# A post-implementation evaluation of BioFire FilmArray Meningitis/Encephalitis panel for pathogen detection in cerebrospinal fluid with a special focus on clinical significance of HHV-6

## TL;DR

This study evaluates a molecular test for detecting pathogens in cerebrospinal fluid and highlights the importance of proper interpretation, especially for HHV-6.

## Contribution

The study emphasizes the need for diagnostic stewardship to avoid misinterpretation of HHV-6 detection in CSF using syndromic panels.

## Key findings

- CSF specimens with elevated white cell count had higher NAAT-positive rates.
- HHV-6 was detected in 48 CSF specimens, often in immunocompromised individuals.
- Syndromic panels without stewardship may detect bystander pathogens like HHV-6.

## Abstract

Syndromic molecular testing for the diagnosis of infections has been advantageous given high sensitivity and rapid diagnostics; however, challenges remain with appropriate interpretation. A post-implementation evaluation of the cerebrospinal fluid (CSF) BioMerieux BioFire FilmArray Meningitis/Encephalitis panel in an adult and pediatric population was performed. The aims were to assess the prevalence and epidemiology of all targets and to correlate laboratory parameters with results from human herpesvirus 6 (HHV-6) detection in CSF to identify opportunities to apply diagnostic stewardship. A retrospective observational study was conducted on CSF Nucleic Acid Amplification Test (NAAT) results performed at a referral laboratory in Australia between 19 March 2022 and 31 July 2023. Laboratory data were extracted, with additional clinical data obtained for the HHV-6 positive subcohort. Of 1,490 CSF specimens identified, 287 (19.3%) had a positive NAAT. Non-neonate CSF specimens with white cell count (WCC) above the normal range had a higher proportion of NAAT-positive rates (35.3%) compared to those with WCC < 5 × 106 cells/L (6.5%) (P < 0.001). A positive NAAT result was detected in 90 (39.1%) specimens in neonates, with enterovirus and parechovirus detected most frequently. Concordance of bacterial and fungal targets and culture results was seen in 16 (33.3%) specimens. Forty-eight CSF specimens had HHV-6 detected, with a median age of 24.3 years (interquartile range: 0.5–58.7) at collection and 10 specimens with a documented immunocompromised status. This study highlights the caution required when utilizing syndromic diagnostic assays for the detection of CSF pathogens without associated diagnostic stewardship strategies and the potential utility of CSF WCC as a criterion for further review.

Utilization of molecular testing methods enables rapid and high-sensitivity diagnostics, which can have significant impacts upon clinical outcomes in meningitis and encephalitis. However, challenges remain with the interpretation of results when syndromic panels are used, such as with the detection of human herpesvirus 6 (HHV-6) in cerebrospinal fluid (CSF). This study aimed to evaluate the BioMerieux BioFire FilmArray Meningitis/Encephalitis panel for the detection of pathogens in CSF in an adult and pediatric population. Data demonstrated that performing CSF nucleic acid amplification testing without diagnostic stewardship strategies in place can be associated with increased detection of potential bystander pathogens, including HHV-6.