As a health-conscious society knowledgeable in mammograms, prostate checks, and the symptoms of stroke and heart attack, it is difficult to comprehend that we are not more aware of sepsis. The statistics paint a stark picture: one in every 20 deaths in the UK is associated with sepsis, killing more people than breast and bowel cancers combined. Around 100,000 people are admitted to hospital in the UK each year with sepsis, and approximately 37,000 lives are lost. The UK Sepsis Trust estimates that sepsis imposes a direct cost of £2.5 billion per year on the NHS.
Known in the past as blood poisoning, sepsis occurs when the immune response launches a catastrophic, systemic assault against a bacterial or fungal infection. Infections usually stay localised to a small area, but if they progress, especially to the bloodstream, the immune system goes into overdrive, battling microbes but causing enormous damage in the process. This extreme immune response causes blood to leak out of blood vessels and into tissues, reducing blood flow and starving organs of their vital oxygen supply. This leads to death in 25-40 per cent of cases, sometimes within days or even hours. Those who survive often have to deal with life-long effects of organ and tissue damage.
Perhaps one reason we are not more aware of this disease is that it is often under-reported as a cause of death. Since sepsis is an immune response, as a diagnosis it becomes entangled with a causative infection instead of receiving the focus another equally deadly disease would engender. Deaths from sepsis are often viewed as deaths from a kidney infection, pneumonia, influenza, meningitis, infection post-surgery, or any number of infectious diseases, diluting its impact in public awareness. It is easier to comprehend a relative dying of infection than from a dangerous immune response to that infection; it seems paradoxical. This likely contributes to a lack of awareness of the true burden of sepsis on our society and our health system.
It is no exaggeration to state that sepsis is a public health emergency, deserving significant public and political attention. Incidence of sepsis is increasing approximately 8-13 per cent per year, due to an increase in our society of patient groups most vulnerable to sepsis. These include the elderly, who are more vulnerable to infections, and type 2 diabetics, whose poor circulation makes it more difficult to fight skin infections before they progress. Others at risk include those who are pregnant or have had recent surgery, those who have been in hospital or have weakened immune systems - such as following chemotherapy - and patients with cirrhosis, HIV, or pressure ulcers. Notably, the rise in antibiotic resistance will also contribute to rising sepsis rates, as infections may progress dangerously while an effective antibiotic is identified.
Studies indicate that early diagnosis and rapid administration of fluids and effective antibiotics are critical to survival. However, symptoms can mimic other less serious illnesses such as flu or gastroenteritis, leading to delays in seeking help and delays in diagnosis. Anyone with an infection who starts to feel sick all over, has a high fever, a rapid heartbeat, fast breathing, or chills and shivering may be experiencing signs of sepsis and should seek the advice of a GP immediately. Symptoms of severe sepsis, which is a medical emergency, include slurred speech, confusion, nausea, diarrhoea, extreme muscle pain, lack of urination, severe breathlessness, discoloured skin, or loss of consciousness. Frighteningly, once the septic immune response is underway, it progresses fast and it is not always possible to switch it off simply by treating the infection.
At Birmingham, together with colleagues at Harvard and Monash Universities, we have recently identified a treatment that reduced sepsis-related mortality in mice by up to 70 per cent). The therapy involved isolating fibroblastic reticular cells (FRCs), expanding them in petri dishes over ten days, and then re-administering them in high numbers, as a single injection. We believe this therapy works because we are harnessing a natural function of FRCs. The FRCs are isolated from lymph nodes, where immune responses often begin, and one of their primary functions is to regulate the activity of certain classes of white blood cells involved in inflammation. It seems that FRCs are similarly able to suppress the overactive white blood cells involved in sepsis. These studies conducted using mouse FRCs look promising, and we intend to test whether human FRCs show similar promise.
In 2013, the Health Service Ombudsman for England released a publication called Time to Act, highlighting the need for improvement in awareness of and rapid diagnosis for severe sepsis, and the importance of compliance with basic standards of care.
The UK Sepsis Trust stress that a healthcare compliance level of 80 per cent for a set of basic standards of care, called the Sepsis Six, may save an estimated 10,000 lives each year in the UK. They suggest it would also save £160 million for the NHS, through reduced time spent in critical care units and hospitals in general, and through reduced litigation costs.
In the UK, we are more involved than ever before in our health. We pay attention to public health campaigns, wear ribbons, shave heads, and donate to research in ever increasing numbers. September 13 is World Sepsis Day, organized by the Global Sepsis Alliance to raise awareness for medical professionals and public alike. It is time to pay attention to sepsis: to know the symptoms, fund the research, and give our family, friends and patients the best possible chance of survival.
Dr Anne Fletcher
Research Fellow, School of Immunity and Infection, University of Birmingham