Encephalitozoon Cuniculi

Synonyms: Encephalitozoon negrii.

Disease: Encephalitozoonosis.

Hosts: Domestic rabbit, house mouse, Norway rat, cottontail, dog. The golden hamster has been infected experimentally. A few human infections with Encephalitozoon have been reported, but they were all actually Toxoplasma.

Location: Encephalitozoon occurs intracellularly in the brain, kidneys, peritoneal exudate, liver, spleen and other organs.

Geographic Distribution: Worldwide.

Prevalence: Perrin (1943) found Encephalitozoon in the brains of 5 of 502 Swiss mice, 2 of 283 Wistar strain albino rats, and 1 of 291 guinea pigs at the National Institutes of Health, Bethesda, Md. It has been encountered sporadically by a number of workers in laboratory rabbits, mice and rats (Frenkel, 1956; Perrin, 1943). In most cases it has been found during routine histologic examination of animals being studied for some other purpose.

Plowright (1952) described 3 cases in a litter of foxhounds in England, and Plowright and Yeoman (1952) found it in a litter of puppies in Tanganyika. They also reviewed the literature on previous reports of what may have been the same organism in dogs. Jungherr (1955) found it in a cottontail rabbit.

Morphology: The trophozoites measure 2.0 to 2.5 by 0.8 to 1.2 u in tissue sections and up to 4.0 by 2.5 u (mean, 2.0 by 1.2 u) in smears (Perrin, 1943a). They are straight to slightly curved rods with both ends bluntly rounded but one end a little larger than the other. The body is sometimes slightly constricted at or near its midpoint. Round or oval forms occasionally occur. The nucleus is compact, round, oval or bandlike, about 1/4 to 1/3 the size of the parasite, and is not central. Pseudocysts containing up to 100 or more trophozoites are found within the nerve cells, macrophages or other tissue cells. Both they and the trophozoites are rarely extracellular.

Life Cycle: The mode of multiplication is unknown. The organism can be transmitted from the mouse, rabbit, rat or guinea pig to other laboratory animals by intracerebral, intravenous, intraperitoneal or other parenteral inoculation of infected brain, liver, spleen or peritoneal exudate (Perrin, 1943a). It has been found in the urine. Congenital infection undoubtedly occurs in mice (Perrin, 1943) and probably in rabbits (Smith and Florence, 1925) and dogs (Plowright, 1952).

Pathogenesis: E. cuniculi causes encephalitis and systemic disease associated with nephritis in rabbits and puppies, and an inapparent infection in laboratory rodents. The great majority of cases in rabbits are also inapparent, being discovered on histologic examination carried out for some other reason. Its true importance in dogs is unknown, since it has been seen very rarely in them.

Encephalitozoonosis is usually a mild, chronic, infection in rabbits, altho paralysis and death may occur. The principal lesions in the brain are tiny, focal granulomata made up of epithelioid cells surrounding a tiny area of necrosis. In fatal cases there may be large necrotic areas and perivascular lymphocytic cuffing. The parasites may occur in or around the necrotic areas. Similar granulomatous lesions may be present in the kidneys and other organs. In the kidneys they occur principally in the epithelial cells of the collecting tubules, which they distend and finally rupture, passing out in the urine (Smith and Florence, 1925).

In mice and rats the principal lesions are meningoencephalitis and, in experimentally infected animals, abdominal enlargement with ascites. Nodular, granulomatous lesions, sometimes with central necrosis, occur thruout the brain. There is slight to moderate focal perivascular infiltration by lymphocytes and a few large mononuclear and plasma cells in the meninges and also in the brain. The parasites may be either within or at the margins of the lesions or even in normal brain tissue at a distance from them. There may be moderate to marked interstitial lymphocytic infiltration in the kidneys, primarily in the cortex. The tubular epithelium may be degenerate or proliferative in the areas of infiltration, and parasites may occur either in the epithelial cells or within the collecting tubules. Similar areas of infiltration may be seen in other organs (Perrin, 1943).

According to Frenkel (1955), treatment with cortisone exacerbates the disease in mice. The parasites proliferate extensively in most organs, and the mice may die.

In the litter of six puppies described by Plowright (1952), the principal signs were posterior weakness and incoordination, apathy, rapid tiring, some loss of condition and signs of ocular involvement. All died between 6 weeks and 15 months of age. Two puppies were affected at 8 to 10 weeks of age in the litter described by Plowright and Yeoman (1952). Both had symptoms resembling those of rabies. They became vicious and bit or attempted to bite people. One had fits of rushing wildly around, and died on the 5th day with uncontrolled spasms of the limbs and jaws. The other had an epileptiform fit, became dull and off feed, but remained quiet under mild sedation. Its retina was dull and greyish, with darker "smoke-wisp" foci, and the optic disc was dull and ill-defined. It died 11 days after the onset.

The principal lesions in both litters were those of encephalitis or meningoencephalomyelitis and interstitial or tubular nephritis similar to those described above in rabbits and rodents. Encephalitozoon was readily seen in the lesions.

Immunity: According to Frenkel (1955), there is no cross immunity between Encephalitozoon and Toxoplasma.

Diagnosis: Encephalitozoonosis is generally diagnosed by finding the causative organisms in tissue sections. They can be differentiated from Toxoplasma on the basis of size, shape and differential staining reactions, as described above.

Cultivation: Encephalitozoon has not been cultivated.

Treatment: None known.

Prevention and Control: In the absence of information on its mode of transmission, little can be said about prevention and control. Sanitation combined with elimination of affected litters, and possibly also of their mothers, may be helpful.