Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study.

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.

Assessing the Feasibility of Typhoid Elimination.

In 1993, the International Task Force on Disease Eradication classified the political will for typhoid eradication as "none." Here we revisit the Task Force's assessment in light of developments in typhoid vaccines and increasing antimicrobial resistance in Salmonella Typhi that have served to increase interest in typhoid elimination. Considering the requisite biological and technical factors for elimination, effective interventions exist for typhoid, and humans are the organism's only known reservoir. Improvements in water supply, sanitation, hygiene, and food safety are critical for robust long-term typhoid control, and the recent Strategic Advisory Group of Experts on Immunization recommendation and World Health Organization prequalification should make typhoid conjugate vaccine more accessible and affordable in low-income countries, which will allow the vaccine to offer a critical bridge to quickly reduce burden. While these developments are encouraging, all current typhoid diagnostics are inadequate, having either poor performance characteristics, limited scalability, or both. No clear solution exists, and this should be viewed as a critical challenge to any elimination effort. Moreover, asymptomatic carriers and limited data and surveillance remain major challenges, and countries considering elimination campaigns will need to develop strategies to identify high-risk populations and to monitor progress over time. Finally, policymakers must be realistic in planning, learn from the planning failures of previous elimination and eradication efforts, and expect unforeseeable shocks and setbacks. In the end, if we assume neither unanticipated breakthroughs in typhoid control nor any chaotic shocks, history suggests that we should expect typhoid elimination to take decades.

Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.

Background: Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. Methods: We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Results: Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Conclusions: Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

Incidence, prevalence and mortality rates of malaria in Ethiopia from 1990 to 2015: analysis of the global burden of diseases 2015.

BACKGROUND: In Ethiopia there is no complete registration system to measure disease burden and risk factors accurately. In this study, the 2015 global burden of diseases, injuries and risk factors (GBD) data were used to analyse the incidence, prevalence and mortality rates of malaria in Ethiopia over the last 25 years. METHODS: GBD 2015 used verbal autopsy surveys, reports, and published scientific articles to estimate the burden of malaria in Ethiopia. Age and gender-specific causes of death for malaria were estimated using cause of death ensemble modelling. RESULTS: The number of new cases of malaria declined from 2.8 million [95% uncertainty interval (UI) 1.4-4.5 million] in 1990 to 621,345 (95% UI 462,230-797,442) in 2015. Malaria caused an estimated 30,323 deaths (95% UI 11,533.3-61,215.3) in 1990 and 1561 deaths (95% UI 752.8-2660.5) in 2015, a 94.8% reduction over the 25 years. Age-standardized mortality rate of malaria has declined by 96.5% between 1990 and 2015 with an annual rate of change of 13.4%. Age-standardized malaria incidence rate among all ages and gender declined by 88.7% between 1990 and 2015. The number of disability-adjusted life years lost (DALY) due to malaria decreased from 2.2 million (95% UI 0.76-4.7 million) in 1990 to 0.18 million (95% UI 0.12-0.26 million) in 2015, with a total reduction 91.7%. Similarly, age-standardized DALY rate declined by 94.8% during the same period. CONCLUSIONS: Ethiopia has achieved a 50% reduction target of malaria of the millennium development goals. The country should strengthen its malaria control and treatment strategies to achieve the sustainable development goals.

Mortality from tetanus between 1990 and 2015: findings from the global burden of disease study 2015.

