Human Prion Disease Surveillance in Washington State, 2006-2017 | Infectious Diseases | JAMA Network Open | JAMA Network
[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Figure.  Definite and Probable Human Prion Disease Cases by Type and Year of Death, Washington State, 2006 to 2017
Definite and Probable Human Prion Disease Cases by Type and Year of Death, Washington State, 2006 to 2017

Results include 137 individuals. CJD indicates Creutzfeldt-Jakob disease.

aSporadic prion disease includes sporadic CJD, variably protease-sensitive prionopathy, and sporadic fatal insomnia.

bFamilial prion disease includes familial CJD and Gerstmann-Sträussler-Scheinker disease.

Table 1.  Human Prion Disease Cases Reported in Washington State, 2006-2017
Human Prion Disease Cases Reported in Washington State, 2006-2017
Table 2.  Demographic Characteristics of 137 Decedents With Definite and Probable Human Prion Disease in Washington State, 2006-2017a
Demographic Characteristics of 137 Decedents With Definite and Probable Human Prion Disease in Washington State, 2006-2017a
Table 3.  Case-Defining Clinical Features for Definite and Probable Human Prion Disease Cases at Any Time of Disease, Washington State, 2006-2017a
Case-Defining Clinical Features for Definite and Probable Human Prion Disease Cases at Any Time of Disease, Washington State, 2006-2017a
1.
Tyler  KL.  Prions and prion diseases of the central nervous system.   Curr Clin Top Infect Dis. 1999;19:226-251.PubMedGoogle Scholar
2.
Holman  RC, Belay  ED, Christensen  KY,  et al.  Human prion diseases in the United States.   PLoS One. 2010;5(1):e8521. doi:10.1371/journal.pone.0008521PubMedGoogle Scholar
3.
Belay  ED.  Transmissible spongiform encephalopathies in humans.   Annu Rev Microbiol. 1999;53:283-314. doi:10.1146/annurev.micro.53.1.283PubMedGoogle ScholarCrossref
4.
Daus  ML.  Disease transmission by misfolded prion-protein isoforms, prion-like amyloids, functional amyloids and the central dogma.   Biology (Basel). 2016;5(1):E2. doi:10.3390/biology5010002PubMedGoogle Scholar
5.
Prusiner  SB.  Prions.   Proc Natl Acad Sci U S A. 1998;95(23):13363-13383. doi:10.1073/pnas.95.23.13363PubMedGoogle ScholarCrossref
6.
Maddox  RA, Person  MK, Blevins  JE,  et al.  Prion disease incidence in the United States: 2003-2015.   Neurology. 2020;94(2):e153-e157. doi:10.1212/WNL.0000000000008680PubMedGoogle ScholarCrossref
7.
Creutzfeldt-Jakob Disease International Surveillance Network. CJD Surveillance Data 1993-2018. 2019. Accessed June 12, 2020. http://www.eurocjd.ed.ac.uk/surveillance%20data%201.html
8.
Will  RG, Ironside  JW, Zeidler  M,  et al.  A new variant of Creutzfeldt-Jakob disease in the UK.   Lancet. 1996;347(9006):921-925. doi:10.1016/S0140-6736(96)91412-9PubMedGoogle ScholarCrossref
9.
Scott  MR, Will  R, Ironside  J,  et al.  Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans.   Proc Natl Acad Sci U S A. 1999;96(26):15137-15142. doi:10.1073/pnas.96.26.15137PubMedGoogle ScholarCrossref
10.
Diack  AB, Head  MW, McCutcheon  S,  et al.  Variant CJD. 18 years of research and surveillance.   Prion. 2014;8(4):286-295. doi:10.4161/pri.29237PubMedGoogle ScholarCrossref
11.
Urwin  PJ, Mackenzie  JM, Llewelyn  CA, Will  RG, Hewitt  PE.  Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study.   Vox Sang. 2016;110(4):310-316. doi:10.1111/vox.12371PubMedGoogle ScholarCrossref
12.
The National CJD Research and Surveillance Unit (NCJDRSU), University of Edinburgh. Variant CJD cases worldwide. Published 2019. Accessed February 3, 2020. http://www.cjd.ed.ac.uk/sites/default/files/worldfigs.pdf
13.
Centers for Disease Control and Prevention. vCJD cases reported in the US. Updated October 9, 2018. Accessed February 3, 2020. https://www.cdc.gov/prions/vcjd/vcjd-reported.html
14.
Centers for Disease Control and Prevention. BSE cases identified in the United States. Updated October 9, 2018. Accessed February 3, 2020. https://www.cdc.gov/prions/bse/case-us.html
15.
