Study design and rationale for the PAASIM project: a matched cohort study on urban water supply improvements and infant enteric pathogen infection, gut microbiome development and health in Mozambique.

INTRODUCTION: Despite clear linkages between provision of clean water and improvements in child health, limited information exists about the health impacts of large water infrastructure improvements in low-income settings. Billions of dollars are spent annually to improve urban water supply, and rigorous evaluation of these improvements, especially targeting informal settlements, is critical to guide policy and investment strategies. Objective measures of infection and exposure to pathogens, and measures of gut function, are needed to understand the effectiveness and impact of water supply improvements. METHODS AND ANALYSIS: In the PAASIM study, we examine the impact of water system improvements on acute and chronic health outcomes in children in a low-income urban area of Beira, Mozambique, comprising 62 sub-neighbourhoods and ~26 300 households. This prospective matched cohort study follows 548 mother-child dyads from late pregnancy through 12 months of age. Primary outcomes include measures of enteric pathogen infections, gut microbiome composition and source drinking water microbiological quality, measured at the child's 12-month visit. Additional outcomes include diarrhoea prevalence, child growth, previous enteric pathogen exposure, child mortality and various measures of water access and quality. Our analyses will compare (1) subjects living in sub-neighbourhoods with the improved water to those living in sub-neighbourhoods without these improvements; and (2) subjects with household water connections on their premises to those without such a connection. This study will provide critical information to understand how to optimise investments for improving child health, filling the information gap about the impact of piped water provision to low-income urban households, using novel gastrointestinal disease outcomes. ETHICS AND DISSEMINATION: This study was approved by the Emory University Institutional Review Board and the National Bio-Ethics Committee for Health in Mozambique. The pre-analysis plan is published on the Open Science Framework platform (https://osf.io/4rkn6/). Results will be shared with relevant stakeholders locally, and through publications.

Global and regional spending on dementia care from 2000-2019 and expected future health spending scenarios from 2020-2050: An economic modelling exercise.

Background: The global burden of dementia is increasing. As diagnosis and treatment rates increase and populations grow and age, additional diagnosed cases will present a challenge to healthcare systems globally. Even modelled estimates of the current and future healthcare spending attributable to dementia are valuable for decision makers and advocates to prepare for growing demand. Methods: We modelled healthcare spending attributable to dementia from 2000 to 2019 and expected estimated future spending from 2020 to 2050 under multiple scenarios. Data were from the Global Burden of Diseases 2019 study and from two systematic literature reviews. We used meta-regression to estimate the fraction of dementia spending that is attributable to dementia for those receiving nursing home-based care and for those receiving community-based care. We used spatiotemporal Gaussian process regression to account for data missingness and model diagnosis and treatment rates, nursing home-based care and community-based care rates, and unit costs for the many countries without their own underlying estimates. Projections of future spending estimate a baseline scenario from 2020 to 2050 based on ongoing growth. Alternative scenarios assessed faster growth rates for dementia diagnosis and treatment rates, nursing home-based care, and healthcare costs. All spending is reported in 2019 United States dollars or 2019 purchasing-power parity-adjusted dollars. Findings: Based on observed and modelled inputs, we estimated that global spending on dementia increased by 4.5% (95% uncertainty interval: 3.4-5.4%) annually from 2000 to 2019, reaching $263 billion (95% uncertainty interval [UI] $199- $333) attributable to dementia in 2019. We estimated total healthcare spending on patients with dementia was $594 billion (95% UI $457-$843). Under the baseline scenario, we estimated that attributable dementia spending will reach $1.6 trillion (95% UI $0.9-$2.6) by 2050. We project it will represent 11% (95% UI 6-18%) of all expected health spending, although it could be as high as 17% (95% UI 10-26%) under alternative scenarios. Interpretation: Health systems will experience increases in the burden of dementia in the near future. These modelled direct cost estimates, built from a relatively small set of data and linear time trends, highlight the magnitude of health system resources expected to be used to provide care and ensure sufficient and adequate resources for aging populations and their caretakers. More data are needed to corroborate these important trends.

