@article{1f9b0462962b4605bd60e0fa549126d1,
title = "Density of upper respiratory colonization with Streptococcus pneumoniae and its role in the diagnosis of pneumococcal pneumonia among children aged <5 years in the PERCH study",
abstract = "Background. Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. Methods. PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. Results. Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P < .001). Conclusions. Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.",
keywords = "Children, Colonization, Etiology, Pneumococcus, Pneumonia",
author = "{PERCH Study Group} and Baggett, {Henry C.} and Watson, {Nora L.} and Knoll, {Maria Deloria} 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 Madhi, {Shabir A.} and Murdoch, {David R.} and Scott, {J. Anthony G.} and Thea, {Donald M.} and Martin Antonio and Awori, {Juliet O.} and Baillie, {Vicky L.} and DeLuca, {Andrea N.} and Driscoll, {Amanda J.} and Julie Duncan and Ebruke, {Bernard E.} and Doli Goswami and Higdon, {Melissa M.} and Karron, {Ruth A.} and Moore, {David P.} and Morpeth, {Susan C.} and Mulindwa, {Justin M.} and Park, {Daniel E.} and Wantana Paveenkittiporn and Barameht Piralam and Christine Prosperi and Sow, {Samba O.} and Tapia, {Milagritos D.} and Khalequ Zaman and Zeger, {Scott L.} and O'Brien, {Katherine L.} and Nicholas Fancourt and Wei Fu and Wangeci Kagucia and Mengying Li and Zhenke Wu and Jane Crawley and Endtz, {Hubert P.} and Lokman Hossain and Yasmin Jahan and Hasan Ashraf and Jessica McLellan and Eunice Machuka and Arifin Shamsul and Zaman, {Syed M.A.} and Grant Mackenzie",
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: Financial support. This work was supported by the Bill & Melinda Gates Foundation (grant 48968 to the International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, for the PERCH study) and the Wellcome Trust of Great Britain (clinical fellowship 098532 to J. A. G. S.). Funding Information: Potential conflicts of interest. 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. 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 (GSK). K. L. K. has received grant funding from Merck Sharp & Dohme. S. A. M. has received honoraria for advisory board participation from Bill & Melinda Gates Foundation, Pfizer, Medimmune, and Novartis and institutional grants from GSK, Novartis, Pfizer, Minervax, and Bill & Melinda Gates Foundation and has served on speakers bureau for Sanofi Pasteur and GSK. All other authors: 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. Publisher Copyright: {\textcopyright} The Author 2017.",
year = "2017",
doi = "10.1093/cid/cix100",
language = "English (US)",
volume = "64",
pages = "S317--S327",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
}