BACKGROUND: Although preventable, tetanus still claims tens of thousands of deaths each year. The patterns and distribution of mortality from tetanus have not been well characterized. We identified the global, regional, and national levels and trends of mortality from neonatal and non-neonatal tetanus based on the results from the Global Burden of Disease Study 2015. METHODS: Data from vital registration, verbal autopsy studies and mortality surveillance data covering 12,534 site-years from 1980 to 2014 were used. Mortality from tetanus was estimated using the Cause of Death Ensemble modeling strategy. RESULTS: There were 56,743 (95% uncertainty interval (UI): 48,199 to 80,042) deaths due to tetanus in 2015; 19,937 (UI: 17,021 to 23,467) deaths occurred in neonates; and 36,806 (UI: 29,452 to 61,481) deaths occurred in older children and adults. Of the 19,937 neonatal tetanus deaths, 45% of deaths occurred in South Asia, and 44% in Sub-Saharan Africa. Of the 36,806 deaths after the neonatal period, 47% of deaths occurred in South Asia, 36% in sub-Saharan Africa, and 12% in Southeast Asia. Between 1990 and 2015, the global mortality rate due to neonatal tetanus dropped by 90% and that due to non-neonatal tetanus dropped by 81%. However, tetanus mortality rates were still high in a number of countries in 2015. The highest rates of neonatal tetanus mortality (more than 1,000 deaths per 100,000 population) were observed in Somalia, South Sudan, Afghanistan, and Kenya. The highest rates of mortality from tetanus after the neonatal period (more than 5 deaths per 100,000 population) were observed in Somalia, South Sudan, and Kenya. CONCLUSIONS: Though there have been tremendous strides globally in reducing the burden of tetanus, tens of thousands of unnecessary deaths from tetanus could be prevented each year by an already available inexpensive and effective vaccine. Availability of more high quality data could help narrow the uncertainty of tetanus mortality estimates.

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

Case-crossover analysis of condom use and herpes simplex virus type 2 acquisition.

BACKGROUND: Although growing evidence suggests that condoms offer moderate protection against herpes simplex virus type 2 (HSV-2), inability to control for unknown or unmeasured confounders associated with sexual activity may reduce the accuracy of the estimates. The case-crossover design offers increased control of individual-level confounders, and was thus used with the aim of producing a more accurate estimate of the effect of condom use on HSV-2 acquisition. METHODS: Data were pooled from 6 prospective studies that measured HSV-2 status at enrollment and over follow-up, and included periodic self-reported condom use and sexual activity. Sexual activity contemporaneous with acquisition was assigned to a case period; earlier sexual activity was assigned to a control period. Conditional logistic regression was used to assess differences in behavior during the case and control periods. RESULTS: One hundred ninety-one eligible participants acquired HSV-2 during follow-up. This approach detected a 3.6% increase in the odds of HSV-2 acquisition with each unprotected act (odds ratio = 1.036; 95% confidence interval: 1.021-1.052), but no increase in the odds of acquisition associated with protected acts (odds ratio = 1.008; 95% confidence interval: 0.987-1.030). CONCLUSIONS: This analysis suggests that condoms offer significant protection against HSV-2 transmission.

Mortality burden attributable to high and low ambient temperatures in China and its provinces: Results from the Global Burden of Disease Study 2019.

Background: Non-optimal temperatures are associated with mortality risk, yet the heterogeneity of temperature-attributable mortality burden across subnational regions in a country was rarely investigated. We estimated the mortality burden related to non-optimal temperatures across all provinces in China in 2019. Methods: The global daily temperature data were obtained from the ERA5 reanalysis dataset. The daily mortality data and exposure-response curves between daily temperature and mortality for 176 individual causes of death were obtained from the Global Burden of Disease Study 2019 (GBD 2019). We estimated the population attributable fraction (PAF) based on the exposure-response curves, daily gridded temperature, and population. We calculated the cause- and province-specific mortality burden based on PAF and disease burden data from the GBD 2019. Findings: We estimated that 593·9 (95% UI:498·8, 704·6) thousand deaths were attributable to non-optimal temperatures in China in 2019 (PAF=5·58% [4·93%, 6·28%]), with 580·8 (485·7, 690·1) thousand cold-related deaths and 13·9 (7·7, 23·2) thousand heat-related deaths. The majority of temperature-related deaths were from cardiovascular diseases (399·7 [322·8, 490·4] thousand) and chronic respiratory diseases (177·4 [141·4, 222·3] thousand). The mortality burdens were observed significantly spatial heterogeneity for both high and low temperatures. For instance, the age-standardized death rates (per 100 000) attributable to low temperature were higher in Western China, with the highest in Tibet (113·7 [82·0, 155·5]), while for high temperature, they were greater in Xinjiang (1·8 [0·7, 3·3]) and Central-Southern China such as Hainan (2·5 [0·9, 5·4]). We also observed considerable geographical variation in the temperature-related mortality burden by causes of death at provincial level. Interpretation: A substantial mortality burden was attributable to non-optimal temperatures across China, and cold effects dominated the total mortality burden in all provinces. Both cold- and heat-related mortality burden showed significantly spatial variations across China. Funding: National Key Research and Development Program.