Washington State Legislature. WAC 246-101-101. Notifiable conditions and the health care provider. Published October 25, 2019. Accessed June 12, 2020. https://apps.leg.wa.gov/WAC/default.aspx?cite=246-101-101
16.
Case Western Reserve University. National Prion Disease Surveillance Center. Updated 2020. Accessed June 12, 2020. http://www.cjdsurveillance.com
17.
Appleby  BS ,Rincon-Beardsley  TD, Appleby  KK, Wallin  MT. Racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease in the United States of America.  PLoS One. 2012;7(6):e38884. doi:10.1371/journal.pone.0038884
18.
Centers for Disease Control and Prevention. Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD), 2018. Updated January 29, 2019. Accessed June 12, 2020. https://www.cdc.gov/prions/cjd/diagnostic-criteria.html
19.
Foutz  A, Appleby  BS, Hamlin  C,  et al.  Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.   Ann Neurol. 2017;81(1):79-92. doi:10.1002/ana.24833PubMedGoogle ScholarCrossref
20.
Bonda  DJ, Manjila  S, Mehndiratta  P,  et al.  Human prion diseases: surgical lessons learned from iatrogenic prion transmission.   Neurosurg Focus. 2016;41(1):E10. doi:10.3171/2016.5.FOCUS15126PubMedGoogle Scholar
21.
Kobayashi  A, Parchi  P, Yamada  M, Mohri  S, Kitamoto  T.  Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.   Neuropathology. 2016;36(3):305-310. doi:10.1111/neup.12270PubMedGoogle ScholarCrossref
22.
Cali  I, Miller  CJ, Parisi  JE, Geschwind  MD, Gambetti  P, Schonberger  LB.  Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.   Acta Neuropathol Commun. 2015;3:37. doi:10.1186/s40478-015-0214-2PubMedGoogle ScholarCrossref
23.
Washington State Office of Financial Management. State of Washington 2020 Population Trends. Published August 2020. Accessed June 12, 2020. https://www.ofm.wa.gov/sites/default/files/public/dataresearch/pop/april1/ofm_april1_poptrends.pdf
24.
Jansen  C, Parchi  P, Capellari  S,  et al.  Human prion diseases in the Netherlands (1998-2009): clinical, genetic and molecular aspects.   PLoS One. 2012;7(4):e36333. doi:10.1371/journal.pone.0036333PubMedGoogle Scholar
25.
Heinemann  U, Krasnianski  A, Meissner  B,  et al.  Creutzfeldt-Jakob disease in Germany: a prospective 12-year surveillance.   Brain. 2007;130(Pt 5):1350-1359. doi:10.1093/brain/awm063PubMedGoogle ScholarCrossref
26.
Gubbels  S, Bacci  S, Laursen  H,  et al.  Description and analysis of 12 years of surveillance for Creutzfeldt-Jakob disease in Denmark, 1997 to 2008.   Euro Surveill. 2012;17(15):20142.PubMedGoogle Scholar
27.
Osterholm  MT, Anderson  CJ, Zabel  MD, Scheftel  JM, Moore  KA, Appleby  BS.  Chronic wasting disease in cervids: implications for prion transmission to humans and other animal species.   mBio. 2019;10(4):e01091-19. doi:10.1128/mBio.01091-19PubMedGoogle Scholar
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Prion Disease Identified in Washington State Deer and Elk, Your Program Must Continue.
    Gary Ordog, MD, DABEM, DABMT | County of Los Angeles, Department of Health Services, (retired)
    Thank you for your paper on Prion Disease. This disease should be a significant worry for Public Health Departments. My understanding is that since your last data collection, prion disease has been identified in at least some deer and elk in the state. The Chronic Wasting Disease (or Deer Zombie Disease) CWD appears to be increasing in incidence in the state as well. The prion is allegedly heat and cold stable (remains 'infectious' even with cooking and freezing). All biological byproducts may remain 'infectious' for extended periods of time (e.g. carcass, excrement, secretions, etc.). Apparently thousands of people in Washington eat deer and elk that they have hunted every year. In conclusion, the surveillance system you describe must be continued as part of the Public Health service.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Views 2,911
    Citations 0
    Original Investigation
    Neurology
    October 16, 2020

