Biomedical Engineering Reference
In-Depth Information
macaques is a lateral flow assay that uses a cocktail of novel
TB antigens to detect antibodies in serum, plasma, or whole
blood. The test has distinct advantages, namely that it does
not require technical expertise, can be stored at room
temperature for up to one year, and gives a rapid
(20 minutes) result. In one published survey, the test had
90% sensitivity and 99% specificity. There was no cross-
reactivity in monkeys known to be infected with M. avium
or M. kansasii (
Lyashchenko et al., 2007
). There is little
published information regarding the test's usefulness in
detecting latent TB infection and less information overall
compared to the interferon-
g
assay or TST. While this
approach holds promise, care should be taken in using it as
a sole diagnostic method given the limited published
information associated with this diagnostic approach.
Other tests that have been used experimentally include
a multiplex microbead immunoassay (MMIA) (
Khan et al.,
2008
) and multiantigen print immunoassasy (MAPIA)
(
Lyashchenko et al., 2000; Brusasca et al., 2003
). Like the
lateral flow assay above, these tests evaluate the presence of
antibodies to a variety of TB antigens. The MMIA requires
specialized equipment to run but has the potential to offer
high throughput for large colonies. Currently, neither test is
commercially available, limiting widespread use.
While intradermal skin testing will likely remain the
backbone of TB screening programs for some time to
come, these new assays hold promise in confirming positive
tests, in diagnosing latent infections, and in differentiating
a positive test due to TB disease or atypical mycobacterium
infection. Use of these tests should be used to augment
a TB screening program especially in quarantine situations
where accurate diagnosis is of paramount importance or in
situations where animals unexpectedly test positive in order
to confirm or interpret results. For example, in closed
colonies where the likelihood of exposure and subsequent
positive test is deemed to be low, a false-positive TST
reaction would otherwise result
negative for the duration of quarantine. Because of the
magnitude of the risk to the rest of the colony and the
difficulty in successfully treating the disease, TST-positive
animals are generally euthanized. If the value of the animal
warrants treatment, a multidrug regimen should be used.
Choice of drugs should be based on culture and sensitivity
and current CDC recommendations, and treatment should
generally be continued for 9
12 months (
Wolf et al., 1988
).
The risk to the colony and personnel, the expense and
difficulty of the treatment, the stress to the animal, and the
impact of these potentially toxic drugs on any research
protocols should be carefully evaluated before therapy is
considered.
e
Screening for Bacterial Disease
Nonhuman primates are subject to infection with a wide
variety of bacterial organisms. A detailed review of specific
bacterial disease is provided elsewhere in this topic. Some
of the more common enteric organisms are Campylobacter
sp., Shigella sp., Yersinia sp., and Salmonella sp. Outbreaks
of any of these diseases can be devastating from both
a colony health and financial perspective and care should be
taken to thoroughly screen animals in quarantine to prevent
exposure to these organisms.
Although it is not practical to culture all clinically
normal animals for all potential pathogenic bacteria, it may
be desirable to screen for some of the more commonly
occurring ones, especially in those animals expected to
experience stress, e.g. in quarantine, during weaning,
during formation of social groups, during shipping, or in an
experimental protocol.
Screening can be performed in a number of ways, most
commonly via culture, PCR, or antigen capture assays.
Bacterial culture is most common and care should be taken
to ensure that those obtaining and processing samples for
bacterial culture are well-trained so as to ensure the highest
possible likelihood of recovering bacterial agents. For some
bacteria, i.e. Campylobacter sp., selective media should be
used and will markedly improve bacterial identification.
Other bacteria may require special culture conditions and
bacterial agents are easily missed if these conditions are not
met.
PCR can also be used as a screening tool but care should
be taken to interpret results in light of clinical findings and
not to overinterpret findings.
in the euthanasia of
a healthy animal.
Additional diagnostics that should be considered in
suspected positive reactors include thoracic radiographs,
culture of sputum and/or feces at specialized labs, and
evaluation of sputum smears. These tests can quickly
recognize TB disease (smear, radiographs), or help to
accurately determine the agent causing a positive reaction
(culture). Unfortunately, culture of tuberculosis organisms
is time consuming and results generally take weeks, if not
months, to confirm. Bacterial isolation remains the gold
standard for the diagnosis of M.
tuberculosis complex
Screening for Viral Disease
Viral diseases cause significant levels of morbidity and
mortality in NHP colonies and screening for these diseases
is imperative in the overall disease surveillance and main-
tenance of colony health. Viral diseases, either overt or
subclinical, can also impact
infection.
If any animal in a group proves to be positive, that
animal should be removed and all animals in the group
should be immediately quarantined. The testing regimen is
the same as that used in an initial quarantine, with testing
every 2 weeks until all remaining animals test consecutively
research goals,
further
