Biomedical Engineering Reference
In-Depth Information
Necropsy as a Tool in Disease Surveillance
In situations where an animal(s) becomes ill for unknown
reasons and diagnostic methodologies fail to determine
a cause, euthanasia with a complete necropsy is an impor-
tant tool in determining the cause of death, risk to other
animals in the colony, and risk to personnel. All animals that
develop natural disease should have a complete gross
necropsy and histopathological evaluation performed at the
time of death to determine the cause of illness and to survey
the colony for disease processes.
Necropsy evaluation should be performed by a veteri-
nary pathologist when one is available, or by a trained
veterinarian if a pathologist is not on site. Prompt
completion of the necropsy is essential to reduce post-
mortem autolysis and improve the ability of the pathologist
to accurately diagnose the condition. Histological evalua-
tion should be performed by a veterinary pathologist with
experience in primate pathology.
Necropsy evaluation should be performed in a system-
atic fashion evaluating all major organ systems visually for
any abnormalities and preserving samples of both abnormal
and normal tissue for histological analysis. It is imperative
that a complete necropsy collection be performed to avoid
missing important lesions that may not be visible to the
naked eye. In most situations, preserving tissues in formalin
is adequate for diagnosis. However, it may be necessary in
some cases to obtain frozen or otherwise preserved samples
for viral identification, PCR analysis, or special staining to
identify organisms.
species used most typically in biomedical research
including rhesus, cynomolgus, and Japanese macaques
( Potkay et al., 1966; Remfry, 1976; Choi et al., 1999; Willy
et al., 1999 ) and has also been reported in New World
species including marmosets and tamarins ( Levy and
Mirkovic, 1971; Chen et al., 2000 ). Scientists have also
used macaques ( McChesney et al., 1997; Premenko-Lanier
et al., 2004; El Mubarak et al., 2007; de Vries et al., 2008;
de Swart, 2009 ) and callitrichids ( Albrecht et al., 1980,
1981; Lorenz and Albrecht, 1980 ) extensively for measles
immunology, pathogenesis, and vaccine research.
Macaques infected with measles commonly present
with a continuum of clinical signs including anorexia,
depression, respiratory distress, conjunctivitis, cutaneous
rash, enteritis, and even death ( McChesney et al., 1997;
Auwaerter et al., 1999; Willy et al., 1999 ). A generalized
eruption of a maculopapular rash is the most easily
recognizable clinical sign and generally follows fever and
respiratory signs ( Renne et al., 1973; Remfrey, 1976;
Montroy et al., 1980 ; Roberts and Andrews, 2008) and
occurs concomitantly with the initiation of viral clearance
( McChesney et al., 1997; El Mubarak et al., 2007 ). Skin
lesions in cynomolgus macaques may be less severe than
the rash in rhesus macaques ( El Mubarak et al., 2007 ).
While the rash has historically been considered a viral
exanthema, there is more recent speculation that the
measles skin rash is immune mediated ( Polack et al., 1999 ).
Measles virus induced immunosuppression can lead to
secondary infections with other viruses, fungi, and/or
bacteria that may be fatal ( Choi et al., 1999 ). Measles
infections in macaques has also been associated with
pathology of the reproductive tract including endometritis,
cervicitis, and abortion ( Renne et al., 1973 ).
Due to the severity of the disease in NHPs, disease
prevention is extremely important in colony management.
Most importantly, it is advisable to have a strict occupa-
tional health program to prevent exposure of closed NHP
colonies to measles virus. However, even in these situa-
tions outbreaks have occurred and for that reason many
colonies choose to vaccinate their animals against measles
virus.
Historically, it was possible to purchase a human
monovalent measles vaccine product (Attenuvax ). A two-
dose vaccine regimen, with an initial dose administered at
approximately 1 year of age and a boost more than 3
months later, appeared to prevent or greatly ameliorate
measles infection. Because maternal antibody can interfere
with vaccine-induced immunity, infant macaques raised
with their mothers should not be vaccinated prior to 6
months of age ( Premenko-Lanier et al., 2004 ). It was also
possible to use a bivalent canine distemper-measles vaccine
(Vanguard-2 ) that proved to be as efficacious as the
human vaccine against measles challenge when given in
a two-dose regimen ( Christe et al., 2002 ).
ANIMAL VACCINATION PROGRAM
The decision to prophylactically immunize NHPs depends
on many factors including species, colony risk (housing,
history, number of animals, use, etc.), safety, cost and
known efficacy of the prophylactic agent, and research
interference. Recommendations and/or current practices
for immunizations of NHPs vary widely among facilities as
management practices and facility design play a crucial
role in determining the need for specific vaccines. Addi-
tionally, individual vaccines may be contraindicated in
some research programs and this should be considered in
the design and implementation of a vaccine program.
Measles
Measles virus is a single-stranded RNA virus of the genus
Morbillivirus from the family Paramyxoviridae and has
been categorized as one of the most contagious human
pathogens ( McChesney et al., 1997 ). Measles infection in
NHPs is a direct result of exposure to infected humans or
exposure to monkeys that have been infected by humans.
Infection has been documented in the Old World NHP
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