Prion Dissemination through the Environment and Medical Practices: Facts and Risks for Human Health

Abstract

Prion diseases are a group of fatal, infectious neurodegenerative disorders affecting various species of mammals, including humans. The infectious agent in these diseases, termed prion, is composed exclusively of a misfolded protein that can spread and multiply in the absence of genetic materials. In this article, we provide an overview of the mechanisms of prion replication, interindividual transmission, and dissemination in communities. In particular, we review the potential role of the natural environment in prion transmission, including the mechanisms and pathways for prion entry and accumulation in the environment as well as its roles in prion mutation, adaptation, evolution, and transmission. We also discuss the transmission of prion diseases through medical practices, scientific research, and use of biological products. Detailed knowledge of these aspects is crucial to limit the spreading of existing prion diseases as well as to prevent the emergence of new diseases with possible catastrophic consequences for public health.

FIG 1

Schematic representation of the life cycle of a prion in the natural ecosystem. Natural dissemination of prions within a natural environment can be achieved by infected animals excreting infectious prions (blood, saliva, mucous, urine, and feces) or by deposition from infected carcasses of dead animals. Over time, gradual accumulation of infectious prions can be found spread throughout the immediate environment bound to solid surfaces (wood, rock, plants, and soil) and can be further disseminated to broader spatial locations through other organisms (insects, worms, scavenger birds, and mammals). Within the highly prion-contaminated environment, reuptake and eventual infection can occur via consumption or contact with contaminated surfaces or materials.

FIG 2

Effect of the natural environment and interspecies transmission in the zoonotic potential of animal prions. The direct transmission of prion disease from animals to humans is likely difficult, except in the case of BSE. Shedding of animal prions to diverse materials within the natural environment may contribute to prion concentration and perhaps mutation, which may increase their potential for human infection. Transmission of the disease to other animal species may facilitate the replication of novel prion conformational strains with altered zoonotic potential. All these processes increase the risk for human infection with novel forms of animal prions.

FIG 3

Potential routes for prion contamination in medical or laboratory research settings. Within a medical or laboratory setting, humans can be exposed to prions via an array of contamination routes, including (i) blood- and plasma-derived products, (ii) surgical equipment, particularly, those made of metals provide excellent surfaces for the binding and retention of prions, (iii) transplants with organs contaminated by prions, (iv) biological drugs derived from prion-contaminated cell lines, (v) large surfaces in medical or research facilities where extensive handling of brain tissue or infectious prion samples may have occurred, (vi) drugs and biological products purified from humans tissues, or (vii) from human biologicals, such as urine.

FIG 4

Strategies for prion biosafety and potential methods of decontamination. Strategies to mitigate the spread of prions in clinically relevant settings are vital to disease prevention. Quality control and testing of potential prion contamination in biological samples (organs, tissues, cells, and fluids) or the sampling from relevant surgical/medical equipment can be most effectively analyzed via highly sensitive molecular diagnostic lab methods, such as PMCA or RT-QuIC. These methodologies may unveil subdetectable quantities of infectious prions which may be overlooked by conventional lab methods (Western blotting and immunohistology). Once a sample has been deemed positive for prion contamination, cleaning and elimination strategies can be used depending on the nature of the contaminated objects. It is possible to attempt the decontamination of the materials with harsh chemicals or enzymatic digestion. In the case of materials which cannot be so facilely decontaminated, incineration is the suggested option to completely remove the infectious agent.