Richard C. Hubbard, DVM
The etiological agent, Clostridium perfringens, is commonly found in soil and has been isolated from the intestinal tracts of nearly all warmblooded species. It is capable of producing disease either by tissue invasion or by production and absorption of exotoxins from the gut. Examples of tissue invasion are gas gangrene in man, a pseudo-malignant edema in livestock, struck in sheep, and subcutaneous abscesses in wild Steller sea lion pups.14 Enterotoxemia1 and overeating disease12 in sheep are examples of exotoxin absorption from the gut. The form the disease takes and the species involved dictates to a large degree its seriousness, the prognosis, and the appropriate corrective measures.
In enterotoxemia of infant Steller and fur seal pups disease is not caused by invasion of the body by the organism but by absorption of the exotoxin produced by bacteria living in the intestinal tract. The symptoms of the disease are the expression of the effects of the absorbed toxin.
The only report in the literature specifically discussing clostridial infection in pinnipeds is by Grafton.5 In this case, a young harbor seal (Phoca vitulina con-color) died from an apparent opportunistic peritonitis and septicemia following rupture of the pancreatic duct. The local abscesses previously referred to in Steller sea lions (Eumetopius jubata)14 are also frequently caused by Clostridium perfringens. These abscesses, which appear to result from bite wounds, are usually subcutaneous and remain localized. The animals tolerate unbroken abscesses for many days, septicemia or11 malignant edema has not been observed, and the abscesses heal WC11 upon draining. The inference is that the wild Steller sea lion lives with, and is fairly resistant to, Clostridium perfringens. However, neither the peritonitis noted by Grafton nor the abscesses reported by Poulter et al is comparable to enterotoxemia in form.
We first recognized enterotoxemia in pinnipeds in the summer of 1966. No in-depth study has yet been possible, so this note can be considered only a preliminary report.
Clostridium perfringens was first isolated from a gaseous cadaver and described by Welch and Nuttal in 1882. In 1898 Veillon and Zuler gave it the name Bacillus perfringens. Not until 1900 did Migulo term it Bacillus welchii in recognition of Welch's original work. The name "Welch bacillus," or Clostridium welchii, has become ingrained in the literature, but the name Clostridium perfringens has clear precedent6 and is now universally used.
This organism is a large gram-positive rod which may become gram-negative in old cultures. Pleomorphism is common under certain growth conditions. It is a spore former, but spore formation may be suppressed by certain media. Capsules are formed in tissue, but not in all media. It is the only nonmotile member of the genus Clostridium.
Four toxin variants, A, B, C, and D, are recognized. Type D is associated with enterotoxemia and overeating disease in sheep.6 The specific antitoxins to these various toxins will in some cases cross-neutralize one or more of the other toxins. Type B antitoxin will usually neutralize the toxins of all four types, but it is the only other one besides Type D that will neutralize Type D toxin. Type D also neutralizes Type A. Type C neutralizes Types A, B, and C.
The chronic, relatively asymptomatic nature of the abscesses found in wild Steller sea lion pups on Ano Nuevo Island implies they have good natural immunity to clostridial infection. It is currently believed this high degree of natural immunity is broken down when pups, already stressed by being orphaned, are further stressed by imperfect artificial diets.14 Several observations support this idea. Enterotoxemia has been observed only in sea lion pups reared as orphans on an artificial diet. Only a few weaned pups contracted the disease, and then it was shortly after weaning. Sick pups that were fasted sometimes improved (reminiscent of overeating disease in sheep). Force feeding aggravated the condition. Consequently it appears this may be a husbandry-excited disease similar to that seen by Newsom and Thorp13 in overeating disease in sheep.
In 1966, four out of four fur seals contracted the disease, one three times. It now seems likely that many of the convulsive deaths in Steller pups were in fact unrecognized enterotoxemia. It may be that the Steller pups have more natural resistance than fur seals which results in a slightly different expression of the disease in the former.
The condition is nearly 100 percent fatal if not treated and therapy is nearly 100 percent effective if applied early.
Problems in studying diseases of wild animals are frequently compounded by the fact that more often than not no significant symptoms are displayed. The situation with regard to enterotoxemia is better, but the reader must keep in mind that the whole syndrome is probably not yet recognized.
