The Human Infectious Dosage of Rhinovirus 39 in a Mono-Dispersed Aerosol

Background: Airborne transmission represents one of the most rapidly spreading and least understood dissemination mechanisms for pathogens. 

Objective: This study determines the human infectious dosage for a common cold virus, rhinovirus 39, in a mono-dispersed aerosol (< 5 micron).

Methods: Mono-dispersed carrier particles containing rhinovirus 39 were produced at 4.7 micron (aerosol) using a vibrating-orifice aerosol generator (VOAG). Fourteen groups of 3 healthy participants each (age range: 18-53, mean age: 26.84) were exposed to increasing viral loads during 20 minute sessions in an air-tight test chamber and followed for 10 consecutive days.  Susceptibility to rhinovirus 39 was assessed by serum-neutralizing antibodies before exposure. The primary outcome measure was detection of virus in daily nasal washes by cell culture and qRT-PCR.  In addition, participants completed a daily self-assessed modified cold symptom score.

Results: The viral exposure load increased from 0.44 Plaque Forming Units (PFU) (0.157 Tissue Culture Infectious Dosage 50 [TCID₅₀]) to 560 PFU (100 TCID₅₀). Cell cultures and qRT-PCR detected rhinovirus in nasal washes in groups 12 (172 PFU [30.2 TCID₅₀]; 1 participant out of 3), 13 (420 PFU [74.1 TCID₅₀]; 2 participants out of 3), and 14 (560 PFU [100 TCID₅₀]; all participants).  The HID₁₀₀ was established at 560 PFU (100 TCID₅₀).  The subjective cold symptom score mostly reflected these findings.  However, some participants in groups 1 to 11 also reported cold symptoms without viral detection.

Conclusions: This is the first attempt to study the HID of a common cold virus in human subjects using carrier particles < 5 micron.  The HID provides the essential threshold for testing the efficacy of preventive measures such as face masks, eye protection, and fit-testing against viral transmission in aerosol form.