Clinical Infectious Diseases SUPPLEMENT ARTICLE

Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study Daniel R. Feikin,1,2 Wei Fu,1,3 Daniel E. Park,1,4 Qiyuan Shi,1 Melissa M. Higdon,1 Henry C. Baggett,5,6 W. Abdullah Brooks,7,8 Maria Deloria Knoll,1 Laura L. Hammitt,1,9 Stephen R. C. Howie,10,11,12 Karen L. Kotloff,13 Orin S. Levine,1,14 Shabir A. Madhi,15,16 J. Anthony G. Scott,9,17 Donald M. Thea,18 Peter V. Adrian,15,16 Martin Antonio,10,19,20 Juliet O. Awori,9 Vicky L. Baillie,15,16 Andrea N. DeLuca,1,21 Amanda J. Driscoll,1 Bernard E. Ebruke,10 Doli Goswami,7 Ruth A. Karron,22 Mengying Li,1,23 Susan C. Morpeth,9,17,24 John Mwaba,25,26 James Mwansa,25,26 Christine Prosperi,1 Pongpun Sawatwong,5 Samba O. Sow,27 Milagritos D. Tapia,13 Toni Whistler,5,6 Khalequ Zaman,7 Scott L. Zeger,28 Katherine L. O’ Brien,1 and David R. Murdoch29,30; for the PERCH Study Groupa 1

Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 2Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; 3Department of Rheumatology, Johns Hopkins School of Medicine, Baltimore, Maryland; 4 Milken Institute School of Public Health, Department of Epidemiology and Biostatistics, George Washington University, District of Columbia; 5Global Disease Detection Center, Thailand Ministry of Public Health–US Centers for Disease Control and Prevention Collaboration, Nonthaburi; 6Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; 7International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka and Matlab; 8Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 9Kenya Medical Research Institute–Wellcome Trust Research Programme, Kilifi; 10Medical Research Council Unit, Basse, The Gambia; 11Department of Paediatrics, University of Auckland, and 12Centre for International Health, University of Otago, Dunedin, New Zealand; 13Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development, Institute of Global Health, University of Maryland School of Medicine, Baltimore; 14Bill & Melinda Gates Foundation, Seattle, Washington; 15Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, and 16Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases Unit, University of the Witwatersrand, Johannesburg, South Africa; 17Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, United Kingdom; 18Center for Global Health and Development, Boston University School of Public Health, Massachusetts; 19Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, and 20Microbiology and Infection Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom; 21Department of Epidemiology, 22Department of International Health, Center for Immunization Research, and 23Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 24 Microbiology Laboratory, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand; 25Department of Pathology and Microbiology, University Teaching Hospital, and 26Zambia Center for Applied Health Research and Development, Lusaka; 27Centre pour le Développement des Vaccins (CVD-Mali), Bamako; 28Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 29 Department of Pathology, University of Otago, and 30Microbiology Unit, Canterbury Health Laboratories, Christchurch, New Zealand

Background.  The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods.  In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results.  The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of

Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study.

The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral lo...
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