Program Schedule

Diagnostic Performance of a Multiplex PCR Assay for Meningitis in an HIV-Infected Population in Uganda

Session: Poster Abstract Session: Diagnostic Microbiology: Viruses/Fungal/AFB/Parasitic
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • Rhein_FilmArray_IDSA 2014 Poster.pdf (483.7 kB)
  • Background: Meningitis remains a worldwide problem, and rapid diagnosis is essential to optimize survival. Delay in diagnosis leads to excess morbidity, mortality and healthcare costs related to unnecessary empiric treatment and isolation procedures.

    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.

    Joshua Rhein, MD1,2, Joann Cloud3, Andrew Hemmert, PhD3, Nathan Bahr, MD2, Satya Bellamkonda3, Cody Oswald3, Eric Lo3, Henry Nabeta, MBChB4, Reuben Kiggundu, MBChB1, Andrew Akampurira5, Darlisha Williams, MPH6, David Meya, MMed6 and David Boulware, MD, MPH6, (1)Infectious Disease Institute, Makerere University, Kampala, Uganda, (2)Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN, (3)BioFire Diagnostics, LLC, Salt Lake City, UT, (4)Infectious Diseases Institute,, Makerere University, Kampala, Uganda, (5)Infectious Diseases Institute, Makerere University, Kampala, Uganda, (6)Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN


    J. Rhein, None

    J. Cloud, BioFire Diagnostics, LLC: Employee, Salary

    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

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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