Biomedical Engineering Reference
In-Depth Information
A negative response indicates the animal has not been
exposed to tuberculosis, has not had time to mount an
immune response, or is incapable of mounting an immune
response due to immunosuppressive disease, recent
measles vaccination, or other reason. Immunization and
subsequent testing with tetanus toxoid may aid in predict-
ing anergic animals (
Davis et al., 1988; Corcoran and Jaax,
1991
).
The palpebral skin test has been and continues to be the
mainstay of TB diagnostics in NHP medicine and is
invaluable when assessing TB status of a large cohort of
animals. Despite its uses, it has significant drawbacks,
especially when assessing the status of an individual
animal. False negative and false-positive reactions are not
uncommon and this makes interpretation of test results
challenging for the primate veterinarian. Animals exposed
to a variety of nontuberculous mycobacteria will often test
positive on intradermal skin tests (
Wachtman et al., 2011a
).
One primary concern is that animals with latent TB
infection may have negative results and these infections can
reactivate, causing active TB disease and putting other
animals at risk. This has led to several outbreaks in recently
imported monkeys, despite repeated negative intradermal
skin tests during their quarantine period (
Garcia et al.,
2004a; Lerche et al., 2008
).
There have been recent advances in TB diagnostics and
a new battery of serological assays are available that can
augment the TB screening program.
The interferon-
g
assay measures the in vitro production
of interferon-
g
when whole blood is stimulated with
M. bovis origin purified protein derivative (bPPD) and
compares those findings to blood stimulated with M. avium
PPD (aPPD) and a negative control. The amount of inter-
feron produced in response to stimulation with different
antigens can be used to differentiate a reaction due to
infection with M. bovis/M. tuberculosis (bPPD
FIGURE 12.4
A grade 4 TST reaction. Obvious swelling of the
palpebrum with drooping of the eyelid and varying degrees of erythema
can be seen. A grade 4 TST is considered positive.
FIGURE 12.5
A grade 5 TST reaction. Swelling and/or necrosis of
the eyelid is shown. A grade 5 TST is considered positive.
specifics of grading, see
Table 12.2
. Equivocal tests should
be repeated using the opposite eyelid. Positive tests should
be confirmed as true positives and no animals in a group
where any animal is questionable or positive should be
moved or exposed to new animals until test results are
confirmed.
aPPD) or
>
atypical mycobacterium (aPPD
bPPD) (
Lerche et al.,
2008
). One such test (PRIMAGAM
) has been USDA
licensed for use in cynomolgus and rhesus macaques.
Evaluations of this test have shown that, compared to
intradermal testing, it has a low sensitivity and high
specificity in detecting TB disease (a positive test is likely
due to TB disease, a negative test does not rule out TB
disease) (
Garcia et al., 2004a; Vervenne et al., 2004; Lin
et al., 2008
). However, use of both tests together improves
sensitivity and specificity. As such, the PRIMAGAM
or
similar tests have particular usefulness as an adjunct to
TST in a comprehensive preventive medicine program and
can help interpret positive results and increase overall
sensitivity and specificity (
Garcia et al., 2004a; Vervenne
et al., 2004; Lerche et al., 2008; Lin et al., 2008; Shipley
et al., 2008
).
A second test that has shown promise in trials and is
USDA approved for use in rhesus and cynomolgus
>
TABLE 12.2
Grading TST Reactions
Grade 1
Slight bruising of eyelid (negative)
Grade 2
Erythema of eyelid without swelling (negative)
Grade 3
Varying degrees of erythema with minimal
swelling (indeterminate)
Grade 4
Obvious swelling with dropping of eyelid
(positive)
Grade 5
Marked swelling and/or necrosis of eyelid
(positive)
