Time Lines of Infection and Disease in Human Influenza: A Review of Volunteer Challenge Studies

• Published in: American journal of epidemiology Vol. 167; no. 7; pp. 775 - 785
• Main Authors: Carrat, Fabrice, Vergu, Elisabeta, Ferguson, Neil M., Lemaitre, Magali, Cauchemez, Simon, Leach, Steve, Valleron, Alain-Jacques
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.04.2008; Oxford Publishing Limited (England); Oxford University Press (OUP)
• Subjects: Analysis. Health state; Biological and medical sciences; Computer Science; Disease transmission; Epidemiology; General aspects; human; Human viral diseases; Humans; Infectious diseases; Influenza; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza A Virus, H3N2 Subtype - pathogenicity; Influenza B virus - pathogenicity; Influenza Vaccines; Influenza virus; Influenza, Human - epidemiology; Influenza, Human - immunology; Influenza, Human - prevention & control; Mathematics; Medical sciences; Public health. Hygiene; Public health. Hygiene-occupational medicine; signs and symptoms; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Virology; Virus Shedding; influenza, human; signs and symptoms; virus shedding; Human; Infection; Virus; Symptomatology; Viral disease; Influenza; Volunteer; human; signs and symptoms; virus shedding; Review; Epidemiology; Bibliographic review; VIRUS SHEDDING; INFLUENZA HUMAN; SIGN AND SYMPTOM; EPIDEMIOLOGIE HUMAINE
• ISSN: 0002-9262; 1476-6256; 1476-6256
• DOI: 10.1093/aje/kwm375

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.