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

The Burden of Escherichia coli Pathotypes among Diarrheic Farm Animals: A Possible Zoonotic Relevance

Pathogenic strains of Escherichia coli possess virulence factors that contribute to both intestinal and extraintestinal infections in both humans and animals. Farm animals can serve as a potential source for these types of E. coli strains. This study aimed to determine the virulence genes and related pathotypes of E. coli isolated from diarrheic farm animals and their public health importance. Rectal swabs were collected from 175 diarrheic farm animals (49 cattle, 69 sheep, and 57 goats). Samples were prepared for isolation of E. coli through enrichment in tryptic soya broth and then plating on Eosin methylene blue agar, whereas the identification of E. coli was performed based on colony morphology, biochemical tests, and molecular confirmation by PCR. Furthermore, the determination of the virulence factors associated with E. coli pathotypes was done by molecular technique to amplify the virulence genes including adhesins (sfa, papC, sepA, etrA, aer, feaG, fsaA, and eaeA), capsule synthesis (rfc), and toxins (cnf1, hlyA, eltA, estA, exhA, stx1, and stx2). Moreover, phylogenetic analysis was done via sequencing of the 16s rRNA genes from the strains that carry virulence genes, as well as the statistical analysis was done through the production of the hierarchically clustered heat map. Pathogenic E. coli was found in 39.4% of the examined animals. Fifteen out of sixteen virulence genes were detected among E. coli isolates from different farm animals, including cattle, sheep, and goats. ExPEC pathotype was predominated among cattle and sheep isolates whereas, ETEC pathotype is more frequent among goat isolates. The sequence analysis of 16s rRNA sequences revealed similarity between farm animal isolates and those from humans that were retrieved from GenBank. In conclusion, this study highlights the potential role of diarrheic farm animals in the epidemiology of pathogenic E. coli pathotypes which may have public health implications

Molecular Detection of Toxigenic Clostridioides difficile among Diarrheic Dogs and Cats: A Mounting Public Health Concern

Nowadays, pet animals are known to be asymptomatic carriers of Clostridioidesdifficile. This study was conducted to investigate the burden of toxigenic C. difficile among diarrheic dogs and cats using direct PCR on fecal samples to reveal better insights about the epidemiology of such toxigenic strains referring to its public health significance. For this purpose, fecal samples were obtained from 58 dogs and 42 cats experiencing diarrhea. Following DNA extraction, the extracted DNA was examined for the occurrence of C. difficile as well as toxigenic strains through the detection of C. difficile 16S rRNA and toxin encoding genes (tcdA, tcdB, cdtA and cdtB) using PCR. Moreover, partial DNA sequencing of toxigenic strains retrieved from dog and cat was carried out. Of 100 examined diarrheic animals, 90 (90%) were C. difficile positive, including 93.1% and 85.7% of dogs and cats, respectively. In addition, toxigenic strains were detected in 13 animals, giving an overall prevalence 13% with the following prevalence rates among dogs and cats 12.1% and 14.3%, respectively. Furthermore, the phylogenetic analysis of the obtained sequence revealed high genetic relatedness of tcdA sequence obtained from a cat to strains of human diarrheic cases to point out the public health threat of such sequence. In conclusion, the direct detection of toxigenic C. difficile using PCR among dogs and cats highlights the potential role of household pets as a source for such strains to human contacts

Leptospirosis in animals and human contacts in Egypt: broad range surveillance

INTRODUCTION: Leptospirosis is a re-emerging zoonotic disease of humans and animals worldwide. The disease is caused by pathogenic species of the genus Leptospira. These organisms are maintained in nature via chronic renal infection of carrier animals, which excrete the organisms in their urine. Humans become infected through direct or indirect exposure to infected animals and their urine or through contact with contaminated water and soil. This study was conducted to investigate Leptospira infections as a re-emerging zoonosis that has been neglected in Egypt. METHODS: Samples from 1,250 animals (270 rats, 168 dogs, 625 cows, 26 buffaloes, 99 sheep, 14 horses, 26 donkeys and 22 camels), 175 human contacts and 45 water sources were collected from different governorates in Egypt. The samples were collected from different body sites and prepared for culture, PCR and the microscopic agglutination test (MAT). RESULTS: The isolation rates of Leptospira serovars were 6.9%, 11.3% and 1.1% for rats, dogs and cows, respectively, whereas the PCR results revealed respective detection rates of 24%, 11.3% and 1.1% for rats, dogs and cows. Neither the other examined animal species nor humans yielded positive results via these two techniques. Only six Leptospira serovars (Icterohaemorrhagiae, Pomona, Canicola, Grippotyphosa, Celledoni and Pyrogenes) could be isolated from rats, dogs and cows. Moreover, the seroprevalence of leptospiral antibodies among the examined humans determined using MAT was 49.7%. CONCLUSIONS: The obtained results revealed that rats, dogs and cows were the most important animal reservoirs for leptospirosis in Egypt, and the high seroprevalence among human contacts highlights the public health implications of this neglected zoonosis

Leptospirosis in animals and human contacts in Egypt: broad range surveillance

INTRODUCTION: Leptospirosis is a re-emerging zoonotic disease of humans and animals worldwide. The disease is caused by pathogenic species of the genus Leptospira. These organisms are maintained in nature via chronic renal infection of carrier animals, which excrete the organisms in their urine. Humans become infected through direct or indirect exposure to infected animals and their urine or through contact with contaminated water and soil. This study was conducted to investigate Leptospira infections as a re-emerging zoonosis that has been neglected in Egypt. METHODS: Samples from 1,250 animals (270 rats, 168 dogs, 625 cows, 26 buffaloes, 99 sheep, 14 horses, 26 donkeys and 22 camels), 175 human contacts and 45 water sources were collected from different governorates in Egypt. The samples were collected from different body sites and prepared for culture, PCR and the microscopic agglutination test (MAT). RESULTS: The isolation rates of Leptospira serovars were 6.9%, 11.3% and 1.1% for rats, dogs and cows, respectively, whereas the PCR results revealed respective detection rates of 24%, 11.3% and 1.1% for rats, dogs and cows. Neither the other examined animal species nor humans yielded positive results via these two techniques. Only six Leptospira serovars (Icterohaemorrhagiae, Pomona, Canicola, Grippotyphosa, Celledoni and Pyrogenes) could be isolated from rats, dogs and cows. Moreover, the seroprevalence of leptospiral antibodies among the examined humans determined using MAT was 49.7%. CONCLUSIONS: The obtained results revealed that rats, dogs and cows were the most important animal reservoirs for leptospirosis in Egypt, and the high seroprevalence among human contacts highlights the public health implications of this neglected zoonosis

Prevalence and phylogenetic characterization of Listeria monocytogenes isolated from processed meat marketed in Egypt

Because of its high case fatality rate, listeriosis locates among the most frequent causes of death due to food-borne illness. In this study, a total of 150 processed meat samples were collected from Giza Governorate, Egypt. Phenotypic and genotypic identification of Listeria monocytogenes was performed using PCR incorporating listeriolysin O virulence gene hlyA followed by DNA sequence analysis. L. monocytogenes was confirmed in 4% of each of beef burger, minced meat, and luncheon samples. Phylogenetic analysis showed that all the six Egyptian isolates have high homology with Colombian isolate (EF030606), except one Egyptian isolate which showed high homology with Indian isolate (EU840690). The public health significance of these pathogens as well as recommended sanitary measures were discussed