Biomedical Engineering Reference
In-Depth Information
Most commonly, tetanus is seen in nonhuman primates
housed outdoors in naturalistic environments where contact
with soil occurs. The majority of these cases occur as
a result of contamination of wounds incurred as a result of
fighting and as postpartum infections. Because of this, most
cases of tetanus in rhesus macaques occur in the breeding
and birth seasons.
until the effects of toxin wear off. Early diagnosis and
aggressive supportive care provide the best opportunities for
positive outcomes. Upon initial presentation, all animals
should be treated with either tetanus immunoglobulin (TIG)
or tetanus antitoxin. TIG passively immunizes animals and
is preferred by some physicians over tetanus antitoxin in the
treatment of tetanus in humans. Tetanus antitoxin is given at
a dose rate of 500
1500 IU/kg, divided between intrave-
nous and subcutaneous routes. Some clinicians feel there is
benefit gained by administering the subcutaneous dose near
the wound where entry of the organism is suspected to have
occurred.
Antibiotic therapy directed at the bacterium should be
instituted at the time of presentation to minimize or elim-
inate the additional production of toxin. While antibiotic
therapy will kill the organism, the effects of the toxin will
remain. Antibiotics of choice for the treatment of C. tetani
include procaine penicillin G, 20 000
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Clinical Signs
Clinical signs of the disease are caused by a powerful
neurotoxin (exotoxin) called tetanospasmin, which
migrates retrograde from the axons of motor nerves in the
vicinity of the active infection to the neuronal cell body in
the spinal cord. The toxin inhibits the function of Renshaw
cells that control duration and intensity of motor neuron
impulses resulting in continuous stimulation of skeletal
muscles.
Clinical signs can be so subtle in the early stages of the
disease that inexperienced clinicians may not recognize or
attribute them to tetanus. Animals in this stage of the
disease may only have minimal changes to their gait that
could be misdiagnosed as a primary musculoskeletal
disease. As the disease progresses the signs most frequently
seen include torpor, reluctance to interact with other
nonhuman primates, inability to prehend food, hypersen-
sitivity to external stimuli, excessive thirst, altered gait, and
difficulty in swallowing. Flexion of the carpal joints and
adduction of the forelimbs is seen before muscle rigidity
progresses to the rear limbs. Piloerection, trismus, opis-
thotonus, and status epilepticus are more severe signs that
indicate progression. If death occurs, it is usually the result
of respiratory muscle paralysis. The clinical course of
disease from diagnosis to death is between 1 and 10 days
(
Rawlins and Kessler, 1982
).
50 000 U/kg i.m.,
b.i.d. (
Hawk et al., 2005; California National Primate
Research Center, 2009
), amoxicillin 11 mg/kg s.q. or i.m.
(
Hawk et al., 2005
) or 6.7
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13.3 mg/kg p.o. (California
National Primate Research Center (CaNPRC), 2009),
ampicillin 5 mg/kg i.m., b.i.d. (
Hawk et al., 2005
)or
25
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8 hours (California National
Primate Research Center (CaNPRC), 2009) and metroni-
dazole (35
50 mg/kg divided q6
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50 mg/kg p.o. s.i.d. or b.i.d. or 7.5 mg/kg i.v.
q.i.d.;
Hawk et al., 2005
; California National Primate
Research Center (CaNPRC), 2009). Metronidazole can be
used in combination with penicillin and amoxicillin.
After administration of TIG and/or tetanus antitoxin and
institution of antibiotic therapy, treatment for tetanus
consists largely of supportive and critical care. Patient
outcome is often directly proportional to the quality and
extent of supportive measures provided. The severity of
clinical signs can vary quite dramatically between cases and
treatment should be tailored for each patient. In severe cases
where seizure activity is present, treatment with midazolam
0.05
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Diagnostics
There are no specific assays to diagnose tetanus. C. tetani is
difficult to culture from wounds. The diagnosis of tetanus is
primarily made by recognizing the somewhat unique
constellation of clinical signs in animals at risk. Risk
factors include animals housed in outdoor environments
where exposure is likely, evidence of contaminated or deep
wounds, and females in the immediate post-partum period.
Animals with wounding to the tail, digits, or more than one
site are significantly more likely to develop tetanus than
animals with injuries to the proximal extremities (
Springer
et al., 2009
). Necropsy findings in cases of tetanus are
nonspecific, and no pathognomonic lesions exist.
0.15 mg/kg i.m. or i.v. (
Hawk et al., 2005
) or diaz-
epam 1 mg/kg i.m. or i.v. (
Hawk et al., 2005
) is indicated. If
seizure activity is refractory to these drugs then phenobar-
bital or general anesthesia can be added to the treatment
regimen. The use of acepromazine is contraindicated
because it lowers the seizure threshold and may increase
seizure activity. It is advisable to lower the lights and
decrease noise in the animal housing room to further
decrease the occurrence of induced seizure activity. Where
available, quiet isolation rooms should be used to house
animals while they are experiencing the most severe clinical
disease. If trismus or severe muscle spasms are present,
animals will be unable to eat and nutritional support will
need to be provided. Liquid diets may be administered
using orogastric or nasogastric tubes, but care must be taken
to avoid aspiration pneumonia. If it is felt that the disease is
progressing rather than resolving at the time of presentation,
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Treatment/Management/Prognosis
The goals of management for tetanus are to neutralize the
toxin, destroy C. tetani bacteria, and provide supportive care
