@article{4cbbfa0193ba4d8f9e5484962048d309,
title = "Evaluation of pneumococcal load in blood by polymerase chain reaction for the diagnosis of pneumococcal pneumonia in young children in the PERCH study",
abstract = "Background. Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. Methods. The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the {"}optimal threshold{"} that distinguished MCPP cases from controls. Results. Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Conclusions. Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.",
keywords = "Blood, Diagnosis, PCR, Pneumococcus, Pneumonia",
author = "{PERCH Study Group} and Knoll, {Maria Deloria} and Morpeth, {Susan C.} and Scott, {J. Anthony G.} and Watson, {Nora L.} and Park, {Daniel E.} 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 O'Brien, {Katherine L.} and Thea, {Donald M.} and Dilruba Ahmed and Martin Antonio and Awori, {Juliet O.} and Baillie, {Vicky L.} and James Chipeta and Deluca, {Andrea N.} and Michel Dione and Driscoll, {Amanda J.} and Higdon, {Melissa M.} and Anchalee Jatapai and Karron, {Ruth A.} and Razib Mazumder and Moore, {David P.} and James Mwansa and Sammy Nyongesa and Christine Prosperi and Phil Seidenberg and Duangkamon Siludjai and Sow, {Samba O.} and Boubou Tamboura and Zeger, {Scott L.} and Murdoch, {David R.} and Madhi, {Shabir A.} and Nicholas Fancourt and Wei Fu and Kagucia, {E. Wangeci} and Mengying Li and Zhenke Wu and Jane Crawley and Endtz, {Hubert P.} and Khalequ Zaman and Doli Goswami and Lokman Hossain and Yasmin Jahan and Hasan Ashraf and Ebruke, {Bernard E.}",
note = "Funding Information: Supplement sponsorship. This article appears as part of the supplement “Pneumonia Etiology Research for Child Health (PERCH): Foundational Basis for the Primary Etiology Results,” sponsored by a grant from the Bill & Melinda Gates Foundation to the PERCH study of Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Funding Information: Potential conflicts of interest. M. D. K. has received funding for consultancies from Merck, Pfizer, and Novartis, and grant funding from Merck. L. L. H. has received grant funding from Pfizer and GlaxoSmithKline. K. L. K. has received grant funding from Merck Sharp & Dohme. S. A. M. has received honoraria for advisory board membership from the Bill & Melinda Gates Foundation, Pfizer, Medimmune, and Novartis; has received institutional grants from GSK, Novartis, Pfizer, Minervax, and the Bill & Melinda Gates Foundation; and has served on speaker{\textquoteright}s bureaus for Sanofi Pasteur and GSK. K. L. O. has received grant funding from GSK and Pfizer and participates on technical advisory boards for Merck, Sanofi Pasteur, PATH, Affinivax, and ClearPath. All other authors report no reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding Information: Financial support. PERCH was supported by the Bill & Melinda Gates Foundation (grant number 48968 to the International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health). J. A. G. S. was supported by a clinical fellowship from the Wellcome Trust of Great Britain (award number 098532). Publisher Copyright: {\textcopyright} The Author 2017.",
year = "2017",
doi = "10.1093/cid/cix149",
language = "English (US)",
volume = "64",
pages = "S357--S367",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
}