Potential Immunomodulatory Effect of Single and Combined Therapies Against Cryptosporidium Infection in Immunosuppressed Mouse Model

Fahmy, Mennat-Elrahman Ahmed; Abdel-Aal, Amany Ahmed; Hassan, S. S.; Shalaby, Maisa Ahmed; Ismail, Mousa A. M.; Khairy, Rasha A.; Fadl, Hanaa O.

doi:10.21608/jesp.2020.131111

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…(2022) reported an oocyst shedding reduction percentage of 54%. The therapeutic e cacy of NTZ in the present study was higher than the results documented byFahmy et al (2020) andEsmat et al (2022) who reported 39% and 38%, respectively.Histopathological examination and the ultrastructural study of ileum tissues obtained from the normal control group showed preserved crypt-villous ratio, intact epithelial lining, regular brush border, normal secretory goblet cells, and intact intracellular junctions. While the infected control group showed disturbed villous architecture, ulcerations, in ammatory in ltration in lamina propria, congestion, dysplasia, decreased numbers of goblet cells, focal or total loss of the brush border microvilli, and destroyed intracellular junctions.…”

contrasting

confidence: 83%

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

Beshay

Nassef

Shafey

et al. 2023

Preprint

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Cryptosporidiosis is one of the most frequent food and water-borne diseases. The disease might be life-threatening in immunosuppressed patients. Unfortunately, the only approved drug, nitazoxanide, is with variable efficacies, particularly in malnourished children and immunocompromised patients. Therefore, there is a need to discover an alternative treatment that could be achieved by targeting the metabolic pathways. One of the important enzymes in the glycolysis pathway of C. parvum is triosephosphate isomerase, which could be hindered by the proton pump inhibitor (PPI) omeprazole. In this study, omeprazole was repurposed against C. parvum infection in experimentally immunosuppressed mice. This study was conducted on five mice groups (n = 10). Group I (Normal Control), group II (Infected Control): Mice were infected orally with 1×105 C. parvum oocysts on the 15th day of DEX induced immunosuppression. Group III (NTZ-treated): infected and treated by NTZ. Group IV (Omeprazole-treated), and lastly, Group V (NTZ + Omeprazole-treated). The result obtained with omeprazole alone was better than nitazoxanide regarding oocyst shedding reduction percentages (84.9% & 56.1%, respectively). Also, it was better regarding restoration of histopathological and ultrastructural architectures, improvement of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and renal functions (urea and creatinine), and the reduction of C. parvum triosephosphate isomerase (TIM) gene expression by RT-PCR. However, the best results were obtained with the combined treatment. Hence, omeprazole could be considered a novel drug option to treat this life-threatening parasitic infection either alone or combined with NTZ, especially in immunosuppressed patients.

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contrasting

confidence: 83%

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

Beshay

Nassef

Shafey

et al. 2023

Preprint

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“…Moreover, numerous studies have reported resolution of Cryptosporidium infection after CD4 T cell reconstitution in AIDS patients given antiretroviral therapy, denoting the importance of such a cell population in the clearance of this opportunistic infection (Schmidt et al, 2004;O'Connor et al, 2011;Dillingham et al, 2011;Ahmadpour et al, 2020). In our earlier work on the dexamethasone immunocompromised mice model, CD4 expression in the treated animals was not elevated enough to the effective level that restores the balanced CD4/CD8 ratio (Fahmy et al, 2020) The present work revealed that the highest level of CD4 expression among the treated mice was in the group which received combined regimen (NTZ+ IVC), whereas, the lowest level was in the single NTZ-treated group, thus suggesting the beneficial effect of the former therapy on the local cellular immune response. This data together with the results of oocyst excretion may signify the superiority of combined (NTZ+ IVC) regimen over the other forms of therapy.…”

Section: Discussionmentioning

confidence: 91%

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

Fahmy

Abdel-Aal

Hassan

et al. 2021

Rev. Bras. Parasitol. Vet.

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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.

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“…NTZ was supplied as suspension 100 mg/ 5 mL (Nanazoxid; from Medizen Pharmaceutical Industries for Utopia Pharmaceuticals). Each mouse in group B, 250 mg/kg/day was administered orally once daily from the fourth-day post-inoculation for ten successive days while a dose of 125 mg/kg/day was used for group D ( Theodos et al, 1998 ; Fahmy et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…It can be life-threatening in the very young, the elderly, and immunosuppressed individuals ( Chen et al, 2002 ; Dong et al, 2020 ). To date, the best therapy for cryptosporidiosis includes fluid and electrolytes replacement, antimotility agents, antiparasitic drugs, nutritional support and reversal of immunosuppression if possible ( Checkley et al, 2015 ; Fahmy et al, 2020 ; Wang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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

Esmat

Abdel-Aal

Shalaby

et al. 2022

Food and Waterborne Parasitology

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Potential Immunomodulatory Effect of Single and Combined Therapies Against Cryptosporidium Infection in Immunosuppressed Mouse Model

Cited by 4 publications

References 29 publications

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

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

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

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