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Can Use of Viral Load Improve Norovirus Clinical Diagnosis and Disease Attribution?

Shioda, K; Barclay, L; Becker-Dreps, S; Bucardo-Rivera, F; Cooper, PJ; Payne, DC; Vinje, J; Lopman, BA (2017) Can Use of Viral Load Improve Norovirus Clinical Diagnosis and Disease Attribution? OPEN FORUM INFECTIOUS DISEASES, 4 (3). ISSN 2328-8957 https://doi.org/10.1093/ofid/ofx131
SGUL Authors: Cooper, Philip John

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Abstract

Abstract Background Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the state-of-the-art diagnostic for norovirus. Cycle threshold (Ct), an indicator of viral load, may be associated with symptomatic disease as well as demographic and outbreak characteristics. Methods Data on (1) outbreak and sporadic cases and (2) asymptomatic controls in the United States and Latin America were analyzed. With multivariate regression models, we assessed relationships between various factors and Ct values, and we calculated odds ratios (ORs) for the presence of symptoms and attributable fractions of norovirus. Receiver-operating characteristic analysis was performed to define an optimal Ct cutoff to identify disease-causing infections. Results Cycle threshold values were lower (ie, higher viral loads) among symptomatic cases (model-adjusted mean ± standard error: 25.3 ± 1.2) compared with asymptomatic controls (28.5 ± 1.4). Cycle threshold values were significantly different across age groups, norovirus genogroups, timing of specimen collection, outbreak settings, and transmission modes. Genogroup II (GII) Ct values were associated with presence of symptoms (OR = 1.1), allowing us to estimate that 16% of diarrheal disease was attributable to norovirus. The optimized Ct cutoff led to poor sensitivity and specificity for genogroup I and GII. Conclusions Cycle threshold values were associated with host, pathogen, and outbreak factors. Cycle threshold values may not effectively distinguish disease-causing infection for individual patients, but they are useful for epidemiological studies aiming to attribute disease.

Item Type: Article
Additional Information: Copyright © 2017, Oxford University Press. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US. All articles in this journal are available under a Creative Commons or Government/Crown open access licence.
Keywords: attributable fractions, cycle threshold, norovirus, real-time PCR, receiver-operating characteristic analysis, attributable fractions, cycle threshold, norovirus, real-time PCR, receiver-operating characteristic analysis
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: OPEN FORUM INFECTIOUS DISEASES
ISSN: 2328-8957
Dates:
DateEvent
3 August 2017Published Online
31 July 2017Accepted
Publisher License: Creative Commons: Public Domain Dedication
Web of Science ID: WOS:000412357400039
URI: https://openaccess.sgul.ac.uk/id/eprint/110551
Publisher's version: https://doi.org/10.1093/ofid/ofx131

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