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Abstract
Cryptosporidium sp. is a gastroenteritis-causing pathogen that may increase mortality and morbidity in immunocompromised patients. Diarrhea is a common problem among acquired immunodeficiency syndrome (AIDS) patients, with 30–60% of patients in developed countries and 90% in developing countries affected. The prevalence of cryptosporidiosis is 3–5% of the global population, with 14.42% of those affected being immunocompromised. There is currently no vaccine available to prevent cryptosporidiosis, while nitazoxanide monotherapy is ineffective in eradicating the organism in immunocompromised hosts and malnourished children. This study aimed to determine the most effective combination therapy for cryptosporidiosis in immunocompromised patients. This study used a systematic review design and implemented eligibility criteria for the literature search across PubMed, ScienceDirect, Epistemonikos, Google Scholar, Nature, Springer, and John Wiley databases. The search utilized specific keywords and Boolean operators, i.e., “Cryptosporidium,” OR “cryptosporidiosis,” AND “combination therapy,” OR “combination treatment,” AND “immunocompromised.” Two cohort studies and two case reports were selected, three of which used a nitazoxanide and azithromycin combination as the intervention, whereas only one cohort study used a nitazoxanide and fluoroquinolone combination. The studies comprised 54 samples from post-kidney transplantation patients and one sample from an acute lymphoblastic leukemia (ALL) patient. The nitazoxanide and fluoroquinolone combination showed superior outcomes than the nitazoxanide and azithromycin combination. The stool clearance was significantly lower with nitazoxanide monotherapy than the nitazoxanide and fluoroquinolone combination (OR=0.65, 95% CI=0.34–0.92, p=0.01). However, it was non-significantly lower with the nitazoxanide and azithromycin combination compared to monotherapy (OR=0.27, 95% CI=0.01–5.77, p=0.24). Nitazoxanide monotherapy exerted a significantly lower effect than the nitazoxanide and fluoroquinolone combination in stopping diarrhea symptoms (OR=0.45, 95% CI=0.21–0.81, p=0.004). In conclusion, a combination therapy using nitazoxanide and fluoroquinolone for cryptosporidiosis in immunocompromised patients offers more favorable outcomes compared to monotherapy, particularly in stopping diarrhea and enhancing stool clearance.
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References
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- Bakliwal, A. et al. (2021) ‘Life-Threatening Cryptosporidium Diarrhea in a Child on Induction Chemotherapy for Acute Lymphoblastic Leukemia’, Cureus [Preprint]. Available at: https://doi.org/10.7759/CUREUS.18340.
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- Meidani, M. et al. (2014) ‘Immunocompromised patients: Review of the most common infections happened in 446 hospitalized patients’, Journal of Research in Medical Sciences, 19(SPEC. ISSUE), pp. 2–3.
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- Priyamvada, P., … S.P. journal of and 2014, ‘Successful eradication of cryptosporidium in kidney transplant recipients–Two case reports’, Elsevier [Preprint]. Available at: https://www.sciencedirect.com/science/article/pii/S221200171400015X (Accessed: 8 August 2023).
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- Rizk, M.A. et al. (2018) ‘Inhibitory effects of fluoroquinolone antibiotics on Babesia divergens and Babesia microti, blood parasites of veterinary and zoonotic importance’, Infection and Drug Resistance, 11, pp. 1605–1615. Available at: https://doi.org/10.2147/IDR.S159519.
- Tang, W., Akakulu, W. and Desai, K. (2022) ‘Pneumatosis intestinalis caused by Cryptosporidium colitis in a non-immunocompromised patient’, IDCases, 27, p. e01372. Available at: https://doi.org/10.1016/j.idcr.2021.e01372.
- Tomazic, M.L., Garro, C. and Schnittger, L. (2017) Mariela L. Tomazic, Carlos Garro, and Leonhard Schnittger 2. Available at: https://doi.org/10.1007/978-3-319-70132-5.
- Tuano, K.S., Seth, N. and Chinen, J. (2021) ‘Secondary immunodeficiencies: An overview’, Annals of Allergy, Asthma and Immunology, 127(6), pp. 617–626. Available at: https://doi.org/10.1016/j.anai.2021.08.413.
- Utami, W.S. et al. (2020) ‘Cryptosporidium Infection Increases the Risk for Chronic Diarrhea Among People Living With HIV in Southeast Asia: A Systematic Review and Meta-Analysis’, Asia-Pacific Journal of Public Health, 32(1), pp. 8–18. Available at: https://doi.org/10.1177/1010539519895422.
References
Ahmadpour, E. et al. (2020) ‘Cryptosporidiosis in HIV-positive patients and related risk factors: A systematic review and meta-analysis’, Parasite, 27. Available at: https://doi.org/10.1051/parasite/2020025.
Ali, S. et al. (2014) ‘Prevalence, clinical presentation and treatment outcome of cryptosporidiosis in immunocompetent adult patients presenting with acute diarrhoea’, Journal of the Pakistan Medical Association, 64(6), pp. 613–618.
Bakliwal, A. et al. (2021) ‘Life-Threatening Cryptosporidium Diarrhea in a Child on Induction Chemotherapy for Acute Lymphoblastic Leukemia’, Cureus [Preprint]. Available at: https://doi.org/10.7759/CUREUS.18340.
Bhadauria, D. et al. (2015) ‘Cryptosporidium infection after renal transplantation in an endemic area’, Transplant Infectious Disease, 17(1), pp. 48–55. Available at: https://doi.org/10.1111/tid.12336.
