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Reed, D. S.

Publications and source records attributed to Reed, D. S..

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A vibrating mesh nebulizer as an alternative to the Collison 3-jet nebulizer for infectious disease aerobiology.

Experimental infection of animals via inhalation containing pathogenic agents is essential to understanding the natural history and pathogenesis of infectious disease as well as evaluation of potential medical countermeasures. We evaluated whether the Aeroneb, a vibrating mesh nebulizer, would serve as an alternative to the Collison, the gold standard for generating infectious bioaerosols. While the Collison possesses desirable properties that have contributed to its longevity in infectious disease aerobiology, concerns have lingered about the volume and concentration of agent required to cause disease and the damage that jet nebulization causes to the agent. For viruses, the ratio of aerosol concentration to nebulizer concentration (spray factor, SF), the Aeroneb was superior to the Collison for four different viruses in a nonhuman primate head-only exposure chamber. Aerosol concentration of influenza was higher relative to fluorescein for the Aeroneb compared to the Collison, suggesting that the Aeroneb was less harsh to viral pathogens than the Collison when generating aerosols. The Aeroneb did not improve the aerosol SF for a vegetative bacterium, Francisella tularensis. Environmental parameters collected during the aerosols indicated that the Aeroneb generated a higher relative humidity in exposure chambers while not affecting other environmental parameters. Aerosol mass median aerodynamic diameter was generally larger and more disperse for aerosols generated by the Aeroneb than what is seen with the Collison but [≥]80% were within the range that would reach the lower respiratory tract and alveolar regions. These data suggest that for viral pathogens, the Aeroneb is a suitable alternative to the Collison 3-jet nebulizer.\n\nImportanceThe threat of aerosolization is often not the natural method of transmission. While selection of an appropriate animal model is vital for these types of experiments, other confounding factors can be controlled through a thorough understanding of experimental design and the effects that different parameters can have on disease outcome. Route of administration, particle size, and dose are all factors which can affect disease progression and need to be controlled. Aerosol research methods and equipment need to be well characterized to optimize the development of animal models for bioterrorism agents.

microbiology

Development, characterization and standardization of a nose-only inhalation exposure system for exposure of rabbits to small particle aerosols containing Francisella tularensis.

Inhalation of Francisella tularensis (Ft) causes pneumonic tularemia in humans, a severe disease with a 30-60% mortality rate. Reproducible delivery of aerosolized virulent bacteria in relevant animal models is essential for evaluating medical countermeasures. Here we developed optimized protocols for infecting New Zealand White (NZW) rabbits with aerosols containing Ft. We evaluated relative humidity, aerosol exposure technique, and bacterial culture conditions to optimize spray factor (SF), a central metric of aerosolization. This optimization reduced both inter-and intra-daily variability and were applicable to multiple isolates of Ft. Further improvements in the accuracy and precision of the inhaled pathogen dose were achieved through enhanced correlation of bacterial culture OD and CFU. Plethysmograph data collected during exposures found that respiratory function varied considerably between rabbits, was not a function of weight, and did not improve with acclimation to the system. Vaccine Strain (LVS)-vaccinated rabbits were challenged via aerosol with human-virulent Ft SCHU S4 that had been cultivated in either Mueller Hinton Broth (MHB) or Brain Heart Infusion (BHI) broth. LVS-vaccinated animals challenged with MHB-SCHU S4 experienced short febrile periods (median: 3.2 days), limited weight loss (< 5%), and longer median survival times (~18 d) that were significantly different than unvaccinated controls. In contrast, LVS-vaccinated rabbits challenged with BHI SCHU S4 experienced longer febrile periods (median: 5.5 days), greater weight loss (> 10%), and median survival times that were not significantly different than unvaccinated controls. These studies highlight the importance of careful characterization and optimization of protocols for aerosol challenge with pathogenic agents.

microbiology