Abstract Introduction

The clinical disease tetanus is caused by the action of exotoxins produced by the vegetative form of the anaerobic spore-forming gram-positive bacteria Clostridium tetani. The organisms are commonly present in feces and are continuously shed into the environment where they sporulate and can persist for years.¹⁶

Tetanus is well known in humans, non-human primates and equines. It occurs in a variety of farm and companion animals including cattle, sheep, goats, pigs, dogs and cats. There have been reports of tetanus in elephants², impala⁸, llama¹⁰, reindeer⁵, macropods¹, and even a falcon¹³. Although no reports of tetanus in giraffes were found in American literature, a German report describes the loss of two zoo giraffes to tetanus.⁶

Clostridium tetani can enter the animal’s body in many ways including through deep wounds, through the genital tract at parturition and into the umbilicus of a neonate. Introduction can occur during procedures such as surgery and even with injection of pharmaceuticals. The organism requires anaerobic conditions such as found in deep or necrotic wounds. Incubation after inoculation typically varies between 3 days and 4 wk. Occasional cases of tetanus do occur as long as several months after the infection is introduced due to the ability of the organism to lie dormant until conditions are favorable. Often by this time no apparent wound is found. Once in anaerobic conditions Clostridium tetani converts to its vegetative form and produces toxins. The tetanus bacteria remains localized as the toxin diffuses to surrounding tissues, enters the lymphatics and ascends retrogradely along axons to the spinal cord or brain stem. The toxin acts by irreversibly blocking the inhibitory synapse of the spinal cord motor neuron resulting in over activity of extensor muscles and the clinical sign of extensor rigidity.^3,14

The clinical signs of tetanus vary between species with classic clinical signs including stiff gait, sawhorse stance, difficulty in prehension and swallowing (“lockjaw”), and prolapsed nictitating membranes. Generalized tetanus is best known but localized cases of tetanus are also seen, especially in those species with more resistance to tetanus such as dogs and cats.

Prevention of tetanus is best accomplished by vaccination. Vaccination with tetanus toxoid stimulates the production of antibodies directed against the neurotoxin which prevents it from binding. Initial vaccination is followed by a booster in 3–6 wk and then given annually. If a vaccinated animal is injured an additional dose of tetanus toxoid may be given. In a non-vaccinated injured animal tetanus antitoxin should be given along with an initial dose of tetanus toxoid followed by a booster dose of tetanus toxoid 3–6 wk later.¹⁴ The tetanus antitoxin provides immediate protection against unbound toxin but this passive immunity lasts only 3–4 wk. On a cautionary note equine-origin tetanus antitoxin is linked to serum hepatitis in a small percentage of horses.^11,12

Treatment goals in an animal exhibiting clinical signs of tetanus are to eliminate local Clostridium tetani infection, neutralize circulating toxin, relax muscle tetany, and provide supportive care. Once toxin is bound it is not possible to reverse binding with treatment. The initial concern upon reaching a diagnosis of clinical tetanus is to administer antitoxin to neutralize unbound toxin. Intravenous administration of antitoxin is superior however it comes with an increased risk of anaphylaxis. Local i.m. injections of small doses of antitoxin around the wound site have been shown to be beneficial in experimental studies on localized tetanus.⁷ In addition, tetanus toxoid should be administered at a separate site since protective humoral immunity is not induced by natural disease.⁴ Antibiotic therapy to kill any vegetative Clostridium tetani organisms is essential to prevent further exotoxin production. Penicillin is the drug of choice with tetracycline as an alternative.⁷ The antibiotic may also be injected in close proximity to the wound site. Tranquilizers, muscle relaxants and anticonvulsants can be administered to reduce the clinical effects of bound toxin.¹⁵

Recovery from tetanus is affected by the dose of toxin exposure, onset of treatment, and occurrence of secondary complications.³ The course of the disease and the prognosis varies between species. In generalized tetanus the prognosis is guarded to poor once clinical signs are apparent. Death most often occurs by asphyxiation due to spastic paralysis of respiratory muscles, laryngospasm, or aspiration pneumonia.⁴

