Biomedical Engineering Reference
In-Depth Information
highlighting the need for good viral screening (
Morton
et al., 2008; Sasseville and Diters, 2008
).
In screening for viral disease, a number of testing
options are available, depending on the virus. These include
viral serology, PCR, multiplex microbead assays, culture,
and others. It is important to recognize that each of these
tests will have certain advantages and disadvantages in
a given situation and, in general, no one diagnostic test will
fit every situation.
The frequency of screening for viral diseases should be
based on an assessment of risk factors at each institution. At
a minimum, in the maintenance of an SPF colony or to have
adequate background information in the event of an
employee injury, serum should be drawn annually for
serology and serum banking. More frequent screening may
be used during the development of SPF colonies or when
specific concerns arise.
Ideally, tests used to screen colonies for diseases should
be highly sensitive. In this situation, one does not want to
inaccurately say a diseased animal is healthy so a test with
a high sensitivity is warranted. If there are a few false-
positives results (low specificity) that is acceptable as these
animals can be retested using other, more specific methods.
In contrast, tests used to diagnose individual animals
and confirm results obtained at screening should be highly
specific. In these situations, it is imperative to accurately
determine whether one animal is infected with a certain
agent, and a test with high specificity ensures that there will
be few false-positive test results.
It is also important to consider overall disease preva-
lence when interpreting test results. When using a highly
sensitive screening test in situations with high disease
prevalence, positive results are likely true-positive results,
that is, a positive result indicates a diseased animal (high
positive predictive value). As disease prevalence decreases,
positive results on that test are more likely to be false-
positives, that is a positive result in a healthy animal. In
a hypothetical situation where disease prevalence is 0%,
every positive test is a false-positive. In this situation, it is
important to devote time and effort to confirming positive
test results using a test with higher specificity so as to rule
out disease in that animal and ensure that the disease
incidence is really 0% (as in confirming B virus status in an
SPF colony). One may also consider using a test with
a higher specificity as a screening test in these situations.
The converse is true for negative test results. As disease
prevalence increases, there are an increased number of false
negative test results. To minimize this, a screening test
should have a high sensitivity thereby reducing the number
of false negative results.
Even small reductions in specificity and sensitivity can
have a big influence on the number of false-positive or
negative results obtained with a given diagnostic test.
Therefore, it is imperative for the primate veterinarian to
understand the limitations of each test and to choose
diagnostic tests based on the situation.
Herpesviruses
Herpesviruses are ubiquitous DNA viruses that infect many
species of animals, including all species of NHPs. There are
three subfamilies of herpesviruses: alphaherpesvirinae,
betaherpesvirinae, and gammaherpesvirinae. All three
subfamilies infect NHPs and cause varying levels of
disease. These viruses are thoroughly reviewed in this
volume and the companion volume (Volume II: Diseases).
From a preventive medicine and viral surveillance point of
view, the most important among these viruses is Macacine
herpesvirus 1 (herpes B virus).
Herpes B is endemic in most Asian macaque colonies.
After infection at a young age from contact with other
animals, the virus establishes latency in neural ganglia and
can be reactivated and shed during periods of stress,
immunosuppression, or illness. Primary viral infection and
shedding may or may not be associated with clinical signs
including oral or genital vesicular lesions and conjuncti-
vitis. While herpes B does not generally cause serious
illness in macaques, it causes serious and life-threatening
disease in humans (
MMWR, 1987; Ward and Hilliard,
2002
). Therefore, prevention of human infection is of
utmost importance.
The most important and effective way to protect
personnel from B virus infection is through thorough
education of the risk factors and appropriate means of
protection from viral infection. Staff should be well versed
in how to manage primate-related injuries and there should
be strong institutional support for these management
practices through a well-designed occupational health and
safety program.
However, screening of colony animals for B virus status
is also an important aspect of herpes B virus risk mitigation.
B virus screening is generally accomplished through repeat
(annual or semiannual) serological assays (
Elmore and
Eberle, 2008; Morton et al., 2008
). The main functions of B
virus serology are to assess the overall level of B virus
infection in a colony, to monitor specific pathogen free
(SPF) colonies for any breaks in SPF status, and to aid in
the establishment of SPF breeding colonies (
Ward et al.,
2000; Wolfensohn and Gopal, 2001; Ward and Hilliard,
2002
). Given its relatively low specificity, interpretation of
serology results in individual animals should be done
cautiously. Viral serology can augment a comprehensive
risk assessment following an employee injury but must be
interpreted in the context of virological status of the colony
as a whole. It is important in these situations to test animals
for active viral shedding using PCR or viral culture.
It is also important to note that while specific pathogen
free colonies have been formed in which animals are
