The Science Behind the Accuracy

FebriDx® = 2 Biomarkers

FebriDx® produces a multiplexed result pattern combining C-reactive protein (CRP) and myxovirus resistance protein A (MxA).

Medical Professional with FebriDx

CRP is an acute phase inflammatory protein that is elevated in the presence of a bacterial infection. Bacterial infection is a potent stimulus of marked CRP elevation. CRP is elevated within 4-6 hours of onset and is correlated with the severity of the infection. Normal CRP is less than 3 mg/L.1 It has been demonstrated that 38-56% of patients with viral acute respiratory infections have CRP levels greater than 20 mg/L which may lead to unnecessary antibiotics being prescribed.2

MxA is an intracellular blood protein that is stimulated by interferon (IFN) alpha/beta cells.3 IFN cells are induced by viruses and form an essential part of the immune system’s defense against viral infections. MxA protein becomes elevated only in the presence of acute viral infections and not in bacterial infections.4

By combining a marker of bacterial infection, CRP, and a marker of viral infection, MxA, the dual biomarker technology of FebriDx® improves the sensitivity and specificity of both markers. Neither CRP nor MxA alone is sensitive or specific enough to differentiate viral from bacterial infections. At low levels, CRP is very sensitive but non-specific at confirming bacterial infection. At high levels, the reverse is true. MxA is specific for viral infections only and will not be elevated in the presence of a bacterial infection.

FebriDx® optimises the sensitivity and specificity of both markers to accurately and reliably differentiate between acute viral and bacterial respiratory infections.

Two prospective, multi-center clinical trials using FebriDx® demonstrated high sensitivity and specificity in differentiating clinically significant viral and bacterial ARIs. These studies reveal a greater accuracy for differentiating viral and bacterial infections than CRP or procalcitonin alone. FebriDx® has a 97-99% NPV to assist in ruling out a bacterial infection.2,12
Clinical Trial Chart

Acute respiratory infections (ARI) are routinely diagnosed and managed in GP settings solely by clinical symptoms and signs. However as viral and bacterial infections clinically present similarly this frequently leads to misdiagnosis and subsequent unnecessary antibiotic treatment. Reducing the diagnostic uncertainty may help identify those patients that will benefit from antibiotic treatment.

A FebriDx® test was performed on 21 patients (aged 3 years to 84 years) who had clinical diagnoses of an acute respiratory infection (upper or lower respiratory tract infection). In each case, a clinical diagnosis was initially made by the GP.

FebriDx® results altered the clinical management plan in 48% (10/21) of the patients tested including two patients that were clinically presumed viral infection that FebriDx® determined a bacterial infection and led to antibiotic therapy. Of note, one of these patients was admitted to the hospital with sepsis. Overall FebriDx® reduced unnecessary antibiotics in 80% (8/10) of clinical cases without any adverse events.

FebriDx® was concluded to have high sensitivity and specificity for identifying a clinically significant infection and differentiating viral from bacterial infection.13

Physician and girl

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2. Shapiro NI, Self WH, Rosen J, et al. 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. Ann Med. 2018;18:1-10.
3. Nakabayashi M, Adachi Y, Itazawa T, et al. MxA-based recognition of viral illness in febrile children by a whole blood assay. Pediatr Res. 2006;60:770-4.
4. Engelmann I, Dubos F, Lobert PE, et al. Diagnosis of viral infections using myxovirus resistance A (MxA). Pediatrics. 2015;135;e985-93.
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9. Kawamura M, Kusano A, Furuya A, et al. New sandwich-type enzyme-linked immunosorbentent assay for human MxA protein in a whole blood using monoclonal antibodies against GTP-binding domain for recognition of viral infection. J Clin Lab Anal. 2012;26:174-83.
10. Gendrel D, Rayond J, Coste J, et al. Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferonalpha for differentiation of bacterial vs. viral infections. Pediatr Infect Dis J. 1999;18(10):875-81.
11. Virkki R, Juven T, Rikalainen H, et al. Differentiation of bacterial and viral pneumonia in children. Thorax. 2002;57:438-41.
12. Self WH, Rosen J, Sharp SC, et al. Diagnostic accuracy of FebriDx: A rapid test to detect immune responses to viral and bacterial upper respiratory infections. J Clin Med. 2017;6(10):E94.
13. Davidson M. FebriDx point-of-care testing to guide antibiotic therapy for acute respiratory tract infection in UK primary care: A retrospective outcome analysis. J Infect Dis Preve Med. 2017;5:165.