Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Environmental exposures : an underrecognized contribution to noncommunicable diseases

Previous attempts to determine the degree to which exposure to environmental factors contribute to noncommunicable diseases (NCDs) have been very conservative and have significantly underestimated the actual contribution of the environment for at least two reasons. Firstly, most previous reports have excluded the contribution of lifestyle behavioral risk factors, but these usually involve significant exposure to environmental chemicals that increase risk of disease. Secondly, early life exposure to chemical contaminants is now clearly associated with an elevated risk of several diseases later in life, but these connections are often difficult to discern. This is especially true for asthma and neurodevelopmental conditions, but there is also a major contribution to the development of obesity and chronic diseases. Most cancers are caused by environmental exposures in genetically susceptible individuals. In addition, new information shows significant associations between cardiovascular diseases and diabetes and exposure to environmental chemicals present in air, food, and water. These relationships likely reflect the combination of epigenetic effects and gene induction. Environmental factors contribute significantly more to NCDs than previous reports have suggested. Prevention needs to shift focus from individual responsibility to societal responsibility and an understanding that effective prevention of NCDs ultimately relies on improved environmental management to reduce exposure to modifiable risks.

Poverty and non-communicable diseases in South Africa

Background: High levels of wealth inequality with improved health statistics in South Africa (SA) provide an important opportunity to investigate non-communicable diseases (NCDs) among the poor. Aims: This paper uses two distinct national data sets to contrast patterns of mortality in rich and poor areas and explore the associations between poverty, risk factors, health care and selected NCDs diseases in South African adults. Methods: Causes of premature mortality in 1996 experienced in the poorest magisterial districts are compared with those in the richest, using average household wealth to classify districts. Logistic and multinomial regression are used to investigate the association of a household asset index and selected chronic conditions, related risk factors and healthcare indicators using data from the 1998 South African Demographic and Health Survey. Results: NCDs accounted for 39% and 33% of premature mortality in rich and poor districts respectively. The household survey data showed that the risk factors hypertension and obesity increased with increasing wealth, while most of the lifestyle factors, such as light smoking, domestic exposure to ``smoky'' fuels and alcohol dependence were associated with poverty. Treatment status for hypertension and asthma was worse for poor people than for rich people. Conclusions: The study suggests that NCDs and lifestyle-related risk factors are prevalent among the poor in SA and treatment for chronic diseases is lacking for poor people. The observed increase in hypertension and obesity with wealth suggests that unless comprehensive health promotion strategies are implemented, there will be an unmanageable chronic disease epidemic with future socioeconomic development in SA.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases

The potential impact of climate change and ultraviolet radiation on vaccine preventable infectious diseases and immunisation service delivery system

Climate change and solar ultraviolet radiation may affect vaccine-preventable infectious diseases (VPID), the human immune response process and the immunization service delivery system. We systematically reviewed the scientific literature and identified 37 relevant publications. Our study shows that climate variability and ultraviolet radiation may potentially affect VPID and the immunization delivery system through modulating vector reproduction and vaccination effectiveness, possibly influencing human immune response systems to the vaccination, and disturbing immunization service delivery. Further research is needed to determine these affects on climate-sensitive VPID and on human immune response to common vaccines. Such research will facilitate the development and delivery of optimal vaccination programs for target populations, to meet the goal of disease control and elimination.

Role of big data in the early detection of Ebola and other emerging infectious diseases

The lack of adequate disease surveillance systems in Ebola-affected areas has both reduced the ability to respond locally and has increased global risk. There is a need to improve disease surveillance in vulnerable regions, and digital surveillance could present a viable approach.

Saliva diagnostics for oral diseases

Oral diseases, or stomatognathic diseases, denote the diseases of the mouth (“stoma”) and jaw (“gnath”). Dental caries and periodontal diseases have been traditionally considered as the most important global oral health burdens. It is important to note that in oral diagnostics, the greatest challenges are determining the clinical utility of potential biomarkers for screening (in asymptomatic people), predicting the early onset of disease (prognostic tests), and evaluating the disease activity and the efficacy of therapy through innovative diagnostic tests. An oral diagnostic test, in principle, should provide valuable information for differential diagnosis, localization of disease, and severity of infection. This information can then be incorporated by the physician when planning treatments and will provide means for assessing the effectiveness of therapy.