Growing up and moving out: Migration and the demographic transition in low- and middle-income nations.

International migration has increased since 1990, with increasing numbers of migrants originating from low- and middle-income countries (LMICs). Efforts to explain this compositional shift have focused on wage gaps and other push and pull factors but have not adequately considered the role of demographic factors. In many LMICs, child mortality has fallen without commensurate economic growth and amid high fertility. This combination increases young adult populations and is associated with greater outmigration: in the poorest countries, we estimate that a one-percentage-point increase in the five-year lagged growth rate of the population of 15-24-year-olds was associated with a 15 per cent increase in all-age outmigrants, controlling for other factors. Increases in growth of young adult populations led to 20.4 million additional outmigrants across 80 countries between 1990 and 2015. Understanding the determinants of these migration shifts should help policymakers in origin and destination countries to maximize their potential positive effects.

Public health utility of cause of death data: applying empirical algorithms to improve data quality.

BACKGROUND: Accurate, comprehensive, cause-specific mortality estimates are crucial for informing public health decision making worldwide. Incorrectly or vaguely assigned deaths, defined as garbage-coded deaths, mask the true cause distribution. The Global Burden of Disease (GBD) study has developed methods to create comparable, timely, cause-specific mortality estimates; an impactful data processing method is the reallocation of garbage-coded deaths to a plausible underlying cause of death. We identify the pattern of garbage-coded deaths in the world and present the methods used to determine their redistribution to generate more plausible cause of death assignments. METHODS: We describe the methods developed for the GBD 2019 study and subsequent iterations to redistribute garbage-coded deaths in vital registration data to plausible underlying causes. These methods include analysis of multiple cause data, negative correlation, impairment, and proportional redistribution. We classify garbage codes into classes according to the level of specificity of the reported cause of death (CoD) and capture trends in the global pattern of proportion of garbage-coded deaths, disaggregated by these classes, and the relationship between this proportion and the Socio-Demographic Index. We examine the relative importance of the top four garbage codes by age and sex and demonstrate the impact of redistribution on the annual GBD CoD rankings. RESULTS: The proportion of least-specific (class 1 and 2) garbage-coded deaths ranged from 3.7% of all vital registration deaths to 67.3% in 2015, and the age-standardized proportion had an overall negative association with the Socio-Demographic Index. When broken down by age and sex, the category for unspecified lower respiratory infections was responsible for nearly 30% of garbage-coded deaths in those under 1 year of age for both sexes, representing the largest proportion of garbage codes for that age group. We show how the cause distribution by number of deaths changes before and after redistribution for four countries: Brazil, the United States, Japan, and France, highlighting the necessity of accounting for garbage-coded deaths in the GBD. CONCLUSIONS: We provide a detailed description of redistribution methods developed for CoD data in the GBD; these methods represent an overall improvement in empiricism compared to past reliance on a priori knowledge.

Prevalence and intensity of soil-transmitted helminth infections of children in sub-Saharan Africa, 2000-18: a geospatial analysis.

BACKGROUND: Driven by global targets to eliminate soil-transmitted helminths as a public health problem, governments have rapidly rolled out control programmes using school and community-based platforms. To justify and target ongoing investment, quantification of impact and identification of remaining high-risk areas are needed. We aimed to assess regional progress towards these targets. METHODS: We did a continental-scale ecological analysis using a Bayesian space-time hierarchical model to estimate the effects of known environmental, socioeconomic, and control-related factors on the prevalence of soil-transmitted helminths, and we mapped the probability that implementation units had achieved moderate-to-heavy intensity infection prevalence of less than 2% among children aged 5-14 years between Jan 1, 2000, and Dec 31, 2018. FINDINGS: We incorporated data from 26 304 georeferenced surveys, spanning 3096 (60%) of the 5183 programmatic implementation units. Our findings suggest a reduction in the prevalence of soil-transmitted helminths in children aged 5-14 years in sub-Saharan Africa, from 44% in 2000 to 13% in 2018, driven by sustained delivery of preventive chemotherapy, improved sanitation, and economic development. Nevertheless, 1301 (25%) of 5183 implementation units still had an estimated prevalence of moderate-to-heavy intensity infection exceeding the 2% target threshold in 2018, largely concentrated in nine countries (in 1026 [79%] of 1301 implementation units): Nigeria, Democratic Republic of the Congo, Ethiopia, Cameroon, Angola, Mozambique, Madagascar, Equatorial Guinea, and Gabon. INTERPRETATION: Our estimates highlight the areas to target and strengthen interventions, and the areas where data gaps remain. If elimination of soil-transmitted helminths as a public health problem is to be achieved in sub-Saharan Africa by 2030, continued investment in treatment and prevention activities are essential to ensure that no areas are left behind. FUNDING: Bill & Melinda Gates Foundation.

