Encephalitozoon cuniculi infection in cats: European guidelines from the ABCD on prevention and management.

OVERVIEW: Encephalitozoon cuniculi is a common obligate intracellular microsporidian parasite of rabbits that is increasingly recognised as a pathogen of cats and other mammalian species. These guidelines aim to review the literature on feline E cuniculi infection and provide recommendations on prevention and management. INFECTION IN CATS: E cuniculi infection should be considered as a differential diagnosis in cases of feline uveitis and cataract formation. It is not significantly associated with either chronic kidney disease or meningoencephalitis. E cuniculi infection is more common in stray or feral cats than in pet cats. DIAGNOSIS AND TREATMENT: Serological tests for antibody detection in the blood are easy to perform and can be useful for diagnosis, but their specificity is low as antibodies have been found in apparently healthy cats. PCR appears to be more sensitive than histopathology for diagnosis, and is more sensitive when performed on cataractous lenses compared with aqueous humour, although ease of sampling is an obvious limitation. Treatment is with fenbendazole for 3 weeks and phacoemulsification to remove microsporidia from cataractous lenses. ZOONOTIC RISK: E cuniculi is a potential zoonotic agent, and there is a particular risk to immunocompromised humans posed by infected rabbits. Albeit infrequent, spore shedding has been identified in cats, so care should be taken around infected cats.

Efficacy of gamma interferon and specific antibody for treatment of microsporidiosis caused by Encephalitozoon cuniculi in SCID mice.

Microsporidia are eukaryotic, obligate, intracellular protists that are emerging pathogens in immunocompromised hosts, including AIDS patients and organ transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by means of adoptive transfer and IFN-gamma administration in SCID mice. While the adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival of SCID mice infected perorally with E. cuniculi, survival was not improved by adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The protective effect of IFN-gamma was confirmed in cytokine therapy experiments in which SCID mice receiving IFN-gamma survived significantly longer than mice receiving mock injections. The administration of serum containing specific antibodies against E. cuniculi was found to prolong the survival of concurrently IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN-gamma is potentially useful as a cytokine therapy for microsporidiosis, especially in CD4(+) T-cell-deficient patients.

Clinical Signs, Diagnosis, and Treatment of Encephalitozoon cuniculi Infection in Rabbits.

Central vestibular dysfunction caused by Encephalitozoon cuniculi frequently mimics the condition of a peripheral disorder. A negative antibody titer rules out E cuniculi as the cause of present clinical signs. Cerebrospinal fluid analysis including polymerase chain reaction is considered an inappropriate diagnostic method for in vivo diagnosis of encephalitozoonosis. The usefulness of glucocorticoid anti-inflammatories in the treatment of encephalitozoonosis is called into question. Encouraging activity early in the course of disease and adding in therapeutic exercise may represent the most important part of therapy in rabbits with vestibular dysfunction associated with encephalitozoonosis.

Microsporidial keratoconjunctivitis in a HIV-seronegative patient treated with debridement and oral itraconazole.

PURPOSE: To report a case of microsporidial keratoconjunctivitis in an HIV-seronegative. METHODS: We report on a 40-year-old woman who presented with acute symptoms of 4 days' duration. Visual acuity was 6/6 in the right eye and 6/6 partial in the left eye. In the left eye, there was diffuse conjunctival congestion with papillary changes. There were multiple raised epithelial lesions in the cornea. RESULTS: Corneal scrapings stained with potassium hydroxide and calcofluor white showed Microsporidium spores in large numbers. These spores with polar staining were also confirmed in Gram stain. One month after initiation of itraconazole, the left eye was quiet. She had a visual acuity of 6/6 in that eye, with faint corneal haze. CONCLUSIONS: We report a rare case of microsporidial keratoconjunctivitis in a HIV-seronegative patient who was treated by debridement and oral itraconazole. Microsporidium should be suspected even in an immunocompetent individual if the corneal examination revealed showed multiple raised epithelial lesions.

Prophylactic and therapeutic immune reconstitution of SCID mice infected with Encephalitozoon cuniculi.

Severe combined immunodeficient (SCID) mice develop lethal infections, resembling opportunistic microsporidiosis of immunocompromised patients, after intraperitoneal (i.p.) inoculations of spores of Encephalitozoon cuniculi. In the present study, SCID mice reconstituted i.p. with 5 x 10(7) spleen cells from naive adult BALB/c mice 14 days prior to the i.p. injection of 10(7) spores were completely resistant to the infection, whereas control infected SCID mice developed clinical disease and died within 17 days post infection (DPI). In another experiment, SCID mice infected i.p. with 10(7) spores of E. cuniculi and after that (on DPI 7) injected i.p. with 5 x 10(7) spleen lymphocytes isolated from immune adult BALB/c mice were partially protected against the parasite (40% of the reconstituted mice survived). In both experiments, high levels of parasite-specific serum antibodies (mostly of the IgG-isotype) were detected in the infected immunocompetent BALB/c mice, whereas virtually no antibodies were found in the infected SCID mice. However, SCID mice reconstituted with either naive spleen cells or immune lymphocytes revealed humoral immune responses comparable with those of immunocompetent mice.

[Encephalitozoon cuniculi and Encephalitozoon intestinalis--causes of opportunistic infections]. / Encephalitozoon cuniculi a Encephalitozoon intestinalis--puvodci oportunních infekcí.

Microsporidia (phylum Microsporidia) are intracellular parasites that infect a wide range of protozoa, invertebrates and vertebrate hosts. Over a 1000 species have been classified into approximately 100 genera. Historically, microsporidial infections in silkworms, honey bees, and salmonid fish have been responsible for significant economic losses. More recently, microsporidiosis has been recognized as an important opportunistic infection in immunologically compromised patients. In this review there is information on the immunobiology of microsporidia Encephalitozoon cuniculi and Encephalitozoon intestinalis which were identified as the most common causative agents of microsporidiosis in mammals. Most of what is known about the immunology of microsporidiosis is based on experiments with the microsporidian Encephalitozoon cuniculi.

Antibodies enhance the protective effect of CD4+ T lymphocytes in SCID mice perorally infected with Encephalitozoon cuniculi.

The role of antibodies in the immune response to microsporidiosis was studied using a novel anti-exospore monoclonal antibody (MAb) P5/H1, which recognizes surface antigens of Encephalitozoon cuniculi. The effect of the MAb on microsporidial infection in vivo was to prolong the survival of previously CD4+ reconstituted, perorally infected and intraperitoneally MAb-treated SCID mice. The MAb decreased the numbers of E. cuniculi spores in peritoneal smears obtained post mortem. These results suggest a possible role for antibodies in protection against perorally acquired E. cuniculi infection.

Intestinal microsporidiosis.

Intestinal microsporidiosis is caused by the protozoan parasites Enterocytozoon bieneusi and Encephalitozoon intestinalis. The disease has been described within the past decade and is found predominantly in acquired immunodeficiency syndrome (AIDS) patients in association with diarrhea. There have been rare reports of infections in immunocompetent patients. Both species of microsporidia invade and multiply within the enterocytes of the small intestine; Encephalitozoon intestinalis also causes a disseminated infection. Electron microscopy has been the mainstay of diagnosis, but improved noninvasive methods of detecting spores in feces are in development. The biology and pathogenicity of the parasites and the pathology and treatment of the disease are poorly understood.

Role of P glycoprotein in the course and treatment of Encephalitozoon microsporidiosis.

Encephalitozoon microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the Encephalitozoon microsporidia, E. cuniculi, E. hellem, and E. intestinalis, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species.