Rapid Test Predicts Sepsis Soon After Infection and Before Organ Damage

In the clinic, sepsis is diagnosed by a symptom-based approach that may include kidney or liver failure, blood clotting or bleeding - which often occurs well after permanent organ damage. Thus, molecular diagnostics that detect infection at early stages of disease to minimize host injury are sorely needed. In a potential paradigm change for sepsis diagnostics, a new test predicted sepsis soon after infection in mice - well before blood clotting and organ failure - enabling early antibiotic treatment and markedly increased survival.

The findings of the collaborative study led by scientists from UC Santa Barbara (Santa Barbara, CA, USA) provide a platform to develop rapid and easy-to-perform clinical tests for early sepsis detection and clinical intervention in human patients. The team succeeded in detecting a catastrophic shift in blood protein abundance soon after infection that can predict sepsis well before disease symptoms and organ damage arise. To carry out the test, a small amount of blood was collected and analyzed for an increase in coagulation proteins that are induced but inactive at early stages of infection. Such detection enabled early antibiotic treatment - well before activated coagulation proteins induced blood clotting - resulting in markedly increased survival in mice. The technology is open source and freely accessible to all.

The study also demonstrated that antibiotics are less effective after blood proteins increase in response to infection. Treatment failure may be due to host injury triggered by excessive blood clotting, providing insight into why delays in antibiotic treatment in human sepsis are associated with increased risk for death. The researchers demonstrated that the changes in blood proteins soon after infection observed in mice were similar to that reported for human sepsis. Thus, they are optimistic that these findings are translatable for the early detection and treatment of sepsis in humans.

“The key finding was identifying proteins in the blood that arise very soon after infection - well before overt disease symptoms,” said professor Michael Mahan of UC Santa Barbara, who led the project. “Early detection is critical for clinical intervention to increase survival in sepsis patients.”

“The future plan is to identify a biopanel of early sepsis blood proteins for incorporation into existing blood tests, enabling sepsis prediction well before excessive blood clotting and permanent organ damage,” explained UCSB scientist Douglas Heithoff who was a part of the research team.

“Currently, one in four patients die of sepsis, with many survivors experiencing lifelong debilitation with cognitive decline,” added UCSB scientist Scott Mahan who participated in the project. “We hope technologies like this offer new ways of delivering state-of-the-art molecular diagnostics that predict sepsis before permanent injury occurs.”

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