Current and Former Staff of the Animal Resources Division, Health Canada

2001 Study

James Brooks CIHR/CBS Post Doctoral Research FellowErling 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)

0

2,000

4,000

6,000

8,000

10,000

12,000

FY 1999 FY 2000

CynomolgusRhesusSquirrelsAfrican GreensOthers

Source: Tom Damercus,

Division of Quarantine, National Center for Infectious Disease, Centers for Disease Control and Prevention

# of

non

-hum

an p

rimat

es

N = 12,744 N = 12,061

Species of NHP used in Canada (1995 - 1999)

0

200

400

600

800

1000

1200

1400

1995 1996 1997 1998 1999

Cynomolgus

Rhesus

Squirrel

African Green

Others

N = 1373 N = 2150 N = 1,621 N = 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 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

Average Monthly NHP Colony Population by Year

0

200

400

600

800

1000

1200

1983 1985 1987 1989 1991 1993 1995 1997 1999 2001

Nu

mb

er

of a

nim

als

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 ParticipantsOccupation % With

OccupationNumber(N=46)

Laboratory AnimalTechnicians

33% 15

LaboratoryTechnicians

28% 13

Animal HealthTechnicians

11% 5

Laboratory Scientists 9% 4Veterinarians 6% 3

Other 13% 6

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

Cynomolgous macaque (461)

Rhesus macaque (263)

Squirrel Monkey (75)

African Green Monkey (36)

Celebes (13)

Chimpanzee (9)

Exposure Patterns

Type of Exposure Exposure Rate (%) N

Fluid Exposure(Any)

90 38/42

Bitten 71 27/38

Needlstick 48 20/42

Scratched 79 30/38

Fluid on Intact Skin 81 34/42

Total Number of Bites Reported By Species

Cynomolgous macaque (205)

Rhesus macaque (46)

Squirrel Monkey (30)

Celebes (3)

Spider Monkey (2)

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

Chi

mp

AG

MC

yno

Bab

oon

Hum

an

1

Hum

an

2

11281

50

36

MW kDa

11281

50

36

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

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10 000 11 000 12 000 13 000

envpol

gagLTR 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

HFV99

9392

98

80

64

57

26

29

90 46

36

49

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, PPHBDr. Paul Gully

Dr. Donald Sutherland

Rick Pilon

Chris Scherf

• Health Canada, HPFBDr. Jocelyn Fournier

• University of OttawaDr Francisco Diaz-Mitoma

• Esoterix Inc.Dr. Richard Heberling

Acknowledgements