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

Tee, Ling Fei; Tan, Toh Leong; Neoh, Hui-min; Jamal, Rahman

doi:10.1590/0037-8682-0300-2018

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Short Communication • Rev. Soc. Bras. Med. Trop. 52 • 2019 • https://doi.org/10.1590/0037-8682-0300-2018 linkcopy

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

Authorship SCIMAGO INSTITUTIONS RANKINGS

INTRODUCTION The nematode Caenorhabditis elegans was used as a biological sensor to detect the urine of sepsis patients (CESDA assay).

METHODS C. elegans was aliquoted onto the center of assay plates and allowed to migrate towards sepsis (T) or control (C) urine samples spotted on the same plate. The number of worms found in either (T) or (C) was scored at 10-minute intervals over a 60-minute period.

RESULTS The worms were able to identify the urine (<48 hours) of sepsis patients rapidly within 20 minutes (AUROC=0.67, p=0.012) and infection within 40 minutes (AUROC=0.80, p=0.016).

CONCLUSIONS CESDA could be further explored for sepsis diagnosis.

Keywords:
Sepsis; C. elegans; Chemotaxis assay; C. elegans Sepsis Detection Assay (CESDA)

Worm location, time	CESDA Index and AUROC
	Sepsis				Infection
	Median ± SD		AUROC^a (95%CI)		Median ± SD		AUROC (95%CI)
	24 hours	48 hours	24 hours	48 hours	24 hours	48 hours	24 hours	48 hours
Quadrant, 10 min	0.095±0.271	0.098±0.256	0.62 (0.41-0.84)	0.60 (0.44-0.77)	0.095±0.272	0.095±0.254	0.57 (0.38-0.77)	0.66 (0.49-0.82)
Quadrant, 20 min	0.053±0.204	0.076±0.206	0.65 (0.39-0.92)	0.59 (0.41-0.78)	0.037±0.227	0.053±0.221	0.60 (0.37-0.83)	0.62 (0.43-0.81)
Quadrant, 30 min	0.123±0.250	0.133±0.249	0.56 (0.32-0.79)	0.62 (0.47-0.78)	0.0133±0.258	0.123±0.251	0.65 (0.47-0.83)	0.59 (0.41-0.77)
Quadrant, 40 min	0.123±0.243	0.132±0.242	0.53 (0.28-0.78)	0.64 (0.43-0.84)	0.137±0.2445	0.123±0.239	0.70 (0.46-0.95)	0.55 (0.37-0.74)
Quadrant, 50 min	0.179±0.242	0.140±0.254	0.62 (0.35-0.89)	0.61 (0.41-0.81)	0.180±0.266	0.137±0.278	0.78 (0.62-0.95)	0.60 (0.40-0.81)
Quadrant, 60 min	0.207±0.250	0.197±0.281	0.59 (0.32-0.87)	0.61 (0.43-0.79)	0.208±0.290	0.194±0.304	0.73 (0.52-0.93)	0.58(0.38-0.77)
Point, 10 min	0.143±0.508	0.219±0.498	0.52 (0.30-0.74)	0.45 (0.26-0.64)	0.165±0.510	0.224±0.494	0.55 (0.35-0.75)	0.45 (0.23-0.67)
Point, 20 min	0.444±0.390	0.452±0.390	0.69 (0.43-0.95)	0.67 (0.46-0.89)	0.402±0.403	0.360±0.399	0.73 (0.41-1.00)	0.63 (0.32-0.94)
Point, 30 min	0.458±0.417	0.457±0.406	0.59 (0.34-0.85)	0.61 (0.41-0.81)	0.463±0.410	0.458±0.394	0.72 (0.46-0.98)	0.70(0.47-0.93)
Point, 40 min	0.508±0.397	0.504±0.388	0.60 (0.36-0.85)	0.66 (0.47-0.86)	0.523±0.384	0.508±0.371	0.76 (0.50-1.00)	0.80*(0.60-1.00)
Point, 50 min	0.577±0.360	0.567±0.405	0.67 (0.44-0.90)	0.56 (0.36-0.77)	0.567±0.365	0.577±0.395	0.70 (0.43-0.96)	0.61 (0.33-0.88)
Point, 60 min	0.524±0.350	0.500±0.391	0.73 (0.52-0.93)	0.64 (0.46-0.83)	0.530±0.358	0.364±0.565	0.82*(0.66-0.97)	0.82*(0.68-0.95)

CESDA	CESD	AUROC	Sn, %	Sp, %	PPV, %	NPV, %	PLR,	NLR,	Acc	Kappa	p*
index for worms found at	A index		(95%CI)	(95%CI)	(95%CI)	(95%CI)	(95%CI)	(95%CI)			(Fisher’s
“point” location	Cut off										Exact Test)
Urine < 48hours (n=45)
Sepsis at 20 min	0.100	0.67	79	64	87	50	2.2	0.3	75.6	0.39	0.012*
			(62-91)	(31-89)	(75-94)	(31-69)	(1.0-4.9)	(0.2-0.7)
Infection at 40 min	0.232	0.80	85	67	94	40	2.5	0.2	82.2	0.40	0.016*
			(69-94)	(22-96)	(84-98)	(21-63)	(0.8-7.9)	(0.1-0.6)
Urine < 24hours (n=36)
Sepsis at 20 min	0.100	0.69	79	71	92	46	2.8	0.29	77.8	0.42	0.018*
			(60-92)	(29-96)	(78-97)	(26-66)	(0.9-9.1)	(0.1-0.7)
Infection at 40 min	0.350	0.76	72	75	95.8	25	2.9	0.4	72.2	0.53	0.098
			(53-86)	(19-99)	(81-99)	(13-42)	(0.5-16.0)	(0.2-0.8)

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[TFN1] ^a
AUROC: area under the receiver operating characteristic curve. *indicates good accuracy (AUROC ≥ 0.80).