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Sepsis associated with 1 in 5 deaths globally, double previous estimate

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Twice as many people as previously believed are dying of sepsis worldwide, according to an analysis, published in The Lancet.

Among them are a disproportionately high number of children in poor areas.

Led by researchers at the University of Pittsburgh and University of Washington schools of medicine, the study revealed 48.9m global cases of sepsis in 2017 and 11m deaths, representing 1 in 5 deaths worldwide.

Sepsis occurs when a person’s organs cease to function properly as the result of an out-of-control immune response to infection. Even if sepsis doesn’t kill its victims, it can create lifelong disabilities in survivors.

The large majority of sepsis cases – 85% in 2017 – occurred in countries with low or middle sociodemographic status. The highest burden was found in sub-Saharan Africa; the South Pacific islands near Australia; and South, East, and Southeast Asia. Sepsis incidence was higher among females than males. By age, the incidence of sepsis peaks in early childhood, with more than 40% of all cases occurring in children under 5.

“We are alarmed to find sepsis deaths are much higher than previously estimated, especially as the condition is both preventable and treatable,” said Dr Mohsen Naghavi, senior author on the study and professor of health metrics sciences at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine. “We need renewed focus on sepsis prevention among newborns and on tackling antimicrobial resistance, an important driver of the condition.”

For their analysis, Naghavi and colleagues leveraged the Global Burden of Disease (GBD) study, a comprehensive epidemiological analysis coordinated by IHME. The GBD 2017 study currently reports on 282 primary causes of death not including sepsis, which is considered an intermediate cause of death. A primary cause of death is the underlying condition (cancer) which leads to the intermediate cause (sepsis) that ultimately results in death.

Previous global estimates for sepsis were limited as they relied upon hospital databases from a select group of middle- and high-income countries. The previous estimates overlooked the substantial burden of sepsis that occurs outside of the hospital, especially in low-income countries. Today’s study findings are unprecedented as they represent mortality both in and out of the hospital.

The study authors analysed annual sepsis incidence and mortality trends from 1990 through 2017 and found rates are improving. In 1990, there were an estimated 60.2m sepsis cases and 15.7m deaths; by 2017, incidence had dropped by 19% to 48.9m cases and deaths by 30% to 11.0m.

The most common underlying cause of sepsis-related death in both 1990 and 2017 was lower respiratory infection.

“I’ve worked in rural Uganda, and sepsis is what we saw every single day. Watching a baby die of a disease that could have been prevented with basic public health measures really sticks with you,” said lead author Dr Kristina E Rudd, assistant professor in Pitt’s department of critical care medicine. “I want to contribute to solving this tragedy, so I participate in research on sepsis. However, how can we know if we’re making progress if we don’t even know the size of the problem? If you look at any top 10 list of deaths globally, sepsis is not listed because it hasn’t been counted.

“So what is the solution? Well, to start with it’s basic public health infrastructure. Vaccines, making sure everyone has access to a toilet and clean drinking water, adequate nutrition for children and maternal health care would address a lot of these cases,” said Rudd, who is also a University of Pittsburgh Medical Centre (UPMC) critical care physician. “But sepsis is still a problem here in the US, where it is the No 1 killer of hospital patients. Everyone can reduce their odds of developing it by getting the flu shot, and the pneumonia vaccine when appropriate. Beyond that, we need to do a better job preventing hospital-acquired infections and chronic diseases, like diabetes, that make people more susceptible to infections.

“Finally, for people in high-income countries who want to help reduce the rates of sepsis in low-income areas, we need to support research into treatments and advocate to our elected officials for the importance of supporting sepsis prevention and control efforts in low-income communities,” Rudd said.

Additional findings include:
In 2017, 33.1m incident cases of sepsis, or two of every three cases, occurred in patients with an underlying infectious condition; the remaining 15.8m incident cases occurred in individuals with underlying injuries or non-communicable diseases.

In countries with low sociodemographic status, the majority of sepsis-related deaths were due to infection, whereas in countries with high sociodemographic status most sepsis-related deaths were associated with non-communicable diseases.

SEPSIS DEATH RATES (ALL AGES), 195 COUNTRIES AND TERRITORIES, 2017
Highest death rates
Central African Republic: 771.1 deaths per 100,000 people
Chad: 566.3
South Sudan: 551.4
Lesotho: 512.8
Somalia: 491.2
Niger: 475.8
Guinea: 460.6
Mali: 455.1
Burkina Faso: 453.1
Sierra Leone: 453.0
Lowest death rates
Qatar: 10.8 deaths per 100,000 people
Kuwait: 17.6
Lebanon: 24.2
Oman: 24.8
Bahrain: 27.1
Maldives: 27.4
United Arab Emirates: 27.5
Saudi Arabia: 29.7
Iceland: 32.4
Jordan: 33.1

SEPSIS INCIDENCE RATES (ALL AGES), 195 COUNTRIES AND TERRITORIES, 2017
Highest incidence rates
Mali: 2,806.9 new cases of sepsis per 100,000 people
Niger: 2,660.0
Chad: 2,659.4
Nigeria: 2,588.1
Sierra Leone: 2,259.7
South Sudan: 2,256.1
Burkina Faso: 2,229.8
Central African Republic: 2,196.1
Guinea: 1,779.5
Democratic Republic of the Congo: 1,683.6
Lowest incidence rates
Qatar: 92.6 new cases per 100,000 people
Kuwait: 115.8
Bahrain: 127.1
United Arab Emirates: 127.6
Oman: 180.7
Macedonia: 190.1
Albania: 190.8
Iceland: 191.6
Montenegro: 195.8
Tunisia: 198.4

Abstract
Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.

Methods: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.
Findings: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.
Interpretation: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.
Funding: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children’s Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Authors
Kristina E Rudd, Sarah Charlotte Johnson, Kareha M Agesa, Katya Anne Shackelford, Derrick Tsoi, Daniel Rhodes Kievlan, Danny V Colombara, Kevin S Ikuta, Niranjan Kissoon, Simon Finfer, Carolin Fleischmann-Struzek, Flavia R Machado, Konrad K Reinhart, Kathryn Rowan, Christopher W Seymour, R Scott Watson, T Eoin West, Fatima Marinho, Simon I Hay, Rafael Lozano, Alan D Lopez, Derek C Angus, Christopher J L Murray, Mohsen Naghavi

Institute of Health Metrics and Evaluation material

The Lancet article summary

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