Effect of Three Drugs against Encephalitozoon cuniculi Infection in Immunosuppressed Mice

Abstract

bMicrosporidia 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.

Limited effect of adaptive immune response to control encephalitozoonosis

“…The efficacy of a treatment in the elimination of microsporidia was originally evaluated by extension of hosts’ survival time using in vivo experimental infections. However, recently published studies showed that treatment with albendazole caused ostensible disappearance of E. cuniculi from all organs and tissues in immunocompetent murine hosts and that microsporidia can spread again from hidden foci after treatment termination or immunosuppression of the host . In the present study, immunocompetent C57Bl/6 mice and CD4 −/− mice were both successfully treated with albendazole; however, only a temporary remission was observed in CD8 −/− mice, with the number of affected organs by the end of the experiment being comparable to that of untreated mice during the acute phase of infection.…”

“…While encephalitozoonosis in SCID mice was characterized by a gradual dispersal leading to death within 5 weeks post-infection, 18 published studies showed that treatment with albendazole caused ostensible disappearance of E. cuniculi from all organs and tissues in immunocompetent murine hosts and that microsporidia can spread again from hidden foci after treatment termination or immunosuppression of the host. 18,39 In the present study, immunocompetent C57Bl/6 mice and CD4 −/− mice were both successfully treated with albendazole; however, only a temporary remission was observed in CD8 −/− mice, with the number of affected organs by the end of the experiment being comparable to that of untreated mice during the acute phase of infection. Our results highlight the importance of determining the mechanisms by which hosts survive an extensive spore load (as in CD4 −/− mice) and how microsporidia escape from both the immune response and current treatments.…”

In vitro antimicrosporidial activity of gold nanoparticles against Heterosporis saurida

“…Only a small number of anti-parasitic drugs are permitted in aquaculture, as the cost of drug development is high and the market small. The few available treatments for microsporidiosis differ in their effectiveness, and as with many drug treatments, there is concern for the pathogens developing resistance to one or multiple antibiotics [ 16 ]. A promising, alternative approach that has received recent attention is the use of metallic nanoparticles, which have distinct advantages over conventional antimicrobial agents [ 17 , 18 ].…”

“…The most widespread antimicrobial compounds are silver and benzalkonium chloride [ 25 , 26 ]. Unfortunately, in a comparable manner where scientists develop new efficient antimicrobial materials, there is no doubt that resistance to silver also is increasing [ 16 ]. Therefore, a number of metals, mainly copper, have been used as an antimicrobial agent.…”

Albendazole-responsive disseminated Tubulinosema acridophagus in a patient with chronic lymphocytic leukaemia

“…On the basis of literature demonstrating antimicrosporidial activity of benzimidazoles [3], therapy with albendazole 400 mg oral twice daily was initiated. After 1 week of therapy, no new lesions had developed and previous lesions had decreased in size and number.…”