Evaluating the Accuracy of Combining two Biomarkers to Differentiate Viral and/or Bacterial Immune Response in Patients with Acute Febrile Respiratory Infection
To determine the accuracy of combining two biomarkers, C-reactive protein (CRP) and Myxovirus A (MxA), to identify an immune response to viral and/or bacterial infection in patients presenting with suspected pharyngitis or lower respiratory tract infection (LRTI) as compared to confirmatory microbiological, radiological, and laboratory testing.
A prospective single center, blinded, clinical feasibility trial was performed at Beth Israel Deaconess Medical Center – a Harvard Medical School teaching hospital – from December 2012-August 2013. Patients with presumed acute febrile respiratory infection consistent with suspected pharyngitis or LRTI were enrolled, as well as age matched controls. Qualifying patients with a clinical diagnosis of pharyngitis or LRTI had oropharyngeal samples sent for viral respiratory polymerase chain reaction (PCR) testing and routine bacterial cell culture. Patients with suspected LRTI also had sputum cultures and a chest x-ray. A venous blood sample was collected, WBC count measured, and an enzyme-linked immunosorbent assay (ELISA) was then used to measure CRP and MxA levels.
The study enrolled 60 patients, 23 with definitive microbiological confirmation of disease (8 enrolled with presumed pharyngitis and 15 with presumed LRTI) as well as 22 controls. The 15 remaining subjects had no definitive microbiological confirmation of disease. A low CRP cut off of 15 mg/L and high CRP cut off of 80 mg/L combined with the presence or absence of MxA levels greater than 40 ng/ml, led to the correct identification of a combined total of 95% (21/22) of the patients negative for infection, 93% (13/14) of bacterial infections, and 78% (7/9) of viral infections [Figure 1].
In isolation, neither CRP (elevated primarily in bacterial infection) nor MxA (elevated primarily in viral infection) alone is sensitive or specific at identifying both viral and/or bacterial infection. However, by simultaneously examining low and high levels of CRP, each in combination with the presence of elevated MxA, it is possible to successfully classify patients with bacterial versus viral etiology of infection. Further validation is warranted for this promising approach.
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