Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study

Melissa M. Higdon; Tham Le; Katherine L. O'Brien; David R. Murdoch; Christine Prosperi; Henry C. Baggett; W. Abdullah Brooks; Daniel R. Feikin; Laura L. Hammitt; Stephen R.C. Howie; Karen L. Kotloff; Orin S. Levine; J. Anthony G. Scott; Donald M. Thea; Juliet O. Awori; Vicky L. Baillie; Stephanie Cascio; Somchai Chuananon; Andrea N. DeLuca; Amanda J. Driscoll; Bernard E. Ebruke; Hubert P. Endtz; Anek Kaewpan; Geoff Kahn; Angela Karani; Ruth A. Karron; David P. Moore; Daniel E. Park; Mohammed Ziaur Rahman; Rasheed Salaudeen; Phil Seidenberg; Somwe Wa Somwe; Mamadou Sylla; Milagritos D. Tapia; Scott L. Zeger; Maria Deloria Knoll; Shabir A. Madhi; Nicholas Fancourt; Wei Fu; E. Wangeci Kagucia; Mengying Li; Zhenke Wu; Nora L. Watson; Jane Crawley; Khalequ Zaman; Doli Goswami; Lokman Hossain; Yasmin Jahan; Hasan Ashraf; Alice Kamau

doi:10.1093/cid/cix150

Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study

Melissa M. Higdon, Tham Le, Katherine L. O'Brien, David R. Murdoch, Christine Prosperi, Henry C. Baggett, W. Abdullah Brooks, Daniel R. Feikin, Laura L. Hammitt, Stephen R.C. Howie, Karen L. Kotloff, Orin S. Levine, J. Anthony G. Scott, Donald M. Thea, Juliet O. Awori, Vicky L. Baillie, Stephanie Cascio, Somchai Chuananon, Andrea N. DeLuca, Amanda J. DriscollBernard E. Ebruke, Hubert P. Endtz, Anek Kaewpan, Geoff Kahn, Angela Karani, Ruth A. Karron, David P. Moore, Daniel E. Park, Mohammed Ziaur Rahman, Rasheed Salaudeen, Phil Seidenberg, Somwe Wa Somwe, Mamadou Sylla, Milagritos D. Tapia, Scott L. Zeger, Maria Deloria Knoll, Shabir A. Madhi, Nicholas Fancourt, Wei Fu, E. Wangeci Kagucia, Mengying Li, Zhenke Wu, Nora L. Watson, Jane Crawley, Khalequ Zaman, Doli Goswami, Lokman Hossain, Yasmin Jahan, Hasan Ashraf, Alice Kamau

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

96 Citations (Scopus)

Abstract

Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIVnegative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

Original language	English
Pages (from-to)	S378-S386
Journal	Clinical Infectious Diseases
Volume	64
DOIs	https://doi.org/10.1093/cid/cix150
Publication status	Published - 1 Jan 2017
Externally published	Yes

Keywords

Bacteria
Biomarker
C-reactive protein
Pneumonia
RSV

UN SDGs

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

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10.1093/cid/cix150

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Higdon, M. M., Le, T., O'Brien, K. L., Murdoch, D. R., Prosperi, C., Baggett, H. C., Brooks, W. A., Feikin, D. R., Hammitt, L. L., Howie, S. R. C., Kotloff, K. L., Levine, O. S., Scott, J. A. G., Thea, D. M., Awori, J. O., Baillie, V. L., Cascio, S., Chuananon, S., DeLuca, A. N., ... Kamau, A. (2017). Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study. Clinical Infectious Diseases, 64, S378-S386. https://doi.org/10.1093/cid/cix150

@article{0759296212e740ce8ba16dfb8619994f,

title = "Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study",

abstract = "Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for {"}confirmed{"} bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to {"}RSV pneumonia{"} (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3\% had CRP ≥40 mg/L. Among 119 HIVnegative cases with confirmed bacterial pneumonia, 77\% had CRP ≥40 mg/L compared with 17\% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77\%) from RSV pneumonia (specificity 82\%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.",

