Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

Abstract

BackgroundChallenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed.Methods and findingsA prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection.ConclusionsThe interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.

FebriDx®: A Rapid Diagnostic Test for Differentiating Bacterial and Viral Aetiologies in Acute Respiratory Infections

“…≥ 20 mg/L for CRP and ≥ 40 ng/mL for MxA), a corresponding (positive) line will appear in the results window [16,19]. These cut-off levels were selected to optimize the sensitivity and specificity of the combination to differentiate between viral and bacterial ARIs [33]. Whereas patients with ARI symptoms and a CRP level < 20 mg/L are likely to have a non-bacterial and/ or self-limiting infection, CRP levels ≥ 20 mg/L are associated with a clinically significant immune response; an MxA level ≥ 40 ng/mL was established as a sensitive cut-off for identifying viral infections [33][34][35].…”

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

“…FebriDx V R (RPS Diagnostics; Sarasota, FL) is a novel, single use disposable point-of-care (POC) diagnostic test designed to rapidly identify clinically significant host immune responses associated with bacterial and viral URIs and to assist with antibiotic prescribing decisions [8][9][10]. Within 10 minutes, FebriDx provides qualitative results for elevated serum levels of c-reactive protein (CRP) and myxovirus resistance protein A (MxA) [8,10]. CRP is an acute phase reactant that when elevated above 20 mg/L, is suggestive of a clinically significant infection, although it cannot differentiate viral or bacterial aetiology independently [11].…”

Acute phase protein response to viral infection and vaccination

“…Particularly, measurements of serum CRP levels have been recommended to distinguish between bacterial and viral diseases [94,95] in those pathologies resulting in febrile condition in children [96]. Immunoassay tests for myxovirus A (MxA) and CRP were the bases of a clinical diagnostic protocol to determine the bacterial or viral etiology of acute respiratory infections [97]. Higher blood levels of CRP can be used to differentiate between bacterial and viral gastrointestinal infection [98,99] and therefore avoiding unnecessary antibiotic therapy.…”