10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Aerodynamic Particle Size Affects Infectivity and Lethality, but not Disease Timecourse, in a Nonhuman Primate Model of Inhalational Melioidosis
JEREMY BOYDSTON, John Yeager, Artemas Herzog, Jill Taylor, David Dawson, Angelo Scorpio, Paul Dabisch, BNBI / DHS NBACC
Abstract Number: 406 Working Group: Infectious Bioaerosol
Abstract Burkholderia pseudomallei, the causative organism of melioidosis, is endemic in Australia and Southeast Asia. While percutaneous inoculation is believed to be a major route of exposure, but recent studies have detected B. pseudomallei in air samples collected during typhoon season suggesting that inhalation may also be a natural route of exposure. While the particle size distribution of naturally occurring aerosols containing B. pseudomallei has not been measured, measurements of naturally occurring aerosols containing other microorganisms suggest a wide range of particle sizes are possible. For many pathogenic microorganisms, there is evidence that aerodynamic particle size is a significant factor influencing the disease presentation and lethality. Therefore, the aim of this study was to determine the influence of aerodynamic particle size on the disease presentation and median lethal dose in a nonhuman primate model of inhalational melioidosis. The results demonstrate that infectious and lethal doses were significantly greater in animals exposed to large particles (MMAD: 11.5 µm, GSD: 1.27) versus small particles (MMAD: 1.5 µm, GSD: 1.39). It is likely that the observed difference between the two groups is due to differences in the regional deposition pattern of the inhaled aerosol. Interestingly, the median time to death, median time to fever, and cytokine responses did not differ between infected animals in the two particle size groups. Minor histopathological differences were also noted between the groups, including an increased incidence of inflammation in the olfactory bulb in non-survivors in the large particle exposed group and a decreased incidence of severe lung inflammation in survivors in the large particle exposed group, but the significance of either histopathological difference to outcome cannot be assessed without additional studies. Taken together, these results suggest that once infection is initiated, melioidosis disease progression is largely independent of differences in aerodynamic particle size and associated differences in pulmonary deposition patterns. Additionally, the results of this study highlight the need for future studies in which the particle size distribution of naturally occurring aerosols containing B. pseudomallei is measured.
All research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.