Aerobiology and Inhalation Exposure to Biological Select Agents and Toxins

Abstract

Aerosol is the most likely route of dissemination of biological select agents and toxins in a bioterrorist attack, regardless of the natural route of exposure to the agent. The use of animal models for testing preventative and therapeutic countermeasures requires knowledge of the pathogenesis of disease after inhalation exposure. Factors that relate to outcome after respiratory exposure include the inherent infectivity and virulence and/or toxicity of the agent in the host under investigation, in addition to characteristics of the aerosol particle and host that affect the delivered dose of, and host response to, the inhaled material. This introductory article discusses the emerging science of aerobiology and the unique features of respiratory tract anatomy, physiology, and immunology that are relevant to the pathogenesis of aerosolized biothreat agents.

Aerosolized Rift Valley Fever Virus Causes Fatal Encephalitis in African Green Monkeys and Common Marmosets

“…It is unclear which transmission route is predominant in natural outbreaks and whether the route of exposure alters the virulence or pathophysiology of RVF. Because RVFV can be infectious when aerosolized, RVFV is considered a potential pathogen that could be used in a bioterror attack (18,32,33). Our prior studies in inbred changes in platelets and coagulation parameters.…”

“…Marmosets inoculated with RVFV subcutaneously developed severe hepatic/hemorrhagic disease, while marmosets inoculated intranasally developed fatal encephalitis. However, only a single dose of RVFV was evaluated, and intranasal inoculation is generally not considered an acceptable substitute for aerosol exposure to a pathogen in pivotal efficacy studies (18,25). Our findings reported here demonstrate that even at the lowest dose tested, 60 PFU, aerosol exposure to RVFV resulted in disease in marmosets as indicated by the febrile response and serum antibody responses after infection, although the LD 50 was 2 logs higher at 3.5 ϫ 10 3 .…”

“…Additional FDA guidance states that the route of infection must be the same as the expected route of exposure for humans (17). For biodefense, aerosol dispersion of a highly pathogenic agent is the most likely form of an attack on human populations (18).…”

“…This prior report did not establish the viral dose required to reproducibly cause disease in marmosets, nor did it address a true aerosol exposure. There is debate over whether intranasal inoculation mimics inhalation of a smallparticle aerosol (18). As part of the process toward meeting the requirements of the FDA's Animal Rule, we have evaluated the disease outcome after aerosol exposure to increasing doses of RVFV in four NHP species that are commonly used in biomedical research.…”

Comparison of nucleic acid extraction platforms for detection of select biothreat agents for use in clinical resource limited settings

“…Biothreat agents, including Bacillus anthracis, Yersinia pestis, Variola virus (vaccinia virus is a surrogate for Variola virus, the causative agent of smallpox), and Venezuelan equine encephalitis virus (VEEV), represent significant public health risks due to high pathogenicity and potential for aerosolization (Roy et al, 2010). Rapid and specific identification of these pathogens is critical for initiation of appropriate containment and therapeutic measures as prognosis is directly impacted by time to diagnosis.…”