Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection.

Staphylococcus aureus is one of the most common pathogens causing keratitis. Surfactant protein D (SP-D) plays a critical role in host defense and innate immunity. In order to investigate the role of SP-D in ocular S. aureus infection, the eyes of wild-type (WT) and SP-D knockout (SP-D KO) C57BL/6 mice were infected with S. aureus (10(7) CFU/eye) in the presence and absence of cysteine protease inhibitor(E64).Bacterial counts in the ocular surface were examined 3, 6, 12, 24 hrs after infection. Bacterial phagocytosis by neutrophils and bacterial invasion in ocular epithelial cells were evaluated quantitatively. S. aureus-induced ocular injury was determined with corneal fluorescein staining. The results demonstrated that SP-D is expressed in ocular surface epithelium and the lacrimal gland; WT mice had increased clearance of S. aureus from the ocular surface (p<0.05) and reduced ocular injury compared with SP-D KO mice. The protective effects of SP-D include increased bacterial phagocytosis by neutrophils (p<0.05) and decreased bacterial invasion into epithelial cells (p<0.05) in WT mice compared to in SP-D KO mice. In the presence of inhibitor (E64), WT mice showed enhanced bacterial clearance (p<0.05) and reduced ocular injury compared to absent E64 while SP-D KO mice did not. Collectively, we concluded that SP-D protects the ocular surface from S. aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis

Mouse SP-D-deficient confirmation in eye tissue.

<p>SP-D gene deficiency was confirmed by PCR analysis with DNA from the lacrimal gland. Primers (GW122/GW123) were used to detect the exon 2 of mouse SP-D gene. WT mice contain 0.5 Kb PCR products but SP-D KO mice do not have the products. KO, SP-D KO mice (lanes 4, 5); WT, WT mice (lanes 6–8); Lanes 2 and 3 are positive (tail DNA from WT mice) and negative (tail DNA from KO mice) control, respectively; Lane 1 is DNA marker. The figure is from representative results in three independent experiments.</p

<i>S</i>. <i>aureus</i> bacteria were efficiently cleared from ocular surface of WT mice compared to SP-D KO mice.

<p>The CFUs recovered from the tear fluid of infected WT mice were examined at 3, 6, 12 or 24 h post-inoculation with <i>S</i>. <i>aureus</i> (10⁷ CFU/eye). Rapid clearance of the bacteria was in time-dependent manner. The CFUs of <i>S</i>. <i>aureus</i> from the ocular surface in infected WT and SP-D KO mice were compared at 3, 6, 12, and 24 h after inoculation of 10⁷ CFU/eye. A significant difference of the recovered bacteria in the tear fluid exists between infected WT and SP-D KO mice after infection. The results were from three independent experiments (n = 8 to 10 mice per group). Data are shown as the median (central black bar in boxes) with upper and lower quartiles (boxed area), and range of the data (error bars).* p<0.05 in Mann-Whitney U test.</p

Cysteine protease inhibitor E₆₄ increased the clearance of the bacteria on the ocular surface in infected WT mouse but not in SP-D KO mice.

<p>The CFUs of bacteria recovered from the tear fluid were examined at 3 h (A), and 6 h (B) after inoculation with <i>S</i>. <i>aureus</i> (10⁷ CFUs/eye) in infected WT and SP-D KO mice in the presence or absence of 10 nM of cysteine protease inhibitor (E₆₄). The CFUs of bacteria were significantly decreased (p<0.05) in the tear fluid of the infected WT mice in the presence of E₆₄ compared to its absence at both 3 and 6 h after infection. But no difference was observed in infected SP-D KO mice between the presence and absence of E₆₄. Furthermore, to examine whether bacterial growth was influenced by the presence of E₆₄, bacteria (10⁶ CFUs of <i>S</i>. <i>aureus</i>) were cultured in PBS with or without 10 nM of E₆₄ for 3 and 6 h and then bacterial CFUs were assessed (C). The results showed no difference of CFUs with and without E₆₄. The results shown are from three independent experiments (n = 8 to 12 mice per group). Data are shown as the median (central black bar in boxes) with upper and lower quartiles (boxed area), and range of the data (error bars).* p<0.05 in Mann-Whitney U test.</p

SP-D promoted <i>S</i>. <i>aureus</i> phagocytosis by neutrophils in ocular surface, but cysteine protease impaired SP-D activity.

