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Seroconversion to Simian Immunodeficiency Virus in Two Laboratory Workers

Simian immunodeficiency viruses (SIVs) are lentiviruses that cause
acquired immunodeficiency syndrome (AlDS)-like illnesses in susceptible
macaque monkeys and are used in the study of AIDS (1). In November
1988, CDC published guidelines to minimize the risk of SIV transmission
to research laboratory workers (2). This report summarizes the
investigation of two laboratory workers who seroconverted following
occupational exposures to SIV. 

Case 1 

In March 1990, a technician at a research laboratory sustained a stick
with a blood-contaminated needle while attempting to disconnect the
vacutainer holder from the needle after obtaining blood from an
anesthetized SIV-infected macaque. The macaque had been inoculated with
SIV 6 months earlier, had seroconverted, was SIV culture-positive, and
was symptomatic. The needle, visibly contaminated with blood,
penetrated a latex glove and produced a deep puncture wound that caused
the thumb to bleed. After removing the glove, the worker immediately
scrubbed the wound with a povidone-iodine solution and then with a 10%
bleach solution. Marked inflammation and swelling developed at the
wound site and persisted for several weeks. The worker was treated with
oral dicloxacillin and warm compresses. The wound site was not
cultured. 

Serum samples collected 1 week before the exposure, 1 week after the
exposure, monthly over the following 12 months, and 19 months later
were tested. None were reactive to human immunodeficiency virus (HIV)-1
by enzyme immunoassay (EIA) or by Western blot (WB) or to HIV-2 or SIV
by whole-virus ElAs. However, serum samples obtained during June 1990-
March 1991 were reactive to a number of synthetic peptides derived
from the transmembrane region of SIV and HIV-2, and the titer to one
of these peptides peaked from June through August 1990, and subse
quently declined. 

Testing by HIV-2 WB first showed reactivity to envelope (env) gp41 from
a sample obtained during July 1990; testing showed a weak reactivity
to group-specific antigen (gag) p27 in all the samples, including the
preexposure sample. SIV WB showed no bands on the serum samples
obtained during March-June 1990 and a weak gag p27 band after July
1990. Radioimmunoprecipitation (RIPA) also showed reactivity to the 
envprotein gp130 in serum samples obtained during August 1990-March
1991, with peak intensity in the sample obtained in August (3). 

Cultures of peripheral blood mononuclear cells (PBMCs) collected
monthly were negative for SIV. Polymerase chain amplification (PCR) of
PBMCs using primers and probes from the gag (4 ) and polymerase (pol)
(5 ) region of SIV with nested amplification in pol, and with pol-,
LTR- and env-nested primers representing consensus sequences of HIV-2
and SIV (5) were also negative (3 ). 

Thirteen months after the exposure, 10 mL of heparinized blood obtained
from the worker was inoculated into a young, healthy, SIV-negative
Rhesus macaque. For 10 months after inoculation, biweekly to monthly
serum samples obtained from the monkey were negative for SIV antibody
by whole-virus EIA and by synthetic peptide ElAs, and the monkey showed
no evidence of SIV infection by PCR. 
 
Case 2 

A laboratory worker at another research facility, first tested in April
1992, was reactive by HIV-2 whole-virus and peptide EIAs and by
SIV-peptide EIA and negative by HIV-1 EIA and WB. HIV-2 WB showed
reactivity to numerous viral proteins including gag, pol, and env. 

The worker had no history of percutaneous or mucous membrane exposure
to SIV. However, during September~ctober 1989, the worker had severe
dermatitis involving the forearms and hands that required treatment
with oral steroids. The worker performed serology on clinical specimens
from SIV-infected monkeys without gloves. The person also worked with
SIV-infected cell cultures, but all procedures were done in a laminar
flow biosafety cabinet with protective wear (laboratory coat and
gloves). 

Serum samples from the laboratory worker obtained during 1988 and one
during November 1989 were thawed and tested and were negative for
HIV-1, HIV-2, and SIV seroreactivity by EIA and WB. A stored serum
sample from the worker obtained during April 1990 was reactive by HIV-2
and SIV EIA, and showed gag and env reactivity by HIV-2 WB. Testing of
nine other serum specimens obtained from the worker during April
1990-April 1992 showed persistent seroreactivity to HIV-2 and SIV.
Serum titers to one peptide derived from the transmembrane region of
HIV-2 showed an increase in titer over this 2-year period. PCR
amplification and viral cultures of PBMCs are pending. 
 
Additional Information 

Neither of the two workers have any risk factors for HIV-1 or HIV-2
infection. Both have been in long-term, monogamous sexual
relationships, and their respective sex partners tested seronegative
for HIV and SIV by EIA and WB. Neither of the two workers had any
illness suggestive of an acute retroviral infection and both remain 
well, with no clinical or laboratory evidence of immunodeficiency. 

