Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples
Johan Lindström1, Kristina Elfving2, Magnus Lindh3
1Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden; Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
Objectives:
In central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results.
Methods:
All cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens.
Results:
Altogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%-93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results.
Conclusions:
Our analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.
Insights
The FilmArray meningitis/encephalitis (ME) panel shows good performance for diagnosing central nervous system infections. However, potential false-negative results for herpes simplex virus type 1 (HSV-1) require further investigation in encephalitis cases.
Area of Science:
- Clinical microbiology
- Infectious disease diagnostics
- Molecular diagnostics
Background:
- Central nervous system (CNS) infections necessitate prompt and accurate diagnosis for effective management.
- Rapid syndromic panel testing offers a potential avenue for guiding clinical decisions.
- The FilmArray meningitis/encephalitis (ME) panel utilizes multiplex PCR to detect 14 common pathogens.
Purpose of the Study:
- To evaluate the performance of the FilmArray ME panel against established diagnostic methods, particularly real-time quantitative PCR for viral detection.
- To assess the diagnostic and clinical significance of any discrepancies observed between the ME panel and reference methods.
- To determine the accuracy of the ME panel for individual pathogens commonly found in CNS infections.
Main Methods:
- Cerebrospinal fluid (CSF) samples submitted for viral diagnostics were analyzed using both the ME panel and in-house real-time PCR for specific viruses (HSV-1, HSV-2, VZV, enteroviruses).
- Pathogens detected by the ME panel were confirmed using standard laboratory diagnostic procedures.
- Discrepant results were thoroughly investigated by analyzing biological and clinical data to ascertain accuracy.
Main Results:
- The ME panel detected 315 pathogens in 4199 CSF samples (7.5% prevalence), with an additional 21 viral targets identified by real-time PCR.
- A total of 55 discrepant results were noted, with 20 false-positive and 21 false-negative results remaining after analysis.
- Specific performance issues included a sensitivity of 82.4% for HSV-1 (with 3 false-negatives), 13 false-negative enterovirus results, and 8 false-positive Streptococcus pneumoniae results.
Conclusions:
- The FilmArray ME panel demonstrates good overall performance in the diagnosis of CNS infections.
- The observed risk of false-negative results for herpes simplex virus type 1 (HSV-1) indicates a need for supplementary testing when encephalitis is clinically suspected.
- Interpretation challenges with enterovirus and Streptococcus pneumoniae results highlight limitations that warrant consideration in clinical practice.
