Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021

Main findings

The COVID-19 pandemic has emerged as one of the most defining global health events of recent history. Our latest comprehensive estimates of cause-specific mortality give insight into the global landscape of disease before and during the first 2 years of the pandemic, revealing the important changes in disease-burden patterns that followed. After more than three decades of consistent improvements in global life expectancy and declining age-standardised death rates, COVID-19 reversed long-standing progress and disrupted trends in the epidemiological transition. As the second leading cause of age-standardised deaths in 2021, COVID-19 had a pronounced influence on the reduction in global life expectancy that occurred. The heterogeneous influence of the disease across the globe provides important insights for improving future pandemic preparedness and ensuring that nations are equitably equipped to respond to new outbreaks. Additionally, our analysis of geographical and temporal trends in mortality enables us to observe the changing patterns in causes of death worldwide. Many causes have exhibited a reduced geographical reach—a reflection of dedicated and persistent mitigation efforts to reduce the burden of certain causes, as well as potential changes to risk-factor exposure. This study offers an opportunity to apply the lessons learned from these successes to further reduce deaths from causes that are now present within smaller, more concentrated areas throughout the world.

The COVID-19 pandemic

The emergence and spread of COVID-19 follows a similar pattern of regional heterogeneity that is common among many leading communicable causes of death, with higher rates of infection and increased fatalities occurring in lower-resource settings.,, Although heterogeneity in COVID-19 outcomes in 2020 and 2021 varied by the income status of a country or territory, outcomes were also directly related to age, government actions to close borders, and the implementation of transmission-reduction policies. This general pattern did not always hold true at the national level, however, where estimates from some high-income countries showed a much greater burden than would have been expected, indicating important opportunities for improved pandemic preparedness and response in these nations. The varying effects across locations emphasises the complexity of the pandemic. Diverse social, economic, and political influences contributed to the variations in death rates observed between locations. In general, areas with advanced health-care systems and robust medical facilities were better able to manage abrupt increases in the number of COVID-19 cases. By contrast, locations with poorer health-care infrastructure were less equipped to handle the surge in infections that occurred, although strong health-care systems did not singularly influence the outcome of the pandemic. Improving preparedness for future pandemics should also include engagement strategies to enhance the trust that individuals place in public health recommendations. Additionally, identifying methods to enhance death-reporting systems and overcome political obstacles to ensure accurate reporting will be crucial steps for monitoring COVID-19 and future pandemic occurrences.,

Our study shows that COVID-19 was one of the leading global causes of death during the first 2 years of the pandemic and provides an opportunity to delineate between the disease's direct and indirect mortality effects as well as its effect on life expectancy. As previously predicted, COVID-19 shifted baseline patterns of mortality for diseases and injuries that were affected by physical-distancing measures and other government-mandated restrictions. Deferred care-seeking during the height of the pandemic also probably contributed to shifts in patterns of mortality for some diseases and injuries and might also have contributed to the emergence of pandemic-related deaths not attributable directly to COVID-19, lower respiratory infections, measles, malaria, or pertussis (OPRM). Deferred care-seeking might also have been a contributing factor in the notable divergence in the age distribution in deaths between COVID-19 and OPRM, whereby COVID-19 deaths were substantially higher in older ages, whereas the highest rate of OPRM was seen in older ages as well as in children younger than 23 months. Mortality might have increased in the youngest ages because caregivers might have hesitated to seek medical care during the peak of the virus's spread. Understanding these disparities is imperative for shaping future health policies and preparedness efforts.

Important trends in life expectancy

Advancements over the past three decades in the prevention and control of infectious diseases have contributed to increases in life expectancy in many locations, increasing the need to support populations living with NCDs. The global decline in life expectancy that occurred in 2020 and 2021 confounds the longer-term trend of increase. Our decomposition analysis suggests that this decline was predominantly a result of the pandemic (combined COVID-19 and OPRM), but the degree of severity varied greatly by location. Although large improvements in many causes—including HIV/AIDS and lower respiratory and enteric infections—somewhat counterbalanced the decline, the decrease in life expectancy was also compounded by increasing rates of mortality from other causes, such as diabetes and kidney diseases.

The effect of COVID-19 on life expectancy showed varying degrees of severity, ranging from a large loss of 4·9 years in Andean Latin America to almost no change in east Asia. From 1990 to 2021, reductions in many of the leading causes of death resulted in overall life-expectancy increases across most regions, despite heavy setbacks for many because of the COVID-19 pandemic. We found that despite Andean Latin America having the largest regional reduction in life expectancy due to the pandemic, overall life-expectancy reductions across the region were tempered by improvements in other causes, with reductions in rates of death from lower respiratory infections and neonatal disorders responsible for an increase in life expectancy of 2·6 years overall between 1990 and 2021. The impressive reductions in neonatal disorders throughout many countries in Andean Latin America have been attributed to the improvements made in implementing effective maternal and neonatal health intervention strategies.