Health effects associated with vegetable consumption: a Burden of Proof study.

Previous research suggests a protective effect of vegetable consumption against chronic disease, but the quality of evidence underlying those findings remains uncertain. We applied a Bayesian meta-regression tool to estimate the mean risk function and quantify the quality of evidence for associations between vegetable consumption and ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke, type 2 diabetes and esophageal cancer. Increasing from no vegetable consumption to the theoretical minimum risk exposure level (306-372 g daily) was associated with a 23.2% decline (95% uncertainty interval, including between-study heterogeneity: 16.4-29.4) in ischemic stroke risk; a 22.9% (13.6-31.3) decline in IHD risk; a 15.9% (1.7-28.1) decline in hemorrhagic stroke risk; a 28.5% (-0.02-51.4) decline in esophageal cancer risk; and a 26.1% (-3.6-48.3) decline in type 2 diabetes risk. We found statistically significant protective effects of vegetable consumption for ischemic stroke (three stars), IHD (two stars), hemorrhagic stroke (two stars) and esophageal cancer (two stars). Including between-study heterogeneity, we did not detect a significant association with type 2 diabetes, corresponding to a one-star rating. Although current evidence supports increased efforts and policies to promote vegetable consumption, remaining uncertainties suggest the need for continued research.

The Burden of Proof studies: assessing the evidence of risk.

Exposure to risks throughout life results in a wide variety of outcomes. Objectively judging the relative impact of these risks on personal and population health is fundamental to individual survival and societal prosperity. Existing mechanisms to quantify and rank the magnitude of these myriad effects and the uncertainty in their estimation are largely subjective, leaving room for interpretation that can fuel academic controversy and add to confusion when communicating risk. We present a new suite of meta-analyses-termed the Burden of Proof studies-designed specifically to help evaluate these methodological issues objectively and quantitatively. Through this data-driven approach that complements existing systems, including GRADE and Cochrane Reviews, we aim to aggregate evidence across multiple studies and enable a quantitative comparison of risk-outcome pairs. We introduce the burden of proof risk function (BPRF), which estimates the level of risk closest to the null hypothesis that is consistent with available data. Here we illustrate the BPRF methodology for the evaluation of four exemplar risk-outcome pairs: smoking and lung cancer, systolic blood pressure and ischemic heart disease, vegetable consumption and ischemic heart disease, and unprocessed red meat consumption and ischemic heart disease. The strength of evidence for each relationship is assessed by computing and summarizing the BPRF, and then translating the summary to a simple star rating. The Burden of Proof methodology provides a consistent way to understand, evaluate and summarize evidence of risk across different risk-outcome pairs, and informs risk analysis conducted as part of the Global Burden of Diseases, Injuries, and Risk Factors Study.

Hand, foot, and mouth disease in China: patterns of spread and transmissibility.

BACKGROUND: There were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in China. METHODS: Using the national surveillance data since 2 May 2008, we summarized the epidemiologic characteristics of the recent outbreaks. Using a susceptible-infectious-recovered transmission model, we evaluated the transmissibility of the disease and potential risk factors. RESULTS: Children ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as the longest delay from symptom onset to diagnosis (2.3 days). Boys were more susceptible than girls (OR = 1.56 [95% confidence interval = 1.56-1.57]). A 1-day delay in diagnosis was associated with increases in the odds of severe disease by 40% (39%-42%) and in the odds of death by 54% (44%-65%). Compared with Coxsackie A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13-18]) and death (OR = 40 [13-127]). The estimated local effective reproductive numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and stayed below 1.2 in other seasons. A higher risk of transmission was associated with temperatures in the range of 70° F to 80°F, higher relative humidity, higher [corrected] wind speed, more precipitation, greater population density, and [corrected] periods during which schools were open. CONCLUSION: Hand, foot, and mouth disease is a moderately transmittable infectious disease, mainly among preschool children. Enterovirus 71 was responsible for most severe cases and fatalities. Mixing of asymptomatically infected children in schools might have contributed to spread the of infection. Timely diagnosis may be [corrected] key to reducing the high mortality rate in infants.

Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries.

BACKGROUND: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance, but social distancing is challenged by high population densities and access to handwashing facilities with soap and water is limited. OBJECTIVES: Our objective was to estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. METHODS: We utilized observational surveys and spatiotemporal Gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study to estimate access to a handwashing station with available soap and water for 1,062 locations from 1990 to 2019. RESULTS: Despite overall improvements from 1990 {33.6% [95% uncertainty interval (UI): 31.5, 35.6] without access} to 2019, globally in 2019, 2.02 (95% UI: 1.91, 2.14) billion people, 26.1% (95% UI: 24.7, 27.7) of the global population, lacked access to handwashing with available soap and water. More than 50% of the population in sub-Saharan Africa and Oceania were without access to handwashing in 2019, and in eight countries, 50 million or more persons lacked access. DISCUSSION: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, and disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries. https://doi.org/10.1289/EHP7200.

The effect of air pollution on deaths, disease burden, and life expectancy across China and its provinces, 1990-2017: an analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Air pollution is an important public health concern in China, with high levels of exposure to both ambient and household air pollution. To inform action at provincial levels in China, we estimated the exposure to air pollution and its effect on deaths, disease burden, and loss of life expectancy across all provinces in China from 1990 to 2017. METHODS: In all 33 provinces, autonomous regions, municipalities, and special administrative regions in China, we estimated exposure to air pollution, including ambient particulate matter pollution (defined as the annual gridded concentration of PM2·5), household air pollution (defined as the percentage of households using solid cooking fuels and the corresponding exposure to PM2·5), and ozone pollution (defined as average gridded ozone concentrations). We used the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 to estimate deaths and disability-adjusted life-years (DALYs) attributable to air pollution, and what the life expectancy would have been if air pollution levels had been less than the minimum level causing health loss. FINDINGS: The average annual population-weighted PM2·5 exposure in China was 52·7 µg/m3 (95% uncertainty interval [UI] 41·0-62·8) in 2017, which is 9% lower than in 1990 (57·8 µg/m3, 45·0-67·0). We estimated that 1·24 million (95% UI 1·08-1·40) deaths in China were attributable to air pollution in 2017, including 851 660 (712 002-990 271) from ambient PM2·5 pollution, 271 089 (209 882-346 561) from household air pollution from solid fuels, and 178 187 (67 650-286 229) from ambient ozone pollution. The age-standardised DALY rate attributable to air pollution was 1513·1 per 100 000 in China in 2017, and was higher in males (1839·8 per 100 000) than in females (1198·3 per 100 000). The age-standardised death rate attributable to air pollution decreased by 60·6% (55·7-63·7) for China overall between 1990 and 2017, driven by an 85·4% (83·2-87·3) decline in household air pollution and a 12·0% (1·4-22·1) decline in ambient PM2·5 pollution. 40·0% of DALYs for COPD were attributable to air pollution, as were 35·6% of DALYs for lower respiratory infections, 26·1% for diabetes, 25·8% for lung cancer, 19·5% for ischaemic heart disease, and 12·8% for stroke. We estimated that if the air pollution level in China was below the minimum causing health loss, the average life expectancy would have been 1·25 years greater. The DALY rate per 100 000 attributable to air pollution varied across provinces, ranging from 482·3 (371·1-604·1) in Hong Kong to 1725·6 (720·4-2653·1) in Xinjiang for ambient pollution, and from 18·7 (9·1-34·0) in Shanghai to 1804·5 (1339·5-2270·1) in Tibet for household pollution. Although the overall mortality attributable to air pollution decreased in China between 1990 and 2017, 12 provinces showed an increasing trend during the past 27 years. INTERPRETATION: Pollution from ambient PM2·5 and household burning of solid fuels decreased markedly in recent years in China, after extensive efforts to control emissions. However, PM2·5 concentrations still exceed the WHO Air Quality Guideline for the entire population of China, with 81% living in regions exceeding the WHO Interim Target 1, and air pollution remains an important risk factor. Sustainable development policies should be implemented and enforced to reduce the impact of air pollution on long-term economic development and population health. FUNDING: Bill & Melinda Gates Foundation; and China National Key Research and Development Program.

