Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Ultrasensitive loop mediated isothermal amplification (US-LAMP) to detect malaria for elimination

Abstract Background Malaria elimination requires diagnostic methods able to detect parasite levels well below what is currently possible with microscopy and rapid diagnostic tests. This is particularly true in surveillance of malaria at the population level that includes so-called “asymptomatic” individuals. Methods The development of the first ultrasensitive loop mediated amplification method capable of detecting malaria from both whole blood and dried blood spots (DBS) is described. The 18S rRNA and corresponding genes that remain stable on DBS for up to 5 months are targeted. Results In the case of Plasmodium falciparum, lower limits of detection of 25 parasite/mL and 50–100 parasite/mL from whole blood and DBS were obtained, respectively. A sensitivity of 97.0% (95% CI 82.5–99.8) and specificity of 99.1% (95% CI 97.6–99.7) was obtained for the detection of all species in asymptomatic individuals from Africa and Asia (n = 494). Conclusion This tool is ideally suited for low middle-income countries where malaria is endemic and ultrasensitive surveillance of malaria is highly desirable for elimination

Prevalence of urinary schistosomiasis and associated risk factors among Abobo Primary School children in Gambella Regional State, southwestern Ethiopia: a cross sectional study

BACKGROUND: In Ethiopia, urinary schistosomiasis caused by Schistosoma haematobium has been known to be endemic in several lowland areas of the country where it causes considerable public health problems, mainly among school-age children. However, information on recent magnitude and risk factors of the disease is lacking, particularly for Gambella area. Therefore, this study aimed to assess the prevalence of urinary schistosomiasis and associated risk factors among Abobo Primary School children in Gambella, southwestern Ethiopia. METHODS: A cross-sectional study involving 304 school children was conducted in Abobo Primary School, Gambella Regional State, southwestern Ethiopia, from February to June 2014. Ten ml of urine sample was collected from each study participant and processed for microscopic examination by the urine filtration method; egg load for positive individuals was determined per 10 ml of urine. Data on socio-demographic characteristics and risk factors were collected using an interview-based questionnaire. The data were entered into and analyzed with SPSS version 20. Logistic regression and odds ratio were used to measure association and strength between variables, respectively. P-value < 0.05 at 95% CI was considered as statistically significant. RESULTS: The prevalence of urinary schistosomiasis was 35.9% (109/ 304) with a mean egg intensity of 8.76 per 10 ml of urine. Being male [AOR (95%CI) = 2.15(1.31, 3.52)], having father as a farmer [AOR (95%CI) = 1.96(1.19, 3.22)] and children living apart from parents [AOR (95% CI): 3.09 (1.14, 8.4)] were significantly associated with urinary schistosomiasis. CONCLUSION: The present study area in Gambella Regional State, southwestern Ethiopia, represents moderate-risk community for urinary schistosomiasis. Sex, father’s occupation and living apart from parents were found to be associated with infection. Treatment of all school-age children and fishermen is required once every 2 years until the prevalence of infection falls below the level of public health importance. It is also recommended to complement praziquantel treatment with supplementary measures such as provision of sanitation facilities and health education

Performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia

Abstract Background Malaria is a major public health problem and an important cause of maternal and infant morbidity in sub-Saharan Africa, including Ethiopia. Early and accurate diagnosis of malaria with effective treatment is the best strategy for prevention and control of complications during pregnancy and infant morbidity and mortality. However, laboratory diagnosis has relied on the identification of malaria parasites and parasite antigens in peripheral blood using Giemsa-stained microscopy or rapid diagnostic tests (RDTs) which lack analytical and clinical sensitivity. The aim of this study was to evaluate the performance of loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria among malaria suspected pregnant women in Northwest Ethiopia. Methods A cross sectional study was conducted from January to April 2016. Pregnant women (n = 87) suspected of having malaria at six health centres were enrolled. A venous blood sample was collected from each study subject, and analysed for Plasmodium parasites by microscopy, RDT, and LAMP. Diagnostic accuracy outcome measures (sensitivity, specificity, predictive values, and Kappa scores) of microscopy, RDT and LAMP were compared to nested polymerase chain reaction (nPCR) as the gold standard. Specimen processing and reporting times were documented. Results Using nPCR as the gold standard technique, the sensitivity of microscopy and RDT was 90 and 70%, and the specificity was 98.7 and 97.4%, respectively. LAMP assay was 100% sensitive and 93.5% specific compared to nPCR. Conclusions This study showed higher sensitivity of LAMP compared to microscopy and RDT for the detection of malaria in pregnancy. Increased sensitivity and ease of use with LAMP in point-of-care testing for malaria in pregnancy was noted. LAMP warrants further evaluation in intermittent screening and treatment programmes in pregnancy

Vitamin D deficiency among newly diagnosed tuberculosis patients and their household contacts: a comparative cross-sectional study

Recent studies suggest that the incidence and severity of tuberculosis is associated with low levels of vitamin D. Even though individuals living in Ethiopia have a high exposure to sunlight which is a source of vitamin D, tuberculosis is still one of the major causes of morbidity and mortality in the country. Therefore, this study aimed to determine the prevalence and associated factors of vitamin D deficiency in newly diagnosed tuberculosis patients, household contacts and community controls in Gondar, Ethiopia

Molecular detection of Enteropathogens from diarrheic stool of HIV positive patients in Gondar, Ethiopia

Abstract Background Infectious diarrhea is a common problem in the developing world, especially among people living with HIV/AIDS. Traditional diagnostic methods such as stool culture and microscopic examination are limited by resources and poor sensitivity. The use of molecular diagnostics for enteropathogen detection in this region of sub-Saharan Africa has not been fully explored. We sought to identify risk factors and characterize enteropathogens from diarrheic stools of HIV-positive patients in Gondar, Ethiopia using multiplex molecular panels targeting key infectious agents. Methods A cross-sectional study of 100 stool samples was performed. Samples were collected consecutively from HIV- positive patients presenting with diarrhea at University of Gondar Hospital clinic, a major center in NW Ethiopia. Genomic DNA was extracted from stool and processed using a multiplex molecular panel Allplex™ [Seegene, Canada]. Correlations between patient characteristics, symptoms, public health risk factors, and enteropathogen type (s) were studied. Eighty-six samples were successfully analyzed by molecular methods. Results The mean age was 35 with 43% male. Eighty percent lived in an urban area, 18% had access to well water only, and 81% practiced proper hand hygiene. The majority of patients (72%) were receiving HAART with a median CD4 cell count of 362/μL. Multiple pathogens were detected in 94% of specimens, with an average of 5 enteropathogens per sample. Common bacteria, viruses, and parasites detected were Shigella spp./enteroinvasive E. coli (80%), enterotoxigenic E. coli (73%), Norovirus (16%) and B. hominis (62%). CD4 cell count < 500/ μL was associated with the presence of viruses (p = 0.004) and the absence of STEC (p = 0.010). The use of HAART or CD4 levels was not associated with the number of enteropathogens detected. Conclusions Diarrheic stool from HIV-positive outpatients in Gondar, Ethiopia had on average 5 enteropathogens present in their stool. Shigellaspp./enteroinvasive E. coli and enterotoxigenic E. coli are the major pathogens, not dissimilar to immunocompetent individuals in low income countries