There have been two recognizably distinct forms, one subacute and the other peracute, both of which can be attributed to toxic effects upon the central nervous system. In either case, the temperature is normal to subnormal. The subacute form is expressed by inappetence for the first 4 to 48 hours. This is followed by progressive onset of otariid ataxia and finally complete inability to rise. Death ensues if the animal is not treated. The peracute form either immediately demonstrates a severe degree of otariid ataxia or it may show convulsions which resemble those seen in canine distemper. In the convulsive forma slight tap over the spine will usually elicit a tonoclonic spasm similar to that seen in mild strychnine poisoning in dogs.
Otariid ataxia is a term that was coined by Hubbard7,8 to describe an apparent neural syndrome of unknown etiology. The animal leaves the impression that the tips of the flippers are sensitive to touching the ground. This is followed in one to three days by a loss of equilibrium, running staggers, and falling. Later there will be extreme weakness and inability to rise. It is now recognized that otariid ataxia may be present in at least two and possibly three conditions--thiamin deficiency, clostridial enterotoxemia, and possibly hypoglycemia. I would like to show a short film at this point to illustrate this condition. The earliest symptom, which of the high toe carriage, is not shown.
Normally loose stools9 are so common in pinnipeds that it is not possible at this time to say whether diarrhea is a symptom. Unthriftiness can be the only symptom when therapy is partially effective.
During the very first phase of the subacute form, a remission can sometimes be achieved by withholding food. Once mild symptoms appear low levels of oral antibiotics help to control the condition, but the animal is not always thrifty. Once antibiotics are discontinued, a clinical case may develop.
Response to Clostridium perfringens Types B and D antitoxin, equine origin,* is dramatic, coming in a matter of hours. Recovery can be expected for the terminally convulsive animal as well as less severe cases, particularly if the convulsions have not been preceded by days of weakening disability. The minimal effective dose has not yet been established, but it is certain that 1 cc per kilogram of body weight, administered subcutaneously, is more than sufficient. To date no serum reaction has been encountered from repeated use.
Newsom and Thorp state that overeating disease in sheep needs no treatment and that an outbreak can be controlled within two days by careful management of intake of concentrated food. Whether a feeding regimen can be established to control the condition in pinnipeds on artifical formula will be decided in the light of future events.
The syndrome, otariid ataxia, appears to be common to thiamin deficiency, clostridial enterotoxemia, and possibly hypoglycemia, and it could be confused with the weakness seen in anaphylaxis or circulatory collapse. In an anaphylactic reaction or circulatory collapse the oral mucosa will be cyanotic. Hypoglycemia can be confirmed or eliminated on the basis of blood sugar levels. High thiamin levels in the diet might eliminate the question of thiamin deficiency, but this cannot always be counted on with certainty. However, each of the three conditions has its specific therapy and differential diagnosis is possible on the basis of response to therapy.
If treatment is to be used as2 method of differential diagnosis, it is suggested that in animals on high thiamin intake the relatively fast acting antitoxin be administered subcutaneously at the time blood is drawn for a glucose level determination. By the time the results from a blood sugar analysis have been received one will usually know the efficacy of the antitoxin. (Blood sugar should be above 110 mg. percent.9) Negative findings in both cases would point to a thiamin deficiency.
If diarrhea proves to be a sole symptom, a differential diagnosis would require distinguishing enterotoxemia from other enteric conditions.
Administration of antitoxin Types B and D every ten days at the rate of 1 cc per kilogram during the nursing period will insure protection.
There is a bacterin against Type D bacteria and a toxoid against Type C toxin. Both have been employed successfully in sheep, but we have administered only five doses to sea lions and no analysis of their effectiveness is available at this time.
It would be desirable now to isolate a toxic filtrate from the intestine of an affected animal and reproduce the disease by injecting the sterile filtrate into a susceptible animal. At the same time, portions of proven toxic filtrates could be treated with individual antitoxins, and their toxicity could again be tested to learn which toxin is responsible. But, this is not simple. Newsom and Thorp13 found only 45 percent of their filtrates were toxic to laboratory animals. After six years of work, they were able to reproduce the disease in sheep with only 12 of their 20 proven toxic filtrates.
