Airborne Transmission of Prions
By Amesh A. Adalja, MD, January 21, 2011
Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, and other infectious diseases caused by prions have long been thought to spread almost exclusively by ingestion and direct inoculation. That assumption has now been challenged by results of a study by Haybaeck and colleagues, who conducted a series of experiments demonstrating airborne transmission of the prion disease, scrapie, to mice.
Prions are small, self-replicating proteins that can be passed intact from one animal to another and have the potential to cause epidemics. They cause disease by binding to and deforming a target protein in the host; typically, they affect the central nervous system and cause degenerative neurological disease.
Fatal Scrapie Infection Following Airborne Exposure
The researchers exposed mice of various genetic stock to aerosolized brain homogenates containing an infectious prion. Some of the mice were genetically engineered to over express the prion’s target protein (tga20 mice), while others were wild type variants. Exposure time, mouse immune status, and concentration of prions in the aerosolized homogenate were varied across study groups. Lower exposure concentrations resulted in subclinical scrapie, but exposure was fatal for all of the tga20 mice exposed to airborne concentrations of at least 2.5% prion for 10 minutes. When tga20 mice were exposed to 20% prion concentrations, 1 minute of exposure resulted in a 100% fatality rate. Longer exposure times of 5 to 10 minutes were required for the same result (100% fatality) in non-tga20 mice. An intact immune system conferred no protection against prion infection.
Implications for Human Disease
Scrapie is an animal disease that is not transmitted to humans, but humans are susceptible to several other prion diseases, all rare, including Creutzfeldt-Jakob disease (sporadic, genetic, iatrogenic, variant), fatal familial insomnia, kuru, and Gerstmann-Sträussler-Scheinker syndrome. This demonstration of aerosolized scrapie transmission in mice may have important implications for humans, particularly if the BSE-derived variant Creutzfeldt-Jakob Disease (vCJD) and other prion diseases are found to be transmissible to humans via aerosol. To date, all reported cases of vCJD (~210) have been linked to consumption of the prion in BSE-laden food or through blood transfusion. However, enhanced epidemiologic investigation of vCJD cases to uncover airborne transmission may be warranted.
Pending additional study results, it also may be prudent to enhance slaughterhouse biosafety standards, which may include providing respirators, to minimize the potential for worker exposure to aerosolized brain materials. Clearly, further study is needed to assess the risk of aerosol transmission of other prion diseases, particularly BSE.
Haybaeck J, Heikenwalder M, Klevenz B, et al. Aerosols transmit prions to immunocompetent and immunodeficient mice. PLoS Pathogens 2011; http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001257. Accessed January 18, 2011.
Bosque PJ, Tyler KL. Prions and prion diseases of the central nervous system (transmissible neurodegenerative diseases). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010.