Biomedical Engineering Reference
In-Depth Information
(
Desrosiers et al., 1989; Murphey-Corb et al., 1989
).
Baboons (
Anderson et al., 1990
) have also been used for
testing the immunogenicity and safety of HIV subunit
vaccines. Chimpanzees are the only nonhuman primates
that can be reproducibly infected with both HIV-1 and HIV-
2, although experimental infection of pig-tailed macaques
(M. nemestrina) with HIV-1 has been reported (
Agy et al.,
1992
). These agents produce lasting infection in chim-
panzees. Chimpanzees have now been protected from HIV-
1 infection for more than 1 year by vaccines (
Girard et al.,
1991; Fultz et al., 1992
) and their primary use for human
AIDS research is in vaccine development and safety
testing, in experimental transfer of passive immunity, and
in pharmocokinetic studies of antiviral drugs (
Fultz et al.,
1989a
).
Chimeric viruses made of HIV and SIV have become
very common for testing vaccines and microbicide efficacy.
Some of these viruses have the HIV envelope while others
use HIV RT. SHIVs are often less pathogenic than most
SIV strains but some have been adapted to the monkey host
and are very pathogenic (
Sato and Johnson, 2007
).
The immediate cause of death in animals with an immune
deficiency syndrome is usually the combination of opportu-
nistic infections and bacterial sepsis associated with
enterocolitis, diarrhea, and profound weight loss rather than
the underlying retroviral infection. Personnel in contact with
these animals are at risk from secondary agents (
Gardner
et al., 1984
) aswell as the underlying virus (
Sotir et al., 1997
).
Until 1992 there was no report of human illness or
infection related to either SIV or SRV even though, retro-
spectively, it became known that these retroviruses have
been responsible for spontaneously occurring disease in
macaques at several primate centers for at least 20 years
(
Stowell et al., 1971; Holmberg et al., 1978; Lowenstein
et al., 1988
). However, two suspected SIV human infec-
tions have been reported. One was a laboratory worker who
suffered a needlestick injury while handling a SIV-infected
monkey. This individual developed antibodies approxi-
mately 3 months after the injury, but the level of antibody
declined over 2 years; no virus was ever isolated and PCR
testing detected no viral sequences. These results indicate
that the infection may have been cleared (
Khabbaz et al.,
1992
). The second was a laboratory worker who handled
SIV-infected blood products without gloves while suffering
from severe dermatitis on the hands and forearms. This
individual developed antibodies to both SIV and HIV-2,
which are very closely related, and levels continued to rise
for 2 years, suggesting chronic infection. These cases
emphasize the need for strict adherence to recommended
guidelines for working with SIV because proper practices
were not observed in each situation. In the dermatitis case,
the individual was working with clinical specimens without
gloves. Although the needlestick did penetrate a glove, the
contaminated needle had been separated from the
vacutainer holder before disposal (
Centers for Disease
Control, 1992b
).
Prevention
Transmission is by parenteral inoculation,
droplet exposure of mucous membranes, and contact
exposure of broken skin; therefore, Animal Biosafety Level
2 is recommended for handling monkeys with SIV infec-
tion. However, Biosafety Level 3 practices and equipment
are recommended for work with purified virus and cultures
of lymphocytes or tissues from animals infected with SIV
and HIV-1 or HIV-2 (
Centers for Disease Control, 1987c
).
Additional guidelines to minimize the potential risk of SIV
transmission to laboratory workers and animal handlers
have been formulated (
Lairmore et al., 1989
).
Poxvirus Infections
Five nonhuman primate diseases caused by poxviruses
also produce human disease. Monkeypox virus, which is
related to smallpox virus, causes a generalized, sometimes
febrile, illness characterized by proliferative vesicular skin
lesions that become pustular and ulcerated. Many human
cases of monkeypox infection have been reported
including several that were fatal in African children
(
Espana, 1971; Breman et al., 1980
). Contact with
monkeys is assumed to have been responsible for these
naturally occurring human cases. Human cases of monkey
pox were reported in 2003 after infected rodents origi-
nating in Africa were imported to the USA (
Sejvar et al.,
2004
). These were the first cases of monkey pox in the
Western Hemisphere and were a reminder of the zoonotic
potential of this virus.
Benign epidermal monkeypox, also known as OrTeCa, is
caused by a virus identical to the causative agent of tanapox
in African children (
Downie et al., 1971
) and is serologically
related to the virus that causes Yaba-like disease (YLD)
(
Whitney, 1976
). The disease caused by these two agents is
characterized by multiple raised epidermal plaques, up to
1.5 cm in diameter. Although infections caused by these
viruses will spread through colonies of susceptible monkeys,
they are not life threatening to the animals. These infections
are important, however, because theymay produce disease in
animal contact personnel. During one outbreak of YLD in
a monkey colony, 11 handlers became infected. The
monkeys developed no symptoms other than 2- to 4-cm, soft-
centered, tumor-like dermal lesions. The disease ran its
course in about 2 weeks. On the other hand, in personnel
infected through monkey-related trauma the dermal lesions
were accompanied by lymphadenopathy and high fever
(
Hull, 1969a
). This virus has ben listed as a Select Agent and
has been used for testing the efficacy of anti-smallpox
treatments.
Yaba poxvirus is an oncogenic virus first isolated from
tumor tissue collected during an epizootic of self-limiting
