Nonhuman Primate Spumavirus Infections Among Persons with Occupational Exposure -- United States, 1996

Nonhuman primate (NHP) species used in biomedical research may be infected with a variety of retroviruses including simian immunodeficiency virus (SIV), simian spumaviruses (i.e., simian foamy viruses {SFV}), simian T-lymphotrophic viruses (STLV), and/or simian type D retroviruses. All of these retroviruses cause life-long infections in NHPs, and some are transmissible through sexual contact, blood, or breastfeeding. Following the detection of SIV infection in a worker with occupational exposure to SIV (1), in 1993 CDC and the National Institutes of Health conducted an anonymous serosurvey using stored specimens collected from U.S. workers with similar exposures. SIV seroreactivity was present in three (0.6%) of 427 stored serum samples (2). As a result of this finding, in 1993 CDC implemented a voluntary testing and counseling surveillance program to link specific exposures or health outcomes with the SIV serostatus of persons with potential occupational exposure to SIV. In 1995, the linked surveillance program was expanded to include voluntary testing and counseling for exposure to SFV, STLV, and simian type D retroviruses. As of November 20, 1996, samples from 231 of the participating volunteer workers had been tested for SFV; infection was documented in three (1.3%). This report presents laboratory findings and case descriptions of these three infections, which indicate that SFV from NHPs can persistently infect exposed humans and may or may not cause disease or be transmitted among humans. Laboratory Findings

An immunofluorescent assay (IFA) using cells infected with SFV serotype 3 identified antibodies to SFV in recently collected serum specimens from all three SFV-infected workers. The three specimens also were positive by Western blot (WB), indicating reactivity to both p70 and p74 gag precursor bands of SFV-3 antigen.

Samples from the three workers also were tested for SFV proviral DNA sequences using polymerase chain reaction (PCR) assays employing primer sets from two regions of the polymerase gene that are conserved among known primate foamy viruses. Samples from all three workers were positive in both regions. Sequencing of the PCR products from one region indicated that the sequences from each worker were distinct from each other; however, all three demonstrated greater than 80% homology to known spumavirus sequences of NHP origin. Subsequent specimens obtained from these three workers also tested positive by IFA, WB, and PCR.

Virus isolation was attempted by co-culturing the peripheral blood lymphocytes (PBLs) of worker 1 with a cell line known to be permissive for spumavirus infection. Reverse transcriptase (RT) activity was detected in co-cultures from worker 1 but not from control co-cultures using PBLs from an unexposed human. Supernatant RT activity was transferred from co-cultures of these PBLs from the infected worker to uninfected cells, which subsequently exhibited cytopathic effect. DNA PCR of these infected cells was positive for SFV. Infected cells were strongly reactive to serum samples from all three workers by both IFA and WB but unreactive to control serum specimens. Electron microscopy indicated that cytoplasmic vesicles in virus-infected cells contained particles with a morphology characteristic of foamy virus. Co-cultures of PBLs from workers 2 and 3 are ongoing.

Antibodies to SFV also were present in serum archived from worker 1 in 1995 and from worker 3 in 1988, and from worker 2 during 1978-1997. Two serum specimens archived from worker 2 in 1967 were seronegative. Case Descriptions

Worker 1 has been employed intermittently for a cumulative total of 20 years during 1961-1997 as a caretaker for NHPs and reported a history of multiple minor injuries and mucocutaneous exposures to NHP blood, body fluids, and fresh tissue. Worker 1 was bitten twice by African green monkeys during the late 1960s or early 1970s; each of these injuries required seven to 10 stitches. Worker 1 is in good health. No serum specimens are available from worker 1 before 1995 or from sexual partners.

Worker 2 is a research scientist who has worked with biologic specimens from NHPs for 30 years and rarely had injuries involving NHP blood, body fluids, or unfixed tissue. In the early 1970s, the worker incurred two puncture wounds, one with an instrument contaminated with chimpanzee blood and one with an instrument that may have been contaminated with baboon body fluids. Worker 2 is in good health and has been in a monogamous sexual relationship without use of barrier contraceptives or spermicides for approximately 20 years. The worker's spouse is negative for SFV infection by both serologic and PCR testing.

Worker 3, a veterinary technician who has worked with NHPs for approximately 30 years, reported multiple minor injuries and associated mucocutaneous exposures to NHP blood, body fluids, or unfixed tissues. In approximately 1980, the worker incurred a severe baboon bite that required multiple stitches. Worker 3 has common chronic diseases of aging but is otherwise in good health. The worker has been in a monogamous sexual relationship for nearly 30 years, during which barrier methods of contraception have not been used and spermicides were used for an approximately 6-month period. The spouse is negative for SFV infection by both serologic and PCR testing.