Informing Rift Valley Fever preparedness by mapping seasonally varying environmental suitability.

BACKGROUND: Rift Valley Fever (RVF) poses a threat to human and animal health throughout much of Africa and the Middle East and has been recognized as a global health security priority and a key preparedness target. METHODS: We combined RVF occurrence data from a systematic literature review with animal notification data from an online database. Using boosted regression trees, we made monthly environmental suitability predictions from January 1995 to December 2016 at a 5 × 5-km resolution throughout regions of Africa, Europe, and the Middle East. We calculated the average number of months per year suitable for transmission, the mean suitability for each calendar month, and the "spillover potential," a measure incorporating suitability with human and livestock populations. RESULTS: Several countries where cases have not yet been reported are suitable for RVF. Areas across the region of interest are suitable for transmission at different times of the year, and some areas are suitable for multiple seasons each year. Spillover potential results show areas within countries where high populations of humans and livestock are at risk for much of the year. CONCLUSIONS: The widespread environmental suitability of RVF highlights the need for increased preparedness, even in countries that have not previously experienced cases. These maps can aid in prioritizing long-term RVF preparedness activities and determining optimal times for recurring preparedness activities. Given an outbreak, our results can highlight areas often at risk for subsequent transmission that month, enabling decision-makers to target responses effectively.

Identifying residual hotspots and mapping lower respiratory infection morbidity and mortality in African children from 2000 to 2017.

Lower respiratory infections (LRIs) are the leading cause of death in children under the age of 5, despite the existence of vaccines against many of their aetiologies. Furthermore, more than half of these deaths occur in Africa. Geospatial models can provide highly detailed estimates of trends subnationally, at the level where implementation of health policies has the greatest impact. We used Bayesian geostatistical modelling to estimate LRI incidence, prevalence and mortality in children under 5 subnationally in Africa for 2000-2017, using surveys covering 1.46 million children and 9,215,000 cases of LRI. Our model reveals large within-country variation in both health burden and its change over time. While reductions in childhood morbidity and mortality due to LRI were estimated for almost every country, we expose a cluster of residual high risk across seven countries, which averages 5.5 LRI deaths per 1,000 children per year. The preventable nature of the vast majority of LRI deaths mandates focused health system efforts in specific locations with the highest burden.

Global, Regional, National, and Subnational Big Data to Inform Health Equity Research: Perspectives from the Global Burden of Disease Study 2017.

Objectives: Everyone deserves a long and healthy life, but in reality, health outcomes differ across populations. We use results from the Global Burden of Disease Study 2017 (GBD 2017) to report patterns in the burden of diseases, injuries, and risks at the global, regional, national, and subnational level, and by sociodemographic index (SDI), from 1990 to 2017. Design: GBD 2017 undertook a systematic analysis of published studies and available data providing information on prevalence, incidence, remission, and excess mortality. We computed prevalence, incidence, mortality, life expectancy, healthy life expectancy, years of life lost due to premature mortality, years lived with disability, and disability-adjusted life years with 95% uncertainty intervals for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries from 1990 to 2017. We also computed SDI, a summary indicator combining measures of income, education, and fertility. Results: There were wide disparities in the burden of disease by SDI, with smaller burdens in affluent countries and in specific regions within countries. Select diseases and risks, such as drug use disorders, high blood pressure, high body mass index, diet, high fasting plasma glucose, smoking, and alcohol use disorders warrant increased global attention and indicate a need for greater investment in prevention and treatment across the life course. Conclusions: Policymakers need a comprehensive picture of what risks and causes result in disability and death. The GBD provides the means to quantify health loss: these findings can be used to examine root causes of disparities and develop programs to improve health and health equity.

