality (eg, death from subacute sclerosing panencephalitis), and studies that did not include country-level data or relevant information on measles cases and deaths, or were for a high-income country. We extracted summary data on measles cases and measles deaths from studies that fitted our inclusion and exclusion criteria. Using these data and a suite of covariates related to measles CFRs, we implemented a Bayesian meta-regression model to produce estimates of measles CFRs from 1990 to 2019 by location and age group. This study was not registered with PROSPERO or otherwise. FINDINGS: We identified 2705 records, of which 208 sources contained information on both measles cases and measles deaths in LMICS and were included in the review. Between 1990 and 2019, CFRs substantially decreased in both community-based and hospital-based settings, with consistent patterns across age groups. For people aged 0-34 years, we estimated a mean CFR for 2019 of 1·32% (95% uncertainty interval [UI] 1·28-1·36) among community-based settings and 5·35% (5·08-5·64) among hospital-based settings. We estimated the 2019 CFR in community-based settings to be 3·03% (UI 2·89-3·16) for those younger than 1 year, 1·63% (1·58-1·68) for age 1-4 years, 0·84% (0·80-0·87) for age 5-9 years, and 0·67% (0·64-0·70) for age 10-14 years. INTERPRETATION: Although CFRs have declined between 1990 and 2019, there are still large heterogeneities across locations and ages. One limitation of this systematic review is that we were unable to assess measles CFR among particular populations, such as refugees and internally displaced people. Our updated methodological framework and estimates could be used to evaluate the effect of measles control and vaccination programmes on reducing the preventable measles mortality burden. FUNDING: Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; and the US National Institutes of Health.

Population-Level Risk Factors Related to Measles Case Fatality: A Conceptual Framework Based on Expert Consultation and Literature Review.

A better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators. Using expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We conducted a literature review by searching PubMed on 31 October 2021 to determine the scope of evidence for the expert-identified indicators. Studies were included if they contained evidence of an association between an indicator and CFR and were excluded if they were from non-human studies or reported non-original data. Included studies were assessed for study quality. Expert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators (average household size, educational attainment, first- and second-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, level of health care available, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, vitamin A treatment, and general malnutrition) and only non-significant associations for five indicators (antibiotic use for measles-related pneumonia, malaria prevalence, percent living in urban settings, pneumococcal conjugate vaccination coverage, vitamin A supplementation). Our study used expert consultation and a literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future measles CFR estimations.

Meningococcal A conjugate vaccine coverage in the meningitis belt of Africa from 2010 to 2021: a modelling study.

Background: As of the end of 2021, twenty-four countries in the African meningitis belt have rolled out mass campaigns of MenAfriVac®, a meningococcal A conjugate vaccine (MACV) first introduced in 2010. Twelve have completed introduction of MACV into routine immunisation (RI) schedules. Although select post-campaign coverage data are published, no study currently comprehensively estimates MACV coverage from both routine and campaign sources in the meningitis belt across age, country, and time. Methods: In this modelling study, we assembled campaign data from the twenty-four countries that had introduced any immunisation activity during or before the year 2021 (Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Côte d'Ivoire, Democratic Republic of the Congo, Ethiopia, Eritrea, the Gambia, Ghana, Guinea, Guinea Bissau, Kenya, Mali, Mauritania, Niger, Nigeria, Senegal, South Sudan, Sudan, Togo and Uganda) via WHO reports and RI data via systematic review. Next, we modelled RI coverage using Spatiotemporal Gaussian Process Regression. Then, we synthesized these estimates with campaign data into a cohort model, tracking coverage for each age cohort from age 1 to 29 years over time for each country. Findings: Coverage in high-risk locations amongst children aged 1-4 in 2021 was estimated to be highest in Togo with 96.0% (95% uncertainty interval [UI] 92.0-99.0), followed by Niger with 87.2% (95% UI 85.3-89.0) and Burkina Faso, with 86.4% (95% UI 85.1-87.6). These countries had high coverage values driven by an initial successful mass immunisation campaign, followed by a catch-up campaign, followed by introduction of RI. Due to the influence of older mass vaccination campaigns, coverage proportions skewed higher in the 1-29 age group than the 1-4 group, with a median coverage of 82.9% in 2021 in the broader age group compared to 45.6% in the narrower age group. Interpretation: These estimates highlight where gaps in immunisation remain and emphasise the need for broader efforts to strengthen RI systems. This methodological framework can be applied to estimate coverage for any vaccine that has been delivered in both routine and supplemental immunisation activities. Funding: Bill and Melinda Gates Foundation.