Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia

• Type of Material: Article
• Authors: Catherine H. Bozio, Emory University; W Dana Flanders, Emory University; Lyn Finelli, Centers for Disease Control and Prevention; Anna M. Bramley, Centers for Disease Control and Prevention; Carrie Reed, Centers for Disease Control and Prevention; Neel R. Gandhi, Emory University; Jorge Vidal Graniel, Emory University; Dean Erdman, Centers for Disease Control and Prevention; Min Z. Levine, Centers for Disease Control and Prevention; Stephen Lindstrom, Centers for Disease Control and Prevention; Krow Ampofo, University of Utah; Sandra R. Arnold, Le Bonheur Children's Hospital; Wesley H. Self, Vanderbilt University; Derek J. Williams, Vanderbilt University; Carlos G. Grijalva, Vanderbilt University; Evan Anderson, Emory University; Jonathan A. McCullers, Le Bonheur Children's Hospital; Kathryn M. Edwards, Vanderbilt University; Andrew T. Pavia, University of Utah; Richard G. Wunderink, Northwestern University; Seema Jain, Centers for Disease Control and Prevention
• Language: English
• Date: 2018-04-01
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: Published by Oxford University Press on behalf of Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.
• Final Published Version (URL): http://dx.doi.org/10.1093/ofid/ofy061
• Title of Journal or Parent Work: Open Forum Infectious Diseases
• ISSN: 2328-8957
• Volume: 5
• Issue: 4
• Start Page: ofy061
• End Page: ofy061
• Grant/Funding Information: S. R. A. reports receiving grants from CDC during the conduct of the study. J. A. M. reports receiving grants from CDC during the conduct of the study.; Additional funding was provided in part by the National Institutes of Health: Grants K24AI114444 (to N. R. G., Principal Investigator [PI]), R21AI112768-01A1 (to J. E. V., PI), K23AI104779 (to D. J. W., PI), R01AG043471 (to C. G. G., PI), K23GM110469 (to, PI), and K23GM110469 (to W. H. S., PI); D. J. W. reports receiving grants from CDC during the conduct of the study.; C. G. G. reports receiving grants from CDC during the conduct of the study; other support from Pfizer, other support from Merck, grants from NIH, grants from AHRQ outside the submitted work.; D. F. reports receiving personal fees from Biogen Idec, outside the submitted work, and owning shares of Johnson and Johnson.; E. J. A. reports receiving grants and non-financial support from MedImmune, grants from Novavax, personal fees from AbbVie, grants from Novavax outside the submitted work.; The Etiology of Pneumonia in the Community study was funded by the Influenza Division in the National Center for Immunizations and Respiratory Diseases at the Centers for Disease Control and Prevention through cooperative agreements with each study site and was based on a competitive research funding opportunity.; K. A. reports receiving grants from CDC during the conduct of the study; other support from GlaxoSmithKline, other support from Cubist Pharmaceuticals outside the submitted work; and collaborating with BioFire Diagnostics, Inc. (formerly Idaho Technology, Inc.) on several NIH grants.; A. T. P. reports receiving grants from CDC during the conduct of the study; personal fees from WebMD, other support from Antimicrobial Therapy Inc., other support from Johnson and Johnson, grants from NIH/BioFire, outside the submitted work.; W. H. S. reports receiving personal fees from Venaxis, Inc, personal fees from Cempra Pharmaceuticals, personal fees from Ferring Pharmaceuticals, personal fees from BioTest AG, personal fees from Abbott Point of Care, from Gilead Pharmaceuticals, outside the submitted work.
• Keywords: Life Sciences & Biomedicine; respiratory viruses; CHILDREN; Infectious Diseases; POLYMERASE-CHAIN-REACTION; multiple imputation; INFLUENZA; SEROLOGY; INFECTIONS; ADULTS; DIAGNOSIS; PCR; Science & Technology; community-acquired pneumonia; VIRAL CULTURE
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

Background: Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. Methods: Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. Results: Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%-4.4% and 0.8%-2.8% in children and adults, respectively; relative differences were 1.1-3.0 times higher. Conclusions: Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.