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Introduction

Central nervous system infections (CNSI), including meningitis and encephalitis, represent significant causes of morbidity and mortality worldwide^[1,2,3]. Often, the early clinical symptoms are nonspecific, which pose a diagnostic challenge for clinicians especially in resource-limited settings. To prevent severe complications and death from CNSI, timely and accurate detection and characterization of pathogens through laboratory testing are crucial.

In recent years, diagnostics in infectious diseases have transitioned from conventional methods to novel technologies that utilize molecular assays capable of identifying presence of pathogens within hours^[4]. The first commercial multiplex polymerase chain reaction (PCR) tool for microbial detection---known as the BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel (BioFire Diagnostics, Salt Lake City, Utah)---was introduced in 2015, which allowed for the simultaneous detection of 14 pathogens from CSF samples. These include 6 bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, Escherichia coli), 7 viruses (Herpes simplex virus 1 [HSV1], Herpes simplex virus 2 [HSV2], Varicella Zoster virus [VZV], Cytomegalovirus [CMV], Human herpesvirus 6 [HHV6], Human Parechovirus [HPeV], and Enterovirus), and 1 yeast (Cryptococcus neoformans/gattii). Studies have demonstrated the ME Panel’s ability to reduce time to diagnosis (TTD) and comparable detection of CNS pathogens with traditional methods such as cultures that have slow turnaround times. Various studies have assessed the diagnostic accuracy of the ME panel against culture studies, showing an overall agreement rate ranging from 93% to 99% along with high sensitivity and specificity^[5]. Moreover, the ME panel only requires approximately 200 microliter (uL) of CSF specimen^[6], thereby potentially avoiding the challenges of multiple assays. Over the years, the ME panel has been increasingly used worldwide due to its clinical utility in diagnosing CNSI.

Previous meta-analyses on commercial ME panels were predominantly drawn from studies conducted in high-income or upper-middle-income countries^[7,8]. While the adoption of this technology has expanded globally, data on the clinical utility of the ME panel in low-income and lower-middle-income countries remain scarce^[9]. This is particularly concerning given that the burden of CNSI is significantly higher in these regions due to factors such as denser living conditions, lower vaccination coverage, and higher prevalence of co-existing health conditions. The lack of robust data from these healthcare settings presents a critical gap in understanding the full potential and challenges of implementing ME panels where they are most needed. This study aims to expand the evidence base by including studies from a broader range of geographic and economic settings, assessing the ME panel's diagnostic accuracy across diverse healthcare environments. As technological advancements and pathogen dynamics continue to evolve, an updated analysis could provide valuable insights into optimizing the use of ME panels for CNSI in a wider array of healthcare contexts.

Given the importance of accurate and timely diagnosis in the management of CNSI, it is essential to explore and assess the effectiveness of both traditional and modern diagnostic methods. Understanding how these methods perform in different clinical settings, especially where resources are limited, is crucial for improving the delivery of care.

Objectives

The primary objective of this study is to provide an updated and comprehensive analysis of the diagnostic accuracy of the commercial multiplex ME panel for each pathogen across diverse healthcare settings. Additionally, it seeks to fill gaps in existing research by incorporating data from low- and lower-middle-income countries, where the burden of CNS infections is greater, and where the implementation of ME panels may face distinct challenges. This expanded approach will offer a more complete understanding of the ME panel’s performance in both resource-rich and resource-limited environments.

Materials and Methods

Protocol

A detailed presentation and description of selected articles used in this review were outlined in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Eligibility Criteria

The researcher applied specific inclusion criteria to ensure the relevance and quality of the selected studies. Articles were included if they met the following conditions: (1) they focused on the utilization of cerebrospinal fluid (CSF) in healthcare settings, such as hospitals, (2) employed molecular methods for the identification of microbial pathogens, (3) involved in vivo or in vitro studies, (4) were full-text publications, and (5) were written in English. Conversely, studies were excluded if they did not take place in healthcare environments, lacked molecular analysis, or were published in languages other than English. No restrictions were imposed on the year of publication, allowing for a comprehensive review of the literature across all time periods. This approach was designed to capture the most relevant and methodologically sound research on the topic.

Information sources, Search Strategy, and Selection Process

In September 2024, a comprehensive electronic search in PubMed, Web of Science, and Embase was performed using keywords such as (CNS infection) (Meningitis/ Encephalitis Panel) (FilmArray) (BioFire) (PCR) OR (culture) AND (CSF) following the PRISMA protocol (Figure 1). The search was restricted to studies investigating CNSI using the BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel. The inclusion criteria encompassed both in vivo and in vitro studies published in English. Non-English papers and studies that did not meet the predefined criteria were excluded. The database search identified 2022 articles potentially applicable for the analysis. After eliminating all duplications, 67 articles were screened. The researcher excluded 44 articles as the articles did not focus on the topic of this review. In total, 23 articles were then subjected to a full-text analysis.

Results

There were a total of 2,022 articles screened, of which 23 were included in the quantitative synthesis (Figure 1). The main characteristics of the included studies are summarized in Table 1. The diagnostic performance of the BioFire ME panel shows notable variability across different pathogens, reflecting both its strengths and limitations in clinical use.

Table 1. Summary of studies included in the meta-analysis (Part 1)

Risk of Bias

Shows the risk of bias and applicability concerns in all studies included. The four key domains of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was applied ^[10] (Figure 4).

Discussion

Overall, the ME Panel consistently demonstrated strong diagnostic capabilities, particularly for viral pathogens, with both sensitivity and specificity often exceeding 90%.

Conclusion

The BioFire® FilmArray® ME Panel demonstrates high diagnostic accuracy, particularly for viral pathogens.

Conclusions

This section is not mandatory, but can be added to the manuscript if the discussion is unusually long or complex.

Conflict of Interest

The authors declare no conflict of interest.

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