US-Diagnosed Variant Creutzfeldt-Jakob Disease in Two Patients Born and Raised in Saudi Arabia

1. US-Diagnosed Variant Creutzfeldt-Jakob Disease in Two Patients Born and Raised in Saudi Arabia Lawrence B. Schonberger, M.D., M.P.H Prion and Public Health Office, Division of High-Consequence Pathogens & Pathology, National Center for Emerging & Zoonotic Diseases Division of High-Consequence Pathogens & Pathology National Center for Emerging and Zoonotic Infectious Diseases

2. Characteristics of the Two vCJD Patients

3. Early Symptoms of the Two vCJD Patients

4. Subsequent Dementia and Duration ofthe Two vCJD Illnesses

5. Diagnostic Test Results on the Two vCJD Patients Results

6. Countries of Residence of 1st US-Diagnosed vCJD Patient by Calendar Years, Age, and Time Intervals Before vCJD Onset *Visited United Kingdom for 4 days in late 1997 and France for 1 and/or 2 weeks in 1995 and/or 1996 (Maximum interval before vCJD onset, 8.1 years)

7. Countries of Residence of 2nd US-Diagnosed vCJD Patient by Calendar Years, Age, and Time Intervals Before vCJD Onset *Visited the United States for 1½ months in 1989 and since 2001, occasionally during vacations each year for up to about 3 months at a time.

8. Acknowledgments Pathologist Pierluigi Gambetti and his staff at the National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA Professors Robert Will and Richard Knight and their staff at the UK CJD Surveillance Unit, Edinburgh, Scotland, UK Neurologist Michael Geschwind and Pathologist Stephen DeArmond and their staff at the University of California, San Francisco, USA State Epidemiologists and their staff at the Arizona, California, North Carolina and Virginia State Departments of Health, USA Neurologists Shireen A. Qureshi, Saudi Arabia and Alireza Atri, USA Pathologist Caterina Giannini, Mayo Clinic, Minnesota, USA Dr. Imad A. Al Jahdall, Chief Preventive Medicine Services Division, Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia Colleagues at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA, particularly members of the Prion and Public Health Office, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases.

9. MRI on Saudi vCJD Patient T2 & Fluid-Attenuated Inversion-Recovery, FLAIR “Pulvinar Sign”

10. Histopathological and Immunohistochemical Findings on Brain Biopsy of First Saudi vCJD Case compared to sCJD, 2004 A C B • H&E of a florid plaque in the present case. • Immunostaining showing florid plaques. • Immunostaining of sCJDMM1 (B and C Mab 3F4).

11. B: magnification 40X – US Patient 50 µm PrP IHC Plaque-like and spider-like formations; HE of the location of the plaque-like formations is unremarkable (mAb 3F4)

12. Thank You! For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov 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. National Center for Emerging and Zoonotic Infectious Diseases Division of High-Consequence Pathogens & Pathology

13. National Prion Disease Pathology Surveillance Center - Referrals, By Year of Death * Disease almost certainly acquired outside the US (UK or Saudi Arabia).