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

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

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

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

Species of NHP used in Canada ( ) N = 1373 N = 2150N = 1,621N = 875 N = 1,131

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

Health Canada Primate Colony 875 Cynomolgus macaques imported from the Philippines 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

Average Monthly NHP Colony Population by Year Number of animals

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

Occupations of Study Participants

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

Person Years of Exposure to NHP Species

Exposure Patterns

Total Number of Bites Reported By Species

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

SFV HC/1/3/6 Infected Cell Lysates Cf2Th/BHK21 Uninfected Host Cell Lysates Representative Screening Immunoblot ChimpAGMCynoBaboonHuman 1Human MW kDa

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

env pol gag LTR Accessory Genes SFV Genome Structure taf Location of 153 bp PCR Fragment in pol gene

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 Neighbor-Joining Phylogenetic Analysis Courtesy of William Switzer, CDC

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

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