    Human Prion Disease Surveillance in Washington State, 2006-2017

    Author Affiliations
    • 1Washington State Department of Health, Shoreline
    • 2Dengue Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, San Juan, Puerto Rico
    • 3Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
    • 4National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio
    • 5Hyland Software, Westlake, Ohio
    • 6Texas Department of State Health Services, Austin
    JAMA Netw Open. 2020;3(10):e2020690. doi:10.1001/jamanetworkopen.2020.20690
    Key Points

    Question  What are the results of human prion disease surveillance in Washington state?

    Findings  In this cross-sectional study using state surveillance data from 2006 to 2017, 143 human prion disease cases were detected, with an average annual age-adjusted incidence consistent with national reports. The majority of cases (94%) were sporadic, and no cases met criteria for a variant Creutzfeldt-Jakob disease diagnosis.

    Meaning  These findings indicate that prion disease surveillance in Washington state is beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion diseases should they occur.

    Abstract

    Importance  Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans.

    Objective  To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017.

    Design, Setting, and Participants  This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020.

    Exposure  Human prion disease diagnosis.

    Main Outcomes and Measures  The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease.

    Results  A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported.

    Conclusions and Relevance  The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state’s enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.

    Introduction

    Prion diseases, also called transmissible spongiform encephalopathies, are a group of rare, fatal, neurodegenerative diseases that occur in animals and humans. These diseases are characterized by the conversion of normal prion proteins into abnormal, pathogenic agents known as prions.1-3 This conversion process can be sporadic, related to a genetic mutation, or induced by the uptake of the pathogenic prions.3,4 The accumulation of prions is associated with neuronal injury leading to spongiform changes in the central nervous system.5

    The most common human prion disease (HPD) is Creutzfeldt-Jakob disease (CJD), with an age-adjusted incidence of 1.2 cases per million population per year in the United States, similar to the incidence reported in other countries.6,7 Sporadic CJD accounts for approximately 85% of CJD cases and familial CJD for 10% to 15%.3 Other less common prion diseases include fatal familial insomnia, sporadic fatal insomnia, Gerstmann-Straüssler-Scheinker disease, variably protease-sensitive prionopathy, and acquired prion disease.

    In 1996, a new, acquired HPD, termed variant CJD (vCJD), was described in the United Kingdom.8 It was linked to the consumption of prion-contaminated beef or beef products from cattle afflicted with bovine spongiform encephalopathy (BSE).9 Later, several patients with vCJD were determined to have contracted their illness through receipt of blood from donors who subsequently developed vCJD.10,11 As of January 2020, 232 cases of vCJD have been described around the world.12 This number includes 4 patients who were diagnosed in the United States but were likely exposed to the infectious agent outside the country.13 Variant and iatrogenic (ie, health care–acquired) CJD accounts for less than 1% of the total number of HPD cases.

    In December 2003, a dairy cow imported from Canada into the state of Washington was diagnosed with BSE. Beef from the slaughtered cow had been processed for human consumption, and a recall of all beef from cattle slaughtered the same day at the involved slaughter plant was requested.14 In response to this incident, the Washington State Department of Health (WA DOH) established an enhanced HPD surveillance system the following year and has maintained a centralized database of all suspected cases in the state since that time. Human prion disease has been a distinct notifiable condition in Washington (Washington Administrative Code 246-101-101) since February 2011. Once clinically diagnosed, cases are to be reported within 3 business days to public health authorities (ie, local health jurisdictions).15 Before 2011, HPD was notifiable under the category of “other rare diseases of public health significance.”

    The objectives of surveillance activities in Washington are (1) to establish background incidence rates and monitor trends in the epidemiology of HPD in the state, (2) to detect the possible emergence of vCJD or a possible new HPD, (3) to detect and help prevent potential iatrogenic CJD, and (4) to facilitate accurate HPD diagnoses. To aid in accomplishing these objectives, and in collaboration with the US Centers for Disease Control and Prevention (CDC), WA DOH personnel work closely with the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University, which is supported by the CDC and sponsored by the American Association of Neuropathologists. A major purpose of the NPDPSC is to provide state-of-the-art diagnostic testing for clinically suspected HPD cases.16

    This article describes the current HPD surveillance system in place in Washington and the epidemiological and clinical results of surveillance activities during the years 2006 through 2017.

