Effect of three drugs against Encephalitozoon cuniculi infection in immunosuppressed mice

Abstract

Microsporidia comprise a large group of obligate intracellular parasites. The microsporidian Encephalitozoon cuniculi causes disseminated infection in immunosuppressed patients with HIV, cancer, or transplants and in the elderly. In vivo and in vitro studies on the effectiveness of drugs are controversial. Currently, there is no effective treatment. We tested albendazole, albendazole sulfoxide, metronidazole, and cyclosporine in mice immunosuppressed with cyclophosphamide and inoculated by the intraperitoneal route with 10(7) E. cuniculi spores. One week after experimental inoculation, the mice were treated with albendazole, albendazole sulfoxide, metronidazole, and cyclosporine. Histological and morphometric analyses were performed to compare the treated groups. The state of immunosuppression was evaluated by phenotyping CD4(+) and CD8(+) T cells by flow cytometry. Nontreated mice showed acute disseminated and fatal encephalitozoonosis. The treatment with benzimidazoles significantly reduced infection until 30 days posttreatment (p.t.), but at 60 days p.t., the infection had recurred. Metronidazole decreased infection by a short time, and cyclosporine was not effective. All animals were immunosuppressed by all the experiments, as demonstrated by the low number of CD4(+) and CD8(+) T cells. We conclude that no drug was effective against E. cuniculi, but the benzimidazoles controlled the infection transiently.

Fig 1

(A) Liver showing nodules of lymphocytic inflammatory cells with E. cuniculi spores (arrow) (H&E; ×400). (B) Spores of E. cuniculi stained by toluidine blue-fuchsin stain (×1,000). (C) Spores of E. cuniculi stained by Gram-Chromotrope stain (×1,000). (D) Spore collection observed in the alveolar septa (H&E; ×1,000). (E) Inflammatory infiltrates in the small intestine (arrow) (H&E; ×1,000). (F) Kidney showing lymphocytic inflammatory cells and E. cuniculi spores (arrow) (H&E; ×1,000).