World Health Organization Influenza-Like Illness Underestimates the Burden of Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults

Koos Korsten, Niels Adriaenssens, Samuel Coenen, Chris C Butler, Theo J M Verheij, Louis J Bont, Joanne G Wildenbeest, RESCEU Investigators, Koos Korsten, Niels Adriaenssens, Samuel Coenen, Christopher Butler, Theo Verheij, Louis Bont, Joanne Wildenbeest, Harish Nair, Harry Campbell, Steve Cunningham, Philippe Beutels, Peter Openshaw, Andrew Pollard, Eva Molero, Adam Meijer, Federico Martinon-Torres, Terho Heikkinen, Thea K Fischer, Maarten van den Berge, Carlo Giaquinto, Michael Abram, Deniz Öner, Jeroen Aerssens, Kena Swanson, Amanda Leach, Sonia Stoszek, Clarisse Demont, Scott Gallichan, Veena Kumar, Ann Falsey, Koos Korsten, Niels Adriaenssens, Samuel Coenen, Chris C Butler, Theo J M Verheij, Louis J Bont, Joanne G Wildenbeest, RESCEU Investigators, Koos Korsten, Niels Adriaenssens, Samuel Coenen, Christopher Butler, Theo Verheij, Louis Bont, Joanne Wildenbeest, Harish Nair, Harry Campbell, Steve Cunningham, Philippe Beutels, Peter Openshaw, Andrew Pollard, Eva Molero, Adam Meijer, Federico Martinon-Torres, Terho Heikkinen, Thea K Fischer, Maarten van den Berge, Carlo Giaquinto, Michael Abram, Deniz Öner, Jeroen Aerssens, Kena Swanson, Amanda Leach, Sonia Stoszek, Clarisse Demont, Scott Gallichan, Veena Kumar, Ann Falsey

Abstract

Background: Respiratory syncytial virus (RSV) surveillance is heavily dependent on the influenza-like illness (ILI) case definition from the World Health Organization (WHO). Because ILI includes fever in its syndromic case definition, its ability to accurately identify acute respiratory tract infections (ARTI) caused by RSV in older adults is uncertain.

Methods: The accuracy of the WHO ILI and a modified ILI (requiring only self-reported fever) case definitions in identifying patients with PCR-confirmed RSV-ARTI was evaluated in community-dwelling older adults (≥60 years) from the prospective European RESCEU cohort study.

Results: Among 1040 participants, 750 ARTI episodes were analyzed including 36 confirmed RSV-ARTI. Due to a general lack of fever, sensitivity for RSV-ARTI was 33% for modified ILI and 11% for ILI. The area under the curve for both ILI definitions was 0.52 indicating poor discrimination for RSV. RSV-ARTI could not be distinguished from all other ARTI based on clinical symptoms.

Conclusions: The use of ILI underestimated the occurrence of RSV-ARTI in community-dwelling older adults up to 9-fold (11% sensitivity). Because worldwide RSV surveillance depends largely on ILI, there is an urgent need for a better approach to measure the occurrence of RSV disease and the impact of future RSV vaccine introduction. Clinical Trials Registration. NCT03621930.

Keywords: ILI; RESCEU; RSV; case definition; older adults; respiratory syncytial virus.

Conflict of interest statement

Potential conflicts of interest. C. B. reports personal fees from Roche, and grants and personal fees from Jannsen Pharmaceuticals. L. B. has regular interaction with pharmaceutical and other industrial partners and is founding chairman of the ReSViNET Foundation; he has not received personal fees or other personal benefits. His institution has received major funding (>€100 000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, Bill and Melinda Gates Foundation, Nutricia (Danone), and MeMed Diagnostics; major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi; major funding from Julius Clinical for participating in the INFORM study sponsored by MedImmune; minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than €20 000); and minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, and Janssen (total annual estimate less than €20 000). T. V. reports grants from Abbott, Becton Dickinson, Bio-Merieux, and Janssen Pharmaceuticals outside the submitted work. All other authors report no potential 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.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Flowchart of study participants and respiratory episodes. Abbreviations: ARTI, acute respiratory tract infection; RESCEU, Respiratory Syncytial Virus Consortium in Europe; RSV, respiratory syncytial virus.
Figure 2.
Figure 2.
Area under the curve plot of performance of case definitions for respiratory syncytial virus. ILI includes measured temperature ≥ 38°C while modified ILI includes also the feeling of being feverish. Abbreviations: ILI, influenza-like illness; IPC, infectious productive cough.

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