Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

Sarah Bridge; Kathy Huppler Hullsiek; Carol Nerima; Emily E. Evans; Edwin Nuwagira; Anna M. Stadelman; Tu Tran; Grace Kim; Kiiza K. Tadeo; Richard Kwizera; James Mwesigye; Jayne Ellis; Fiona V. Cresswell; David B. Meya; Conrad Muzoora; David R. Boulware; Joshua Rhein

doi:10.1016/j.mycmed.2021.101170

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

Sarah Bridge, Kathy Huppler Hullsiek, Carol Nerima, Emily E. Evans, Edwin Nuwagira, Anna M. Stadelman, Tu Tran, Grace Kim, Kiiza K. Tadeo, Richard Kwizera, James Mwesigye, Jayne Ellis, Fiona V. Cresswell, David B. Meya, Conrad Muzoora, David R. Boulware, Joshua Rhein

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English (US)
Article number	101170
Journal	Journal de Mycologie Medicale
Volume	31
Issue number	3
Early online date	Jun 24 2021
DOIs	https://doi.org/10.1016/j.mycmed.2021.101170
State	Published - Sep 2021

Bibliographical note

Funding Information:
This research was supported by the United States Fogarty International Center ( K01TW010268 , R25TW009345 ), National Institute of Neurologic Diseases and Stroke ( R01NS086312 ), National Institute of Allergy and Infectious Diseases ( T32AI055433 ). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016–2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15–011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z ). FVC is an honorary fellow of the Makerere University – Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743 ). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743 ) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union.

Funding Information:
This research was supported by the United States Fogarty International Center (K01TW010268, R25TW009345), National Institute of Neurologic Diseases and Stroke (R01NS086312), National Institute of Allergy and Infectious Diseases (T32AI055433). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016?2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15?011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z). FVC is an honorary fellow of the Makerere University ? Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union.

Publisher Copyright:
© 2021 SFMM

Keywords

Cryptococcal meningitis
HIV
Meningitis
Multiplex PCR
Sensitivity
Uganda

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mycmed.2021.101170

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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. (2021). Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population. Journal de Mycologie Medicale, 31(3), Article 101170. https://doi.org/10.1016/j.mycmed.2021.101170

Bridge, S, Hullsiek, KH, Nerima, C, Evans, EE, Nuwagira, E, Stadelman, AM, Tran, T, Kim, G, Tadeo, KK, Kwizera, R, Mwesigye, J, Ellis, J, Cresswell, FV, Meya, DB, Muzoora, C, Boulware, DR & Rhein, J 2021, 'Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population', Journal de Mycologie Medicale, vol. 31, no. 3, 101170. https://doi.org/10.1016/j.mycmed.2021.101170

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title = "Evaluation of the BioFire{\textregistered} FilmArray{\textregistered} Meningitis/Encephalitis panel in an adult and pediatric Ugandan population",

abstract = "Background: Meningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire{\textregistered} FilmArray{\textregistered} 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.",

keywords = "Cryptococcal meningitis, HIV, Meningitis, Multiplex PCR, Sensitivity, Uganda",

author = "Sarah Bridge and Hullsiek, {Kathy Huppler} and Carol Nerima and Evans, {Emily E.} and Edwin Nuwagira and Stadelman, {Anna M.} and Tu Tran and Grace Kim and Tadeo, {Kiiza K.} and Richard Kwizera and James Mwesigye and Jayne Ellis and Cresswell, {Fiona V.} and Meya, {David B.} and Conrad Muzoora and Boulware, {David R.} and Joshua Rhein",

note = "Funding Information: This research was supported by the United States Fogarty International Center ( K01TW010268 , R25TW009345 ), National Institute of Neurologic Diseases and Stroke ( R01NS086312 ), National Institute of Allergy and Infectious Diseases ( T32AI055433 ). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016–2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15–011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z ). FVC is an honorary fellow of the Makerere University – Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743 ). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743 ) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union. Funding Information: This research was supported by the United States Fogarty International Center (K01TW010268, R25TW009345), National Institute of Neurologic Diseases and Stroke (R01NS086312), National Institute of Allergy and Infectious Diseases (T32AI055433). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016?2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15?011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z). FVC is an honorary fellow of the Makerere University ? Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union. Publisher Copyright: {\textcopyright} 2021 SFMM",

year = "2021",

month = sep,

doi = "10.1016/j.mycmed.2021.101170",

language = "English (US)",

volume = "31",

journal = "Journal de Mycologie Medicale",

issn = "1156-5233",

publisher = "Elsevier Masson",

number = "3",

}

TY - JOUR

T1 - Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

AU - Bridge, Sarah

AU - Hullsiek, Kathy Huppler

AU - Nerima, Carol

AU - Evans, Emily E.

AU - Nuwagira, Edwin

AU - Stadelman, Anna M.

AU - Tran, Tu

AU - Kim, Grace

AU - Tadeo, Kiiza K.

AU - Kwizera, Richard

AU - Mwesigye, James

AU - Ellis, Jayne

AU - Cresswell, Fiona V.

AU - Meya, David B.

AU - Muzoora, Conrad

AU - Boulware, David R.

AU - Rhein, Joshua

N1 - Funding Information: This research was supported by the United States Fogarty International Center ( K01TW010268 , R25TW009345 ), National Institute of Neurologic Diseases and Stroke ( R01NS086312 ), National Institute of Allergy and Infectious Diseases ( T32AI055433 ). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016–2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15–011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z ). FVC is an honorary fellow of the Makerere University – Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743 ). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743 ) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union. Funding Information: This research was supported by the United States Fogarty International Center (K01TW010268, R25TW009345), National Institute of Neurologic Diseases and Stroke (R01NS086312), National Institute of Allergy and Infectious Diseases (T32AI055433). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Sarah Bridge was a 2016?2017 Doris Duke International Clinical Research Fellow supported by the Doris Duke Research Foundation. RK and DM are supported through the DELTAS Africa Initiative grant # DEL-15?011 to THRiVE-2, from Wellcome Trust grant # 107742/Z/15/Z and the UK government. FVC is supported through a Wellcome Trust Clinical PhD Fellowship (Grant no. 210772/Z/18/Z). FVC is an honorary fellow of the Makerere University ? Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union. Publisher Copyright: © 2021 SFMM

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - Cryptococcal meningitis

KW - HIV

KW - Meningitis

KW - Multiplex PCR

KW - Sensitivity

KW - Uganda

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DO - 10.1016/j.mycmed.2021.101170

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SN - 1156-5233

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JO - Journal de Mycologie Medicale

JF - Journal de Mycologie Medicale

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ER -

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

Abstract

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PubMed: MeSH publication types

UN SDGs

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