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Tuberculosis is devastating in nonhuman primate colonies,
resulting in acute, fulminant disease in some species and a more
insidious, chronic syndrome in others.
The tuberculin skin test is the most widely used diagnostic
test, but is somewhat unreliable and results in false positive and
more catastrophic false negative diagnoses.
The objectives of this study were to determine the efficacy
and predictability of current methods for diagnosis of tuberculosis
in three species of Cercopithecines and to follow the course of
disease in species in which little is known regarding susceptibility
to infection. Six
rhesus (Macaca mulatta), six cynomolgus (M. fascicularis)
and five African Green monkeys (Chlorocebus aethiops) were
intratracheally inoculated with 100 colony-forming units of Mycobacterium
tuberculosis (Erdman strain).
Five guinea pigs (Cavia porcellus) were similarly
challenged simultaneously to assure pathogenicity of the inoculum;
all studies were conducted under biosafety level 3 conditions.
Animals were monitored daily for behavior, appetite, general
health, and clinical signs of disease such as coughing and were
euthanized for persistent inappetence, weight loss or manifestation
of disease, or at the end of the seven month study period.
Animals were monitored every other week for intradermal
response to mammalian old tuberculin (MOT) in the palpebrum and
abdomen, response to purified protein derivative (PPD) in the
abdomen; samples were collected for erythrocyte sedimentation rate
and serologic assay for antibodies to M. tuberculosis; and
animals were weighed and given a complete physical examination. Every two weeks for the first month, then monthly
thereafter, samples were collected for complete blood counts and
clinical chemistry analysis and for lymphocyte proliferation
response to several stimulants (including PPD).
Monthly, animals were radiographed and tracheal washes were
collected for direct smears, polymerase chain reaction (PCR)
analysis and culture. Several
results from this study were remarkable.
Surprisingly, African Green monkeys were most sensitive to
infection, even more so than guinea pigs; African Green monkeys were
euthanized with clinical signs of acute tuberculosis at 44-52 days
post-infection (PI). Rhesus monkeys were moderately susceptible; five of six
were euthanized with clinical signs of tuberculosis between four and
six months PI, with the final animal euthanized at the end of the
study period. Five of
six cynomolgus were euthanized at the end of the seven-month
experiment; one was euthanized six months PI with acute inappetence
and mild weight loss. Infection
was confirmed postmortem in all animals via culture and PCR of
various tissues. Intradermal
tests using MOT were uniformly negative two weeks PI, were quite
predictive 4-8 weeks PI, then resulted in false negatives throughout
the remainder of the study in the rhesus and cynomolgus monkeys.
Intradermal PPD testing was not diagnostic at any point
during the experiment. Finally,
radiology was very predictive; all animals had evidence of pulmonary
consolidation of varying severity with associated intermittent to
severe coughing throughout the course of infection.
In conclusion, adjunctive methods of diagnosis of
tuberculosis, such as radiography and monitoring for coughing are
valuable and reliance on intradermal testing alone is not sufficient
to adequately diagnose tuberculosis in these Old World species of
nonhuman primates.
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