    Methods

    This cross-sectional study was conducted using data obtained through the HPD surveillance system in Washington state for HPD cases with date of death from January 1, 2006, through December 31, 2017. Prion disease surveillance is a component of regular WA DOH duties; associated activities are not considered research and are not reviewed by an ethics committee. The presentation and discussion of study findings followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

    Case Finding

    The WA DOH receives prion disease reports from 3 main sources: the NPDPSC, death certificate data, and health care professionals, including physicians and infection control professionals. On rare occasions, notifications from the general public have also been received.

    The NPDPSC provides a WA DOH prion epidemiologist (including L.S.-G. or L.L.) with a copy of the results of brain autopsies and tests performed at the center for Washington residents or those ordered by Washington health care professionals. Among the possible tests are cerebrospinal fluid (CSF) Tau protein, CSF 14-3-3 protein, second-generation real-time quaking-induced conversion (RT-QuIC), brain biopsy, and blood PRNP genotyping. For some cases, the center may arrange for expert reviews of available magnetic resonance imaging results. The prion epidemiologist combines these NPDPSC data with available WA DOH information from case reports and investigations.

    All patients in Washington with at least 1 positive test result (ie, positive 14-3-3, positive RT-QuIC, or tau protein level >1150 mg/mL) are investigated. Patients for whom clinical or epidemiological suspicion persists despite negative results are discussed with the CDC to determine the need for additional follow-up. The WA DOH conducts most of the investigations, although some of the 35 local health jurisdictions in the state conduct their own.

    The WA DOH prion epidemiologist maintains routine and frequent communication with the State Vital Statistics epidemiologist. All death certificates with literal text and/or codes corresponding with HPDs (eg, Creutzfeldt-Jakob, fatal familial insomnia, prion disease, Gerstmann-Sträussler-Scheinker) are reviewed to determine whether the case is in the prion epidemiologist’s database and to establish whether further follow-up is necessary.

    Case Investigation

    Data on demographics, clinical presentation and course, and infection prevention and control are collected. Race and ethnicity are obtained from the demographics section of available medical records, if noted, with options being defined by the hospitals and medical institutions; otherwise, these data are obtained from the death certificate. These characteristics were assessed because previous studies have shown differences in prion disease incidence by race.6,17

    After notification of a suspected case, the prion epidemiologist obtains and reviews medical records and tests results. Facilities where the patient had been hospitalized are contacted, and interviews with clinicians, infection control professionals, and/or families are pursued to collect information on clinical presentation and risk factors for acquired prion disease, such as previous neurosurgery or receipt of a cadaver-derived pituitary hormone. Information regarding prion diseases and infection control measures are shared with infection control professionals.

    The prion epidemiologist encourages health care professionals to discuss the possibility of autopsy with the patient’s caregivers when appropriate to obtain neuropathological confirmation of the diagnosis. Information regarding the NPDPSC’s autopsy service is given to the health care professional; information regarding other services available at the NPDPSC (eg, genetic testing for familial prion disease) and support services (eg, CJD Foundation) is given to families.

    Cases of CJD are classified as sporadic (definite, probable, or possible), familial, or iatrogenic according to the current CDC Diagnostic Criteria.18 Cases lacking histopathological confirmation, genetic testing, and information indicating an iatrogenic source of infection or familial disease are classified as sporadic by default. Cases with insufficient information available for designation as definite, probable, or possible CJD are classified as physician-diagnosed CJD, provided CJD is listed as a cause of death on the death certificate and a prion disease diagnosis cannot be ruled out. Cases are followed until a prion disease diagnosis is excluded or confirmed or the patient dies. If biopsy or autopsy is performed, the follow-up continues until final results of brain tissue tests are received, a type of prion disease is established, and the case is closed.

    Cases in which the patient is younger than 55 years or those with unusual clinical presentation or diagnostic results, concerning exposures, or any other special characteristics are discussed with the CDC and the NPDPSC in order to determine the need for further testing or public health measures.

