Use of a Human Influenza Challenge Model to Assess Person-to-Person Transmission: Proof-of-Concept Study

• Published in: The Journal of infectious diseases 2012-01, Vol.205 (1), p.35-43
• Main Authors: Killingley, Ben, Enstone, Joanne E., Greatorex, Jane, Gilbert, Anthony S., Lambkin-Williams, Rob, Cauchemez, Simon, Katz, Jacqueline M., Booy, Robert, Hayward, Andrew, Oxford, John, Bridges, Carolyn B., Ferguson, Neil M., Van-Tarn, Jonathan S. Nguyen
• Format: Article
• Language: English
• Subjects: Adult; Aerosols; Antibodies; Antibodies, Viral - blood; Biological and medical sciences; Data transmission; Disease transmission; Diseases; Feasibility Studies; Female; Fundamental and applied biological sciences. Psychology; Humans; Infections; Infectious diseases; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza virus; Influenza, Human - blood; Influenza, Human - diagnosis; Influenza, Human - transmission; Male; Medical sciences; Microbiology; Models, Biological; Quarantines; Symptoms; Viruses; Volunteerism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir701

Background. Influenza transmission in humans remains poorly understood. In particular, the relative contribution of contact, large droplet, and aerosol transmission is unknown. The aims of this proof-of-concept study were to determine whether an experimentally induced influenza infection is transmissible between humans and whether this would form a viable platform for future studies. Methods. In a quarantine facility, healthy volunteers ("donors") were inoculated with A/Wisconsin/67/2005 (H3N2) influenza virus via intranasal drops. On study days 2 and 3 "recipient" volunteers were exposed to donors under close living conditions. Volunteers socialized for 30 hours during a 2-day period. Infection was confirmed by ≥1 positive results from polymerase chain reaction, virus culture, or serology. Results. After inoculation, 4 of 9 donors developed symptoms consistent an influenza-like illness (ILI) and 7 of 9 were proven to be influenza-infected. After exposure, 4 of 15 recipients developed symptoms of ILI and 3 of 15 were proven to be infected. Serum collected within 2 days of study initiation indicated that 1 donor and 3 recipients were seropositive at study initiation. After adjustment for preexposure immunity, the overall secondary attack rate was 25% (3 of 12). Conclusions. Experimental human exposure studies offer an attractive potential method for answering outstanding questions related to influenza transmission and the evaluation of interventions to reduce it.