Case Study

A 14-yr-old 760-kg male reticulated giraffe (Giraffa camelopardalis reticulata) was allowed access in a large mixed-species exhibit with a 5-yr-old male greater kudu (Tragelaphus strepsiceros). The animals had shared the same exhibit since arrival of the kudu 4 yr earlier as a juvenile but had been separated due to increased aggressive territorial behavior of the kudu. Officially the plan had been for these animals to remain separate and reintroduction was done without the approval or notification of the primary keeper and veterinary staff. While the animals were on exhibit together a keeper observed the kudu gore the giraffe. The keeper could not determine the depth of penetration or the amount of contact from his vantage point of the incident. The giraffe was isolated in a restraint chute for veterinary examination. An 8-cm long laceration was noted on the right side of the thorax just caudal to the elbow. The wound appeared to extend full thickness through the skin and into the muscle layers. A rib was partially visualized. The wound was swabbed and probed with a dilute flushing povidone-iodine solution (Poviderm^TM Solution, Vet US Animal Health, Burns Veterinary Supply, Inc., Rockville Centre, NY, USA) soaked gauze on long forceps. Probing revealed the wound to extend 3–4 cm under the skin. The wound did not appear to penetrate the chest and respiration was normal. The animal was very nervous and agitated in the chute and would not stand for extensive flushing of the wound. By the tenth day the wound was clear, dry, and scabbed over. The animal exhibited no further clinical signs for approximately 2 wk.

Sixteen days after the initial injury the giraffe began to exhibit behavioral changes. His keepers noted partial anorexia and increased salivation. The wound was palpated and appeared almost completely healed. The nictitans appeared inflamed bilaterally. For days seventeen through twenty post-injury, the animal showed some difficulty masticating and swallowing but did continue to eat his hay, pellets, and produce. Feces and urine were normal in quantity and appearance. On day eighteen he was placed in a chute. A blood sample was collected and evaluated to have normal CBC and chemistries. Rectal temperature was 99 degrees Fahrenheit. The wound was reopened with forceps, probed and flushed. At this point differentials for the inflamed nictitans included a possible allergic or infectious condition.

On the evening of the twenty-first day the giraffe exhibited an obvious “sawhorse” stance. The nictitans remained inflamed bilaterally and were now recognized as prolapsed. Difficulty in mastication and swallowing along with a decreased interest in food were noted. The animal was also salivating excessively and grinding his teeth. At this time the clinical signs along with the history of injury 3 wk prior determined a diagnosis of tetanus due to Clostridium tetani infection. The preventive medicine protocol in place at the Toledo Zoo prior to the injury did not include tetanus prophylaxis for giraffe. Tetanus toxoid (Clostridium perfringens type C & D - tetani bacterin - toxoid, Vision^TM CD-T with SPUR®, Bayer Corporation, Shawnee Mission, KS 66201 USA) 2 ml i.m. and procaine/benzathine penicillin (DURA-PEN, penicillin g benzathine and penicillin G procaine injectable suspension, Anthony Products Co, Irwindale, CA, USA) 6,000 U/kg of each drug i.m. were administered with powdered charge darts (Cap-Chur^TM Darts, Palmer Cap-Chur^TM Equipment, Inc., Powder Springs, GA, USA).