keywords = "Bacteria, Biomarker, C-reactive protein, Pneumonia, RSV",

author = "Higdon, \{Melissa M.\} and Tham Le and O'Brien, \{Katherine L.\} and Murdoch, \{David R.\} and Christine Prosperi and Baggett, \{Henry C.\} and Brooks, \{W. Abdullah\} and Feikin, \{Daniel R.\} and Hammitt, \{Laura L.\} and Howie, \{Stephen R.C.\} and Kotloff, \{Karen L.\} and Levine, \{Orin S.\} and Scott, \{J. Anthony G.\} and Thea, \{Donald M.\} and Awori, \{Juliet O.\} and Baillie, \{Vicky L.\} and Stephanie Cascio and Somchai Chuananon and DeLuca, \{Andrea N.\} and Driscoll, \{Amanda J.\} and Ebruke, \{Bernard E.\} and Endtz, \{Hubert P.\} and Anek Kaewpan and Geoff Kahn and Angela Karani and Karron, \{Ruth A.\} and Moore, \{David P.\} and Park, \{Daniel E.\} and Rahman, \{Mohammed Ziaur\} and Rasheed Salaudeen and Phil Seidenberg and Somwe, \{Somwe Wa\} and Mamadou Sylla and Tapia, \{Milagritos D.\} and Zeger, \{Scott L.\} and Knoll, \{Maria Deloria\} and Madhi, \{Shabir A.\} and Nicholas Fancourt and Wei Fu and Kagucia, \{E. Wangeci\} and Mengying Li and Zhenke Wu and Watson, \{Nora L.\} and Jane Crawley and Khalequ Zaman and Doli Goswami and Lokman Hossain and Yasmin Jahan and Hasan Ashraf and Alice Kamau",

year = "2017",

month = jan,

day = "1",

doi = "10.1093/cid/cix150",

language = "English",

volume = "64",

pages = "S378--S386",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

}

Higdon, MM, Le, T, O'Brien, KL, Murdoch, DR, Prosperi, C, Baggett, HC, Brooks, WA, Feikin, DR, Hammitt, LL, Howie, SRC, Kotloff, KL, Levine, OS, Scott, JAG, Thea, DM, Awori, JO, Baillie, VL, Cascio, S, Chuananon, S, DeLuca, AN, Driscoll, AJ, Ebruke, BE, Endtz, HP, Kaewpan, A, Kahn, G, Karani, A, Karron, RA, Moore, DP, Park, DE, Rahman, MZ, Salaudeen, R, Seidenberg, P, Somwe, SW, Sylla, M, Tapia, MD, Zeger, SL, Knoll, MD, Madhi, SA, Fancourt, N, Fu, W, Kagucia, EW, Li, M, Wu, Z, Watson, NL, Crawley, J, Zaman, K, Goswami, D, Hossain, L, Jahan, Y, Ashraf, H & Kamau, A 2017, 'Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study', Clinical Infectious Diseases, vol. 64, pp. S378-S386. https://doi.org/10.1093/cid/cix150

TY - JOUR

T1 - Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study

AU - Higdon, Melissa M.

AU - Le, Tham

AU - O'Brien, Katherine L.

AU - Murdoch, David R.

AU - Prosperi, Christine

AU - Baggett, Henry C.

AU - Brooks, W. Abdullah

AU - Feikin, Daniel R.

AU - Hammitt, Laura L.

AU - Howie, Stephen R.C.

AU - Kotloff, Karen L.

AU - Levine, Orin S.

AU - Scott, J. Anthony G.

AU - Thea, Donald M.

AU - Awori, Juliet O.

AU - Baillie, Vicky L.

AU - Cascio, Stephanie

AU - Chuananon, Somchai

AU - DeLuca, Andrea N.

AU - Driscoll, Amanda J.

AU - Ebruke, Bernard E.

AU - Endtz, Hubert P.

AU - Kaewpan, Anek

AU - Kahn, Geoff

AU - Karani, Angela

AU - Karron, Ruth A.

AU - Moore, David P.

AU - Park, Daniel E.

AU - Rahman, Mohammed Ziaur

AU - Salaudeen, Rasheed

AU - Seidenberg, Phil

AU - Somwe, Somwe Wa

AU - Sylla, Mamadou

AU - Tapia, Milagritos D.

AU - Zeger, Scott L.

AU - Knoll, Maria Deloria

AU - Madhi, Shabir A.

AU - Fancourt, Nicholas

AU - Fu, Wei

AU - Kagucia, E. Wangeci

AU - Li, Mengying

AU - Wu, Zhenke

AU - Watson, Nora L.

AU - Crawley, Jane

AU - Zaman, Khalequ

AU - Goswami, Doli

AU - Hossain, Lokman

AU - Jahan, Yasmin

AU - Ashraf, Hasan

AU - Kamau, Alice

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIVnegative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

AB - Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIVnegative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

KW - Bacteria

KW - Biomarker

KW - C-reactive protein

KW - Pneumonia

KW - RSV

U2 - 10.1093/cid/cix150

DO - 10.1093/cid/cix150

M3 - Article

SN - 1058-4838

VL - 64

SP - S378-S386

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

ER -

Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH study

Abstract

Keywords

UN SDGs

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