Time lines of infection and disease in human influenza: A review of volunteer challenge studies

Fabrice Carrat*, Elisabeta Vergu, Neil M. Ferguson, Magali Lemaitre, Simon Cauchemez, Stephen Leach, Alain Jacques Valleron

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    853 Citations (Scopus)


    The dynamics of viral shedding and symptoms following influenza virus infection are key factors when considering epidemic control measures. The authors reviewed published studies describing the course of influenza virus infection in placebo-treated and untreated volunteers challenged with wild-type influenza virus. A total of 56 different studies with 1,280 healthy participants were considered. Viral shedding increased sharply between 0.5 and 1 day after challenge and consistently peaked on day 2. The duration of viral shedding averaged over 375 participants was 4.80 days (95% confidence interval: 4.31, 5.29). The frequency of symptomatic infection was 66.9% (95% confidence interval: 58.3, 74.5). Fever was observed in 37.0% of A/H1N1, 40.6% of A/H3N2 (p = 0.86), and 7.5% of B infections (p = 0.001). The total symptoms scores increased on day 1 and peaked on day 3. Systemic symptoms peaked on day 2. No such data exist for children or elderly subjects, but epidemiologic studies suggest that the natural history might differ. The present analysis confirms prior expert opinion on the duration of viral shedding or the frequency of asymptomatic influenza infection, extends prior knowledge on the dynamics of viral shedding and symptoms, and provides original results on the frequency of respiratory symptoms or fever.

    Original languageEnglish
    Pages (from-to)775-785
    Number of pages11
    JournalAmerican Journal of Epidemiology
    Issue number7
    Publication statusPublished - Apr 2008


    • Influenza, human
    • Signs and symptoms
    • Virus shedding


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