    Data Collection and Statistical Analysis

    All investigated cases (confirmed or not) are included in a confidential line list maintained by the WA DOH prion epidemiologist. Cases are also included in the Public Health Information Management System database. This database contains demographic, clinical, and infection control information regarding patients with notifiable conditions reported to WA DOH. When available, medical records for the HPD cases reported and investigated in Washington with date of death between January 1, 2006, and December 31, 2017, were reviewed and the abstracted information analyzed. Data analysis was conducted from June 1, 2016, to July 1, 2020.

    Tau protein results were available from 2007 through 2017, second-generation RT-QuIC results were available starting in April 2015, and 14-3-3 results were available for the full 12 years included in this study. Incidence rates and demographic statistics were calculated based on cases classified as sporadic prion disease (definite or probable), familial prion disease, or iatrogenic CJD. Information regarding onset, clinical presentation, CSF test results, electroencephalography results, brain imaging studies, and pathology results were analyzed using SAS statistical software, version 9.4 (SAS Institute, Inc). Average annual age-adjusted incidence rates were calculated using the year 2000 as the standard population. Statistical significance was set at P < .05, and a 2-sided P value was calculated from the 95% CIs of the rate difference assuming a normal distribution.

    Results

    A total of 143 HPD cases in Washington with date of death during 2006 through 2017 were detected (Table 1) and classified according to CDC criteria. Most of the cases (n = 134 [93.7%]) were classified as sporadic prion disease, 8 cases (5.6%) as familial prion disease, and 1 case (0.7%) as iatrogenic CJD. No cases of vCJD were identified. The average annual age-adjusted prion disease incidence was 1.5 per million population per year. For the periods 2006-2009, 2010-2012, 2013-2015, and 2015-2017, the incidence was 1.6, 1.3, 1.5, and 1.5 cases per million population, respectively, demonstrating stability. Demographic characteristics are described in Table 2. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38 to 84 years). Most patients were White (n = 124 [92.5%] among 134 with reported race), and slightly over half were male (n = 70 [51.1%]). Average annual age-adjusted incidence between men and women (1.6 vs 1.4 per million, respectively) was not different (P = .35). The highest average annual age-specific incidence rate, 9.1 per million, was observed in those aged 75 to 84 years.

    Of the total 134 sporadic prion disease cases, 92 (68.7%) were neuropathologically confirmed (ie, definite cases); these cases included sporadic CJD (n = 90 [97.8%]), sporadic fatal insomnia (n = 1 [1.1%]), and variably protease-sensitive prionopathy (n = 1 [1.1%]) (Figure). Among the 90 definite sporadic CJD cases, 38 (42.2%) were the MM1 subtype, 10 (11.1%) were MV1, 10 (11.1%) were VV2, 8 (8.9%) were MM1-2, 8 (8.9%) were MV1-2, 7 (7.8%) were MV2, 5 (5.6%) were VV1-2, and 3 (3.3%) were MM2; 1 sporadic CJD case for whom frozen autopsy tissue was unavailable for analysis was considered by NPDPSC to be consistent with the MM(MV)1 subtype. Of the remaining sporadic prion disease cases (n = 42), most were classified as probable CJD (n = 36 [85.7%]). Test results for second-generation RT-QuIC in CSF were available for 10 of the probable CJD cases, 9 of which were positive, indicating likely true prion disease given the test’s very high specificity.19 Four of the 42 cases (9.5%) met criteria for possible CJD, and the remaining 2 cases lacked sufficient information for classification and were designated as physician-diagnosed cases; both of these patients were older than 60 years, making a vCJD diagnosis unlikely.

    Of the 8 familial prion disease cases, 7 were familial CJD, and 1 was Gerstmann-Straüssler-Scheinker disease. All familial cases were classified as definite, including 2 that lacked neuropathologic testing but met clinical criteria and had a genetic mutation and/or positive family history. Three of the familial CJD cases had the E200K mutation; the remaining 4 cases had T183A, T188R, or D178N mutations, or a 5 octapeptide insert. The Gerstmann-Straüssler-Scheinker case had a 9 octapeptide insert.