It seems reasonable that the pathology of this condition can now be elucidated. Prior to recognizing this disease we more than likely have confused the lesions of enterotoxemia with other conditions.
Recommendations for proper dosage of antitoxin both in therapy and prophylaxis need refinement.
As research into the nutrition of pinnipeds continues, it is hoped that better diets may eliminate or reduce the frequency of the disease.
A disease of orphaned otariids on artificial diet has been described which responds dramatically to Clostridium perfringens antitoxin Types B and D. This disease, like overeating disease in sheep, is associated with feeding management. Some of the characteristics common to enterotoxemia in sheep as described by Bennetts1 and overeating disease as described by Newsom and Cross12 are present in Steller sea lion and fur seal pups.
Upon seeing the motion picture accompanying this presentation Mr. J. B. Siebenaler of Marine Life, Rapid City, South Dakota, stated he had experienced the otariid ataxia syndrome depicted. It occurred in very young (25-30 lbs) California sea lions on a thiamin intake of 16.8 mg per day. These pups were on a whole fish diet. Ile reported a diarrhea did accompany the condition he saw. Three out of five animals in two groups were involved. One died, then the dosage of thiamin was increased to 50 mg/day, after which one survived and one died.
This investigation was supported in part by the Public Health Services Research grant NB 04736 from the Division of Research Grants, National Institutes of Health.
Bennetts, H. W., 1932. Infectious enterotoxemia of sheep in Western Australia. Commonwealth of Australia Council for Science and Industry, Research Bulletin 57.
Erickson, E., 1962. Diseases of seals in the Copenhagen Zoo. Nord. Vet.-Med., Vol. 14, Suppl. 1, 141-149.
Fisher, L. E., 1965. Views of a zoo administrator-veterinarian. J. Am. Vet. Med. Assn. 147:1037-1043.
Geraci, J. R., R. M. Sauer, and W. Medway, 1966. Erysipelas in dolphins. Ain. J. Vet. Res. 27:597-606,
Grafton, T. S., 1967. Investigation of the sudden death of a female harbor seal (Phoca vitulina con-color). Aquarium Symposium Section, 47th Ann. Meeting Am. Soc. Icthy. and Herpetology.
Hagan, W. A., The Infectious Diseases of Domestic Animals. Comstock Publishing Co., New York, 1944.
Hubbard, R.C., 1965. Husbandry, housing and care of seals and sea lions. Presented at the 16th Ann. Meeting, Animal Care Panel, Philadelphia, Nov. 15-19.
Hubbard, Richard C., 1966. Notes on the housing, husbandry, and care of seals and sea lions. In Rice, C. E., ed. Proc. Third Ann. Conf. on Biological Sonar and Diving Mammals. Stanford Research Institute, Menlo Park, California.
Hubbard, Richard C., Husbandry and laboratory animal care of pinnipeds. In Rice, C. E., ed., Behavior and physiology of seals, sea lions, and walruses. Appleton Century Crofts, New York. In press.
Keyes, Mark C., Nutrition of pinnipeds. In Rice, C. E., ed., Behavior and physiology of seals, sea lions, and walruses. Appleton Century Crofts, New York. In press.
Merchant, I. A., 1942. Veterinary Bacteriology. The Iowa State College Press, Ames, Iowa.
Newsom, I. E., and F. Cross, 1934. Feedlot diseases of lambs. Colorado Exp. Sta. Bul. 409.
Newsom, I. E., and F. Thorp, Jr., 1938. The toxicity of intestinal filtrates from lambs dead of overeating. J. Am. Vet. Med. Assn. 93:165.
Poulter, T. C., T. C. Pinney, R. Jennings, and R. C. Hubbard, 1965. The rearing of Steller sea lions. In Rice, C. E., ed., Proc. Second Ann. Conf. on Biological Sonar and Diving Mammals. Stanford Research Institute, Menlo Park, California.
Prior to publication another reference to a clostridial infection in a pinniped has come to light: Keyes, Mark C., 1963. Necrotic hemorrhagic enteritis in a seal. Small An.Clin. 3:627.