Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice

Abstract

The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

A Cryptosporidium parvum vaccine candidate effect on immunohistochemical profiling of CD4, CD8, Caspase-3 and NF-κB in mice

“…Regarding the immune-scoring percentage, we reported high CD4 and low CD8 antibody expression in the noninfected nonimmunized groups. This was consistent with Fahmy et al [35], who found that healthy noninfected mice exhibited a higher intestinal expression of local CD4 T cells than CD8 cells.…”

“…However, Fahmy et al [35] demonstrated overexpression of CD8 over CD4 cells in the C. parvum-infected mice intestines, which reversed the balanced CD4/CD8 ratio. The C. parvum-infected mice exhibiting high CD8 expression did not show improvement in either parasite load or pathological consequences, as the CD4 and CD8 cells were observed on the 10th day of infection (when the oocysts shedding, and pathological lesions were high).…”

Nitazoxanide, Ivermectin, and Artemether effects against cryptosporidiosis in diabetic mice: parasitological, histopathological, and chemical studies

“…GVI showed better efficacy of reducing the oocyst shedding than GV both in the duodenal contents (63.79%, and 58.38% respectively) and stool examinations (87.10% and 83.42% respectively). Our results are comparable to (Fahmy et al 2021 ) who reported reduction of Cryptosporidium oocyst shedding in the stool of infected mice treated with NTZ by 63% whereas the group of mice treated with IVC showed reduction by 82%. In the present study, mice were inoculated with 10 3 oocysts while in their study the inoculum was 10 4 oocysts.…”

“…Using NTZ, IVC, or ART caused a statistically significant elevation of blood glucose level of the corresponding study groups compared to the infected control group ( P -value < 0.001). Our results are comparable to a study reported that a significant improvement was noted on the histopathological changes at the ileal region of different groups of infected immunosuppressed mice treated with IVC alone or combination of NTZ and IVC or NTZ with Selenium, or IVC with selenium but no significant improvement was noted when NTZ was used alone (Fahmy et al 2021 ).…”

Efficacy of clofazimine and nitazoxanide combination in treating intestinal cryptosporidiosis and enhancing intestinal cellular regeneration in immunocompromised mice

“…Mice were classified into four groups of immunosuppressed (6 mice/group) ( Huang and Yang, 2002 ; Fahmy et al, 2021 ) Group A: infected only; Group B: infected and treated with NTZ; Group C: infected and treated with CFZ; Group D: infected and treated with half-dose nitazoxanide + half-dose clofazimine.…”