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Background: People who inject drugs may be at excess risk of acquiring vaccine-preventable diseases and negative associated health outcomes, but experience barriers to vaccination. We aimed to determine vaccination coverage among people who inject drugs globally., Methodology: We conducted systematic searches of the peer-reviewed and grey literature, date limited from January 2008 to August 2023, focusing on diseases for which people who inject drugs are at elevated risk for and for which an adult vaccination dose is recommended (COVID-19, hepatitis A, hepatitis B, human papillomavirus, influenza, pneumococcal disease, tetanus). To summarise available data, we conducted a narrative synthesis., Results: We included 78 studies/reports comprising 117 estimates of vaccination coverage across 36 countries. Most estimates were obtained from high income countries (80%, n=94). We located estimates for hepatitis B vaccination in 33 countries, which included 18 countries with data on serological evidence of vaccine-derived hepatitis B immunity (range: 6-53%) and 22 countries with self-report data for vaccine uptake (<1-96%). Data for other vaccines were scarcer: reported hepatitis A vaccination coverage ranged 3-89% (five countries), COVID-19 ranged 4-84% (five countries), while we located estimates from fewer than five countries for influenza, tetanus, pneumococcal disease, and human papillomavirus., Conclusion: Estimates were sparse but where available indicative of suboptimal vaccination coverage among people who inject drugs. Improving the consistency, timeliness, and geographic coverage of vaccine uptake data among this population is essential to inform efforts to increase uptake., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the past 3 years, LD has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior and Seqirus. AP has received investigator-initiated untied educational grants from Seqirus. JG is a consultant or advisor and has received research grants from AbbVie, Abbott, bioLytical, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Roche. GJD has received research grants from AbbVie and Gilead Sciences. These companies and organisations had no knowledge of or role in the design, conduct, interpretation, or publication of these findings. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Investigate the cascade of care for chronic hepatitis B (CHB) and estimate impacts of increasing treatment uptake on attributable burden, according to jurisdiction., Methods: A mathematical model of CHB in Australia was utilised, combined with notifiable disease and Medicare data. We estimated the proportion with CHB who were diagnosed, engaged in care and receiving treatment in each state/territory, and projected future mortality., Results: The highest uptake of all measures was in New South Wales, however, the largest increase over time occurred in Northern Territory. No jurisdiction is due to meet 2022 targets of treatment uptake or mortality reduction. Previously declining mortality is predicted to plateau or increase in all jurisdictions except Northern Territory. The largest gap in the cascade of care was most commonly diagnosed individuals not engaged in care; however, in Victoria and Tasmania it was lack of diagnosis., Conclusions: Measures of the cascade of care varied substantially between jurisdictions; while all require improvements to reduce mortality, the specific gaps vary, as do potential impacts., Implications for Public Health: Improving the cascade of care for CHB will require jurisdictionally tailored approaches. If improvements are not made, more deaths will occur due to CHB in most states and territories., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hospital-based contact tracing aims to limit spread of COVID-19 within healthcare facilities. In large outbreaks, this can stretch resources and workforce due to quarantine of uninfected staff. We analysed the performance of a manual contact tracing system for healthcare workers (HCW) at a multi-site healthcare facility in Melbourne, Australia, from June-September 2020, during an epidemic of COVID-19., Methods: All HCW close contacts were quarantined for 14 days, and tested around day 11, if not already diagnosed with COVID-19. We examined the prevalence and timing of symptoms in cases detected during quarantine, described this group as proportions of all close contacts and of all cases, and used logistic regression to assess factors associated with infection., Results: COVID-19 was diagnosed during quarantine in 52 furloughed HCWs, from 483 quarantine episodes (11%), accounting for 19% (52/270) of total HCW cases. In 361 exposures to a clear index case, odds of infection were higher after contact with an infectious patient compared to an infectious HCW (aOR: 4.69, 95% CI: 1.98-12.14). Contact with cases outside the workplace increased odds of infection compared to workplace contact only (aOR: 7.70, 95% CI: 2.63-23.05). We estimated 30%, 78% and 95% of symptomatic cases would develop symptoms by days 3, 7, and 11 of quarantine, respectively., Conclusion: In our setting, hospital-based contact tracing detected and contained a significant proportion of HCW cases, without excessive quarantine of uninfected staff. Effectiveness of contact tracing is determined by a range of dynamic factors, so system performance should be monitored in real-time., (Copyright © 2021 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the impact of an enhanced viral hepatitis surveillance program on data completeness and on epidemiological assessment of affected populations., Methods: Notified cases of non-acute hepatitis B and C were analysed to determine demographic characteristics and risk factors during the period prior to July 2015-June 2016, and during enhanced surveillance of the period July 2016-June 2017, during which time doctors were contacted for information about new diagnoses., Results: During the enhanced period, completeness for country of birth and Indigenous status doubled for both hepatitis B and hepatitis C, from 18-37% to 48-65%. The incidence ratio of hepatitis C among Aboriginal and Torres Strait Islander people increased from eight-fold to 11.4-fold, and the proportion of hepatitis B cases reported as born in China and Vietnam relative to other countries increased. New data fields identified that 12% of hepatitis C diagnoses occurred in a correctional facility, and 2% of hepatitis B cases were healthcare workers., Conclusions: Improved data completeness highlighted the underlying epidemiology of chronic viral hepatitis, demonstrating the increased burden of infection among specific priority populations. Implications for public health: Enhanced surveillance provides greater insight into the epidemiology of chronic viral hepatitis, identifying groups at risk and opportunities for public health action., (© 2019 The Authors.)