Improving and Expanding Estimates of the Global Burden of Disease Due to Environmental Health Risk Factors.

BACKGROUND: The Global Burden of Disease (GBD) study, coordinated by the Institute for Health Metrics and Evaluation (IHME), produces influential, data-driven estimates of the burden of disease and premature death due to major risk factors. Expanded quantification of disease due to environmental health (EH) risk factors, including climate change, will enhance accuracy of GBD estimates, which will contribute to developing cost-effective policies that promote prevention and achieving Sustainable Development Goals. OBJECTIVES: We review key aspects of the GBD for the EH community and introduce the Global Burden of Disease-Pollution and Health Initiative (GBD-PHI), which aims to work with IHME and the GBD study to improve estimates of disease burden attributable to EH risk factors and to develop an innovative approach to estimating climate-related disease burden-both current and projected. METHODS: We discuss strategies for improving GBD quantification of specific EH risk factors, including air pollution, lead, and climate change. We highlight key methodological challenges, including new EH risk factors, notably evidence rating and global exposure assessment. DISCUSSION: A number of issues present challenges to the scope and accuracy of current GBD estimates for EH risk factors. For air pollution, minimal data exist on the exposure-risk relationships associated with high levels of pollution; epidemiological studies in high pollution regions should be a research priority. For lead, the GBD's current methods do not fully account for lead's impact on neurodevelopment; innovative methods to account for subclinical effects are needed. Decisions on inclusion of additional EH risk-outcome pairs need to be guided by findings of systematic reviews, the size of exposed populations, feasibility of global exposure estimates, and predicted trends in exposures and diseases. Neurotoxicants, endocrine-disrupting chemicals, and climate-related factors should be high priorities for incorporation into upcoming iterations of the GBD study. Enhancing the scope and methods will improve the GBD's estimates and better guide prevention policy. https://doi.org/10.1289/EHP5496.

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

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 disease's 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 5 × 5 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 94 336 and 118 500 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.

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

BACKGROUND: Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. METHODS: For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. FINDINGS: Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. INTERPRETATION: Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. FUNDING: The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme.

The global economic burden of dengue: a systematic analysis.

BACKGROUND: Dengue is a serious global burden. Unreported and unrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue and current estimates of the incidence and costs of dengue have substantial uncertainty. Objective, systematic, comparable measures of dengue burden are needed to track health progress, assess the application and financing of emerging preventive and control strategies, and inform health policy. We estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries). METHODS: We used the latest dengue incidence estimates from the Institute for Health Metrics and Evaluation's Global Burden of Disease Study 2013 and several other data sources to assess the economic burden of symptomatic dengue cases in the 141 countries and territories with active dengue transmission. From the scientific literature and regressions, we estimated cases and costs by setting, including the non-medical setting, for all countries and territories. FINDINGS: Our global estimates suggest that in 2013 there were a total of 58·40 million symptomatic dengue virus infections (95% uncertainty interval [95% UI] 24 million-122 million), including 13 586 fatal cases (95% UI 4200-34 700), and that the total annual global cost of dengue illness was US$8·9 billion (95% UI 3·7 billion-19·7 billion). The global distribution of dengue cases is 18% admitted to hospital, 48% ambulatory, and 34% non-medical. INTERPRETATION: The global cost of dengue is substantial and, if control strategies could reduce dengue appreciably, billions of dollars could be saved globally. In estimating dengue costs by country and setting, this study contributes to the needs of policy makers, donors, developers, and researchers for economic assessments of dengue interventions, particularly with the licensure of the first dengue vaccine and promising developments in other technologies. FUNDING: Sanofi Pasteur.