The relation between viral shedding and clinical course in natural influenza infections

Session V – Cowling, Benjamin – Abstract 1 of 3

Title of Contribution: The relation between viral shedding and clinical course in natural influenza infections
Author(s): L Lau1, BJ Cowling1, KY Cheng1, VJ Fang1, KH Chan2, TM Uyeki3, PM Houck4, JSM Peiris2, GM Leung1
Affiliation(s): 1Department of Community Medicine and School of Public Health, the University of Hong Kong; 2Department of Microbiology, the University of Hong Kong; 3Influenza Branch, National Center for Infectious Diseases, CDC; 4Division of Global Migration and Quarantine, National Center for Infectious Diseases, CDC.


Abstract:

Background: Whereas many volunteer challenge studies have evaluated the course of experimental influenza virus infection and viral shedding, much less is known about the dynamics between the clinical course of naturally acquired influenza infection and viral shedding.

Methods: A community-based randomised control trial to study non-pharmaceutical interventions was conducted in 2007 and 2008. Index cases were recruited from outpatient clinics and their household contacts were followed for 7-10 days to evaluate secondary infections. A longitudinal series of nose and throat swabs from 75 household contacts who had laboratory-confirmed infection were tested by quantitative RT-PCR to measure their viral loads at 3-day intervals. Symptom scores for each subject were calculated based on daily symptom diaries kept by each household member.

Results: The peak viral shedding observed for natural influenza A virus infection occured on the day of symptom onset with a downward trend after this time. Influenza B viral loads were more variable over time with initial shedding starting as early as 2 days prior to symptom onset in some cases. Trends in symptoms scores for upper respiratory (sore throat & runny nose) and lower respiratory (cough & phlegm) symptoms were quite similar, peaking at day 0, after which there was a decline in average score. Systemic (fever ≥37.8°C, headache & muscle pain) symptoms score peaked at the same time as respiratory symptoms but declined at a faster rate. We detected 8/75 RT-PCR confirmed secondary cases with no clinical symptoms (asymptomatic) and we detected viral shedding in 10/75 cases prior to symptom onset.

Discussion: We found that viral shedding typically peaked on the same day as symptom onset, and systemic symptoms declined more rapidly than respiratory symptoms. The faster decline of systemic symptoms is generally consistent with evidence from the experimental infection literature although the time lines for viral shedding and symptom onset are slightly different, perhaps due to the age range in our data (including children) or varying levels of pre-existing immunity.