Health disparities across the counties of Kenya and implications for policy makers, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provided comprehensive estimates of health loss globally. Decision makers in Kenya can use GBD subnational data to target health interventions and address county-level variation in the burden of disease. METHODS: We used GBD 2016 estimates of life expectancy at birth, healthy life expectancy, all-cause and cause-specific mortality, years of life lost, years lived with disability, disability-adjusted life-years, and risk factors to analyse health by age and sex at the national and county levels in Kenya from 1990 to 2016. FINDINGS: The national all-cause mortality rate decreased from 850·3 (95% uncertainty interval [UI] 829·8-871·1) deaths per 100 000 in 1990 to 579·0 (562·1-596·0) deaths per 100 000 in 2016. Under-5 mortality declined from 95·4 (95% UI 90·1-101·3) deaths per 1000 livebirths in 1990 to 43·4 (36·9-51·2) deaths per 1000 livebirths in 2016, and maternal mortality fell from 315·7 (242·9-399·4) deaths per 100 000 in 1990 to 257·6 (195·1-335·3) deaths per 100 000 in 2016, with steeper declines after 2006 and heterogeneously across counties. Life expectancy at birth increased by 5·4 (95% UI 3·7-7·2) years, with higher gains in females than males in all but ten counties. Unsafe water, sanitation, and handwashing, unsafe sex, and malnutrition were the leading national risk factors in 2016. INTERPRETATION: Health outcomes have improved in Kenya since 2006. The burden of communicable diseases decreased but continues to predominate the total disease burden in 2016, whereas the non-communicable disease burden increased. Health gains varied strikingly across counties, indicating targeted approaches for health policy are necessary. FUNDING: Bill & Melinda Gates Foundation.

On the road to universal health care in Indonesia, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: As Indonesia moves to provide health coverage for all citizens, understanding patterns of morbidity and mortality is important to allocate resources and address inequality. The Global Burden of Disease 2016 study (GBD 2016) estimates sources of early death and disability, which can inform policies to improve health care. METHODS: We used GBD 2016 results for cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth, healthy life expectancy, and risk factors for 333 causes in Indonesia and in seven comparator countries. Estimates were produced by location, year, age, and sex using methods outlined in GBD 2016. Using the Socio-demographic Index, we generated expected values for each metric and compared these against observed results. FINDINGS: In Indonesia between 1990 and 2016, life expectancy increased by 8·0 years (95% uncertainty interval [UI] 7·3-8·8) to 71·7 years (71·0-72·3): the increase was 7·4 years (6·4-8·6) for males and 8·7 years (7·8-9·5) for females. Total DALYs due to communicable, maternal, neonatal, and nutritional causes decreased by 58·6% (95% UI 55·6-61·6), from 43·8 million (95% UI 41·4-46·5) to 18·1 million (16·8-19·6), whereas total DALYs from non-communicable diseases rose. DALYs due to injuries decreased, both in crude rates and in age-standardised rates. The three leading causes of DALYs in 2016 were ischaemic heart disease, cerebrovascular disease, and diabetes. Dietary risks were a leading contributor to the DALY burden, accounting for 13·6% (11·8-15·4) of DALYs in 2016. INTERPRETATION: Over the past 27 years, health across many indicators has improved in Indonesia. Improvements are partly offset by rising deaths and a growing burden of non-communicable diseases. To maintain and increase health gains, further work is needed to identify successful interventions and improve health equity. FUNDING: The Bill & Melinda Gates Foundation.