Gender-specific differences of interaction between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study

Background Little information exists regarding the interaction effects of obesity with long-term air pollution exposure on cardiovascular diseases (CVDs) and stroke in areas of high pollution. The aim of the present study is to examine whether obesity modifies CVD-related associations among people living in an industrial province of northeast China. Methods We studied 24,845 Chinese adults, aged 18 to 74 years old, from three Northeastern Chinese cities in 2009 utilizing a cross-sectional study design. Body weight and height were measured by trained observers. Overweight and obesity were defined as a body mass index (BMI) between 25–29.9 and ≥ 30 kg/m2, respectively. Prevalence rate and related risk factors of cardiovascular and cerebrovascular diseases were investigated by a questionnaire. Three-year (2006–2008) average concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), and ozone (O3) were measured by fixed monitoring stations. All the participants lived within 1 km of air monitoring sites. Two-level logistic regression (personal level and district-specific pollutant level) was used to examine these effects, controlling for covariates. Results We observed significant interactions between exposure and obesity on CVDs and stroke. The associations between annual pollutant concentrations and CVDs and stroke were strongest in obese subjects (OR 1.15–1.47 for stroke, 1.33–1.59 for CVDs), less strong in overweight subjects (OR 1.22–1.35 for stroke, 1.07–1.13 for CVDs), and weakest in normal weight subjects (OR ranged from 0.98–1.01 for stroke, 0.93–1.15 for CVDs). When stratified by gender, these interactions were significant only in women. Conclusions Study findings indicate that being overweight and obese may enhance the effects of air pollution on the prevalence of CVDs and stroke in Northeastern metropolitan China. Further studies will be needed to investigate the temporality of BMI relative to exposure and onset of disease.

Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

Corrections: Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population (Annals of the Rheumatic Diseases (2011) 70, (1793-1797))

Patrick Danoy, Meng Wei, Hadler Johanna, et al. Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population. Ann Rheum Dis 2011;70:1793–97. The following authors were listed as contributing equally to the study...

Genetic studies of common rheumatological diseases

Editorial

Grass pollen allergens globally: The contribution of subtropical grasses to burden of allergic respiratory diseases

Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily-specific differences, at T- and B-cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world. © 2014 John Wiley & Sons Ltd.

Cytokine mRNA expression and IFN-γ production of immunised nematode resistant and susceptible lambs against natural poly-generic challenge

IL-2, IL-4 and IFN-γ mRNA expression, and production of IFN-γ was examined in mesenteric lymph node cells (MLNC) and CD4+ enriched T cell populations of nematode resistant (R) and susceptible (S) line lambs by use of RT-PCR and ELISA. Five R and S line lambs that were immunised by repeated oxfendazole-abbreviated infections and 5 non-immunised R and S line lambs were used. All lambs grazed nematode infected pasture for 107 days. Immunisation enhanced the resistant status in both R and S lambs. MLNC obtained from slaughtered animals were stimulated with Con A or T. colubriformis specific antigen. Non-stimulated MLNC of immunised lambs expressed higher levels of IL-4 mRNA and lower levels of IL-2 mRNA than non-immunised lambs. MLNC of immunised R and S line lambs stimulated with antigen for 24 h expressed detectable amounts of IL-4 mRNA that was not seen in non-immunised controls. CD4+ T cell enriched cell populations of immunised R and S lambs and non-immunised R lambs expressed moderate to high levels of IL-4 mRNA. Con A stimulated MLNC of immunised R and S lambs expressed high levels IFN-γ mRNA and produced high amounts of IFN-γ. Lower levels were present in non-immunised controls. The results indicate that R line lambs and immunised S line lambs respond to natural nematode challenge with a predominating IL-4 cytokine response when compared to non-immunised S lambs.

Increased risk of emergency hospital admissions for children with renal diseases during heatwaves in Brisbane, Australia

Background Heatwaves have a significant impact on population health including both morbidity and mortality. In this study we examined the association between heatwaves and emergency hospital admissions (EHAs) for renal diseases in children (aged 0–14 years) in Brisbane, Australia. Methods Daily data on EHAs for renal diseases in children and exposure to temperature and air pollution were obtained for Brisbane city from January 1, 1996 to December 31, 2005. A time-stratified case-crossover design was used to compare the risks for renal diseases between heatwave and non-heatwave periods. Results There were 1565 EHAs for renal diseases in children during the study period. Heatwaves exhibited a significant impact on EHAs for renal diseases in children after adjusting for confounding factors (odds ratio: 3.6; 95% confidence interval: 1.4–9.5). The risk estimates differed with lags and the use of different heatwave definitions. Conclusions There was a significant increase in EHAs for renal diseases in children during heatwaves in Brisbane, a subtropical city where people are well accustomed to warm weather. This finding may have significant implications for pediatric renal care, particularly in subtropical and tropical regions.