Jeffrey D. Stanaway

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 GBDs 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.

Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis

BackgroundLiver cirrhosis is a major yet largely preventable and underappreciated cause of global health loss. Variations in cirrhosis mortality at the country level reflect differences in prevalence of risk factors such as alcohol use and hepatitis B and C infection. We estimated annual age-specific mortality from liver cirrhosis in 187 countries between 1980 and 2010.MethodsWe systematically collected vital registration and verbal autopsy data on liver cirrhosis mortality for the period 1980 to 2010. We corrected for misclassification of deaths, which included deaths attributed to improbable or nonfatal causes. We used ensemble models to estimate liver cirrhosis mortality with uncertainty by age, sex, country and year. We used out-of-sample predictive validity to select the optimal model.ResultsGlobal liver cirrhosis deaths increased from around 676,000 (95% uncertainty interval: 452,863 to 1,004,530) in 1980 to over 1 million (1,029,042; 670,216 to 1,554,530) in 2010 (about 2% of the global total). Over the same period, the age-standardized cirrhosis mortality rate decreased by 22%. This was largely driven by decreasing cirrhosis mortality rates in China, the US and countries in Western Europe. In 2010, Egypt, followed by Moldova, had the highest age-standardized cirrhosis mortality rates, 72.7 and 71.2 deaths per 100,000, respectively, while Iceland had the lowest. In Egypt, almost one-fifth (18.1%) of all deaths in males 45- to 54-years old were due to liver cirrhosis. Liver cirrhosis mortality in Mexico is the highest in Latin America. In France and Italy, liver cirrhosis mortality fell by 50% to 60%; conversely, in the United Kingdom, mortality increased by about one-third. Mortality from liver cirrhosis was also comparatively high in Central Asia countries, particularly Mongolia, Uzbekistan and Kyrgyzstan, and in parts of sub-Saharan Africa, notably Gabon.ConclusionsLiver cirrhosis is a significant cause of global health burden, with more than one million deaths in 2010. Our study identifies areas with high and/or rapidly increasing mortality where preventive measures to control and reduce liver cirrhosis risk factors should be urgently strengthened.Please see related commentary: http://www.biomedcentral.com/1741-7015/12/159/abstract.

The global burden of dengue: an analysis from the Global Burden of Disease Study 2013

BACKGROUND Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. METHODS We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. FINDINGS We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353-10 649) in 1992, to a peak of 11 302 (6790-13 722) in 2010. This yielded a total of 576 900 (330 000-701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million-17·2 million) apparent cases in 1990, to 58·4 million (23·6 million-121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000-1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million-1·98 million) disability-adjusted life-years in 2013. INTERPRETATION Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. FUNDING Bill & Melinda Gates Foundation.

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

Summary 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.

Changes in health in England with analysis by English region and areas of deprivation: findings of the Global Burden of Disease Study 2013

Summary 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.

Hand, Foot and Mouth Disease in China: Patterns of Spread and Transmissibility during 2008-2009

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, lower wind speed, more precipitation, greater population density, and 16 [13–18] 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 40 [31–127] key to reducing the high mortality rate in infants.

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 Evaluations 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

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

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.

The burden of Chagas disease: estimates and challenges.

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, lower wind speed, more precipitation, greater population density, and 16 [13–18] 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 40 [31–127] key to reducing the high mortality rate in infants.

Nutrient Intake and Anemia Risk in the Women's Health Initiative Observational Study

Chagas disease, caused by infection with the protozoa Trypanosoma cruzi is transmitted most often by Triatominae insect vectors, but also through blood transfusion, organ transplant, and congenital transmission. Between 5 and 18 million people are currently infected and the infection is estimated to cause more than 10,000 deaths annually. The disease has 3 phases: acute, indeterminate, and chronic. The acute phase immediately follows infection. It is typically asymptomatic but produces fever and malaise in up to 5% of people. The indeterminate phase is asymptomatic. More than one-half of those infected will remain in this phase for life and never experience long-term sequelae. After a decade or more, 20% to 30% of people will experience chronic cardiovascular Chagas disease with sequelae including heart failure, arrhythmias, and thromboembolism. Another 15% to 20% will experience chronic digestive sequela including megaesophagus and megacolon. A complete accounting of the burden of Chagas disease requires estimating the prevalence of the infection, the prevalence of each of its sequelae among those with the infection, and the number of deaths attributable to the infection. Attempts to estimate Chagas disease prevalence are complicated by several challenges imposed by the diseases extreme spatial heterogeneity, quickly evolving temporal trends, the decades-long lag between infection and symptomatic disease, biased prevalence data, incomplete recognition of Chagas-attributable deaths, limited data on sequela, and a near total absence of data outside of endemic countries. Even though researchers have found methodological approaches to dealing with these challenges, there is a need for better data.