Sepsis is a result of severe infection, though the infection may be localized (peritonitis, pneumonia, urinary tract infection, catheter-related infection, etc.). Patients with weakened immune systems are at particularly high risk of contracting sepsis. When sepsis occurs in a hospital or other healthcare facility following major surgery or trauma, the infection is referred to as a nosocomial (or hospital-acquired) infection.
All bacteria, even those naturally present on the skin or in the throat, and which are normally non-pathogenic, can trigger the onset of sepsis. Fungal infections are another potential cause, and certain viruses (SARS, H1N1 influenza, hemorrhagic fever viruses) can also induce a similar response. Meningitis (purpura fulminans) is a rare cause of sepsis that can occur in healthy young people, as can toxic shock syndrome due to tampon use.
Throughout history, sepsis has been known under several different names. In the past it was referred to as Hospital Gangrene (also known as nosocomial fever or putrid fever), a common affliction of soldiers whose battle wounds frequently became infected. The most famous example of this is without a doubt Richard the Lionheart, who died in 1199 following an arrow wound that became infected. The term puerperal fever has been used to describe infections contracted by women after childbirth. This is how Lucrezia Borgia died in 1519 after giving birth to her 7th child. The French doctor Armand Trousseau was the first to suggest a similarity between nosocomial gangrene and puerperal fever.
It was the Hungarian doctor Ignaz Semmelweis, who showed the importance of hygiene and handwashing in preventing contamination of women after childbirth in Vienna in 1847. But the contagious nature of puerperal fever had already been suspected by the Scottish doctor Alexander Gordon more than half a century earlier. In 1869, two Alsatian doctors, Victor Feltz (1835-1893) and Léon Coze (1819-1896), first discovered bacteria in the bloodstream of a patient suffering from puerperal fever. Louis Pasteur, in collaboration with the Port-Royal, Cochin and Lariboisière maternity wards in Paris, confirmed these observations in 1879-80 and recommended improved hygiene during childbirth.
In 2002, sepsis was defined as a systemic inflammatory response syndrome due to infection and characterized by at least two of the following symptoms: fever or hypothermia, rapid breathing and heart rate, increase or decrease in white blood cell count. In 2016 a new definition of sepsis was developed and it is now defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.
Sepsis is characterized by excessive production of inflammatory mediators, often referred to as a "cytokine storm” due to the massive overproduction of cytokines (chemical mediators that allow our cells to communicate with each other). Around 25% of sepsis survivors suffer cognitive impairment.
Today, sepsis tends to affect either the very young, such as newborns (neonatal sepsis), or the elderly (Pope John Paul II died of sepsis in 2005). However, sepsis can also affect adults in their prime. Notable examples include Agnès Souret, the first Miss France, who died at the age of 26 and the actor Guillaume Depardieu who died aged 37.
Every five seconds, someone dies of sepsis somewhere in the world. In industrialized countries, sepsis is responsible for as many deaths as heart attacks, with 95 cases of sepsis reported for every 100,000 inhabitants in the under 65 age group and 1,220 cases recorded for the over 65s. In developing countries, puerperal sepsis remains a major cause of death for women after childbirth (18,000 deaths per year), while neonatal sepsis is estimated to claim the lives of more than 350,000 newborns.
In France, sepsis proves fatal for 27% of patients, but for those suffering from the most severe form of sepsis (septic shock) the fatality rate can be as high as 50%. In France, the estimated number of deaths from sepsis is 30,000. Looking forward, the number of cases is expected to double within the next 50 years. This is particularly due to population aging.
Despite such high fatality rates, sepsis lags far behind other conditions in terms of research priorities. In industrialized countries, even though sepsis affects 1.8 times more people than heart conditions, it receives 13 times less funding for research, and 32 times less funding than for AIDS research. We can only hope that WHO’s recognition of sepsis as a global health priority in 2017 will make a difference to these figures.
Sepsis patients in intensive care are treated with antibiotics and given appropriate support to sustain the body's vital functions.
In over twenty years, despite the significant progress made in understanding the pathophysiology of sepsis, no new therapies have emerged. Numerous costly clinical trials have ended in failure and the only new drug put on the market (Xigris®) was finally withdrawn in 2011 because its efficacy could not be sufficiently proven. New concepts must therefore be developed and more rapid diagnostic tests that would enable patients to be treated with antibiotics sooner. This last point is key because every hour gained increases the patient’s chance of survival.
New weapons to fight bacteria
At the Institut Pasteur
The Human Histopathology and Animal Models Unit, led by Fabrice Chrétien, specializes in neurological and muscle complications following sepsis, and investigates the link between systemic inflammation and the onset of neurodegenerative diseases or muscle complaints. Research focuses on the role played by two types of cells in the nervous system (microglial cells and astrocytes) and that of muscle stem cells. Using transgenic mice (which enable identification of the aforementioned cells) and experimental peritonitis models, the scientists study the activation status of microglial cells and their interaction with astrocytes. This same approach is used to study the effects of sepsis on muscle regeneration capacity.