Diagnostic Performance of a Multiplex PCR Assay for Meningitis in an HIV-Infected Population in Uganda
Methods: From January-April 2014, cerebrospinal fluid (CSF) from 39 HIV-infected persons with suspected meningitis in Kampala, Uganda was collected at time of diagnosis (n=18) and among persons with cryptococcal meningitis at therapeutic lumbar punctures (n=53). Standard bacterial, mycobacterial and fungal CSF diagnostics were performed on site. Cryopreserved CSF specimens (200 mcL) were then analyzed on the FilmArray™ System using a Meningitis/Encephalitis PCR panel (BioFire Diagnostics, Salt Lake City, UT; research use only). The panel targets 16 common pathogens: 6 bacterial, 8 viral, and Cryptococcus neoformans/gattii speciation. Operators were blinded to microbiology results. We assessed the diagnostic performance of the panel.
Results: The FilmArray™ multiplex PCR panel detected Cryptococcus in the CSF of all patients diagnosed with a first episode of cryptococcal meningitis by quantitative fungal cultures (n=14) with 100% sensitivity and specificity. In second episodes, the FilmArray™ system was able to differentiate between fungal relapse (n=2) vs paradoxical immune reconstitution syndrome (IRIS) and/or sterile cultures (n=4). In patients receiving antifungal therapy, FilmArray™ predicted follow up culture sterility with 67% negative predictive value. The first possible case of C. gattii meningitis in Uganda was detected. EBV was frequently detected in this HIV-infected population regardless of whether or not they had active cryptococcal infection [77% with (n=35) and 100% without (n=4) cryptococcosis]. Other pathogens detected included CMV (n=3), HSV-2 (n=2), HHV-6 (n=2), VZV (n=1), Streptococcus pneumoniae (n=1).
Conclusion: The FilmArray™ multiplex PCR panel offers a promising platform for the rapid diagnosis of CNS infections. PCR testing appears to be particularly useful in cryptococcal disease, distinguishing species, predicting culture sterility, and differentiating IRIS from culture-positive cryptococcal relapse in patients with recurrent symptoms.
A. Hemmert, BioFire Diagnostics: Employee, Salary
N. Bahr, None
S. Bellamkonda, BioFire Diagnostics, LLC: Employee, Salary
C. Oswald, BioFire Diagnostics, LLC: Employee, Salary
E. Lo, BioFire Diagnostics, LLC: Employee, Salary
H. Nabeta, None
R. Kiggundu, None
A. Akampurira, None
D. Williams, None
D. Meya, None
D. Boulware, None
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