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Use of a human influenza challenge model to assess person-to-person transmission: proof-of-concept study
Ben Killingley1, Joanne E Enstone, Jane Greatorex
1Division of Epidemiology and Public Health, University of Nottingham. ben.killingley@nottingham.ac.uk
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.