    The iatrogenic CJD case was associated with cadaver-derived human growth hormone administration during childhood and is part of an ongoing US outbreak of human growth hormone–associated CJD.20 It also had the unusual, distinct pathological phenotype reported as likely specific for iatrogenic CJD.20-22

    Cases were reported from 26 of 35 local health jurisdictions (74.3%). There was no clear geographic clustering. One-third of the cases (n = 55 [38.4%]) occurred among residents of King and Pierce counties, which include the cities of Seattle and Tacoma and represent 41% of the state’s population.23

    A majority of all prion disease cases (n = 99 [69.2%]), including 9 of the 15 cases (60.0%) in patients younger than 55 years at death, were neuropathologically confirmed by brain biopsy (n = 3), autopsy (n = 89), or both (n = 7). The annual percentage of cases confirmed by neuropathology ranged from 56.3% to 90.0%. Of the 99 confirmed cases, 85 (85.9%) had a CSF 14-3-3 protein result available; of those, 67 (78.8%) had a positive test result, whereas 10 (11.8%) were ambiguous and 8 (9.4%) were negative. Seven of the 8 confirmed cases with a negative 14-3-3 protein result also had the Tau protein test performed; 2 had a Tau protein level greater than 1150 mg/mL, and 5 did not.

    Case-defining symptoms and signs reported for sporadic prion disease patients are summarized in Table 3. All patients presented with rapidly progressive dementia. Cerebellar abnormalities were reported in 103 cases (75.2%), and approximately half of patients reported extrapyramidal abnormalities (n = 68 [49.6%]) and visual abnormalities (n = 61 [44.5%]). Akinetic mutism and pyramidal signs were the least commonly reported clinical features. The WA DOH surveillance activities described in the Methods continue uninterrupted, and no vCJD diagnoses have been made in Washington after the time frame of this study.

    Discussion

    Since the identification of a BSE-positive dairy cow in the state in 2003, WA DOH, in collaboration with the CDC and the NPDPSC, has been conducting HPD surveillance. During the 12-year period evaluated in this cross-sectional study, the vast majority of HPD cases identified were classified as sporadic CJD, and no vCJD cases were detected. The average annual age-adjusted incidence, 1.5 cases per million population, was stable during this period with no apparent geographical clustering. Higher incidence rates were reported among decedents who were male, White, and aged 55 years or older, congruous with national findings.6 The finding of an average annual age-adjusted incidence slightly higher than the national rate, 1.2 per million, may be at least partially explained by the enhanced prion disease surveillance conducted in Washington, which has led to improved case detection. Efforts have been made in the state to increase awareness among neurologists and other medical providers regarding prion disease and the services available at the NPDPSC for diagnosis and confirmation purposes.

    The median age at death (66 years) is comparable to national findings and findings from other industrialized countries.24-26 As expected, the vast majority of cases occurred among persons aged 55 years or older. The proportion of people aged 65 years or older in Washington increased from 12.3% in 2010 to 16.2% in 201923; as the state population continues to age, a corresponding increase in the number of HPD cases is expected. According to official estimates for 2010,24 82.3% of Washington state residents are White, 7.3% are Asian, 3.7% are Black, and 1.8% are American Indian/Alaska Native. Consistent with previous studies,2,6 White decedents were overrepresented in our findings, comprising 92.5% of the definite and probable HPD cases.

    Since 2003, 5 additional cases of BSE, all atypical, have been identified in other states; no further BSE cases have been reported in Washington, which remains the only state where classic BSE has been found.14 This fact, combined with the recall of beef products in Washington after the BSE-infected cow’s slaughter, increases the importance of the state’s human prion disease surveillance.

    Recently, concerns about the potential for chronic wasting disease (CWD), a prion disease of deer, elk, and moose, to transmit to humans have also been raised.27 Chronic wasting disease has not yet been found in Washington despite extensive surveillance conducted between 2001 and 2012, when more than 5000 animals were tested without finding any positive results. Currently, the Washington Department of Fish and Wildlife conducts surveillance targeting only animals with clinical signs of CWD. Should CWD be found in Washington in the future, ongoing HPD surveillance will be beneficial in assessing whether there is any connection between animal and human disease.

    Limitations

    A limitation of this study is that only partial medical records were available for some patients, and the complete clinical presentation of the disease, including initial signs and symptoms, was sometimes difficult to ascertain. This limitation could potentially influence case classification, because some actual criteria and findings may not have been considered. In addition, the highly specific second-generation RT-QuIC CSF test was not regularly used by NPDPSC until 2015. Most cases, however, had neuropathologic confirmation. Collaboration with the NPDPSC, which performs the majority of premortem tests, enables a timely notification to WA DOH of suspected cases in the state and thus contributes to the number of subsequent autopsies performed.

