EBOLA VIRUS INFECTION FOLLOWING A LARGE PARTICLE AEROSOL

Abstract

Aerosol particle deposition patterns of inhaled aerosol particles are known to affect the virulence of inhaled bioaerosol pathogens. Small particle (0.5‒3 μm) aerosols typically deposit within the alveolar regions of the lungs, whereas large particle (≥12 μm) aerosols tend to deposit within the nasopharyngeal and tracheobronchial regions of the upper respiratory tract in non-human primates (NHPs). A few studies have evaluated pulmonary disease following small particle Ebola virus (EBOV) aerosol inhalation in rhesus macaques, but characterization of upper respiratory tract infection following large particle EBOV inhalation has not been studied. This study determined lethality and characterization of disease course in rhesus macaques following a large particle EBOV aerosol deposition into the nasopharyngeal region. A secondary objective of the study is to characterize the immune response to large particle aerosol inhalation. Each NHP was monitored for respiratory disease by 18F-Fluorodeoxyglucose positron emission tomography computed tomography imaging. Serial hematology and serology assays were also performed to track disease progression throughout the 28-day study. NHPs exposed to target aerosol doses of 1000‒10,000 plaque-forming units of EBOV had the upper respiratory tract as a major site of virus-induced pathology. Other pathology findings were similar to an intramuscular EBOV challenge. However, NHPs exposed to a low dose (100 plaque-forming units) of large particle EBOV aerosol did not have any clinical signs or symptoms of EBOV disease and survived through to the study end. These results demonstrate that particle deposition can indeed alter disease course and can be a starting point in exploring the heterogeneity of EBOV virulence seen in humans. These data are also useful in evaluating possible droplet transmission of EBOV.