Global-, Regional-, and National-Level Impacts of the COVID-19 Pandemic on Tuberculosis Diagnoses, 2020-2021.

Evaluating cross-country variability on the impact of the COVID-19 pandemic on tuberculosis (TB) may provide urgent inputs to control programs as countries recover from the pandemic. We compared expected TB notifications, modeled using trends in annual TB notifications from 2013-2019, with observed TB notifications to compute the observed to expected (OE) ratios for 170 countries. We applied the least absolute shrinkage and selection operator (LASSO) method to identify the covariates, out of 27 pandemic- and tuberculosis-relevant variables, that had the strongest explanatory power for log OE ratios. The COVID-19 pandemic was associated with a 1.55 million (95% CI: 1.26-1.85, 21.0% [17.5-24.6%]) decrease in TB diagnoses in 2020 and a 1.28 million (0.90-1.76, 16.6% [12.1-21.2%]) decrease in 2021 at a global level. India, Indonesia, the Philippines, and China contributed the most to the global declines for both years, while sub-Saharan Africa achieved pre-pandemic levels by 2021 (OE ratio = 1.02 [0.99-1.05]). Age-stratified analyses revealed that the ≥ 65-year-old age group experienced greater relative declines in TB diagnoses compared with the under 65-year-old age group in 2020 (RR = 0.88 [0.81-0.96]) and 2021 (RR = 0.88 [0.79-0.98]) globally. Covariates found to be associated with all-age OE ratios in 2020 were age-standardized smoking prevalence in 2019 (ß = 0.973 [0.957-990]), school closures (ß = 0.988 [0.977-0.998]), stay-at-home orders (ß = 0.993 [0.985-1.00]), SARS-CoV-2 infection rate (ß = 0.991 [0.987-0.996]), and proportion of population ≥65 years (ß = 0.971 [0.944-0.999]). Further research is needed to clarify the extent to which the observed declines in TB diagnoses were attributable to disruptions in health services, decreases in TB transmission, and COVID-19 mortality among TB patients.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019.

BACKGROUND: Cambodia was recently removed from the World Health Organization's (WHO's) top 30 high tuberculosis (TB) burden countries. However, Cambodia's TB burden remains substantial, and the country is on the WHO's new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020. METHODS: We leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes. RESULTS: In 2019, there were 6500 (95% uncertainty interval 4830-8680) deaths due to all-form TB and 50.0 (43.8-57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9-69.4) per 100,000 population for mortality and 330.5 (289.0-378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3-21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3-15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2-37.9) of TB deaths, smoking accounted for 27.0% (20.2-33.3), and diabetes accounted for 12.5% (7.1-19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2-62.2). DISCUSSION: Despite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis.

BACKGROUND: Household contacts of people with pulmonary tuberculosis (TB) have greater risk of developing TB. Recent guidelines conditionally recommended TB preventive treatment (TPT) for household contacts of any age living in TB high-incidence countries, expanding earlier guidance to provide TPT to household contacts under five. The all-age population of household contacts has not been estimated. METHODS: Our model-based estimation included 20 countries with >80% of incident TB globally in 2019. We developed country-specific distributions of household composition by age and sex using bootstrap resampling from health surveys and census data. We incorporated age-, sex-, year-, and location-specific estimates of pulmonary TB incidence from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the population in each country sharing a household with someone with incident pulmonary TB, and quantified uncertainty using a Monte Carlo approach. FINDINGS: We estimate that 38 million [95% uncertainty interval (UI) 33- 43 million] individuals lived in a household with someone with incident pulmonary TB in 2019 in these 20 countries. Children under five made up 12% of the population with household exposure, while adults were 65%. Zimbabwe, Mozambique, Zambia, and Pakistan had the highest proportion of the population with household exposure, while India had the highest number of contacts (11·4 million, 95% UI 9·7-13·4 million). INTERPRETATION: Expanding TPT evaluation to household contacts of all ages in high-incidence countries could include a population more than 7-times larger than the under-5 contacts previously prioritized. This would substantially increase the impact of household contact investigation on reducing TB morbidity and mortality. FUNDING: JMR is supported by the National Institute of Allergy and Infectious Diseases (K01 AI138620). This research was funded in part by a 2020 developmental grant from the University of Washington / Fred Hutch Center for AIDS Research, an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. This work was funded in part by the National Science Foundation (DMS-1839116).

