Biomedical Engineering Reference
In-Depth Information
B virus occurred. Twenty-three of the cases were linked to
bites, splashes, needle sticks, or scratches from infected
animals. The other cases were linked to indirect exposure to
the virus, such as contaminated biological specimens,
laboratory glassware, cages, or droplet aerosols (
Palmer,
1987; Weigler, 1992; Holmes et al., 1995a
). In only four
cases was B virus matched to rhesus isolates recovered at
the time of injury. In many of the cases where no identifi-
cation of the macaque responsible for B virus transmission
existed, infections occurred in facilities where multiple
species of macaques were used, particularly rhesus and
long-tailed macaques. There were few survivors in the early
cases (
Hull, 1973
). However, survival improved markedly
in human cases treated early with the antiviral drugs
acyclovir and gancyclovir, although the drugs appeared
only to suppress the infection and lifetime treatment was
necessary (
Holmes et al., 1995b; Krug et al., 2010
). In the
years that followed up to 2010, there were nearly two dozen
survivors among whom three reactivations of infection
occurred in two persons. Other survivors who had high
antibody titers of B virus specific antibodies experienced no
apparent reactivations. Reactivations were clinically asso-
ciated with severe morbidities in both patients (J. Hilliard,
personal communication, 2010).
The most serious incident ever recorded of human
infection with B virus occurred in 1985 at the Navy's
Aeromedical Research Laboratory in Pensacola, Florida
(
Palmer, 1987
). Four people were infected, one indirectly
through fomite transmission, and two animal caretakers
died. This provided yet another reminder of the seriousness
of the B virus problem and its prevalence in rhesus
monkeys. It also raised concerns about the potential acti-
vation of latent B virus infections in monkeys that might be
infected, naturally or experimentally, with retroviruses
causing immunodeficiency. Already looming as a potential
problem, based on the discovery of SIV, was whether there
would be enough monkeys to meet the needs of AIDS
research.
And B virus was not the only infectious agent associ-
ated with the research use on nonhuman primates. There
were at least 83 cases of diseases transmitted by monkeys to
humans, including 23 deaths. Hepatitis (
Hillis, 1961
) and
Marburg virus (
Kissling et al., 1968
) infection represented
two of the more important ones. Clearly some action was
required to deal with these problems.
Concerns about B virus and the other agents pathogenic
to humans associated with the use of nonhuman primates as
well as AIDS research all provided good arguments for
emphasizing more SPF breeding. The NIH responded by
providing funds appropriated for AIDS research and
making six awards in 1989 to establish the SPF Breeding
and Research Program (M. A. April, personal communi-
cation, 1990). These projects were projected by 1995 to
produce 500 SPF rhesus monkeys per year
identifiable simian retroviruses, B virus, and Ebola
(filovirus) infection. However, without extended NIH
support, the projects were eventually phased out and the
breeders were redistributed to other projects.
Ebola Virus and Interruption of Imports
In 1990, the CDC and the New York Department of Health
took steps that resulted in suspending the importation of
macaques from southeast Asia. These actions resulted from
the discovery of Ebola infection in long-tailed macaques
imported from the Philippines (
Dalgard et al., 1989
)by
a CRO in Reston, Virginia. The clinico-pathological
features of the disease, in which the Ebola infections were
found to have occurred concurrently with an outbreak of
simian hemorrhagic fever, were well described (
Dalgard
et al., 1992
). Ebola virus had a fearsome reputation for
causing highly fatal human infections in Africa and was
also related to Marburg virus, another filovirus well known
for monkey-associated deaths in laboratory workers
(
Centers for Disease Control, 2005
).
The outbreak in Reston was sensational and well
described in The Washington Post and the nonfictional
topic on the subject, The Hot Zone (
Cohen, 1989; Preston,
1994
). The clinical-pathological features of the disease, in
which both the virus causing simian hemorrhagic fever
and one that morphologically resembled the Ebola virus
highly pathogenic for humans, were identified and well
described (
Dalgard et al., 1992
). Military personnel from
the Army's Medical Research Institute of Infectious
Diseases at Fort Detrick, in full protective gear, arrived at
the site and destroyed all the monkeys that had been
exposed. Follow-up studies indicated that antibody
evidence of infections with the agent, which became
known as Ebola Reston, had occurred at the CRO in
Reston and elsewhere in several laboratory workers
without the occurrence of clinical disease. This suggested
that the strain of Ebola virus involved was not as
hazardous for people as initially feared (
Miller et al.,
1990
). Nevertheless, the CDC, seriously concerned with
the possibility of a deadly outbreak of Ebola virus in
people resulting from contact with infected imported
monkeys, imposed a de facto suspension of such imports
until importers could provide assurances that their proce-
dures for handling nonhuman primates during transit and
quarantine had been strengthened to meet CDC's guide-
lines (
Centers for Disease Control, 1990a,b
). As a result of
CDC's actions, imports of nonhuman primates into the
USA essentially ceased for months (S. Hursh, personal
communication, 2010). While there continued to be
serological evidence of Ebola virus-related infection in
nonhuman primate imports, there were no clinical cases of
human infection associated with them and the instances
were dealt with without incident.
free of
