Influenza A illness and viral aerosol shedding from symptomatic
naturally infected and experimentally infected cases
Abstract
Background: It has long been known that nasal inoculation with influenza
A virus produces asymptomatic to febrile infections. Uncertainty
persists about whether these infections are sufficiently similar to
natural infections for studying human-to-human transmission. Methods: We
compared influenza A viral aerosol shedding from volunteers nasally
inoculated with A/Wisconsin/2005 (H3N2) and college community adults
naturally infected with influenza A/H3N2 (2012-2013), selected for
influenza-like illness with objectively measured fever or a positive
Quidel QuickVue A&B test. Propensity scores were used to control for
differences in symptom presentation observed between experimentally and
naturally infected groups. Results: Eleven (28%) experimental and 71
(86%) natural cases shed into fine particle aerosols
(p<0.001). The geometric mean (geometric standard deviation)
for viral positive fine aerosol samples from experimental and natural
cases was 5.1E+3 (4.72) and 3.9E+4 (15.12) RNA copies/half hour,
respectively. The 95th percentile shedding rate was 2.4 log10 greater
for naturally infected cases (1.4E+07 versus 7.4E+04). Certain
influenza-like illness related symptoms were associated with viral
aerosol shedding. The almost complete lack of symptom severity
distributional overlap between groups did not support propensity score
adjusted shedding comparisons. Conclusions: Due to selection bias, the
natural and experimental infections had limited symptom severity
distributional overlap precluding valid, propensity score adjusted
comparison. Relative to the symptomatic naturally infected cases, where
high aerosol shedders were found, experimental cases did not produce
high aerosol shedders. Studying the frequency of aerosol shedding at the
highest observed levels in natural infections without selection on
symptoms or fever would support helpful comparisons.