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)

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

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.

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

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

CDC Data Addressing SFV TransmissibilityNonhuman 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

CDC Data Addressing SFV Transmissibility Human to human – Virus presence in body fluids

Specimen# People

PCR +

# Serial

Samples# People Virus +

# Serial

Samples

PBLs 10 of 10 > 2x 4 of 9 < 2x

Throat Swab

2 of 4 < 2x 1 of 4 < 2x

Saliva 1 of 4 < 2x 0 of 4 <2x

Urine 1 of 1 1 - -

Semen 1 of 1 1 - -

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

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

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

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

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