Reported by: D Neumann-Haefelin, MD, M Schweizer, PhD, Univ of Freiburg, Germany. Retrovirus Disease Br, Div of AIDS, STD, and TB Laboratory Research; Molecular Pathology and Ultrastructure Activity and Office of the Director, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Natural SFV infections in NHPs have not been definitively associated with disease. In comparison, infections of NHPs with the other retroviruses may result in a broad clinical spectrum, ranging from asymptomatic infection to life-threatening immunodeficiency syndromes or lymphoproliferative disorders. The transmission routes of SFVs among NHPs remain undefined, but the prevalence of seroreactivity is high among captive adult NHPs (3).

Characterization of spumavirus infection in humans is limited. Early studies described a relatively high rate of seroreactivity to spumaviruses among human populations not known to be exposed to NHPs. However, these studies lacked definitive evidence of human infection and were not subsequently confirmed. Improved diagnostic assays have not documented evidence of foamy virus infection in large populations (approximately 8000 persons) (3-7). Therefore, the findings in this report underscore the importance of the identification of seroreactivity in the three workers occupationally exposed to NHPs. Persistent infection in these three workers is indicated by the PCR identification of SFV genome sequences in biologic specimens from all three and isolation of the virus from one. Infection with SFV has been confirmed previously in only two persons, both of whom had occupational risks for infection; associated disease was not reported in either person (3).

Based on prospective surveillance, the prevalence of exposures to NHP blood, body fluid, and tissues is high among occupationally exposed workers. The risk for exposure was highest for animal-care workers and persons performing invasive procedures, and increased with duration of occupational risk. Needlestick or mucocutaneous exposures were reported by 35% of workers with a median of 7.5 years of occupational risk (CDC, unpublished data, 1997).

The potential that xenotransplantation (the use of living biologic material from nonhuman species in humans for medical purposes) may introduce new infectious agents to humans emphasizes the need for characterization of the ability of simian retroviruses to infect and/or cause disease in humans (8,9). The sources for xeno-grafts have included baboons. Surveillance of persons at occupational risk for exposure to retroviruses from NHPs may quantify risks for xenograft transmission of these viruses and provide information on their pathogenicity to and transmissibility among humans. Surveillance also will provide information on the implications of xenograft procurement from SFV-infected animals.

The risks for developing disease in these SFV-infected workers or for transmission of infection by them to other humans remains undefined. CDC is continuing efforts to further define the health status of and to identify additional archived serum from these three workers and to define further the prevalence and health implications of infection with SFV and other simian retroviruses among persons at occupational risk for infection. Measures for decreasing the frequency of human exposure to NHP retroviruses include training and educating workers, adhering to universal precautions, using work practices or engineering controls to reduce exposure to sharp instruments, and using personal protection equipment for bite prevention (10).

References

1. Khabbaz RF, Heneine W, George JR, et al. Brief report: infection of a laboratory worker with simian immunodeficiency virus. N Engl J Med 1994;330:172-7.

2. CDC. Anonymous survey for simian immunodeficiency virus (SIV) seropositivity in SIV laboratory researchers -- United States, 1992. MMWR 1992;41:814-5.

3. Schweizer M, Turek R, Hahn H, et al. Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans. AIDS Res Hum Retroviruses 1995;11:161-70.

4. Schweizer M, Turek R, Reinhardt M, Neumann-Haefelin D. Absence of foamy virus DNA in Graves' disease. AIDS Res Hum Retroviruses 1994;10:601-5.

5. Heneine W, Musey VC, Sinha SD, et al. Absence of evidence for human spumaretrovirus sequences in patients with Graves' disease {Letter}. J Acquire Immune Defic Syndr Hum Retrovirol 1995;9:99-101.

6. Rosener M, Hahn H, Kranz M, Heeney J, Rethwilm A. Absence of serological evidence for foamy virus infection in patients with amyotrophic lateral sclerosis. J Med Virol 1996; 48:222-6.

7. Ali M, Taylor GP, Pitman RJ, et al. No evidence of antibody to human foamy virus in widespread human populations. AIDS Res Hum Retroviruses 1996;12:1473-83.

8. Chapman LE, Folks TM, Salomon DR, Patterson AP, Eggerman TE, Noguchi PD. Xenotransplantation and xenogeneic infections. N Engl J Med 1995;333:1498-501.

9. US Department of Health and Human Services. Draft Public Health Service (PHS) guideline on infectious disease issues in xenotransplantation. Federal Register 1996;61:49920-32.

10. CDC. Guideline to prevent simian immunodeficiency virus infection in laboratory workers and animal handlers. MMWR 1988;37:693-704.

    
    

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