In a recent JAMA Network Open study, researchers explore whether a point-of-care immunoassay called FebriDx could differentiate between bacterial and virus-induced immune responses during acute respiratory infections based on myxovirus resistance protein A (MxA) and C-reactive protein. CRP) from finger prick blood samples.
Study: Diagnostic accuracy of a point-of-care test of bacterial and viral biomarkers in the ambulatory setting. Image credit: Illustration Forest / Shutterstock.com
background
Most outpatient visits in the United States are associated with acute respiratory infections such as pneumonia, sinusitis, pharyngitis, and bronchitis. These respiratory infections can be bacterial or viral in nature or non-infectious, and it is often difficult to identify the etiological agent. Diagnostic uncertainty leads doctors to overprescribe antibiotics to rule out possible bacterial infections and prevent sepsis, thus contributing to antibiotic resistance.
An accurate diagnostic test could help prescribe the correct drugs and prevent the misuse of antibiotics. The FebriDx Bacterial and Viral Diagnostic Test is a 10-minute point-of-care immunoassay that can measure MxA and CRP levels from finger-prick blood samples and distinguish between viral and bacterial respiratory infections.
CRP levels are nonspecific indicators of inflammation and infection, while MxA levels are modulated by type 1 interferons secreted in response to viral infections. Therefore, elevated CRP levels without an increase in MxA levels would indicate a bacterial infection.
Although the principles underlying the FebriDx test are logical, the ability of the test to differentiate between bacterial and viral respiratory infections needs to be verified.
About the study
The prospective, blinded observational study included participants aged 1 to 21 years, 22 to 64 years, and 65 years or older who presented to outpatient clinics with fever and clinical symptoms of acute respiratory infections such as nasal congestion, cough , sore throat and rhinorrhea. .
A matched control group with no signs or symptoms of infection was also included. Individuals on antiviral medications, antibiotics, live immunization, interferon therapy, immunosuppression, major surgery, or myocardial infarction were excluded from the study.
Fingerstick blood samples were collected from all study participants. In addition, comparative tests were performed to conclusively classify the disease as a bacterial or viral infection.
Comparison tests included multiplex polymerase chain reaction (PCR) testing of oro- and nasopharyngeal swabs for a panel of respiratory infections, as well as quantitative real-time PCR (RT-qPCR) for several viruses, including herpes simplex, Epstein-Barr viruses. virus, gonorrhea virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
PCR tests for Fusobacterium necrophorum and human bocavirus were also performed. In addition, complete blood counts and serum levels of calcitonin and anti-Epstein Barr immunoglobulin M (IgM) antibodies were also measured.
Participants were followed up after seven days to confirm the diagnosis. Test performance was also analyzed based on the demographic factors of sex, race, and ethnicity. Based on the comparator algorithm, diagnostic accuracy was calculated by comparing the FebriDx results to the final diagnosis.
Results of the study
A sensitivity of 93.2% and a negative predictive value of 98.7% were reported for FebriDx to detect and rule out bacterial infections. Comparatively, the assay was associated with 88% specificity and 89.7% positive predictive value for detecting viral respiratory infections compared to the results of the comparator algorithm.
FebriDx confirmed bacterial infections with a negative predictive value and 100% sensitivity, thus indicating its potential to guide antibiotic treatment. The low positive predictive value of 58.1% for bacterial infections could be attributed to overprescription of antibiotics. However, use of the diagnostic test showed a 2.4:1 decrease in antibiotic prescriptions based on accurate clinical diagnoses.
Because CRP levels are not specific for bacterial infections and are increased during infections with viruses such as influenza and SARS-CoV-2, it is not a reliable indicator of bacterial infections. On the other hand, the elevation of MxA proteins during viral infections makes the comparative levels of CRP and MxA a more reliable indicator for detecting bacterial and viral infections.
Simultaneous detection of MxA and CRP levels was found to diagnose bacterial and viral respiratory infections with a specificity range of 76–94% and 80–95%, respectively.
Conclusions
The current study investigated the accuracy and sensitivity of the FebriDx point-of-care immunoassay for distinguishing between bacterial and viral respiratory infections from fingerstick blood samples.
To this end, this immunoassay achieved the pre-specified criteria for the successful detection of host immune responses induced by bacteria or viruses. In addition, FebriDx could conclusively rule out bacterial infections, thereby eliminating the need for unnecessary antibiotic prescriptions.
Increasing the rate of accurate diagnoses through the use of FebriDx can help reduce adverse reactions and the development of antibiotic resistance in bacteria.
Journal reference:
- Shapiro, NI, Filbin, MR, Hou, et al. (2022). Diagnostic accuracy of a point-of-care test of bacterial and viral biomarkers in the ambulatory setting. JAMA Network Open 5(10), e2234588. doi:10.1001/jamanetworkopen.2022.34588.