By day 22 keepers reported the giraffe was interested in food but had difficulty with prehension and mastication resulting in no ingestion of bananas, hay or pellets. Water intake of 2.5 gallons overnight was recorded. A literature review of tetanus in domestic and exotic animals was accomplished and a consultation was made with a large animal clinician at Michigan State University College of Veterinary Medicine. Recommendations were made for administration of tetanus antitoxin, antibiotic and tranquilizers with treatment dosages extrapolated from equine treatment protocols. The giraffe was moved into a chute for treatment daily from this point on. Treatment for the next few days included daily wound flushing, s.i.d. to b.i.d. doses of up to 35000 IU equine origin tetanus antitoxin (Professional Biological Company, Denver, CO, USA) administered i.v., up to 3500 IU tetanus antitoxin s.c., and procaine penicillin (penicillin G procaine, Hanford United States Veterinary Products, G.C. Hanford Mfg. Co., Syracuse, NY, USA) 20,000 U/kg s.c. b.i.d. During the course of treatment one dose each of selenium with vitamin E (BO-SE®, Schering-Plough Animal Health Corp., Union, NJ, USA) 0.05 IU/kg selenium with 2 IU/kg vitamin E s.c. and vitamin B complex (Vitamin B Complex 150, AmVet™, Neogen Corp., Lexington, KY, USA) 6.0 mg thiamine portion/kg were given. Initially it was decided not to use tranquilizers due to concern that the giraffe would become recumbent in the chute but on day twenty-four mild sedation with xylazine (X-JECT E 100, VetUS Animal Health, Burns Veterinary Supply) 53 µg/kg i.m. was performed. This dose aided in handling the animal for treatment and he did remain standing. A blood sample was collected and evaluated to be within the ISIS range.

On day 25 the giraffe was noticeably weaker, had increased salivation, and was resting with his head on a fence. He was placed in a chute where he collapsed and began regurgitating large amounts of rumen fluid. The animal was unresponsive to stimuli and the decision was made to euthanatize him. Pentobarbital sodium (Euthasol®, Diamond Animal Health, Inc., Des Moines, IA, USA) 13,650 mg i.v. was administered.

At gross necropsy the wound was found to be approximately 10 cm caudal to the point of the right elbow. A healing granulation tract extended dorsally into the subcutaneous tissue, traveled through the rib cage and into the chest cavity 23 cm dorsal to the entrance of the wound. At this level there was a large 15-cm diameter pocket of caseous necrotic material. Adhesions to the abscessed area were present on the right cranial medial lung lobe and pericardium. The affected lung lobes were also dark grey and firm.

Histologic diagnosis confirmed the chronic abscess in the thoracic cavity, showed serous atrophy of fat, and a membranoproliferative glomerulonephropathy. There are no classic histologic lesions of tetanus.

Bacterial culture of the abscess at necropsy did not confirm Clostridium tetani. Attempts to isolate C. tetani from wounds often fails because of the low concentration of organisms and the requirement for strict anaerobic culture conditions.⁷

Discussion

The implications of this case at the Toledo Zoo were many. Prior to this case primates, equids, elephants, and camelids were vaccinated for tetanus prophylactically. Now the vaccination protocol has been changed to include annual vaccination with tetanus toxoid for hoofstock, including giraffe.

Since experiencing a case of tetanus first hand, vigilance is heightened for this disease possibility. The importance of continued animal training and operant conditioning for medical procedures along with improved chutes, squeezes and handling facilities has been emphasized. Following injury, increased consideration is given to aggressive wound cleansing, antibiotic treatment, administration of tetanus toxoid and/or tetanus antitoxin. Tetanus is a differential as an aftereffect of injury even when wounds appear to be healing or to have healed normally. Early identification and intervention are key for an improved chance of recovery.

Possible medical problems related to mixed-species exhibits were brought to the forefront. Territorial behavior within and between species can result in severe injury and stress to the animals. Unfortunately, compatibility is not always predictable. Prior to obtaining this kudu our giraffe had shared the same exhibit with a different adult male kudu for many years without incident.

Finally, we were reminded that communication within the zoo is of utmost importance. A breakdown in communication between zoo personnel in this case contributed to the giraffe being placed in danger when a policy had been made not to put these animals together again. Efforts to increase communication between zoo staff members and document agreed upon protocols are in effect.

Acknowledgments

Pamela G. Walker, DVM, MS, DACVIM - Assistant Professor Food Animal Medicine and Surgery, Michigan State University College of Veterinary Medicine

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