Human prion disease surveillance in Spain, 1993-2018: an overview

ABSTRACT

In Spain, human transmissible spongiform encephalopathies (TSEs) have been undergoing continuous surveillance for over 25 years. In 1995, the system was launched as an EU Concerted Action, with EU surveillance network procedures being incorporated from 2002 onwards. The aim of this report was to describe performance and outcomes of this surveillance system across the period 1993–2018. Neurology and public health specialists from every region reported cases to a central hub at the Carlos III Health Institute, Madrid. In all, eight accidentally transmitted cases and five definite variant Creutzfeldt-Jakob disease (vCJD) patients were reported. All vCJD cases were diagnosed between 2005 and 2008. Two of these were family/dietary-related and spatially linked to a third. Yearly incidence of sporadic CJD per million was 1.25 across the period 1998–2018, and displayed a north-south gradient with the highest incidence in La Rioja, Navarre and the Basque Country. Genetic TSEs were observed to be clustered in the Basque Country, with a 4-fold incidence over the national rate. A total of 120 (5.6%) non-TSE sporadic, conformational, rapidly progressing neurodegenerative and vascular brain disorders were reported as suspect CJD. We conclude that TSEs in Spain displayed geographically uneven, stable medium incidences for the sporadic and genetic forms, a temporal and spatial family cluster for vCJD, and decreasing numbers for dura-mater-associated forms. The vCJD surveillance, framed within the EU network, might require continuing to cover all prion disorders. There is need for further strategic surveillance research focusing on case definition of rapid-course, conformational encephalopathies and surgical risk.

KEYWORDS:

• Transmissible spongiform encephalopathies
• creutzfeldt-jakob disease
• surveillance
• epidemiology
• prion proteins
• registries
• spain

Statements

The Spanish CJD Study and Surveillance Group (Grupo para el Estudio y Vigilancia de las EETH del Consejo Interterritorial del Sistema Nacional de Salud) is composed of:

— Spanish National Register of Human Transmissible Spongiform Encephalopathies (Almazán J, Avellanal F, Calero M, De Pedro-Cuesta J, Martínez P, Ruiz M, Tello O, García López FJ.), National Epidemiology Centre and Unit of Spongiform Encephalopathies, National Microbiology Centre, Health Institute Carlos III, Madrid.

— Department of Pathology, University Hospital Fundación Alcorcón (Guerrero C, Rebolledo A), Alcorcón.

— CIEN Foundation, Foundation Research Centre of Neurological Diseases (Calero M, Rábano A).

— Regional epidemiologic and clinical coordinators in 2020: Andalusia: Heras JA, Varo A, Guillén J; Aragon: Alonso JP, Juanas FE, Ladrero O, López del Val J; Asturias: Huerta, I, Margolles M, Asensi A; Balearic Islands: Grau P, Nicolau A, Sureda B; Canary Islands: Izquierdo A, C. Muñoz, Pérez MC; Cantabria: Galán M, Martínez F, Polo JM; Castile-La Mancha: Cabeza C, Gutiérrez G, Humanes S; Castile and León: Goñi M, Marcos H; Catalonia: Domínguez A, Nos C; Valencian Region: Escudero J, Guiral S, Marín C; Extremadura: Casado I, Fuentes A, López M. Ramírez JM, Sánchez JF; Galicia: Losada I, Malvar A, Navarro C, Robles A; Madrid: Del Ser T, Frank A, Muñoz J, Pichiule M, Ramírez R; Murcia: Barranco MI, Castán Y, Contreras MA, García-Fulgueiras A, Pina R; Navarre: Barricarte A, Castilla J, Tuñón I; Basque Country: Arteagoitia JM, Zarranz JJ; La Rioja: Blanco A, Gil A, Martínez E, Marzo ME, Perucha M; Ceuta: Carrillo FJ, Rivas AI; Melilla: Castrillejo D, Duque G.

Acknowledgments

Authors would like to acknowledge the generous contribution made by multiple persons in the form of support for and collaboration with the Spanish CJD Study and Surveillance Group, and to the following in particular: notifying clinicians and pathologists and temporary members active at the registry (Alcalde E, Cuadrado JI, Mahíllo I, Martínez-Martín P, Plitt C, Ruiz Bremón A, Sevillano MD, Cuadrado Corrales N); colleagues at the National Epidemiology Centre (Tello O and Cano R); members of the Coordination Centre for Health Alerts and Emergencies of the Spanish Ministry of Health (Sierra MJ, Simón F), and Mrs. Lindsay T, Ward HJ, and Professors Will RG and Ironside J at the Edinburgh CJD Unit for advice and support. Finally, the authors would also like to thank Dr Ana Cabello for early perception of atCJD cases, and Michael Benedict for his English language revision of this paper.

Ethics

Review by Ethics Committee was not needed due to Public Health involvement.

Disclosure of potential conflicts of interest

All authors declare absence of conflict of interest.

Author contributions

Concept and design: Jesús de Pedro-Cuesta, Javier Almazán-Isla, Fernando J García López

Acquisition, analysis or interpretation of data: Javier Almazán-Isla, Fuencisla Avellanal, María Ruiz-Tovar, Miguel Calero, Jesús de Pedro-Cuesta

Drafting of the manuscript: Jesús de Pedro-Cuesta, Fernando J. García López, Laura Tejedor-Romero, Javier Almazán-Isla, Miguel Calero

Critical revision of the manuscript for important intellectual content: Jesús de Pedro-Cuesta, Javier Almazán-Isla, Laura Tejedor-Romero, María Ruiz-Tovar, Fuencisla Avellanal, Alberto Rábano, Miguel Calero, Fernando J. García López and all regional epidemiologic and clinical coordinators.

Statistical analysis: Javier Almazán-Isla

Obtained funding: Jesús de Pedro-Cuesta

Administrative, technical, or material support: Javier Almazán-Isla, Fuencisla Avellanal, María Ruiz-Tovar, Fernando J García López

Supervision: Jesús de Pedro-Cuesta

Additional information

Funding

This work was basically funded by the Spain’s Ministry of Health and the Carlos III Health Institute. Additional funding was obtained from the EU Research Commission, Concerted Actions (BIOMED2 Contract No. BMH4-CT97-2216, QLRG3-CT-2002-81223), EU Joint Program – Neurodegenerative Disease Research (JPND – DEMTEST, Spanish Health Research Fund, FIS PI11/03021 and PI12/00045), EUROCJD (funded by DG SANCO, 2003201), research grants by the Carlos III Health Institute (PI08/0139), NEUROPRION (an EU Network of Excellence funded by Framework 6 Programme, FOOD CT 2004 056579), the Spanish Centro de Investigaciones en Enfermedades Neurológicas (CIEN C03-06), and Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED) networks.Role of funders: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript;EU Research Commission [Concerted Actions (BIOMED2 Contract No. BMH4-CT97-2216, QLRG3-CT-2002-81223),];