Efficacy of combined atorvastatin and paromomycin in treating experimental cryptosporidiosis in immunosuppressed mice.

BACKGROUND: Cryptosporidiosis, mainly caused by Cryptosporidium hominis and C. parvum, is a waterborne disease posing significant risks to immunosuppressed individuals. The limited efficacy of Nitazoxanide in such cases highlights the need for alternative and combination therapies. Paromomycin inhibits parasite protein synthesis, while statins show promising anti-cryptosporidial effects. OBJECTIVES: The study evaluates combined Atorvastatin and Paromomycin therapy for treating cryptosporidiosis in immunosuppressed mice, focusing on intestinal and extra-intestinal pathology and oxidative stress biomarkers. METHODOLOGY: Fifty immunosuppressed male CD1 Swiss albino mice were randomly assigned into five groups: control non-infected, infected control, and three treatment groups (Paromomycin, Atorvastatin, combination). All infected groups received 1 × 104 C. parvum oocysts. The combination group received Atorvastatin (20 mg/kg/day) and Paromomycin (250 mg/kg/day) for five days. Efficacy was assessed by oocyst shedding, histopathology, and biomarker levels at day 14 post-infection. RESULTS: Combination therapy reduced oocyst shedding by 72.3% and showed near-normal tissue architecture. Atorvastatin monotherapy was more effective than Paromomycin alone (49.3% vs. 30.2%). Combination therapy resulted in minimal pathological changes and lower inflammation across organs (intestine, liver, and lung). Oxidative stress biomarkers indicated ongoing oxidative stress with Paromomycin, whereas Atorvastatin suggested an antioxidant effect at the time point of the research. CONCLUSION: Combined Atorvastatin and Paromomycin showed superior efficacy over monotherapies, reducing parasite load, improving tissue pathology, and modulating oxidative stress in immunosuppressed mice.