Background

In 2017, the World Health Organisation designated sepsis a global health priority, which is unsurprising as in 2020 sepsis became the leading global cause of death. Estimated to be responsible for 20% of all-cause global deaths’ sepsis is ahead of cardiovascular disease and cancer. Even in countries with highly developed health care systems such as the UK and the US, there are over 50,000 and 250,000 sepsis related deaths a year, respectively, and an even greater number of sepsis survivors left with life altering injuries or after-effects. It is widely accepted that the chances of surviving sepsis increase with earlier diagnosis and yet a major impediment to improving sepsis survival rates remains - the lack of a fast, reliable diagnostic technology to identify a causative agent of infection. Reliance on slow, low-sensitivity culture methods means that patients are normally treated empirically, typically with broad-spectrum antimicrobials. Thus, patients may not receive timely intervention or the optimum treatment and care pathway, with consequences for infection outcome, as well as implications for the development and spread of antimicrobial resistance. A fast and reliable diagnostic test for the early detection of sepsis will therefore have a major impact on mortality and morbidity associated with the leading cause of death worldwide.

Technology Overview

-What is the technology?

This technology uniquely leverages the properties of liposomes as a key element of this diagnostic tool, to provide not only the identification of the causative agents of infection but a quantitative assessment of the infectious burden. This is because many bacterial pathogens produce protein toxins that bind to the lipid component of host cell membranes. Researchers use liposomes exploit this natural interaction to sequester bacterial toxins, such as the pneumococcal toxin Pneumolysin (PLY),the main virulence factor, from small volumes (~ 5 ml) of patient blood and liposome-bound toxin is detected using a patented detection technology (). Researchers have developed this technology for the detection of Streptococcus pneumoniae, Streptococcus pyogenes and MRSA toxins

The technology can be used to detect the infectious agent and quantify the infection burden for difficult to diagnose single disease states such as pneumococcal meningitis, which can be a cause of sepsis, or multiplexed to cover the major bacterial causative species of sepsis.

-How does the technology perform?

The technology has a number of critical performance advantages:

• Ultra-sensitivity essential for use in early stages of infection - detection of toxins as low as 5 ng/ml.
• Fast - the assay takes 60 minutes from collection of blood to diagnosis.
• Good specificity/sensitivity characteristics – in testing on CSF samples from patients with suspected pneumococcal meningitis (n=27) using the approach illustrated above, specificity of 85.7% and sensitivity of 80% was achieved.
• Inexpensive and uses standard laboratory equipment

Further development to achieve this performance level in a multiplex test would provide a best in class, rapid, sensitive and selective diagnostic test for the early detection of sepsis and identification of the causative agent, leading to faster and more effective treatment and reducing the contribution to accelerating antibiotic resistance from unnecessary or ineffective treatments.

Benefits

-How is our technology better than what is currently available?

Blood culture remains the gold standard for identification of bacterial species, but it takes too long and suffers from low sensitivity. Inflammation markers may rise during early stages of sepsis, but many inflammatory conditions cause CRP to rise and hence this is not specific. A meta-analysis of procalcitonin testing as an indicator of sepsis showed a mean specificity of 79% and selectivity of 77% but these results must be carefully interpreted as it can falsely identify low procalcitonin in localised infections and tissue injuries of any kind can elevate procalcitonin levels even without infection.

There are several Molecular assays – such as multiplexed PCR, but this is likely to be replaced by sequencing. The disadvantage is the sample needs extensive processing to prepare the DNA for amplification. Manual kits (SeeGene) are an excessive workload for routine labs and automation is expensive. Testing blood culture is too slowand requires high microbial load or processing of larger volumes. T2 Biosystems have an assay but this requires a bespoke instrument.

The advantages of our assay is that it is quick, less than 1 hour turn around, it is highly sensitive, can measure very low levels of bacterial toxin (5ng/ml), it is inexpensive to run, and uses a simple methodology and standard laboratory instrumentation. Most importantly, our assay can identify the infecting bacterial species. The fact that it is a direct detection assay of bacterial toxin rather than acting as a biomarker of systemic infection also means that there are less potentially confounding clinical factors than with tests such as procalcitonin and other sepsis-related biomarkers.

Opportunity

The university are seeking a Licensee with the expertise in assay development and obtaining the associated regulatory approvals to develop this technology into a kit suitable for use in clinical diagnostic laboratories.