The immunomodulatory activity of secnidazole–nitazoxanide in a murine cryptosporidiosis model

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Madbouly N.; El Amir A.; Kader A.A.; Rabee I.; Farid A.

Journal: Journal of Medical Microbiology

Publisher: Microbiology Society

Publication Date: 1 March 2021

Volume / Issue: Volume 70 / Issue 3

Article No.: 1327

ISSN: 222615

DOI: 10.1099/jmm.0.001327

Scopus: View on Scopus

PubMed: 33625354

Document Type: Article

Authors and Affiliations

Madbouly N., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; El Amir A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Kader A.A., Department of Parasitology, Theodore Bilharz Research Institute, Giza, Egypt; Rabee I., Department of Parasitology, Theodore Bilharz Research Institute, Giza, Egypt; Farid A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt

Abstract

Introduction. Cryptosporidium parvum causes intestinal parasitic infections affecting both immunosuppressed and immunocompetent individuals. Gap statement. Given the absence of effective treatments for cryptosporidiosis, especially in immunodeficient patients, the present study was designed to assess the therapeutic efficacy of secnidazole (SEC) and its combination with nitazoxanide (NTZ) in comparison to single NTZ treatment in relation to the immune status of a murine model of C. parvum infection. Methodology. The infected groups were administered NTZ, SEC or NTZ–SEC for three or five successive doses. At days 10 and 12 post-infection (p.i.), the mice were sacrificed, and the efficacy of the applied drugs was evaluated by comparing the histopathological alterations in ileum and measuring the T helper Th1 (interferon gamma; IFN-γ), Th2 [interleukin (IL)-4 and IL-10] and Th17 (IL-17) cytokine profiles in serum. Results. The NTZ–SEC combination recorded the maximal reduction of C. parvum oocyst shedding, endogenous stages count and intestinal histopathology, regardless of the immune status of the infected mice. The efficacy of NTZ–SEC was dependent on the period of administration, as the 5 day-based treatment protocol was also more effective than the 3 day-based one in terms of immunocompetence and immunosuppression. The present treatment schedule induced an immunomodulatory effect from SEC that developed a protective immune response against C. parvum infection with reduced production of serum IL-17, IFN-γ, IL-4 and IL-10. Conclusions. Application of NTZ–SEC combined therapy may be useful in treatment of C. parvum, especially in cases involving immunosuppression. © 2021 The Authors.

Keywords

C. parvum; Immunomodulation; Nitazoxanide; Secnidazole; Animals; Antiprotozoal Agents; Cryptosporidiosis; Cryptosporidium parvum; Cytokines; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Ileum; Immunocompromised Host; Male; Metronidazole; Mice; Nitro Compounds; Parasite Load; Thiazoles; amebazole; dexamethasone; dexazone; gamma interferon; interleukin 10; interleukin 17; interleukin 4; nanazoxid; antiprotozoal agent; cytokine; nitro derivative; thiazole derivative; animal experiment; animal model; animal tissue; Article; combination drug therapy; controlled study; cytokine response; developmental stage; drug efficacy; enzyme linked immunosorbent assay; feces analysis; histopathology; immune deficiency; immune response; immunocompetence; monotherapy; mouse; nonhuman; oocyst; priority journal; protein blood level; Th1 cell; Th2 cell; treatment duration; treatment response; animal; blood; disease model; drug administration; drug effect; immunocompromised patient; immunology; parasitology; pathology

Citation Information

Scopus Citations: 13

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