Bouzid, M. et al. (2013) ‘Cryptosporidium pathogenicity and virulence’, Clinical Microbiology Reviews, 26(1), pp. 115–134. Available at: https://doi.org/10.1128/CMR.00076-12.
Certad, G. et al. (2017) ‘Pathogenic Mechanisms of Cryptosporidium and Giardia’, Trends in Parasitology, 33(7), pp. 561–576. Available at: https://doi.org/10.1016/j.pt.2017.02.006.
Lanternier, F., K. Amazzough, L. Favennec, M. F. Mamzer-Bruneel, H. Abdoul, J. Tourret, et al. 2017. Cryptosporidium spp. infection in solid organ transplantation: the nationwide “transcrypto” study. Transplantation. 101(4):826–830.
Deltombe, C. et al. (2020) ‘Cryptosporidiosis and microsporidiosis as causes of diarrhea in kidney and/or pancreas transplant recipients’, Medecine et Maladies Infectieuses, 50(5), pp. 407–413. Available at: https://doi.org/10.1016/j.medmal.2019.07.010.
Efstratiou, A., Ongerth, J.E. and Karanis, P. (2017) ‘Waterborne transmission of protozoan parasites : Review of worldwide outbreaks - An update 2011 e 2016’, Water Research, 114, pp. 14–22. Available at: https://doi.org/10.1016/j.watres.2017.01.036.
Esmat, M. et al. (2022) ‘Efficacy of clofazimine and nitazoxanide combination in treating intestinal cryptosporidiosis and enhancing intestinal cellular regeneration in immunocompromised mice’, Food and Waterborne Parasitology, 27(May), p. e00161. Available at: https://doi.org/10.1016/j.fawpar.2022.e00161.
Florescu, D., transplantation, U.S.-W. journal of and 2016, undefined (no date) ‘Cryptosporidium infection in solid organ transplantation’, ncbi.nlm.nih.gov [Preprint]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036118/ (Accessed: 8 August 2023).
Gerace, E., Presti, V.D.M. Lo and Biondo, C. (2019) ‘ Cryptosporidium infection: epidemiology, pathogenesis, and differential diagnosis ’, European Journal of Microbiology and Immunology, 9(4), pp. 119–123. Available at: https://doi.org/10.1556/1886.2019.00019.
Higgins, J. and J. Thomas. 2022. Cochrane handbook for systematic reviews of interventions. https://training.cochrane.org/handbook/current.html.
Laurent, F., Parasitology, S.L.-L.-I.J. for and 2017, ‘Innate immune responses play a key role in controlling infection of the intestinal epithelium by Cryptosporidium’, Elsevier [Preprint]. Available at: https://www.sciencedirect.com/science/article/pii/S002075191730245X (Accessed: 8 August 2023).
Lee, S. et al. (2017) ‘The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis’, journals.plos.org [Preprint]. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185906 (Accessed: 8 August 2023).
Meidani, M. et al. (2014) ‘Immunocompromised patients: Review of the most common infections happened in 446 hospitalized patients’, Journal of Research in Medical Sciences, 19(SPEC. ISSUE), pp. 2–3.
Mohebali, M. et al. (2020) ‘Cryptosporidium infection among people living with HIV/AIDS in Ethiopia: a systematic review and meta-analysis’, Taylor & Francis [Preprint]. Available at: https://www.tandfonline.com/doi/abs/10.1080/20477724.2020.1746888 (Accessed: 8 August 2023).
Page, M.J. et al. (2021) ‘The PRISMA 2020 statement: An updated guideline for reporting systematic reviews’, The BMJ, 372. Available at: https://doi.org/10.1136/bmj.n71.
Priyamvada, P., … S.P. journal of and 2014, ‘Successful eradication of cryptosporidium in kidney transplant recipients–Two case reports’, Elsevier [Preprint]. Available at: https://www.sciencedirect.com/science/article/pii/S221200171400015X (Accessed: 8 August 2023).
Pumipuntu, N. and Piratae, S. (2018) ‘Cryptosporidiosis: A zoonotic disease concern’, Veterinary World, 11(5), pp. 681–686. Available at: https://doi.org/10.14202/vetworld.2018.681-686.
Rizk, M.A. et al. (2018) ‘Inhibitory effects of fluoroquinolone antibiotics on Babesia divergens and Babesia microti, blood parasites of veterinary and zoonotic importance’, Infection and Drug Resistance, 11, pp. 1605–1615. Available at: https://doi.org/10.2147/IDR.S159519.
Tang, W., Akakulu, W. and Desai, K. (2022) ‘Pneumatosis intestinalis caused by Cryptosporidium colitis in a non-immunocompromised patient’, IDCases, 27, p. e01372. Available at: https://doi.org/10.1016/j.idcr.2021.e01372.
Tomazic, M.L., Garro, C. and Schnittger, L. (2017) Mariela L. Tomazic, Carlos Garro, and Leonhard Schnittger 2. Available at: https://doi.org/10.1007/978-3-319-70132-5.
Tuano, K.S., Seth, N. and Chinen, J. (2021) ‘Secondary immunodeficiencies: An overview’, Annals of Allergy, Asthma and Immunology, 127(6), pp. 617–626. Available at: https://doi.org/10.1016/j.anai.2021.08.413.
Utami, W.S. et al. (2020) ‘Cryptosporidium Infection Increases the Risk for Chronic Diarrhea Among People Living With HIV in Southeast Asia: A Systematic Review and Meta-Analysis’, Asia-Pacific Journal of Public Health, 32(1), pp. 8–18. Available at: https://doi.org/10.1177/1010539519895422.