Apart from a few cases of iatrogenic and familial human transmissible spongiform encephalopathies (TSEs) or prion diseases, the cause of Creutzfeldt–Jakob disease (CJD) remains unknown. In this paper we investigated the possibility that dental procedures may represent a potential route of infection. This was assessed by using the experimental model of scrapie in hamster. In the first part of this study we found that after intraperitoneal inoculation, oral tissues commonly involved in dental procedures (gingival and pulp tissues) bore a substantial level of infectivity. We also found high scrapie infectivity in the trigeminal ganglia, suggesting that the scrapie agent had reached the oral tissues through the sensitive terminal endings of the trigeminal nerves. In the second part of the study we inoculated a group of hamsters in the tooth pulp and showed that all of them developed scrapie disease. In these animals, we detected both infectivity and the pathological prion protein (PrPsc) in the trigeminal ganglion homolateral to the site of injection but not in the controlateral one. This finding suggests that the scrapie agent, and likely other TSE agents as well, spreads from the buccal tissues to the central nervous system through trigeminal nerves. Although these findings may not apply to humans affected by TSEs, they do raise concerns about the possible risk of transmitting these disorders through dental procedures. Particular consideration should be taken in regard to new variant CJD patients because they may harbour more infectivity in peripheral tissues than sporadic CJD patients.
ArakawaK.,
NagaraH.,
ltoyamaY.,
Doh-uraK.,
TomokaneN.,
TateishiJ.,
GotoI.1991; Clustering of three cases of Creutzfeldt–Jakob disease near Fukuoka City, Japan. Acta Neurologica Scandinavica 84:445–447
BaldaufE.,
BeekesM.,
DiringerH.1997; Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord. Journal of General Virology 78:1187–1197
BeekesM.,
BaldaufE.,
DiringerH.1996; Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. Journal of General Virology 77:1925–1934
BrownP.,
GajdusekD. C.,
GibbsC. J.Jr,
AsherD. M.1985; Potential epidemic of Creutzfeldt–Jakob disease from human growth hormone therapy. New England Journal of Medicine 313:728–731
BruceM. E.,
WillR. G.,
lronsideJ. W.,
McConnellI.,
DrummondD.,
SuttieA.,
McCardieL.,
ChreeA.,
HopeJ.,
BirkettC.,
CousensS.,
FraserH.,
BostockC. J.1997; Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:489–501
CochiusJ. I.,
BurnsR. J.,
BlumbergsP. C.,
MackK.,
AldermanC. P.1990; Creutzfeldt–Jakob disease in a recipient of human pituitary- derived gonadotrophin. Australian and New Zealand Journal of Medicine 20:592–593
el HachimiK. H.,
ChaunuM. P.,
CervenakovaL.,
BrownP.,
FoncinJ. F.1997; Putative neurosurgical transmission of Creutzfeldt–Jakob disease with analysis of donor and recipient: agent strains. Comptes Rendus de I’Académie des Sciences. Série III, Sciences de la Vie 320:319–328
GroschupM. H.,
WeilandF.,
StraubO. C.,
PfaffE.1996; Detection of scrapie agent in the peripheral nervous system of a diseased sheep. Neurobiology of Disease 3:191–195
GuiroyD. C.,
ShankarS. K.,
GibbsC. J.Jr,
MessenheimerJ. A.,
DasS.,
GajdusekD. C.1989; Neuronal degeneration and neurofilament accumulation in the trigeminal ganglia in Creutzfeldt–Jakob disease. Annals of Neurology 25:102–106
KimberlinR. H.,
WalkerC. A.1979; Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. Journal of Comparative Pathology 89:551–562
KimberlinR. H.,
WalkerC. A.1982; Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection. Journal of the Royal Society of Medicine 75:618–624
KimberlinR. H.,
WalkerC. A.1986; Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. Journal of General Virology 67:255–263
KimberlinR. H.,
FieldH. J.,
WalkerC. A.1983a; Pathogenesis of mouse scrapie: evidence for spread of infection from central to peripheral nervous system. Journal of General Virology 64:713–716
KimberlinR. H.,
HallS. M.,
WalkerC. A.1983b; Pathogenesis of mouse scrapie: evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. Journal of the Neurological Sciences 61:315–325
LangC. J.,
HeckmannJ. G.,
NeundorferB.1998; Creutzfeldt–Jakob disease via dural and corneal transplants. Journal of the Neurological Sciences 160:128–139
McBrideP. A.,
BeekesM.1999; Pathological PrP is abundant in sympathetic and sensory ganglia of hamsters fed with scrapie. Neuroscience Letters 265:135–138
MuramotoT.,
KitamotoT.,
TateishiJ.,
GotoI.1993; Accumulation of abnormal prion protein in mice infected with Creutzfeldt–Jakob disease via intraperitoneal route: a sequential study. American Journal of Pathology 143:1470–1479
PocchiariM.,
SchmittingerS.,
MasulloC.1987; Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters. Journal of General Virology 68:219–223
van DuijnC. M.,
Delasnerie-LaupretreN.,
MasulloC.,
ZerrI.,
de SilvaR.,
WientjensD. P. W. M.,
BrandelJ.-P.,
WeberT.,
BonavitaV.,
ZeidlerM.,
AlperovitchA.,
PoserS.,
GranieriE.,
HofmanA.,
WillR. G.1998; Case-control study of risk factors of Creutzfeldt–Jakob disease in Europe during 1993–95. Lancet 351:1081–1085
WellsG. A. H.,
HawkinsS. A. C.,
GreenR. B.,
AustinA. R.,
DexterI.,
SpencerY. I.,
ChaplinM. J.,
StackM. J.,
DawsonM.1998; Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Veterinary Record 142:103–106
WillR. G.1996; Surveillance of prion diseases in humans. In Methods in Molecular Medicine. Prion Diseases pp 119–137 Edited by
BakerH. F.,
RidleyR. M.
Totowa, New Jersey: Humana Press;
WillR. G.,
MatthewsW. B.1982; Evidence for case-to- case transmission of Creutzfeldt–Jakob disease. Journal of Neurology, Neurosurgery and Psychiatry 45:235–238
WillR. G.,
lronsideJ. W.,
ZeidlerM.,
CousensS. N.,
EstibeiroK.,
AlperovitchA.,
PoserS.,
PocchiariM.,
HofmanA.,
SmithP. G.1996; A new variant of Creutzfeldt–Jakob disease in the UK. Lancet 347:921–925
XiY. G.,
CardoneF.,
PocchiariM.1994; Detection of proteinase-resistant protein (PrP) in small brain tissue samples from Creutzfeldt–Jakob disease patients. Journal of the Neurological Sciences 124:171–173