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New blood test could lead to better treatment for sepsis

Thursday 14 November 2019

"Blood test for sepsis could save lives of thousands of children," reports the Mail Online.

Researchers in the US have developed a test for 5 proteins, which they say allows them to identify people with sepsis who have a high, medium or low risk of dying from the condition. They hope this will eventually help doctors identify the best treatments for individual patients.

Sepsis, sometimes called blood poisoning, is when the body's immune system over-reacts to an infection, causing inflammation and damage to the body's own tissues and organs. Anyone with an infection can get sepsis, although it is more common in babies and people over 75.

One of the challenges in treating sepsis is that symptoms can develop and worsen extremely quickly. So, a test that can confirm a diagnosis of sepsis before this happens should help reduce the risk of serious complications and, in some cases, deaths.

The test is still experimental. However, early experiments in mice suggest people at a high risk of dying from sepsis might benefit from higher doses of antibiotics than would normally be given.

Sepsis is a medical emergency. Find out more about the symptoms and what to do if you think someone may have sepsis.

Where did the story come from?

The researchers who contributed to the study came from 16 institutions in the US, mainly children's hospitals. The research was led by Cincinnati Children's Hospital Medical Center. It was funded by grants from the US National Institutes of Health and Cincinnati Children's Hospital. The study was published in the peer-reviewed journal Science Translational Medicine.

The Mail Online did a good job of reporting a complicated study.

What kind of research was this?

The researchers carried out a series of experiments, testing children with sepsis and then experimenting on mice to explore the results further. This is early-stage experimental research that may one day result in better treatment, but there is much more research to be done.

What did the research involve?

In earlier experiments, researchers had identified 5 proteins created by the body during sepsis, plus a measure of platelets (components in blood that make clots). They hoped the test, called Persevere II, would work to predict who was at highest risk of dying from sepsis.

They used the test on 461 children admitted to hospitals with sepsis, and divided them into 3 groups – high, medium and low risk of death within 28 days. They then looked to see how accurately the test predicted what happened to the children. All children were treated as normal for sepsis in their admitting hospital.

The researchers then developed a mouse equivalent of the test, to see whether it would also predict survival in mice given sepsis in a laboratory experiment. They later investigated whether the higher-risk mice had more inflammation or more bacteria than low-risk mice. In 2 further experiments, they tested whether giving the high-risk mice steroids for inflammation, or higher-dose antibiotics to fight bacteria, changed their chances of survival. They also checked to see whether blocking 1 of the 5 proteins produced by the body and measured in the test affected the outcome.

Finally, researchers checked the results of the children with sepsis. They wanted to see if those classified as high risk by the Persevere II test were more likely to have had bacteria in their blood tests.

What were the basic results?

The researchers found the Persevere II test worked well to identify the risk level of children with sepsis. Almost all of the patients categorised as low risk survived, while just over half (55%) of those categorised as high risk survived. The test correctly identified as high risk 86% of those who did not survive (86% sensitivity) and correctly identified as low risk 69% of those who survived (69% specificity).

The test also worked well when predicting mice at high and low risk. Further experiments on mice showed high-risk mice had more signs of inflammation in the lungs and throughout the body as well as bigger colonies of bacteria from their infection.

Tests also showed that giving high-risk mice the anti-inflammatory drug dexamethasone or placebo made no difference to their survival, but they were more likely to survive if given high-dose antibiotics.

Mice given a drug to block 1 of the proteins used in the test were more likely to survive for 10 days, but the difference was small enough that the results could have come about by chance.

The researchers found that children who had been identified as high risk by the Persevere II test were more likely to have had bacteria cultured from their blood. While this is not a direct measure of the size of the bacteria colony, larger colony sizes are more likely to be able to be cultured after blood tests.

How did the researchers interpret the results?

The researchers said: "On the basis of our findings, we suggest that Persevere II might identify a subgroup of children with septic shock [sepsis] who will benefit most from targeted therapeutic drug monitoring to ensure optimal dosing of antibiotics."

Conclusion

Because little is known about why sepsis happens after some infections, and how exactly it develops, it is hard to develop new treatments. Treatments have stayed the same for many years, and sepsis is a life-threatening condition.

This study is the first for many years to make some progress in our understanding of sepsis. It opens up possibilities for research into potential drugs that could be used in the future. This study also suggests ways in which the Persevere II test could be used to identify people at high risk of life-threatening sepsis, so they can be treated quickly and with the most appropriate dose of antibiotics.

However, this is very early-stage research. Just because a treatment works for mice does not mean it will work for humans. Translating results from a species to another, as the researchers do in this study, does not always work. Higher-dose antibiotics have not been tested for children identified as at high risk of life-threatening sepsis. Higher than usual doses could have damaging effects.

The Persevere II test is still being worked on, so is not yet generally available for doctors to use. In a media interview, a researcher said it is about 2 years away from being made available.

Sepsis can be hard to spot. There are lots of possible symptoms.

Find out more about spotting the signs of sepsis.

Analysis by Bazian
Edited by NHS Website