Sarah E Ray

Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis

Summary Background Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the diseases contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. Methods We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5u2008×u20085 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. Findings Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016 was estimated to be substantially less than the recommended threshold to prevent outbreaks. Overall, we estimated that vaccination coverage levels achieved by 2016 avert between 94u2008336 and 118u2008500 cases of yellow fever annually within risk zones, on the basis of conservative and optimistic vaccination scenarios. The areas outside at-risk regions with predicted high receptivity to yellow fever transmission (eg, parts of Malaysia, Indonesia, and Thailand) were less extensive than the distribution of the main urban vector, A aegypti, with low receptivity to yellow fever transmission in southern China, where A aegypti is known to occur. Interpretation Our results provide the evidence base for targeting vaccination campaigns within risk zones, as well as emphasising their high effectiveness. Our study highlights areas where public health authorities should be most vigilant for potential spread or importation events. Funding Bill & Melinda Gates Foundation.

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.

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.

Vulnerability to snakebite envenoming: a global mapping of hotspots

Summary Background Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. Methods We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but <5 species occurrence records), and group C (EOR map and ≥5 species occurrence records). For group C species, we did a multivariate environmental similarity analysis using the 2008 WHO EOR maps and newly available evidence. Using these data and the EOR maps, we produced contemporary range maps for medically important venomous snake species at a 5u2008×u20085 km resolution. We subsequently triangulated these data with three health system metrics (antivenom availability, accessibility to urban centres, and the Healthcare Access and Quality [HAQ] Index) to identify the populations most vulnerable to snakebite morbidity and mortality. Findings We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. Interpretation Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. Funding Bill & Melinda Gates Foundation.

“Rapid impact” 10 years after: The first “decade” (2006–2016) of integrated neglected tropical disease control

New data from the Global Burden of Disease (GBD) Study 2016 indicate substantial declines in the prevalence and disease burden (as measured in disability-adjusted life years [DALYs]) of six of the seven neglected tropical diseases (NTDs) targeted by integrated mass drug administration (MDA) over the previous decade.

Burden of disease in Brazil, 1990–2016: a systematic subnational analysis for the Global Burden of Disease Study 2016

Summary Background Political, economic, and epidemiological changes in Brazil have affected health and the health system. We used the Global Burden of Disease Study 2016 (GBD 2016) results to understand changing health patterns and inform policy responses. Methods We analysed GBD 2016 estimates for life expectancy at birth (LE), healthy life expectancy (HALE), all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and risk factors for Brazil, its 26 states, and the Federal District from 1990 to 2016, and compared these with national estimates for ten comparator countries. Findings Nationally, LE increased from 68·4 years (95% uncertainty interval [UI] 68·0–68·9) in 1990 to 75·2 years (74·7–75·7) in 2016, and HALE increased from 59·8 years (57·1–62·1) to 65·5 years (62·5–68·0). All-cause age-standardised mortality rates decreased by 34·0% (33·4–34·5), while all-cause age-standardised DALY rates decreased by 30·2% (27·7–32·8); the magnitude of declines varied among states. In 2016, ischaemic heart disease was the leading cause of age-standardised YLLs, followed by interpersonal violence. Low back and neck pain, sense organ diseases, and skin diseases were the main causes of YLDs in 1990 and 2016. Leading risk factors contributing to DALYs in 2016 were alcohol and drug use, high blood pressure, and high body-mass index. Interpretation Health improved from 1990 to 2016, but improvements and disease burden varied between states. An epidemiological transition towards non-communicable diseases and related risks occurred nationally, but later in some states, while interpersonal violence grew as a health concern. Policy makers can use these results to address health disparities. Funding Bill & Melinda Gates Foundation and the Brazilian Ministry of Health.

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.)

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

Summary 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.

Global variation in bacterial strains that cause tuberculosis disease: a systematic review and meta-analysis

BackgroundThe host, microbial, and environmental factors that contribute to variation in tuberculosis (TB) disease are incompletely understood. Accumulating evidence suggests that one driver of geographic variation in TB disease is the local ecology of mycobacterial genotypes or strains, and there is a need for a comprehensive and systematic synthesis of these data. The objectives of this study were to (1) map the global distribution of genotypes that cause TB disease and (2) examine whether any epidemiologically relevant clinical characteristics were associated with those genotypes.MethodsWe performed a systematic review of PubMed and Scopus to create a comprehensive dataset of human TB molecular epidemiology studies that used representative sampling techniques. The methods were developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We extracted and synthesized data from studies that reported prevalence of bacterial genotypes and from studies that reported clinical characteristics associated with those genotypes.ResultsThe results of this study are twofold. First, we identified 206 studies for inclusion in the study, representing over 200,000 bacterial isolates collected over 27xa0years in 85 countries. We mapped the genotypes and found that, consistent with previously published maps, Euro-American lineage 4 and East Asian lineage 2 strains are widespread, and West African lineages 5 and 6 strains are geographically restricted. Second, 30 studies also reported transmission chains and 4 reported treatment failure associated with genotypes. We performed a meta-analysis and found substantial heterogeneity across studies. However, based on the data available, we found that lineage 2 strains may be associated with increased risk of transmission chains, while lineages 5 and 6 strains may be associated with reduced risk, compared with lineage 4 strains.ConclusionsThis study provides the most comprehensive systematic analysis of the evidence for diversity in bacterial strains that cause TB disease. The results show both geographic and epidemiological differences between strains, which could inform our understanding of the global burden of TB. Our findings also highlight the challenges of collecting the clinical data required to inform TB diagnosis and treatment. We urge future national TB programs and research efforts to prioritize and reinforce clinical data collection in study designs and results dissemination.

Progress toward eliminating TB and HIV deaths in Brazil, 2001–2015: a spatial assessment

BackgroundBrazil has high burdens of tuberculosis (TB) and HIV, as previously estimated for the 26 states and the Federal District, as well as high levels of inequality in social and health indicators. We improved the geographic detail of burden estimation by modelling deaths due to TB and HIV and TB case fatality ratios for the more than 5400 municipalities in Brazil.MethodsThis ecological study used vital registration data from the national mortality information system and TB case notifications from the national communicable disease notification system from 2001 to 2015. Mortality due to TB and HIV was modelled separately by cause and sex using a Bayesian spatially explicit mixed effects regression model. TB incidence was modelled using the same approach. Results were calibrated to the Global Burden of Disease Study 2016. Case fatality ratios were calculated for TB.ResultsThere was substantial inequality in TB and HIV mortality rates within the nation and within states. National-level TB mortality in people without HIV infection declined by nearly 50% during 2001 to 2015, but HIV mortality declined by just over 20% for males and 10% for females. TB and HIV mortality rates for municipalities in the 90th percentile nationally were more than three times rates in the 10th percentile, with nearly 70% of the worst-performing municipalities for male TB mortality and more than 75% for female mortality in 2001 also in the worst decile in 2015. The same municipality ranking metric for HIV was observed to be between 55% and 61%. Within states, the TB mortality rate ratios by sex for municipalities in the worst decile versus the best decile varied from 1.4 to 2.9, and HIV varied from 1.4 to 4.2. The World Health Organization target case fatality rate for TB of less than 10% was achieved in 9.6% of municipalities for males versus 38.4% for females in 2001 and improved to 38.4% and 56.6% of municipalities for males versus females, respectively, by 2014.ConclusionsMortality rates in municipalities within the same state exhibitedxa0nearly as much relative variation as within the nation as a whole. Monitoring the mortality burden at this level of geographic detail is critical for guiding precision public health responses.