The reduction in life expectancy in southern sub-Saharan Africa also exceeded the global average by a substantial margin, with a reduction of 3·4 years due to COVID-19. Although life expectancy in the region was substantially affected by the COVID-19 pandemic, the reduction was also attributable to high mortality rates from HIV/AIDS. Some nations with high pandemic-related death tolls were among those already burdened by high rates of other infectious diseases. Several countries in southern sub-Saharan Africa navigated the challenges of the pandemic, alongside long histories of combatting some of the highest HIV/AIDS prevalence rates in the world., A subset of countries were faced with a triple burden of COVID-19, HIV/AIDS, and tuberculosis. The combined burden of these causes across southern sub-Saharan Africa was not offset by sufficient improvements in mortality from other causes, leading to an overall reduction in the region's life expectancy of more than 4 years over the entire study period.

Cause-specific patterns of mortality concentration

Estimates of mortality concentration reflect shifting patterns of disease over time, from diseases that have a widespread presence moving to more geographically reduced subsets of the global population. These changes highlight differences between populations and their progress towards reducing mortality due to diseases and injuries. These findings also provide an important opportunity to improve how best public health practices are applied to further disease reduction. Broadly, widespread declines in many communicable diseases resulted in mortality from these causes exhibiting more concentrated geographical distributions in 2021 relative to patterns seen in 1990. The degree of mortality concentration estimated by this study for enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, and tuberculosis reflects substantial global progress in reducing mortality from these causes over the study period, underscoring the success of several public health campaigns, global commitments, and improvements in communicable-disease programmes.,, Estimates of mortality concentration can be used to examine where disease mitigation strategies have been successful, where they can be further implemented to reduce inequality, and where more research might be needed to develop effective treatment and intervention strategies.

Notably, our estimates support previous findings that show deaths from malaria are becoming increasingly concentrated and are now particularly concentrated within western sub-Saharan Africa, with an additional corridor running through central Africa and into Mozambique. Countries in western sub-Saharan Africa with the highest under-5 death rates from malaria in 2021 included Burkina Faso, Sierra Leone, and Niger. This concentration of malaria mortality reflects both differential rates of population growth across Africa, as well as the varying rates of progress in reducing transmission, most notably by malaria nets treated with long-lasting insecticide and in strengthening case management. At a time of growing threats to progress against malaria, including emerging parasite and vector resistance and budgetary pressures, but also amid promising new tools such as second vaccine for malaria, it is more important than ever that changing patterns of mortality are quantified and understood.,

Enteric infections showed large disease concentration. Under-5 deaths from enteric infections were largely concentrated within sub-Saharan Africa and south Asia. Countries in sub-Saharan Africa and south Asia with the highest under-5 death rates from enteric infections in 2021 included Chad, South Sudan, and the Central African Republic. There are many contributing factors that should be considered when examining how to reduce enteric infections in the remaining concentrated locations. Alongside the provision of oral rehydration solution and rotavirus vaccines, critical public health improvements such as in water, sanitation, and hygiene might have contributed to decreases in enteric deaths., Childhood growth failure, also a leading risk factor for deaths from lower respiratory infections, malaria, and measles, must be addressed through interventions to improve women's health including anaemia, promotion of early exclusive breastfeeding, and management of acute malnutrition, among others., Countries with the highest burden of infectious disease mortality in children younger than 5 years tend to be geographically clustered, suggesting multisectoral approaches are necessary to continue reducing mortality in the countries with the highest rates.

A broad and recurring theme from this study is that reductions in enteric infections contributed to improved life expectancies over the past several decades. The reductions in childhood mortality associated with diarrhoeal diseases that have occurred across many parts of Africa,,, can also be partly explained by many combined local efforts in improved immunisation; access to water, sanitation, and hygiene facilities;, breastfeeding; oral rehydration therapy; and zinc supplementation, alongside global initiatives such as the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea. Given that enteric disease-related mortality and specifically diarrhoeal disease-related mortality continued to decline during the COVID-19 pandemic, the post-pandemic period might offer opportunities to accelerate progress on prevention and treatment. Diarrhoeal diseases are particularly amenable to public health intervention, and given this cause's high burden among children, we must continue to direct resources towards its prevention., Several locations still do not have the necessary financing, governance, and political commitment to reduce rates of enteric infections. To accelerate progress in reducing enteric disease-related mortality, routine and catch-up immunisation programmes must be strengthened and expanded, including building on the global success of the rotavirus roll-out and countering disruptions in childhood immunisation during the pandemic. Additionally, efforts should focus on advancing candidate vaccines against enterotoxigenic Escherichia coli, norovirus, and shigella.,,,,

