Comments on Haybaeck, Heikenwalde, Klevenz et al. Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice. PLoS Pathog 7(1): e1001257. (2011) Published January 13 2011. doi:10.1371/journal.ppat.1001257
This is a very interesting and tantalizing scientific study that examines the ability of prions to enter the central nervous system after coming in contact with the nasal mucosa. The finding that direct exposure of the nasal mucosa to 4x10E5 scrapie prion allows detection of these infectious particles in the brains of a wide variety of mice is intriguing. Perhaps even startling. More troubling is the finding that the ‘obligatory replicative phase in lymphoid organs’ is not required for effective infection of the central nervous system.
Of course, this carefully conducted study then leaves the reader with the distinct feeling that breathing of aerosols that may contain prions is inherently dangerous or risky… It is important to remember that this manuscript is the first to address the issue of HAZARD and not RISK. Risk is the product of hazard AND exposure. Therefore, if something is highly hazardous but is encountered at low levels in the environment, the risk is significantly reduced. Conversely, exposure to large amounts of even the most mildly hazardous materials may pose unacceptable risk.
The probability is extraordinarily low of encountering an aerosol of prion particles outside of the highly rarefied environment of an experimental neuropathology laboratory. Given that prions are typically found integrated into a tissue, it is difficult to imagine how an aerosol might be generated absent the vigorous agitation of fecal matter eliminated from an affected animal. Which brings us to the dose. The amount of protein used in the studies is extraordinarily high. It would be nigh on impossible to generate a breathable mist in the general environment with protein levels that high without the individual noticing.
In summary, this is an exciting scientific study that highlights the POSSIBILITY of prion particles gaining access to the brain via inhalation. The study identifies new mechanisms of ‘infection’ and the role of the immune system in promoting/inhibiting the appearance of prions in the CNS. However, the study was not designed to address the issue of risk (and in the absence of a dose-response study, stretches to justify some of its conclusions). While additional studies are required to ascertain the precise risk of infection by inhalation, the available epidemiology to date does not support alarm regarding widespread exposure and conversion to neuropathologic disease. Nevertheless, additional information gathered in occupational settings where exposures might approach those deemed ‘high’ would aid in the determination of risk.
Some Facts About Prion Disease
- Prions produce ‘spongiform’ change in the brains of affected organisms. The neuropathic picture is invariably associated with neuronal cell death and loss of synaptic connections between neurons, and swelling of astrocytes (support cells) to form small vacuoles or holes that give rise to the ‘spongy’ appearance under the microscope.
- The most common forms in humans are Creutzfeld-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and kuru.
- Prion disease is not limited to humans, sheep may develop scrapie and cattle suffer from bovine spongiform encephalopathy. In cases of human cannibalism, kuru may ensue.
- Approximately 85% of all cases of human prion disease are sporadic and approximately 15% of cases are inherited through mutation of the human PrP gene in an autosomal dominant fashion. The PrP protein is found in particularly high levels in neurons.
- CJD typically affects adults (40 – 65) and has been diagnosed in more than 50 countries.
- There is no significant difference in incidence between males and females.
- In humans younger than 30, the incidence is approximately 5 in 1,000,000,000. In individuals greater than 30 years of age the incidence is approximately 1 in 1,000,000.
(Sources:’Neuropathology’ by Ellison and Love; Mosby, London and ‘Greenfield’s Neuropathology, Vol II., Arnold, London)
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