Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets.
BACKGROUND
The routes by which humans acquire influenza H5N1 infections have not been fully elucidated. Based on the known biology of influenza viruses, four modes of transmission are most likely in humans: aerosol transmission, ingestion of undercooked contaminated infected poultry, transmission by large droplets and self-inoculation of the nasal mucosa by contaminated hands. In preparation of a study to resolve whether H5N1 viruses are transmissible by aerosol in an animal model that is a surrogate for humans, an inhalation exposure system for studies of aerosolized H5N1 viruses in ferrets was designed, assembled, and validated. Particular attention was paid towards system safety, efficacy of dissemination, the viability of aerosolized virus, and sampling methodology.


RESULTS
An aerosol generation and delivery system, referred to as a Nose-Only Bioaerosol Exposure System (NBIES), was assembled and function tested. The NBIES passed all safety tests, met expected engineering parameters, required relatively small quantities of material to obtain the desired aerosol concentrations of influenza virus, and delivered doses with high-efficacy. Ferrets withstood a mock exposure trial without signs of stress.


CONCLUSIONS
The NBIES delivers doses of aerosolized influenza viruses with high efficacy, and uses less starting material than other similar designs. Influenza H5N1 and H3N2 viruses remain stable under the conditions used for aerosol generation and sample collection. The NBIES is qualified for studies of aerosolized H5N1 virus.
Tuttle
Richard S
RS
Aerosol Research and Engineering Laboratories, 13300 West 98th Street, Lenexa, Kansas 66215, USA.
Sosna
William A
WA
Daniels
Deirdre E
DE
Hamilton
Sara B
SB
Lednicky
John A
JA
D000336:Aerosols / Q000032:analysis*; D000818:Animals; D002642:Chick Embryo; D004195:Disease Models, Animal; D004867:Equipment Design; D005260:Female; D005289:Ferrets; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000635:transmission* / Q000821:virology; D019570:Inhalation Exposure; D009330:Nebulizers and Vaporizers / Q000821:virology; D014773:Virology / Q000379:methods*
D000336:Aerosols