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Effect of three drugs against Encephalitozoon cuniculi infection in immunosuppressed mice
Maria Anete Lallo1, Lidiana F Vidoto da Costa, João Manoel de Castro
1Environmental and Experimental Pathology, Paulista University (UNIP), São Paulo, Brazil. maria.lallo@cruzeirodosul.edu.br
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.
Insights
No effective treatment exists for Encephalitozoon cuniculi infections. While benzimidazoles transiently controlled the parasite in immunosuppressed mice, the infection recurred, highlighting the need for novel therapeutic strategies.
Area of Science:
- Infectious Diseases
- Parasitology
- Immunology
Background:
- Encephalitozoon cuniculi is an opportunistic microsporidian parasite causing severe infections in immunocompromised individuals.
- Current therapeutic options for E. cuniculi are limited and controversial, with no consistently effective treatments available.
Purpose of the Study:
- To evaluate the efficacy of albendazole, albendazole sulfoxide, metronidazole, and cyclosporine against Encephalitozoon cuniculi infection in an immunosuppressed mouse model.
Main Methods:
- Mice were immunosuppressed using cyclophosphamide and infected with E. cuniculi spores.
- Treatment groups received albendazole, albendazole sulfoxide, metronidazole, or cyclosporine post-infection.
- Histological, morphometric, and flow cytometry analyses were used to assess infection burden and immune status (CD4+, CD8+ T cells).
Main Results:
- Nontreated mice developed fatal disseminated encephalitozoonosis.
- Benzimidazoles (albendazole, albendazole sulfoxide) significantly reduced infection for 30 days, but recurrence was observed by 60 days post-treatment.
- Metronidazole provided short-term reduction, while cyclosporine showed no efficacy. Immunosuppression was confirmed in all animals.
Conclusions:
- No tested drug demonstrated sustained efficacy against Encephalitozoon cuniculi infection.
- Benzimidazoles offered transient control, indicating a need for further research into more effective and durable treatments for microsporidiosis.
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