<p>After inoculation with 10⁷ CFUs of bacteria or bacteria with 10nM E₆₄ for 6h, tear fluid was collected and the cells were mounted on slides by cytospin centrifugation method. The cells were stained and one hundred randomly selected neutrophils per slide were analyzed at x1,000 magnification. Neutrophils that phagocytized at least one bacterium were counted as bacteria-positive neutrophils. The phagocytic index (PI) was calculated as the percentage of bacteria-positive neutrophils multiplied by the average number of bacteria per bacteria-positive neutrophils. Panel A shows neutrophils with bacteria stained using the Hema-3 Stain Kit. Panel B shows PI in infected WT and SP-D KO mice. “#” marked neutrophils. Arrows point to <i>S</i>. <i>aureus</i>. Scale bars: 3 μm. The results shown are from three independent experiments (n = 8 to 12 mice per group). All values represent mean ± SE. * p<0.05 in student’s t test.</p

SP-D inhibited <i>S</i>. <i>aureus</i> invasion in ocular epithelial cells but <i>S</i>. <i>aureus</i> cysteine protease impaired SP-D activity.

<p>After a 6-h inoculation of <i>S</i>. <i>aureus</i>, tear fluid sedimentation was applied to slides by cytospin centrifugation. <b>Panel one (A-F)</b>: The slides were stained and analyzed by light microscope under oil immersion(X1000). Adherence and internalization steps of bacteria for each condition (A-D) were counted as invaded bacteria (arrow). The invasion index (E) and percentages of invaded epithelial cells (F) were calculated, as described in the Methods. Invasion index of invaded bacteria in KO mice was higher (p<0.05) compared with WT mice. E₆₄ treatment could reduce the index in WT mice but not in SP-D KO mice. <b>Panel two (G-L)</b>: To confirm epithelial cells collected from mouse tear fluid, immunohistochemistry and immunocytochemistry analyses were performed with pancytokeratins AE1/AE3. (G) Hematoxylin and eosin (H&E) staining of murine skin. Arrow shows epithelial cell. (H) Positive control. Immunohistochemistry revealed the epithelial cells (arrow) of murine skin to be positive for pancytokeratin AE1/AE3. (I) H&E staining of murine lymph nodes. (J) Negative control. Immunohistochemistry indicated the lymph node to be negative for pancytokeratin AE1/AE3. (K) Immunocytochemistry revealed a positive immunoreaction for cytokeratin AE1/AE3 was present throughout the cytoplasm of the epithelial cells in tear fluid (arrow). (L) Negative control. Same protocol was applied but the primary antibody was replaced with isotype-matched goat IgG. Scale bars: (A-D) 10 μm, (G-J) 100μm, (K-L) 20 μm. WT, WT mice. KO, SP-D KO mice. Cycles indicate murine skin. “#” and “@” mark murine epithelial cell and lymph node, respectively. The results are from three independent experiments (n = 8 to 12 mice per group).All values represent mean ± SE. * p<0.05 in student’s t test.</p

Comparison of eye injury of WT and SP-D KO mice after <i>S</i>. <i>aureus</i> infection in the presence or absence of E₆₄.

<p>Mouse corneal integrity (eye injury) was examined using fluorescein staining method after inoculation of <i>S</i>. <i>aureus</i> for 24 h. The results show increased fluorescein staining (arrows) in the cornea of SP-D KO mice compared to WT mice. E₆₄ treatment could reduce fluorescein staining in WT mice but not in SP-D KO mice. Corneal fluorescein staining scores in SP-D KO mice were higher than that in WT mice (B). WT, WT mice. KO, SP-D KO mice. The figures shown are from three independent experiments (n = 8 to 10 mice per group). Data are shown as the median (central black bar in boxes) with upper and lower quartiles (boxed area), and range of the data (error bars).* p<0.05 in Mann-Whitney U test.</p