The Dynamic Relationship Between Clinical Symptomatology and Viral Shedding in Naturally Acquired Seasonal and Pandemic Influenza Virus Infections

Abstract

Background: Although the pattern of viral shedding over time has been documented in volunteer challenge studies, understanding of the relationship between clinical symptomatology and viral shedding in naturally acquired influenza infections in humans remains limited.

Methods: In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals and identified 224 secondary cases of natural influenza virus infection in the household setting. We examined the dynamic relationship between patterns of clinical symptomatology and viral shedding as quantified using reverse transcription polymerase chain reaction and viral culture in 127 cases with a clinical picture of acute respiratory infection.

Results: Viral shedding in influenza A virus infections peaked on the first 1-2 days of clinical illness, and decreased gradually to undetectable levels by day 6-7, matching closely with the dynamics of clinical illness. Viral shedding in influenza B virus infections rose up to 2 days prior to symptom onset and persisted for 6-7 days after onset with a bimodal pattern.

Conclusions: Our results suggest that while clinical illness profiles may serve as a proxy for clinical infectiousness in influenza A virus infections, patients may potentially be infectious even before symptom onset or after clinical improvement in influenza B virus infections.

Keywords: influenza; symptoms; viral shedding.

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Patterns of viral shedding and clinical symptomatology in naturally acquired influenza A and B virus infections by day relative to acute respiratory illness (ARI) onset (day 0). First column: 33 cases with pandemic A(H1N1); second column: 73 cases with seasonal A(H1N1); third column: 69 cases with seasonal A(H3N2); and fourth column: 49 cases with seasonal B influenza B viral infections. First row: Viral shedding (circles) and the geometric mean viral shedding (solid lines) of collected nose and throat swab (NTS) specimen by reverse transcription polymerase chain reaction assay (RT-PCR). The lower limit of detection of RT-PCR was approximately 900 copies/mL (gray line). Second row: Median tissue culture infectious dose (TCID50) (circles) and the geometric mean TCID50 of collected NTS specimens. Third row: Mean number of symptoms and signs for subjects with influenza virus infection, splitting into respiratory (dotted line) and systemic (solid line). Bottom row: Mean tympanic temperature recorded. ARI onset is defined as at the first day with ≥2 of the 7 symptoms or signs listed in Table 2. Individuals with asymptomatic or subclinical infections were excluded.

Figure 2.

Scatterplot showing correlation (R2) and line of best fit between tympanic temperature and influenza viral shedding by reverse transcription polymerase chain reaction (RT-PCR) by day since acute respiratory illness (ARI) onset in 175 cases with naturally acquired influenza A virus infections. ARI onset is defined as at the first day with ≥2 of the 7 symptoms or signs listed in Table 2.