    Conclusions

    In this cross-sectional study of Washington state’s HPD surveillance system, findings suggest that the demographic characteristics of patients with prion disease between 2006 and 2017 were consistent with national findings. Despite a statewide prion disease surveillance program being in place since 2004, neither vCJD nor another new prion disease has been detected in the state. Given the long incubation periods associated with prion diseases, ongoing vigilance and collaboration with surveillance partners continue to be necessary.

    Back to top
    Article Information

    Accepted for Publication: August 5, 2020.

    Published: October 16, 2020. doi:10.1001/jamanetworkopen.2020.20690

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Sánchez-González L et al. JAMA Network Open.

    Corresponding Author: Liliana Sánchez-González, MD, MPH, Centers for Disease Control and Prevention, 1324 Calle Cañada, San Juan, Puerto Rico, 00920 (naq5@cdc.gov).

    Author Contributions: Dr Sánchez-González had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Sanchez-Gonzalez, Maddox, Schonberger, Lofy, DeBolt, Belay.

    Acquisition, analysis, or interpretation of data: Sanchez-Gonzalez, Maddox, Appleby, Blevins, Person, Lewis, Lofy, DeBolt, Belay, Harker.

    Drafting of the manuscript: Sanchez-Gonzalez, Maddox, DeBolt.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Maddox, Person, Harker.

    Obtained funding: Schonberger, Appleby.

    Administrative, technical, or material support: Appleby, Blevins, Lewis, Lofy, DeBolt.

    Supervision: Schonberger, Appleby, Lofy, DeBolt, Belay.

    Conflict of Interest Disclosures: Dr Appleby reported receiving grants from the Centers for Disease Control and Prevention during the conduct of the study and financial support for test development from Ionis outside the submitted work. Dr Lewis reported receiving grants from the US Centers for Disease Control and Prevention during the conduct of the study. No other disclosures were reported.

    Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

    References
    1.
    Tyler  KL.  Prions and prion diseases of the central nervous system.   Curr Clin Top Infect Dis. 1999;19:226-251.PubMedGoogle Scholar
    2.
    Holman  RC, Belay  ED, Christensen  KY,  et al.  Human prion diseases in the United States.   PLoS One. 2010;5(1):e8521. doi:10.1371/journal.pone.0008521PubMedGoogle Scholar
    3.
    Belay  ED.  Transmissible spongiform encephalopathies in humans.   Annu Rev Microbiol. 1999;53:283-314. doi:10.1146/annurev.micro.53.1.283PubMedGoogle ScholarCrossref
    4.
    Daus  ML.  Disease transmission by misfolded prion-protein isoforms, prion-like amyloids, functional amyloids and the central dogma.   Biology (Basel). 2016;5(1):E2. doi:10.3390/biology5010002PubMedGoogle Scholar
    5.
    Prusiner  SB.  Prions.   Proc Natl Acad Sci U S A. 1998;95(23):13363-13383. doi:10.1073/pnas.95.23.13363PubMedGoogle ScholarCrossref
    6.
    Maddox  RA, Person  MK, Blevins  JE,  et al.  Prion disease incidence in the United States: 2003-2015.   Neurology. 2020;94(2):e153-e157. doi:10.1212/WNL.0000000000008680PubMedGoogle ScholarCrossref
    7.
    Creutzfeldt-Jakob Disease International Surveillance Network. CJD Surveillance Data 1993-2018. 2019. Accessed June 12, 2020. http://www.eurocjd.ed.ac.uk/surveillance%20data%201.html
    8.
    Will  RG, Ironside  JW, Zeidler  M,  et al.  A new variant of Creutzfeldt-Jakob disease in the UK.   Lancet. 1996;347(9006):921-925. doi:10.1016/S0140-6736(96)91412-9PubMedGoogle ScholarCrossref
    9.
    Scott  MR, Will  R, Ironside  J,  et al.  Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans.   Proc Natl Acad Sci U S A. 1999;96(26):15137-15142. doi:10.1073/pnas.96.26.15137PubMedGoogle ScholarCrossref
    10.
    Diack  AB, Head  MW, McCutcheon  S,  et al.  Variant CJD. 18 years of research and surveillance.   Prion. 2014;8(4):286-295. doi:10.4161/pri.29237PubMedGoogle ScholarCrossref
    11.
    Urwin  PJ, Mackenzie  JM, Llewelyn  CA, Will  RG, Hewitt  PE.  Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study.   Vox Sang. 2016;110(4):310-316. doi:10.1111/vox.12371PubMedGoogle ScholarCrossref
    12.
    The National CJD Research and Surveillance Unit (NCJDRSU), University of Edinburgh. Variant CJD cases worldwide. Published 2019. Accessed February 3, 2020. http://www.cjd.ed.ac.uk/sites/default/files/worldfigs.pdf
    13.
    Centers for Disease Control and Prevention. vCJD cases reported in the US. Updated October 9, 2018. Accessed February 3, 2020. https://www.cdc.gov/prions/vcjd/vcjd-reported.html
    14.
    Centers for Disease Control and Prevention. BSE cases identified in the United States. Updated October 9, 2018. Accessed February 3, 2020. https://www.cdc.gov/prions/bse/case-us.html
    15.
    Washington State Legislature. WAC 246-101-101. Notifiable conditions and the health care provider. Published October 25, 2019. Accessed June 12, 2020. https://apps.leg.wa.gov/WAC/default.aspx?cite=246-101-101
    16.
    Case Western Reserve University. National Prion Disease Surveillance Center. Updated 2020. Accessed June 12, 2020. http://www.cjdsurveillance.com
    17.
    Appleby  BS ,Rincon-Beardsley  TD, Appleby  KK, Wallin  MT. Racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease in the United States of America.  PLoS One. 2012;7(6):e38884. doi:10.1371/journal.pone.0038884
    18.
    Centers for Disease Control and Prevention. Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD), 2018. Updated January 29, 2019. Accessed June 12, 2020. https://www.cdc.gov/prions/cjd/diagnostic-criteria.html
    19.
    Foutz  A, Appleby  BS, Hamlin  C,  et al.  Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.   Ann Neurol. 2017;81(1):79-92. doi:10.1002/ana.24833PubMedGoogle ScholarCrossref
    20.
    Bonda  DJ, Manjila  S, Mehndiratta  P,  et al.  Human prion diseases: surgical lessons learned from iatrogenic prion transmission.   Neurosurg Focus. 2016;41(1):E10. doi:10.3171/2016.5.FOCUS15126PubMedGoogle Scholar
    21.
    Kobayashi  A, Parchi  P, Yamada  M, Mohri  S, Kitamoto  T.  Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.   Neuropathology. 2016;36(3):305-310. doi:10.1111/neup.12270PubMedGoogle ScholarCrossref
    22.
    Cali  I, Miller  CJ, Parisi  JE, Geschwind  MD, Gambetti  P, Schonberger  LB.  Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.   Acta Neuropathol Commun. 2015;3:37. doi:10.1186/s40478-015-0214-2PubMedGoogle ScholarCrossref
    23.
    Washington State Office of Financial Management. State of Washington 2020 Population Trends. Published August 2020. Accessed June 12, 2020. https://www.ofm.wa.gov/sites/default/files/public/dataresearch/pop/april1/ofm_april1_poptrends.pdf
    24.
    Jansen  C, Parchi  P, Capellari  S,  et al.  Human prion diseases in the Netherlands (1998-2009): clinical, genetic and molecular aspects.   PLoS One. 2012;7(4):e36333. doi:10.1371/journal.pone.0036333PubMedGoogle Scholar
    25.
    Heinemann  U, Krasnianski  A, Meissner  B,  et al.  Creutzfeldt-Jakob disease in Germany: a prospective 12-year surveillance.   Brain. 2007;130(Pt 5):1350-1359. doi:10.1093/brain/awm063PubMedGoogle ScholarCrossref
    26.
    Gubbels  S, Bacci  S, Laursen  H,  et al.  Description and analysis of 12 years of surveillance for Creutzfeldt-Jakob disease in Denmark, 1997 to 2008.   Euro Surveill. 2012;17(15):20142.PubMedGoogle Scholar
    27.
    Osterholm  MT, Anderson  CJ, Zabel  MD, Scheftel  JM, Moore  KA, Appleby  BS.  Chronic wasting disease in cervids: implications for prion transmission to humans and other animal species.   mBio. 2019;10(4):e01091-19. doi:10.1128/mBio.01091-19PubMedGoogle Scholar
    ×