Our study also found that some vaccine-preventable diseases, such as measles, have shown widespread reductions in mortality rates and were geographically concentrated. Under-5 deaths from measles were concentrated within western and eastern sub-Saharan Africa. Although multiple factors contribute to decreases in infectious disease burden, improvements in measles mortality have largely been attributable to the global availability of a safe and effective vaccine against measles, producing life-long immunity, with two-dose efficacy exceeding 95%. Measles incidence has decreased dramatically where vaccination efforts have been successful, including North America, South America, Europe, and Australia;,,,, although, since 2016, endemic measles transmission has been re-established in ten countries that previously had achieved measles elimination. We found that, as of 2021, measles mortality was concentrated in countries and regions with insufficient access to the measles vaccine, particularly in sub-Saharan Africa. Although valuable insights can be drawn from countries that have achieved measles control through effective vaccination programmes and surveillance systems, interventions still must be tailored to the affected communities and countries for successful reductions in mortality.

Some infectious diseases, such as HIV/AIDS, also showed mortality concentration. Deaths from HIV/AIDS were largely concentrated within sub-Saharan Africa, most notably southern sub-Saharan Africa. Countries in sub-Saharan Africa with the highest age-standardised mortality rate in 2021 included Lesotho, Eswatini, and Botswana. Countries in sub-Saharan Africa with the highest under-5 death rates from HIV in 2021 included Lesotho, Equatorial Guinea, and Guinea-Bissau. This concentration highlights how HIV-control campaigns, preventative measures,, improved treatment with the emergence of antiretroviral therapy, access to testing and health care, and research advancements might have contributed to the reduced global mortality of HIV. Despite these successes, substantial barriers remain to reducing HIV mortality, such as stigma discouraging people from accessing treatment and care,, insufficient health-care infrastructure, access to testing, coverage of antiretroviral therapy, and complications due to co-occurring diseases such as tuberculosis and HIV. Preventative measures are particularly important for the reduction of HIV mortality because HIV prevalence is the primary contributor to high mortality rates. Although countries can learn from successful HIV campaigns and strategies, global support is needed to ensure HIV treatment and preventative measures are accessible to all populations at risk.,,

In many high-income nations, the overall rate of neonatal deaths decreased between 1990 and 2021, becoming more concentrated over time. Deaths from neonatal disorders in 2021 were concentrated within sub-Saharan Africa and south Asia. Countries in these regions with the highest under-5 death rates from neonatal disorders in 2021 included Mali, South Sudan, and Sierra Leone. However, the disparity in mortality between high-income and low-income countries and regions highlights inequality in progress. Newborn care that can reduce mortality includes resuscitation, prevention of hypothermia and infection, in-facility delivery, and exclusive breastfeeding., Neonatal mortality might be reduced globally if policy makers examine the strategies that led to successes elsewhere.

Conversely, although the burden of many NCDs has also been reducing, these causes have typically not followed the same pattern of mortality concentration seen in CMNN diseases. These trends emphasise a key distinction in the spatial dynamics of NCDs compared with many communicable diseases. Although non-communicable causes might not exhibit the same degree of concentration as communicable causes, the mortality burden has changed in distribution, reducing over time in high-income countries and regions, while persisting in low-income countries and regions. Age-standardised mortality rates due to NCDs decreased in most locations within the high-income; Latin America and the Caribbean; north Africa and the Middle east; and central Europe, eastern Europe, and central Asia super-regions between 1990 and 2021. However, NCDs in the south Asia; sub-Saharan Africa; and southeast Asia, east Asia, and Oceania super-regions have either increased or decreased at notably lower levels in 2021 compared with in 1990. Examples of this trend include ischaemic heart disease, neoplasms, and stroke, all of which largely declined over the study period—although their reductions have been widely dispersed and not as targeted as the CMNN causes. These findings show that NCDs do not appear to be moving towards more condensed geographical locations over time in the same way that many CMNN diseases are, which could make interventions and policies more complex to implement.

Ultimately, the extent of mortality concentration reflects both the progress achieved in health-care advancements and the shortcomings that persist in their equitable implementation. Disease concentration is evidence that there are effective interventions and policies that have successfully reduced disease burden in many locations, but these innovations have not been equitably distributed throughout the world or have been ineffective at addressing the specific challenges certain populations face. There remains a global need to improve access to new interventions and vaccines, to invest in the implementation of validated public health policies, and to strategise with geographical sources of disease in mind. Future efforts should continue the ongoing mitigation of communicable diseases, focusing on locations where these causes have become more geographically concentrated, while also initiating efforts to combat chronic causes within low-resourced settings. Additionally, patterns of high geographical concentration among infectious causes and low geographical concentration among chronic causes reflect the global epidemiological transition, wherein mortality rates of infectious deaths declined throughout most years of our study. The increased concentration of a cause of death, particularly communicable diseases, illustrates success in mitigation that can be adapted within the countries and regions with mortality concentration identified in our study, with the potential to greatly reduce mortality from those causes of death.