Data FAQs Reporting Resources
Overview
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of progressive neurodegenerative disorders in humans and animals. The causative agents of TSEs are believed to be prions. The term “prions” refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. Prion diseases are always fatal and have long incubation periods that are often measured in years. Creutzfeldt-Jakob disease (CJD) is the most common human prion disease. Sporadic CJD (also called classic CJD) makes up 85-95% of all CJD cases, followed by familial or genetic CJD with 5-15% of cases; <1% of cases are iatrogenic or variant CJD.
Organism/Etiologic Agent
Prion (infectious protein)
Transmission
- Sporadic CJD (sCJD) – No recognizable pattern of transmission or is unknown
- Familial CJD (fCJD) – Inherited
- Iatrogenic CJD (iCJD) - Iatrogenic CJD is associated with certain surgical or
medical procedures, for example neurosurgical procedures, corneal transplants,
dura mater grafts, and administration of contaminated pituitary hormones
- Iatrogenic CJD cases from dural graft transplants and use of pituitary
hormones (human growth hormone) from cadavers have been largely eliminated due
to use of synthetic dural grafts.
- Cases due to contaminated equipment occurred before the routine
implementation of sterilization procedures currently used in healthcare
facilities, and no cases have been reported since 1976. Refer to CDC’s website for CJD infection
control and prevention recommendations.
- Variant CJD (vCJD) – Has been associated with consumption of beef products from cattle infected with bovine spongiform encephalopathy (BSE or “mad cow disease”); several iatrogenic cases of transfusion-related vCJD have been reported in the United Kingdom (donors developed vCJD or symptoms of vCJD after donation)
No vCJD cases have been linked to exposure in the United States.
Symptoms
- Sporadic CJD (sCJD) – Symptoms may include rapidly progressive dementia,
myoclonus, ataxia, and vision and speech difficulties. Sporadic CJD typically
occurs in persons greater than 55 years of age. The median duration from illness
onset to death is 4-5 months.
- Familial CJD (fCJD) – Symptoms and duration of illness closely resemble sCJD
but can vary within families and depend on the type of genetic mutation.
Familial CJD cases have only a slightly younger mean age of onset compared with
sCJD cases.
- Iatrogenic CJD (iCJD) – Symptoms vary depending on the mode of transmission,
but clinical and pathological features are often indistinguishable from sCJD. Human
gonadotropin and growth hormone treatment, as well as dura mater grafts, tend
to begin as a cerebellar syndrome early in the disease course. However,
infected dura mater grafts have also been noted to cause symptoms that relate
to the anatomic placement of the graft. The age at onset depends on the age at
exposure, and on the incubation period. The reported or estimated mean time of
occurrence is 9-10 years after administration of human growth hormone and dural
graft transplants but can be from 5-40+ years. For additional information on
iCJD see the Iatrogenic
Creutzfeldt-Jakob Disease, Final Assessment
article.
- Variant CJD (vCJD) – Symptoms may include early
psychiatric/behavioral symptoms and dysesthesia/paresthesia progressing to
ataxia, dementia, chorea/dystonia or myoclonus, and/or akinetic mutism. Variant
CJD typically occurs in persons less than 55 years of age (mean age in the
United Kingdom is 28 years), and the mean duration of illness is 13-14
months.
Treatment & Prevention
There is no known prevention or treatment that will
stop progression of these fatal diseases.
Recent Texas Trends
Prion disease surveillance in the
United States provides a better understanding of prions and the diseases they
cause. Prion disease surveillance monitors the occurrence of prion diseases in
the United States, but it also monitors for the emergence of vCJD and other
potentially preventable new prion diseases, as well as for rare classic forms
of prion diseases that are attributable to medical procedures. Prion disease
surveillance also helps assess the efficacy of ongoing U.S. prevention
measures.
