ABSTRACT

Aerosol exposure is the most probable route in a biological warfare or terrorist attack [1]. In natural aerosol infections, only a few biological agents are considered either obligate or opportunistic airborne pathogens (e.g.,

Mycobacterium tuberculosis

,

influenza) [2]. Because natural aerosol infection is a poor surrogate for studying airborne infection, modeling these interactions within a controlled experimental setting allows for intensive study of the process of aerosol-acquired disease. The modern history of studying aerosolized infectious disease agents using a homogenous synchronized experimental aerosol dates back to early-20th-century efforts involving the infection of guinea pigs with aerosolized

M. tuberculosis

[3]. From these early studies to present-day investigations, important distinctions can be drawn between modeling natural infection and experimental infection. Natural infection, or the use of the communicability of an infectious agent to cause disease, is very much a different process than experimental infection. Natural infection of a naïve

host from the aerosolized secretions (e.g., a cough or sneeze) of an infected host relies on a variety of uncontrollable factors, the majority of which are propagated by the clinical course of disease in the infected host. Characteristics of the infectious agent (infectious stability), amount (concentration), particle size, and form (particle constituents) of a biological aerosol are highly variable when clinically ill animals are used for the purposes of infection. Performing this type of exposure will result in an asynchronous exposure and heterogeneous infection, significantly affecting experimental design and the desired biological outcome. Controlled experimental infection, in contrast, allows the researcher to exert control over a wide range of experimental parameters to generate a biological response in a group of animals exposed to an approximately similar dose. The design and operation of the laboratory apparatus to support this type of experimentation is technically and logistically demanding, and coordination between the biological and engineering sciences is critical to successful aerosol challenge.