Introduction
There is uncertainty about the extent to which the site of initial
exposure within the pulmonary tree influences influenza virus infection
risk and severity between humans. Experimental nasal instillation
produces a range of illness from asymptomatic, symptomatic, to febrile.
Studies that challenged humans by nasal instillation of virus, and
others that challenged with aerosolized virus suggest that upper
respiratory mucosal exposure, as opposed to airborne exposure may result
in a higher proportion of milder, afebrile
illnesses.1–3 Anisotropic infection is defined by
Milton as infection whereby transmission mode influences illness
presentation,4 and has been used to characterize human
influenza.5 To minimize health risk associated with
experimental human influenza infection, the majority of human challenge
models have adopted viral inoculation by nasal
instillation.6 Associations between symptomatology and
nasal and throat mucosal viral load following symptom onset have been
reported among volunteers receiving intranasal influenza virus challenge
and among secondary household cases in Hong Kong.7–9Other analyses of these household transmission data did not find
temporal associations between symptom severity and upper respiratory
viral load;10 and observed upper respiratory mucosal
viral loads11,12 or respiratory
symptoms13 to be poorly predictive of transmission to
household secondary cases, suggesting that other biomarkers of contagion
such as exhaled breath aerosols should be explored. The current study
compares fine aerosol shedding between influenza A/H3 nasally inoculated
and naturally infected cases to test whether experimental, nasal induced
infections have similar risk and rate of fine aerosol shedding compared
with natural cases infected by any mode.