Reported by: Retrovirus Diseases Br, Div of Viral and Rickettsial
Diseases, and Laboratory Investigations Br, Div of HtV/AlDS, National
Center for Infectious Diseases, CDC. 

Editorial Note: SIVs are primate lentiviruses morphologically similar
and biologically related to HIV-1 and HIV-2 (6,7). These viruses share
with HIV-1 and HIV-2 a tropism for CD4-bearing Iymphocytes and monocyte
macrophages and can also grow in vitro in human PBMCs. Although they
infect some nonhuman primate species without causing disease,
experimental infection of other susceptible nonhuman primate species
has shown that SIVs can cause chronic wasting syndromes and a disease 
similar to AIDS (1). SIV is genetically and antigenically related to
HIV-2, resulting in substantial serologic cross-reactivity (8). A
recent report of SIV-like HIV-2 isolates among West African persons
suggests the possibility that SIV and HIV-2 may represent a single
group of viruses (9). In both laboratory workers reported here, the 
serologic reactivity detected cannot be differentiated from that of
HIV-2. 

The declining antibody titers following a peak 3-5 months after the
exposure of the first patient suggest that the worker did not become
persistently infected with SIV. However, persistence of antibody over
2 years and an increase in titer suggest that the second patient might
have become infected. The implications of seroconversion without
demonstrable infection and the health consequences of seroconversion
for these workers are unknown. 

This report reemphasizes the need for laboratory and animal workers in
SIV research laboratories to strictly adhere to recommended guidelines
and procedures while working with SIV (2). In both cases, departures
from recommended safety procedures occurred: in the case of the
percutaneous exposure, the vacutainer holder was disconnected before
disposal of the contaminated needle; and in the second case, despite
open skin lesions and without use of gloves, work was performed on 
clinical specimens. A similar case was reported of a laboratory worker
with dermatitis on exposed skin who acquired HIV-1 infection in the
laboratory (10 ). 

The 3-month time lapse from exposure to seroconversion for the first
worker emphasizes the need for a follow-up of at least 3~ months for
persons sustaining unintentional exposures to SIV. In addition, the
whole-virus HIV-2 and SIV ElAs were less sensitive than peptide-based
ElAs, HIV-2/SIV WBs, and RlPAs in detecting seroreactivity; therefore,
investigation of persons sustaining exposures to SIV should include
these sensitive assays. 

The frequency of exposures in SIV research laboratories and the risk
of seroconversion in SIV laboratory and animal-care workers have not
been well defined. Approximately 200-300 persons are working with these
agents in U.S. Iaboratories. CDC has investigated two other persons
with percutaneous exposures involving cuts with scalpels during
necropsies on SIV-infected animals. Neither have shown any evidence of
seroconversion up to 6 months after the incidents. CDC, in
collaboration with the National Institutes of Health, is conducting a
serosurvey of workers in federally funded SIV research facilities to
estimate the prevalence of such seroreactivity in persons with
potential exposure to SIV. 
 
References 
1. Letvin NL. Animal models for AIDS. Immunol Today 1990;11 :322-6. 
2. CDC. Guidelines to prevent simian immunodeficiency virus infection
in laboratory workers and animal handlers. MMWR 1988;37:693-4,699-704. 
3. Khabbaz RF, Rowe T, Murphey-Corb M, et al. Simian immunodeficiency
virus needlestick accident in a laboratory worker. Lancet
1992;340:271-3. 
4. Villinger F, Powell JD, Jehuda-Cohen T, et al. Detection of occult
simian immunodeficiency virus SIVsmm infection in asymptomatic
seronegative nonhuman primates and evidence for variation in SIV gag
sequence between in vivo- and in vitro-propagated virus. J Virol 
1991 ;65:1855-62. 
5. Allan JS, Short M, Taylor ME, et al. Species-specific diversity
among simian immunodeficiency viruses from African green monkeys. J
Virol 1991 ;65:2816-28. 
6. Daniel MD, Letvin NL, King NW, et al. Isolation of T-cell tropic
HTLV-III-like retrovirus from macaques. Science 1985;228:1201-4. 
7. Fultz PN, McClure HM, Anderson DC, Swenson RB, Anand R, Srinivasan
A. Isolation of T-lymphotropic retrovirus from naturally infected sooty
monkeys (Cercocebusatys). Proc Natl Acad Sci USA 1986;83:6286-90. 
8. Hirsch VM, Zack PM, Vogel AP, Johnson PR. Simian immunodeficiency
virus infection of macaques: end-stage disease is characterized by
widespread distribution of proviral DNA in tissues. J Infect Dis
1988;163:976-88. 
9. Gao F, Yue L, White AT, et al. Human infection by genetically
diverse SIVsm-related HIV-2 in West Africa. Nature 1992;358:495-9. 
10. CDC. 1988 Agent summary statement for human immunodeficiency virus
and report on laboratory-acquired infection with human immunodeficiency
virus. MMWR 1988;37(S-4)