Sepsis is the development of an inflammatory response throughout the body due to an infection. It affects people all over the world, with around 1 in 1,000 in the population developing the syndrome based on estimates from the United States, United Kingdom and Europe.

However, the incidence of sepsis is believed to be larger in countries with more infectious diseases. It accounts for a large portion of the world’s fatalities, making it of utmost interest to understand and prevent.

Multiple black crusts at forehead in middle age man who presented with severe sepsis and septic shock. Image Credit: TisforThan / Shutterstock

Incidence of Sepsis

Measuring the incidence of sepsis can be difficult. Many studies to date have focused on patients in the intensive care unit (ICU) who are diagnosed with sepsis, while other studies have shown that 40% of patients with sepsis never require intensive care.

There are also types of sepsis, wherein severe sepsis involves acute organ dysfunction and septic shock involves organ dysfunction as well as low blood pressure that is not alleviated by treatment with intravenous fluids. Apart from nation-specific limitations of occurrences of sepsis, there is uneven focus given to the types of sepsis in epidemiological studies.

With this in mind, more robust estimates have been generated. In the United States, 700,000 cases of sepsis were estimated in 2000, meaning it occurs to 240.4 per 100,000 of the population. Severe sepsis occurs at 81 per 100,000 in the United States. Septic shock data is limited in comparison, but shows that of general hospital admissions, 25% of sepsis patients advance to septic shock.

The incidence of sepsis is believed to increase every year. It is estimated that the increase is at 9% annually, but caution should be taken as this may reflect increased awareness of sepsis as well as actual increase. The increase can be due to increasing age of the population, since the elderly are one demographic more at risk of developing sepsis. Other reasons for the increase include an increasing problem of chronic health conditions, and increased use of immunosuppressive therapy, transplantation, chemotherapy, or invasive procedures. For example, the 2000 estimate of sepsis in the United States was 240 cases per 100,000 in the population. By 2001, a new estimate placed this at 300 cases per 100,000 in the population.

While the incidence of sepsis may be increasing, evidence suggests it is becoming less mortally dangerous. From 1979 to 2000, the in-hospital mortality of sepsis shrank from 28% to 18%. This trend was confirmed in a study from 2012. This study highlighted that admittance to ICU with severe sepsis increased from 7.2% to 11.1%, while mortality decreased from 35% to 18%. All in all, sepsis is trending to become more common but less deadly.

Demographic

Certain demographic groups of the population appear to be more commonly victims of sepsis than others. Males tend to develop the syndrome more often than women, although there does not appear to be a difference in mortality rates. This discrepancy can potentially be caused by sex hormones’ effect on the immune system and cardiovascular cytokine signaling, which is critical to propagation of sepsis. Black men and the elderly are other groups more at risk for developing sepsis. This is hypothesized to be due to socio-economic bias, wherein black men and other non-white Americans who are at higher risk for developing sepsis have worse access to healthcare on time, more poverty, and more chronic health conditions such as HIV or diabetes. However, when such factors are controlled for they still face increased risk of developing sepsis, which potentially indicates there are genetic factors at play as well.

Toll-like receptor 4 (TLR4) and Toll-like receptor 1 (TLR1) are receptors highly implicated in the immune system. Polymorphisms (different forms) in these receptors have been linked to increased susceptibility to septic shock caused by Gram-negative bacteria. One TLR4 polymorphism, Asp299Gly, may be related to protection against cerebral malaria and is common in people from sub-Saharan Africa. It is believed that polymorphisms in Toll-like receptors can potentially be responsible for the ethnic differences in development and severity of sepsis.

An increase in chronic health conditions is one reason behind the rise in sepsis cases. Afflicted people, who have conditions such as cancer, liver disease, and diabetes, represent 50% of severe sepsis cases. For cancer patients specifically, they are five times more likely to develop sepsis than healthy individuals, and 55% more likely to die from it. It is often because of other chronic health conditions that older demographics are more at risk for developing sepsis.