1. Current and Former Staff of the Animal Resources Division, Health Canada 2001 Study James Brooks CIHR/CBS Post Doctoral Research Fellow Erling Rud Head, Clinical Research, Animal Resources Division, HPFB Paul Sandstrom Associate Director Bureau of HIV/AIDS, STD & TB, CIDPC Simian Foamy Virus Infection Among Individuals Occupationally Exposed to Non Human Primates

2. Outline Rationale for the Health Canada SFV Study Trends in primate importation/utilization Description of Health Canada Animal Resources Division primate colony Results of Health Canada Study of Human SFV Infection Among Animal Workers

3. Background Macaque spp. have historically been among the most common NHP’s used in research Currently cynomolgus macaques (Macaca fascicularis) represent the vast majority of imported NHP’s Despite frequent occupational exposure there had not been a documented case of human SFV infection originating from macaques

4. Last 2 years importation of NHP in U.S.A. (1999, N = 12,744; 2000, N = 12,061) Source: Tom Damercus, Division of Quarantine, National Center for Infectious Disease, Centers for Disease Control and Prevention # of non-human primates N = 12,744N = 12,061

5. Species of NHP used in Canada (1995 - 1999) N = 1373 N = 2150N = 1,621N = 875 N = 1,131

6. Study Objective To screen for human SFV infection of macaque origin using assays optimized for macaque SFV

7. Health Canada Primate Colony 875 Cynomolgus macaques imported from the Philippines 1983-1984 Currently houses approximately 240 monkeys Previously housed up to 1200 monkeys Prior to 1983 a mixture of cynomolgus and rhesus macaques Herpes B free colony 80% seropositive for SFV

8. Average Monthly NHP Colony Population by Year Number of animals

9. Study Design Anonymous, un-linked convenience sample of workers having contact with non-human primates or their blood and tissues Screened using immunoblot Target antigen SFV1, SFV3, SFV6 & SFV-HC infected cell culture lysates Confirmation using PCR amplification from PBLs of a 153 bp fragment located within the pol gene

10. Occupations of Study Participants

11. Characteristics of Study Participants Average age 45 years M:F Ratio 56:44 Average of 13 years of exposure to Cynomolgus macaques Average of 10 years of exposure to Rhesus macaques

12. Person Years of Exposure to NHP Species

13. Exposure Patterns

14. Total Number of Bites Reported By Species

15. Results of SFV Study 2 out of the 46 participants have positive serological tests for foamy virus infection (4% of study participants) 1 of the 46 participants has been confirmed as infected with SFV by PCR from PBLs Preliminary evidence suggests that this human SFV infection is of macaque origin

16. SFV HC/1/3/6 Infected Cell Lysates Cf2Th/BHK21 Uninfected Host Cell Lysates Representative Screening Immunoblot ChimpAGMCynoBaboonHuman 1Human 2 112 81 50 36 MW kDa 112 81 50 36

17. Exposure Histories of SFV Infected Humans Both individuals report : –prolonged and ongoing exposure to cynomolgus macaques –previous exposure to rhesus macaques –events involving exposure to blood and/or body fluids, including bites, scratches or surgical injuries, from macaque species

18. 0 10002000300040005000600070008000900010 00011 00012 00013 000 env pol gag LTR Accessory Genes SFV Genome Structure taf Location of 153 bp PCR Fragment in pol gene

19. 0.05 c1f c3f Human 1 c10f SFV 1 (macaque) Hamlyn’s guenon African Green Monkey SFV 3 Drill Mandrill Patas Monkey Papio urinus Baboon Papio anubis Papio cynocephalus Gorilla Chimpanzee HFV 99 93 92 98 80 64 57 26 29 90 46 36 49 Neighbor-Joining Phylogenetic Analysis Courtesy of William Switzer, CDC

20. Pattern of Blood Donation 3% of eligible Canadians donate blood on a regular basis (Canadian Blood Services) 54% (25/46)of study participants reported at least one donation of blood or blood products ever. 88% (22/25) of Animal workers that reported blood donation also reported bites by NHP’s

21. Canadian Institutes of Health Research Canadian Blood Services Health Canada, CIDPC, PPHB Dr. Paul Gully Dr. Donald Sutherland Rick Pilon Chris Scherf Health Canada, HPFB Dr. Jocelyn Fournier University of Ottawa Dr Francisco Diaz-Mitoma Esoterix Inc. Dr. Richard Heberling Acknowledgements