1. CDC Investigations Relevant to Potential for Simian Foamy Virus Transmission by Transfusion Louisa Chapman, MD, MSPH OD, DASTLR, NCID, CDC & HIV and Retrovirology Branch Division of AIDS, STD, and TB Laboratory Research National Center for Infectious Diseases Centers for Disease Control and Prevention (CDC)

2. Completed CDC Investigations – Unlinked Serosurvey of Zoo Workers Sandstrom et al. Lancet 2000; 355: 551-552. –Unlinked serosurvey of 322 zoo workers –4 seropositive by Wb with combined antigens from: SFV-6 (chimpanzee) SFV-3 (African green monkey SFV-2 (macaque) –Single antigen testing indicated infection with chimpanzee-like SFV –4/133 with potential contact with NHPs –0/189 workers without NHP contact

3. Ongoing CDC Investigations – Survey of Workers Occupationally Exposed to NHPs “Voluntary seroprevalence study of nonhuman primate retrovirus infections among occupationally exposed workers” –Enrolls self-selected workers –Tests for variety of simian retrovirus infections Strengths: –Identify persons infected with simian retroviruses Weaknesses: –Enrollment biases –Limited confidence in extrapolated prevalences –Limited ability to identify specific risk factors Heneine et al Nature Medicine 1998; 4: 403-7.

4. Ongoing CDC Investigations – Long Term Follow Up “Long Term Follow up of Persons Infected with Unusual Retroviruses” (not recognized to be endemic in humans) –Follow infected persons & close contacts 5 years –Health status; risk factors for acquisition / transmission; clinical laboratory testing; biological fluid specimens collected annually Strengths: –Prospective characterization of infections –Characterization of health status –Study for secondary transmission Weaknesses: –Incomplete health records and specimen collection –Enrollment biases –Incomplete contact enrollment

5. Ongoing CDC Investigations – Look Back “Investigational Look Back Study for Recipients of Blood Products from Simian Foamy Virus (SFV) Infected Donor” –Identified recipients of blood products from SFV-infected donors –Tests recipients for infection Strengths: –Information on infection status of recipients of blood products from infected donors Weaknesses: –Absence of information on infectivity of blood products –Limited power due to very small numbers

6. CDC Data Addressing SFV Transmissibility Nonhuman primate to human 11/279 workers identified seroreactive (3.7%) –Likely overestimates prevalence in exposed population 1994 serosurvey 5/472 (1.05%) seroreactive 10/11 provided PBLs – all PCR + –Origin: chimpanzee (n=5), baboon (n=4), and African green monkey (n=1) –All exposed to / some injured by implicated species Duration exposure 4–41 yr (median 21) –Documentable seropositivity 2–25 yr (mean 19.5?) 6/11 SFV+ enrolled for long term follow up –4-41 yrs exposure (median 21 yr); 10-24 yr SFV+ (mean 17.5 yr) –All: mucocutaneous exposures & skin penetrating injuries

7. CDC Data Addressing SFV Transmissibility Human to human – Virus presence in body fluids Specimen # People PCR + # Serial Samples # People Virus + # Serial Samples PBLs10 of 10> 2x4 of 9< 2x Throat Swab 2 of 4< 2x1 of 4< 2x Saliva1 of 4< 2x0 of 4<2x Urine1 of 11-- Semen1 of 11--

8. CDC Data Addressing SFV Transmissibility Human to human – Contact testing 6 wives of SFV+ men tested negative –Mean documented exposure 14.5 years 6/10 SFV+ report blood donation –1 stopped prior to infection –4 donated after seroreactive Case A – a traceable blood donor Over 2 years, SFV isolated from: –PBLs 2 of 3 attempts –Throat swabs 1 of 2 attempts –PCR + cell pellets from saliva, urine, semen

9. CDC Data Addressing SFV Transmissibility Human to human – Blood product recipient testing Case A – 6 donations between 1992 & 1997 1993 & 1994 donations: Plasma  manufactured derivatives –1 lot albumin & 3 lots plasma protein fraction negative by Western blot & RT-PCR 11 transfusable components –2  manufactured nontransfusable reagents –2 not traceable –7 transfused 3 – 35 days after donation

10. CDC Data Addressing SFV Transmissibility Human to human – Blood product recipient testing 1 recipient FFP  died day of transfusion 1 recipient PRC  died 4 yrs later of Crohn’s disease 1 recipient PLT  not available for testing 2 recipients PRC  negative after 7 yr each 1 recipient RC-filtered  negative after 1 yr 8 m 1 recipient PLT  negative after 5 yr 11 m

11. CDC Data – Does Infection = Disease? 0/10 report health problems suggestive infection 5 enrolled for long term follow up –Age 41 – 65 yr (mean 51) One time clinical testing – confirmation pending: –2 completely WNL –3 with occasional values that minimally exceed limits of normal Confirmatory testing not yet available Values likely unrelated to infection

12. Questions for Future Study CDC – continue to: –Characterize human SFV infections –Document health histories over time –Search to secondary transmission –Conduct trace back studies when possible New Initiatives: –Investigate prevalence in workers exposed to feral nonhuman primates