Objectives: To review the use of data linkage by Australian state and territory communicable disease control units, and to identify barriers to and enablers of data linkage to inform communicable disease surveillance and control activities., Methods: Semi-structured telephone interviews were carried out with one key informant from communicable disease control units in all eight Australian states and territories between October 2017 and January 2018., Results: Key informants from all Australian states and territories participated in the interview. A variety of existing practices were identified, with few jurisdictions making systematic use of available data linkage infrastructure. Key barriers identified from the review included: a lack of perceived need; system factors; and resources. Existing regulatory tools enable data linkage to enhance communicable disease surveillance and control., Conclusions: We identified considerable variation in the use of data linkage to inform communicable disease surveillance and control activities between jurisdictions. We suggest that routinely collected, disparate data are systematically integrated into existing surveillance and response policy cycle to improve communicable disease prevention and control efforts. Implications for public health: Existing gaps in communicable disease surveillance data may affect prevention and control efforts. Data linkage is recognised as a valuable method to close surveillance gaps and should be used to enhance the value of publicly held health data., (© 2018 State Government of Victoria, Department of Health & Human Sciences.)

Objective: To estimate the cultural and linguistic diversity in Australians currently living with chronic hepatitis B (CHB), the majority of whom were born overseas, and to identify trends in this diversity over time., Methods: Estimates were generated by combining Australian census country of birth information with seroprevalence data generated from antenatal serology linked with surveillance notifications. The number of people living with CHB was assessed according to country of birth using the 2011 and 2016 censuses., Results: The total number of Australian residents living with CHB increased by 20% between 2011 and 2016, substantially outpacing population growth. The most common country of birth continued to be China, with the number of Chinese-born Australians living with CHB increasing by 60% in the 5-year period. Decreased numbers were observed for people born in European countries., Conclusions: The epidemiology of chronic hepatitis B in Australia has shifted over time due to changing migration patterns, with increases in many countries in the Asia-Pacific, African and Middle Eastern regions. Implications for public health: Interventions to improve the health of people living with CHB are imperative, and these up-to-date estimates identify priority groups and communities, which are constantly changing., (© 2018 The Authors.)

Background: Comparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden - incidence, prevalence, mortality, disability-adjusted life years (DALYs) - and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD)., Methods: The general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors., Results: In 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908-217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061-49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2-29.8) of total deaths and 17.0% (95% UI: 15.0-19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1-37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24 th based on ASIR and ASDR, respectively., Conclusion: The incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The burden of notifiable diseases in Aboriginal and Torres Strait Islander Victorians cannot be accurately estimated due to under-reporting of Indigenous status. We used data linkage to improve completeness of Indigenous status in people notified with viral hepatitis and gonococcal infection., Methods: Notifications made between 2009 and 2010 were linked with Victorian hospitalisation data (1997-2011). Notification rates by Indigenous status and rate ratios were calculated before and after linkage., Results: There were 12,448 cases of hepatitis B, hepatitis C and gonococcal infection notified in Victoria in 2009-2010, with Indigenous status missing in 61.6%, 67.8%, 33.1% of these conditions, respectively. Of the total notified cases, 82% were able to be linked. Following linkage, the proportion of notifications with missing Indigenous status decreased to less than 0.2% for all conditions. Age-standardised notification rates among both Aboriginal people and non-Aboriginal people increased for all conditions., Conclusions: Data linkage improved completeness of Indigenous status in notifications for viral hepatitis and gonococcal infection in Victoria. Completeness of these data is integral to monitoring progress in closing the Indigenous life expectancy gap., Implications: Greater emphasis is needed on addressing prevention, treatment and care for viral hepatitis and sexually transmissible infections for Indigenous Victorians., (© 2015 Public Health Association of Australia.)