Infant and Young Child Feces Management and Enabling Products for Their Hygienic Collection, Transport, and Disposal in Cambodia.

In Cambodia, children's feces are rarely disposed of in an improved sanitation facility. This study examines current practices and the role that enabling products may play in increasing hygienic management of infant and young child (IYC) feces in households with access to improved sanitation. A survey was conducted with the primary caregiver of a child under 5 years of age in 130 homes with an improved latrine in 21 villages across two provinces in Cambodia. Two focus group discussions per province were conducted after the survey to obtain caregiver feedback on new enabling products for hygienic management. Among caregivers, 63% reported child feces disposal in an improved latrine but only 36% reported doing so consistently. Besides child age, years of latrine ownership, caregiver age, consistency of adult latrine use, and presence of child feces management tools in the latrine were associated with hygienic disposal. The youngest caretakers with the newest latrines and youngest children were least likely to dispose of IYC feces hygienically, representing a key target group for interventions to improve hygienic disposal in Cambodia. Reusable diapers, child-friendly potties, and possibly latrine seats, that offer child safety, time and cost savings, and easy disposal and cleaning could potentially facilitate hygienic disposal for these ages.

Building alliances for improving newborn health in Latin America and the Caribbean.

The regional Latin American and Caribbean (LAC) Neonatal Alliance and national neonatal alliances in Bolivia, El Salvador, and Peru were studied through in-depth interviews and a review of publications. Findings were analyzed to distill successful strategies, structures, and tools for improving neonatal health by working through alliances that can be replicated at the regional or national level. The studies found the following factors were the most critical for successful outcomes from alliance work: inclusion of the Ministry of Health as a leader or primary stakeholder; a committed, diverse, technically expert, and horizontal membership; the presence of champions for neonatal health at the national level; development of a shared work plan based on feasible objectives; the use of shared financing mechanisms; the use of informal and dynamic organizational structures; and a commitment to scientific evidence-based programming. The relationship between the regional and national alliances was found to be mutually beneficial.

Building alliances for improving newborn health in Latin America and the Caribbean / Alianzas para mejorar la salud de los recién nacidos en América Latina y el Caribe

The regional Latin American and Caribbean (LAC) Neonatal Alliance and national neonatal alliances in Bolivia, El Salvador, and Peru were studied through in-depth interviews and a review of publications. Findings were analyzed to distill successful strategies, structures, and tools for improving neonatal health by working through alliances that can be replicated at the regional or national level. The studies found the following factors were the most critical for successful outcomes from alliance work: inclusion of the Ministry of Health as a leader or primary stakeholder; a committed, diverse, technically expert, and horizontal membership; the presence of champions for neonatal health at the national level; development of a shared work plan based on feasible objectives; the use of shared financing mechanisms; the use of informal and dynamic organizational structures; and a commitment to scientific evidence-based programming. The relationship between the regional and national alliances was found to be mutually beneficial.

Se estudiaron la Alianza de Salud Neonatal para América Latina y el Caribe a escala regional, y las alianzas nacionales de salud neonatal de Bolivia, El Salvador y Perú, mediante entrevistas exhaustivas y un análisis de las publicaciones. Se analizaron los resultados para extraer las estrategias, las estructuras y las herramientas eficaces para mejorar la salud neonatal trabajando mediante alianzas que puedan repetirse a escala regional o nacional. Los estudios descubrieron que los factores más decisivos para obtener resultados exitosos del trabajo mediante alianzas fueron los siguientes: la inclusión de los ministerios de salud como líderes o interesados directos principales; una afiliación comprometida, diversa, técnicamente experta y horizontal; la presencia de promotores de la salud neonatal a escala nacional; la formulación de un plan de trabajo compartido basado en objetivos factibles; la utilización de mecanismos de financiamiento compartido; el uso de estructuras organizativas informales y dinámicas; y un compromiso con la programación científica basada en datos probatorios. Se observó que la relación entre las alianzas regionales y nacionales resultaba mutuamente beneficiosa.