Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population
Open accessAbstract
Background Meningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire® FilmArray® Meningitis/Encephalitis multiplex PCR panel (BioFire ME) in HIV-infected adults and HIV-infected and uninfected children presenting with suspected meningitis in Uganda.Methods We tested cerebrospinal fluid (CSF) using a stepwise meningitis diagnostic algorithm including BioFire ME. We determined the diagnostic performance of BioFire ME for cryptococcal meningitis, using cryptococcal antigen (CrAg) and CSF culture as reference standards, and assessed other central nervous system (CNS) pathogens identified by the panel.Results We evaluated 328 adult and 42 pediatric CSF specimens using BioFire ME. Of the adult CSF samples tested, 258 were obtained at baseline, and 70 were obtained from repeat lumbar punctures in cryptococcal meningitis. For Cryptococcus, sensitivity was 82%, specificity was 98%, PPV was 98%, and NPV was 79% in baseline specimens using CSF CrAg as the reference standard. Among follow-up specimens, a negative BioFire ME for Cryptococcus predicted CSF culture sterility with 84% NPV. Overall sensitivity was decreased at low fungal burdens: 29% for 0-99 Cryptococcus CFU/mL compared to 94% for ≥100 CFU/mL in baseline specimens. Other pathogens detected included E. Coli, H. influenzae, S. pneumoniae, CMV, enterovirus, HSV, HHV-6, and VZV. Two specimens tested positive for S. pneumoniae and one for Cryptococcus in the pediatric population.Conclusions Multiplex PCR is a promising rapid diagnostic test for meningitis in adults and children in resource-limited settings. Cryptococcus at low fungal burdens in CSF may be missed by BioFire ME.
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Very few studies on FA-ME clinical utility were conducted in low-resource settings.
“Moreover, very few of these studies were conducted in LRS [22, 23].”
From Clinical utility of the FilmArray® meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting – a prospective study in Southwestern Uganda (2025) · cites this paper as [22]
The Discussion (page unavailable) calls this study among the first to evaluate multiplex PCR meningitis testing in children in a resource-limited setting. The Introduction (page unavailable) says such testing is emerging in low-income countries. These passages support the idea that studies in these settings were uncommon, but the explicit rarity statement is limited to pediatric testing, not FA-ME clinical-utility studies generally. (LLM, conf=0.79)
Experimental — accuracy not yet measuredFalse positive streptococcal and false negative Herpes simplex virus 1/2 and C. neoformans/gatii detections by FA-ME have been previously reported.
“False positive streptococcal and false negative Herpes simplex virus 1/2 and C. neoformans/gatii detections have been previously reported [13, 18, 22, 37].”
From Clinical utility of the FilmArray® meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting – a prospective study in Southwestern Uganda (2025) · cites this paper as [22]
The Results (Adult Cohort; page unavailable) report 27 false-negative BioFire ME results for Cryptococcus, and the Discussion describes previously reported missed cryptococcal meningitis. The paper does not establish false-positive streptococcal or false-negative HSV-1/2 detections; its Statistical analyses section says no reference standards were used to confirm pathogens other than Cryptococcus. (LLM, conf=0.88)
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- Authors
- Bridge, S., Hullsiek, K. H., Nerima, C., Evans, E. E., Nuwagira, E., Stadelman, A. M., Tran, T., Kim, G., Tadeo, K. K., Kwizera, R., Mwesigye, J., Ellis, J., Cresswell, F. V., Meya, D. B., Muzoora, C., Boulware, D. R., & Rhein, J.
- Affiliations
- University of Minnesota (US)
- Mbarara University of Science and Technology (UG)
- University of Virginia (US)
- Infectious Diseases Institute (UG)
- Hospital for Tropical Diseases (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Bridge, Sarah
- Boulware, David R.
- ORCID
- Venue
- Journal of Medical Mycology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 31
- Issue
- 3
- Pages
- 101170
- ISSN
- 1156-5233 (ISSN-L)
- PMC
- PMC9983612
- OpenAlex
- W3174169320
- Cited by
- 38
- References
- 20
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 11 · 2023: 9 · 2022: 7
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal de Mycologie Médicale (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS086312)
- Wellcome Trust (107742/Z/15/Z)
- National Institute of Allergy and Infectious Diseases (T32AI055433)
- Doris Duke Charitable Foundation
- European Commission
- Department for International Development, UK Government
- Makerere University
- African Academy of Sciences
- Medical Research Council
- Government of the United Kingdom (107743, 210772/Z/18/Z)
- New Partnership for Africa's Development
- John E Fogarty International Center (K01TW010268, R25TW009345)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- multiplex PCR, cryptococcal meningitis, cerebrospinal fluid, cryptococcal antigen, sensitivity and specificity, HIV-infected adults, pediatric meningitis, fungal burden, resource-limited settings, Uganda
- MeSH terms
- Adult, Child, Encephalitis, Escherichia coli, Humans, Meningitis, Uganda, Meningitis, Cryptococcal, Multiplex Polymerase Chain Reaction
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