CJD has been a NOTIFIABLE CONDITION in Texas since
1998, and it was likely under-reported and misdiagnosed for many years. For
over 10 years now, Texas has carried out enhanced surveillance (passive and
active surveillance) for CJD, including sporadic, familial/genetic, and acquired
(iatrogenic and variant) CJD. The success of this program is demonstrated by
the identification and confirmation of sporadic (sCJD), familial (fCJD) and variant
(vCJD) CJD, as well as cases of Variably Protease Sensitive Prionopathy (VPSPr),
Fatal Familial Insomnia (FFI), sporadic Fatal Insomnia (sFI), and Gerstmann-Sträussler-Scheinker
(GSS) syndrome. From 2010-2019 Texas reported 244 sCJD, 16 fCJD, 1 vCJD, 3
VPSPr, 3 FFI, and 2 sFI cases. Texas also investigates higher priority cases,
such as cases in persons <55 years old, as vCJD is rarely found in individuals >55 years
old, reported possible clusters, potential iatrogenic cases, and cases with
risk factors that could expose them to other prion diseases, such as chronic
wasting disease of deer and elk.
In 2014, Texas had the 4th
US variant CJD case; the person was likely exposed to the infectious agent
before moving to the United States. A full description of the case can be found
at: http://wwwnc.cdc.gov/eid/article/21/5/pdfs/14-2017.pdf
Maheshwari A, Fischer M, Gambetti
P, Parker A, Ram A, Soto C, Concha-Marambio L, Cohen Y, Belay ED, Maddox RA,
Mead S, Goodman C, Kass JS, Schonberger LB,Hussein HM. Recent US Case of
Variant Creutzfeldt-Jakob Disease-Global Implications. Emerg Infect Dis. 2015
May;21(5):750-9. doi:10.3201/eid2105.142017. PubMed PMID: 25897712; PubMed
Central PMCID: PMC4412247.
The Centers for Disease Control
and Prevention (CDC) reports a worldwide (including the United States) CJD
incidence rate of approximately 1-1.5 cases per million population per year, but
rates up to 2 cases per million are not unusual.
In Texas, the average rate of
deaths per million population due to CJD over the past 10 years (2010-2019) is
0.99 cases per million population per year. The average rate over two
consecutive 5-year periods, 2010-2014 & 2015-2019, are 0.84 & 1.13
(cases per million population per
year), respectively. There has been an increase in CJD cases over the last
several years, and this can be attributed to several factors. The population of
Texas is increasing, the availability of a new more sensitive test, the
“Real-Time Quaking Induced Conversion (RT-QuIC)” test, in 2015, as well as
increased awareness of this testing and confirmatory testing available at the
National Prion Disease Pathology Surveillance Center (NPDPSC), has increased
the surveillance capacity for human prion diseases in Texas (increased
reporting and antemortem diagnosis of CJD). The intensity of surveillance
methods can influence the reported incidence of CJD, and other prion diseases. CDC
also updated their criteria for classifying a CJD case which was implemented in
Texas in 2019. The combination of a positive RT-QuIC cerebrospinal fluid (CSF
or spinal fluid) result with neuropsychiatric symptoms allows for decreased
reliance on the presence of specific neurologic symptoms to classify a case of
CJD. This has permitted the classification of CJD cases that previously may not
have been counted. The change in the CJD criteria is evidence of the
incorporation of scientific data into surveillance system approaches to more
accurately count cases. In 2019, the number of CJD cases and the rate of CJD
increased, however, in the majority of cases brain tissue was examined and
there were no unusual findings. Also, only four of the 2019 cases were <55
years of age, all of whom had autopsies, and the brain tissue analysis did not
reveal any unusual neuropathology. Fluctuations in the data obtained via surveillance
systems is expected, and small changes in case counts can lead to larger
changes in rates. However, with increased surveillance in Texas, a rate closer
to 1.5 cases per million population may be more representative of CJD cases in
Texas. This data will continue to be evaluated on an ongoing basis.
Better diagnostic testing has
improved CJD surveillance in Texas. In 2014, NPDPSC began offering a new
ante-mortem CSF test, the RT-QuIC test, which is a test for the
abnormal/pathogenic form of the prion protein in the CSF. Though this test may
aid physicians in the investigation of illness with rapidly progressive
dementia, it is not a confirmatory test. Neuropathological analysis of
autopsied whole brain tissue remains the only method for confirming or ruling-out
prion disease.
Brain tissue is preferably
obtained by autopsy rather than biopsy, as neuropathological analysis of
biopsied brain tissue cannot rule out prion disease, and brain biopsies are generally
not required unless a physician is trying to exclude an alternative treatable
disease. Efforts continue to educate the public and medical providers of the
importance of confirming a prion disease diagnosis and the services available
to those interested in confirmatory testing. Please see the NPDPSC website for more information
about the services offered.
