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bioRxiv · 10.1101/144873

Rapid Detection of Sepsis using CESDA: the Caenorabditis elegans Sepsis Detection Assay

Tee, L. F.·Tan, T. L.·Neoh, H.-m.·Jamal, R.
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Abstract

Sepsis is a life-threatening condition which could be alleviated by rapid diagnosis and appropriate antibiotic administration. However, currently available laboratory tests for sepsis diagnosis lacks sensitivity and specificity; they also have long turn-around times. In this proof-of-concept study, the nematode Caenorhabditis elegans was used as a biological sensor to detect urine of sepsis patients in an assay designated as the C. elegans Sepsis Detection Assay (CESDA). From January to June 2016, 45 patients who were admitted to the Emergency Department of a university hospital due to suspected sepsis were included into the study. Urine samples were obtained from these patients and healthy controls and spotted onto CESDA assay plates. Subsequently, C. elegans were aliquoted onto the centre of the plates and allowed to migrate freely. Number of worms found in either spots or quadrants of the plates containing control or suspected sepsis samples were scored in 10 minute intervals in a 60-minute duration. The CESDA index was then calculated for each sample, where an index near +1 represented attraction of the worms towards the sample, while an index near -1 signified repulsion. Confirmatory diagnosis for suspected sepsis samples was determined using a combination of clinical criteria assessment and standard laboratory protocols. All patients who were positive for sepsis were found to have a CESDA index of > 0.1 (positive predictive value, PPV [≥]87%). In addition, the worms were able to differentiate urine of sepsis patients from control as early as 20 minutes (p=0.012). Interestingly, the assay was also able to identify infection within 40 minutes of the test (AUROC = 0.80, p= 0.016). The rapidity of CESDA in sepsis and infection identification as well as the usability of urine samples which are non-invasive towards the patient in this method makes it an interesting protocol to be further explored for sepsis diagnosis.

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Tee, L. F., Tan, T. L., Neoh, H.-m., Jamal, R.. 2017-06-12. Rapid Detection of Sepsis using CESDA: the Caenorabditis elegans Sepsis Detection Assay. https://doi.org/10.1101/144873

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