Objective: To estimate the level of access to diagnosis, management and treatment for people living with chronic hepatitis B (CHB) in Australia, and to identify the gaps in clinical care for people living with CHB., Methods: Analysis of publicly available population level data including infectious disease notifications, Medicare and Pharmaceutical Benefits Scheme utilisation data, census-based estimates of CHB prevalence and burden, and mathematical modelling., Results: In 2012, of the estimated 218,567 Australians living with CHB, 57% had been diagnosed, 17,367 people (8%) received recommended HBV DNA viral load testing (without treatment) and 10,987 (5%) received antiviral therapy., Conclusions: This analysis reveals substantial gaps in the cascade of care for CHB in Australia, most notably in diagnosis (with 43% undiagnosed) and in recommended yearly monitoring (87% not in care). The number receiving therapy represents only one-third of those estimated to require treatment to prevent progressive liver disease and liver cancer., Implications: These findings demonstrate that the majority of those affected are not receiving guideline-based care; highlight the need for improvements in opportunistic screening, engagement in care, and access to therapy; and provide a method to assess the impact of public health and clinical interventions in response to CHB over time., (© 2015 Public Health Association of Australia.)

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration., Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets., Findings: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990., Interpretation: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The number of Australians living with chronic hepatitis B (CHB) is thought to be increasing, as are adverse outcomes including cirrhosis and liver cancer, however, robust, up-to-date estimates of this burden are limited. Contemporary estimates of the prevalence of CHB in Australia are essential to guide appropriate public health and clinical responses., Methods: This study used census-based methodology attributing risk of CHB by country of birth and Aboriginal and Torres Strait Islander status, augmented with priority risk-group based estimates. Deterministic mathematical modelling was used for comparison and for validation of census-derived estimates., Results: An estimated 218,000 Australians (plausible range 192,000-284,000) are living with CHB, a significant increase over previous estimates. The prevalence derived using mathematical modelling was similar, at 204,000. Notable differences were observed by geographic area in both prevalence and the populations predominantly affected. It is estimated that only 56% of people living with CHB in Australia have been diagnosed and notified., Conclusions: The prevalence of CHB in Australia is increasing, with 1% of the population now estimated to be affected. The majority of the burden is experienced by people born overseas in endemic areas, with more than 95% of new cases of CHB entering the population through migration., Implications: It is imperative that more attention and greater resources are devoted to addressing CHB in Australia; to increase the proportion of Australians affected who have been diagnosed and who are on treatment, in accordance with the First National Hepatitis B Strategy., (© 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.)

Background: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex., Methods: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions., Findings: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted., Interpretation: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs)., Methods: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis., Findings: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa., Interpretation: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time., Methods: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden., Findings: In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania., Interpretation: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background & Aims: Studies have shown that GB virus C (GBV-C) infection leads to reduced liver disease in hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection. Considering that the underlying mechanism(s) are unknown, we aim to identify differential gene and protein expression associated with GBV-C in HCV/HIV co-infection that may be responsible for reduced liver disease., Methods: Liver, peripheral blood mononuclear cells (PBMCs), and plasma samples were collected from 43 HCV/HIV patients. Plasma was tested for GBV-C RNA by RT-PCR with NS5B gene primers. A microarray was performed on the liver and RT-qPCRs on the liver/PBMC samples. Hepatic protein expression was measured by immunohistochemistry., Results: Sixteen out of 43 patients had GBV-C RNA. GBV-C was associated with reduced hepatic fibrosis (p=0.005) and inflammation (p=0.007). The microarray analysis of the liver samples (n=10) showed down-regulation of genes critical to intra-hepatic T-cell signaling associated with GBV-C. Quantitative RT-PCR of the liver samples (n=13) confirmed the down-regulation of lymphocyte-specific protein tyrosine kinase (LCK) (p=0.02) and docking protein 2 (DOK2) (p=0.04). No differences in the expression levels of these genes were observed in PBMCs (n=22) according to the GBV-C status. The hepatic expression of the LCK protein, measured by immunohistochemistry (n=36), was decreased in CD3-positive T-cells within portal tracts associated with GBV-C (p=0.003). This remained significant in multivariate analysis controlling for hepatic fibrosis and inflammation (p=0.027). No differences were observed in plasma cytokine concentrations (n=25) or ex-vivo peripheral T-cell responses (n=13) versus GBV-C status., Conclusions: GBV-C infection is associated with down-regulation of critical genes involved in intra-hepatic T-cell signaling in HCV/HIV co-infection. This may be relevant to the pathogenesis of reduced HCV-related liver disease in HIV co-infection., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)