Sarah Bridge1, Kathy Huppler Hullsiek2, Carol Nerima3, Emily E Evans4, Edwin Nuwagira3, Anna M Stadelman4, Tu Tran4, Grace Kim5, Kiiza K Tadeo6, Richard Kwizera6, James Mwesigye3, Jayne Ellis7, Fiona V Cresswell8, David B Meya6, Conrad Muzoora3, David R Boulware9, Joshua Rhein10. 1. Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda; University of Minnesota, 689 23rd Ave SE, Minneapolis 55455, MN, United States; University of Virginia, Charlottesville, VA, United States. Electronic address: sarahbridge.md@gmail.com. 2. University of Minnesota, 689 23rd Ave SE, Minneapolis 55455, MN, United States. 3. Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda. 4. Mbarara University of Science and Technology, P.O Box 1410, Mbarara, Uganda; University of Minnesota, 689 23rd Ave SE, Minneapolis 55455, MN, United States. 5. University of Virginia, Charlottesville, VA, United States. 6. Infectious Disease Institute, College of Health Sciences, Makerere University, PO Box 22418, Kampala, Uganda. 7. Infectious Disease Institute, College of Health Sciences, Makerere University, PO Box 22418, Kampala, Uganda; Hospital for Tropical Diseases, University College London, NHS Foundation Trust, London, United Kingdom. 8. Infectious Disease Institute, College of Health Sciences, Makerere University, PO Box 22418, Kampala, Uganda; Clinical Research Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E, 7HT, United Kingdom; UVRI-MRC London School of Hygiene and Tropical Medicine Research Unit, Entebbe, Uganda. 9. University of Minnesota, 689 23rd Ave SE, Minneapolis 55455, MN, United States. Electronic address: boulw001@umn.edu. 10. University of Minnesota, 689 23rd Ave SE, Minneapolis 55455, MN, United States; Infectious Disease Institute, College of Health Sciences, Makerere University, PO Box 22418, Kampala, Uganda.
Abstract
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.
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.
Authors: James Milburn; Kwana Lechiile; Keatlaretse Siamisang; Christopher G Williams; Leah Owen; Ezekiel Gwakuba; Tichaona Machiya; Tshepo Leeme; Hannah E Barton; Ronan Doyle; Mark W Tenforde; Madisa Mine; David M Goldfarb; Margaret Mokomane; Joseph N Jarvis Journal: Open Forum Infect Dis Date: 2022-05-17 Impact factor: 4.423
Authors: George R Thompson; David R Boulware; Nathan C Bahr; Cornelius J Clancy; Thomas S Harrison; Carol A Kauffman; Thuy Le; Marisa H Miceli; Eleftherios Mylonakis; M Hong Nguyen; Luis Ostrosky-Zeichner; Thomas F Patterson; John R Perfect; Andrej Spec; Dimitrios P Kontoyiannis; Peter G Pappas Journal: Open Forum Infect Dis Date: 2022-03-04 Impact factor: 4.423