Causes of death among children aged 5-14 years in the WHO European Region: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: The mortality burden in children aged 5-14 years in the WHO European Region has not been comprehensively studied. We assessed the distribution and trends of the main causes of death among children aged 5-9 years and 10-14 years from 1990 to 2016, for 51 countries in the WHO European Region. METHODS: We used data from vital registration systems, cancer registries, and police records from 1980 to 2016 to estimate cause-specific mortality using the Cause of Death Ensemble model. FINDINGS: For children aged 5-9 years, all-cause mortality rates (per 100 000 population) were estimated to be 46·3 (95% uncertainty interval [UI] 45·1-47·5) in 1990 and 19·5 (18·1-20·9) in 2016, reflecting a 58·0% (54·7-61·1) decline. For children aged 10-14 years, all-cause mortality rates (per 100 000 population) were 37·9 (37·3-38·6) in 1990 and 20·1 (18·8-21·3) in 2016, reflecting a 47·1% (43·8-50·4) decline. In 2016, we estimated 10 740 deaths (95% UI 9970-11 542) in children aged 5-9 years and 10 279 deaths (9652-10 897) in those aged 10-14 years in the WHO European Region. Injuries (road injuries, drowning, and other injuries) caused 4163 deaths (3820-4540; 38·7% of total deaths) in children aged 5-9 years and 4468 deaths (4162-4812; 43·5% of total) in those aged 10-14 years in 2016. Neoplasms caused 2161 deaths (1872-2406; 20·1% of total deaths) in children aged 5-9 years and 1943 deaths (1749-2101; 18·9% of total deaths) in those aged 10-14 years in 2016. Notable differences existed in cause-specific mortality rates between the European subregions, from a two-times difference for leukaemia to a 20-times difference for lower respiratory infections between the Commonwealth of Independent States (CIS) and EU15 (the 15 member states that had joined the European Union before May, 2004). INTERPRETATION: Marked progress has been made in reducing the mortality burden in children aged 5-14 years over the past 26 years in the WHO European Region. More deaths could be prevented, especially in CIS countries, through intervention and prevention efforts focusing on the leading causes of death, which are road injuries, drowning, and lower respiratory infections. The findings of our study could be used as a baseline to assess the effect of implementation of programmes and policies on child mortality burden. FUNDING: WHO and Bill & Melinda Gates Foundation.

Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013.

OBJECTIVE:  To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events. DESIGN:  Systematic review and Bayesian dose-response meta-analysis. DATA SOURCES:  PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:  Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied. RESULTS:  174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity <600 MET minutes/week), the risk reduction for those in the highly active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to 0.811) for ischemic stroke. CONCLUSIONS:  People who achieve total physical activity levels several times higher than the current recommended minimum level have a significant reduction in the risk of the five diseases studied. More studies with detailed quantification of total physical activity will help to find more precise relative risk estimates for different levels of activity.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.

Identifying otolaryngology systematic review research gaps: comparing Global Burden of Disease 2010 results with Cochrane Database of Systematic Review content.

IMPORTANCE: Burden of disease should inform research prioritization. OBJECTIVE: To determine whether systematic reviews and protocols published in the Cochrane Database of Systematic Reviews (CDSR) appropriately reflect disease burden for otolaryngologic conditions as measured by the Global Burden of Disease (GBD) 2010 project. DESIGN: Two investigators independently assessed 10 otolaryngologic conditions in CDSR for systematic review and protocol representation from March to June 2014. The otolaryngologic diseases were matched to their respective GBD 2010 disability-adjusted life-years (DALYs) to assess their correlation. MAIN OUTCOMES AND MEASURES: Relationship of CDSR representation (based on systematic reviews and protocols) with percentage of total 2010 DALYs, 2010 DALY rank, and DALY percentage change from 1990 to 2010 for 10 otolaryngologic conditions. RESULTS: All 10 otolaryngologic conditions were represented by at least 1 systematic review in CDSR. The number of reviews and protocols in CDSR was well matched with GBD 2010 disability metrics for only 1 disease, mouth cancer. Upper respiratory infections, otitis media, thyroid cancer, and cleft lip and cleft palate were overrepresented in CDSR, and esophageal cancer, "other hearing loss," nasopharynx cancer, larynx cancer, and "cancer of other part of pharynx and oropharynx" were underrepresented. CONCLUSIONS AND RELEVANCE: The representation of otolaryngologic conditions in CDSR correlates poorly with DALY metrics. The results of this study may guide future research prioritization and allocation of funds.