A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever

Figures & data

Table 1. Demographics.

			Gender		Race				Ethnicity
Presence of fever (observed hyperthermia)	Sample size	Age (years) (range; mean)	Females	Males	Asian	Black	White	Other	Hispanic	NonHispanic
Reported within last 3 days or exhibited on enrollment	220	2–86;	134	86	5	65	114	36	56	164
		36.8
Exhibited upon enrolment	121	2–86;	68	53	3	45	48	25	31	90
		36.9

Table 2. Reference standard results.

Reference standard classification criterion	n	Organisms detected
Bacterial	34
Throat culture positive for bacteria commonly causing pharyngitis and PCT ≥ 0.10 ng/ml	16	11 Group A Streptococcus
		2 Group A Streptococcus + rhinovirus
		2 Group C Streptococcus
		1 Group G Streptococcus
Throat culture positive for other bacteria and PCT ≥ 0.15 ng/ml	3	1 S. aureus
		2 S. aureus + F necrophorum
NP/OP PCR positive for atypical bacteria and PCT ≥ 0.10 ng/ml	8	5 F necrophorum
		2 Group A Streptococcus + F necrophorum
		1 F necrophorum + Group A
		Streptocoocus non A, C, G
Throat culture negative or contaminant, PCR negative, and PCT PCT ≥ 0.25 ng/ml	4	4 none
Throat culture negative or contaminant, PCR negative, and PCT between 0.15 ng/ml and 0.25 ng/ml, and WBC >15k or bands present	2	2 none
Physician panel over-read classified as bacterial after algorithm suggested negative	1	rhinovirus
Viral	124
NP/OP positive PCR for pathogenic virus	96	54 influenza A
		2 influenza A + rhinovirus
		3 influenza A + coronavirus
		1 influenza A + adenovirus
		19 influenza B
		1 influenza B + rhinovirus
		4 parainfluenza virus
		4 RSV
		5 hMPV
		3 adenovirus
NP/OP sample PCR positive for rhinovirus or coronavirus plus PCT ≥ 0.1ng/ml, WBC ≥ 10,000 cells/mcL, lymphocytosis ≥ 4000, or the presence of bands	14	6 rhinovirus
		7 coronavirus
		1 rhinovirus + coronavirus
Throat culture negative or contaminant, PCR negative or contaminant, and PCT between 0.15 ng/ml and 0.25 ng/ml and WBC < 15 k, and no bands present	11	6 none
		1 S. aureus
		4 Group B Streptococcus
Negative	62
Throat culture negative or contaminant, NP/OP PCR negative, and PCT < 0.15 ng/ml	33	33 none
Throat culture positive for bacteria commonly causing pharyngitis and PCT < 0.10 ng/ml	6	6 Group A Streptococcus
NP/OP sample PCR positive for rhinovirus or coronavirus plus PCT < 0.1ng/ml, WBC < 10,000 cells/mcL, lymphocytosis < 4000, and no presence of bands	10	6 rhinovirus
		1 rhinovirus + S. pneumococcus
		1 rhinovirus +1 H. parainfluenzae
		1 coronavirus
		1 coronavirus + H. parainfluenzae + S. aureus
Throat culture positive for other bacteria and PCT <  0.15 ng/ml	13	5 S. aureus
		2 Group B Streptococcus
		2 F. necrophorum
		1 R. planticola
		1 M. catarrhalis
		1 H. parainfluenzae
		1 Serratia Marcescens

Table 3. FebriDx performance values with and without hyperthermia at time of enrolment.

Sample size (n)	Confirmation of fever (Hyperthermia)	Diagnosis	Sensitivity % and [95% CI]	Specificity % and [95% CI]	PPV % and [95% CI]	NPV % and [95% CI]
220	Reported within last 3 days or exhibited on enrolment	Bacterial	85 (29/34) [69–95]	93 (183/196) [89–96]	69 ( 29/42 ) [56–79]	97 (183/188) [94–99]
		Viral	90 (111/124) [83–94]	76 (73/96) [66–84]	83 (111/134) [77–87]	85 (73/86) [77–90]
121	Exhibited on enrolment	Bacterial	95 (19/20) [77–100]	94 (95/101) [88–98]	76 (19/25) [59–87]	99 (95/96) [93–100]
		Viral	90 (72/80) [81–96]	78 (32/41) [62–89]	89 (72/81) [82–93]	80 (32/40) [67–89]

Table 4. FebriDx compared to other host protein and gene expression tests.

Device	Population	Sample size	Confirmed fever at time of testing (hyperthermia)	Non-febrile – reported fever within past 3 days	Bacterial sensitivity	Bacterial specificity	Bacterial positive predictive value	Bacterial negative predictive value	Time to results (minutes)	Citation
FebriDx Qualitative	Outpatient/ER	220	55% (121)	45% (99)	85%	93%	69%	97%	10	Current
MxA + CRP	Outpatient/ER	121	100% (121)	None	95%	94%	76%	99%	10	study
Standalone PCT 0.25 ng/ml	Outpatient	220	55% (121)	45% (99)	41%	94%	54%	90%	20
Standalone CRP 20mg/L	Outpatient	209	55% (115)	45% (94)	81%	51%	23%%	94%	5 to 30
FebriDx Qualitative MxA + CRP	Outpatient/ER	205	13% (26)	87% (179)	80%	93%	63%	97%	10	[8]
CRP + TRAIL + IP-10	Inpatient	124	96% (119)	4% (5)	91%	93%			120	[39]
Standalone CRP 20 mg/L	Inpatient	124	96% (119)	4% (5)	96%	58%			5 to 30	[39]
CRP + TRAIL + IP-10	Inpatient	443	100% (443)	0%	86.70%	91.10%	60.50%	97.80%	120	[40]
Standalone Procalcitonin 0.5 ng/ml	Inpatient	506	100% (506)	0%	85%	87.10%	51.70%	97.20%	5 to 30	[40]
CRP + TRAIL + IP-10	Inpatient	307	100% (361)	0%	93.80%	89.80%			120	[41]
Standalone PCT 0.5 ng/ml	Inpatient/ER	307	100% (307)	0%	63.10%	82.30%			20	[41]
Standalone CRP 40 mg/L	Inpatient/ER	307	100% (307)	0%	88.20%	73.20%			5 to 30	[41]
Gene expression	Inpatient	1057	100% (1057)	0%	94%	59.8	98.30%	29.20%	240 to 360	[42]

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