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

A SURVEY OF TREATMENT PRACTICES FOR FEBRILE ILLNESSES AMONG TRADITIONAL HEALERS IN THE NIGERIAN MIDDLE BELT ZONE

This survey was conducted to investigate the pattern of treatment practices for febrile illnesses among one hundred and eighty five traditional healers from the Nigerian Middle belt zone ethnomedicine. Data collection was through use of the semi structure questionnaire administered by trained interviewers recruited from the study sites - Gboko and Katsina Ala Local Government Areas. A total of 176 (95.1%) reportedly diagnosed through the presenting complaints and symptoms and 3 (1.6%) made diagnoses through divination. All the respondents indicated their referral practices, with 100 (54.1%) of the respondents reported that they had once referred clients. Respondents listed 164 plants used in the preparation of the various treatment modalities. Institution of treatment follows this diagnostic practice. Treatment of different febrile illnesses involve the use of liquid herbs, powdered herbs, medicinal scarifications, incantations and sacrifices which suggests the confidence this group has in the efficacy of their herbs for treating febrile illnesses. An appreciable level of referral 54.1% practice was also found among the traditional healers. The findings of this study strengthen the need to recognize the traditional health practitioners in the treatment of health problems especially febrile illnesses, and to establish quality control mechanism in partnership with them to improve their treatment practices

Comparison of the specificity of antibodies to VAR2CSA in Cameroonian multigravidae with and without placental malaria:a retrospective case-control study

BACKGROUND: Antibodies (Ab) to VAR2CSA prevent Plasmodium falciparum-infected erythrocytes from sequestrating in the placenta, i.e., prevent placental malaria (PM). The specificity of Ab to VAR2CSA associated with absence of PM is unknown. Accordingly, differences in the specificity of Ab to VAR2CSA were compared between multigravidae with and without PM who had Ab to VAR2CSA. METHODS: In a retrospective case–control study, plasma collected from Cameroonian multigravidae with (n = 96) and without (n = 324) PM were screened in 21 assays that measured antibody levels to full length VAR2CSA (FV2), individual VAR2CSA DBL domains, VAR2CSA domains from different genetic backgrounds (variants), as well as proportion of high avidity Ab to FV2. RESULTS: Multigravidae with and without PM had similar levels of Ab to FV2, the six VAR2CSA DBL domains and different variants, while the proportion of high avidity Ab to FV2 was significantly higher in women without PM at delivery (p = 0.0030) compared to women with PM. In a logistic regression model adjusted for gravidity and age, the percentage of high avidity Ab to FV2 was associated with reduced likelihood of PM in multigravidae. A 5 % increase in proportion of high avidity Ab to FV2 was associated with a nearly 15 % lower likelihood of PM. CONCLUSION: Ab avidity to FV2 may be an important indicator of immunity to PM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-015-1023-6) contains supplementary material, which is available to authorized users

High levels of antibodies to multiple domains and strains of VAR2CSA correlate with the absence of placental malaria in Cameroonian women living in an area of high Plasmodium falciparum transmission

Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity

Research Paper - A SURVEY OF TREATMENT PRACTICES FOR FEBRILE ILLNESSES AMONG TRADITIONAL HEALERS IN THE NIGERIAN MIDDLE BELT ZONE

This survey was conducted to investigate the pattern of treatment practices for febrile illnesses among one hundred and eighty five traditional healers from the Nigerian Middle belt zone ethnomedicine. Data collection was through use of the semi structure questionnaire administered by trained interviewers recruited from the study sites - Gboko and Katsina Ala Local Government Areas. A total of 176 (95.1%) reportedly diagnosed through the presenting complaints and symptoms and 3 (1.6%) made diagnoses through divination. All the respondents indicated their referral practices, with 100 (54.1%) of the respondents reported that they had once referred clients. Respondents listed 164 plants used in the preparation of the various treatment modalities. Institution of treatment follows this diagnostic practice. Treatment of different febrile illnesses involve the use of liquid herbs, powdered herbs, medicinal scarifications, incantations and sacrifices which suggests the confidence this group has in the efficacy of their herbs for treating febrile illnesses. An appreciable level of referral 54.1% practice was also found among the traditional healers. The findings of this study strengthen the need to recognize the traditional health practitioners in the treatment of health problems especially febrile illnesses, and to establish quality control mechanism in partnership with them to improve their treatment practices

A survey of treatment practices for febrile illnesses among Traditional Healers in the Nigerian Middle Belt Zone

This survey was conducted to investigate the pattern of treatment practices for febrile illnesses among one hundred and eighty five traditional healers from the Nigerian Middle belt zone ethnomedicine. Data collection was through use of the semi structure questionnaire administered by trained interviewers recruited from the study sites - Gboko and Katsina Ala Local Government Areas. A total of 176 (95.1%) reportedly diagnosed through the presenting complaints and symptoms and 3 (1.6%) made diagnoses through divination. All the respondents indicated their referral practices, with 100 (54.1%) of the respondents reported that they had once referred clients. Respondents listed 164 plants used in the preparation of the various treatment modalities. Institution of treatment follows this diagnostic practice. Treatment of different febrile illnesses involve the use of liquid herbs, powdered herbs, medicinal scarifications, incantations and sacrifices which suggests the confidence this group has in the efficacy of their herbs for treating febrile illnesses. An appreciable level of referral 54.1% practice was also found among the traditional healers. The findings of this study strengthen the need to recognize the traditional health practitioners in the treatment of health problems especially febrile illnesses, and to establish quality control mechanism in partnership with them to improve their treatment practices. Key words: fever, traditional, treatment practices, Nigeria, middle belt Afr. J. Trad. Comp. Alt. Med. Vol.2(3) 2005: 337 - 34

Boletín de Segovia: Número 133 - 1913 noviembre 5

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

MOESM2 of Comparison of the specificity of antibodies to VAR2CSA in Cameroonian multigravidae with and without placental malaria: a retrospective case–control study

Additional file 2. Testing mouse anti-human monoclonal antibodies for cross-reactivity (median fluorescent intensities tabulated)