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Prevalence, Genetic Diversity, and Risk Factors of Cryptosporidium spp. in HIV/AIDS Patients: An Updated Systematic
Farzad Mahdavi1, Mohammad Reza Mohammadi2, Shayan Heidari3
1Department of Medical Parasitology and Mycology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran, zums.ac.ir.
Background:
Cryptosporidium spp. is a major opportunistic pathogens in HIV/AIDS patients, contributing substantially to morbidity and mortality worldwide. Despite advances in HIV/AIDS management, the global burden, genetic diversity, and risk factors of cryptosporidiosis in this high-risk group remain incompletely understood.
Methods:
We conducted a systematic review and meta-analysis of cross-sectional and case-control studies published between January 1, 2017, and June 10, 2025, in accordance with PRISMA 2020 guidelines. Literature searches were performed in PubMed, Scopus, Embase, and Web of Science, supplemented by Google Scholar. Eligible studies reported the prevalence of Cryptosporidium spp. in HIV/AIDS patients, with or without comparison groups, using microscopy, serology, or molecular methods. Data extraction was performed independently by two reviewers, and study quality was assessed using the JBI checklist. Random-effects models were applied in Comprehensive Meta-Analysis software, with subgroup analyses and meta-regression conducted to explore prevalence and heterogeneity.
Results:
A total of 89 studies were included. The pooled prevalence of Cryptosporidium spp. among HIV/AIDS patients was 9.5% (95% CI: 7.6-11.8). Based on 17 case-control studies, HIV-positive individuals had a significantly higher risk of infection compared to HIV-negative controls (OR: 3.5, 95% CI: 2.1-5.9). Subgroup analyses revealed higher pooled prevalence in smaller studies, medium-HDI and lower-middle-income countries, and African and Central American settings. Pooled prevalence did not differ significantly across diagnostic methods. Among HIV/AIDS patients positive for Cryptosporidium spp., 39.8% were aged ≤ 30 years and 64.7% were > 30 years. Females represented 54.5% of positives, slightly higher than males at 45.8%. Most infected patients had CD4 counts ≤ 200 cells/μL (62.5%), compared to 43.2% with counts > 200. Diarrhea was present in 78.4% of positive cases, versus 43.8% among those without infection. Meta-regression confirmed a significant inverse association between sample size and prevalence (β = -0.0019, p = 0.003). Molecular data identified diverse species and subtypes, with C. hominis and C. parvum predominating but zoonotic species such as C. meleagridis, C. felis, C. viatorum, C. canis, C. suis, C. andersoni, and C. cuniculus also reported. Sensitivity analyses showed no single study significantly influenced the pooled prevalence. Funnel plot asymmetry and Egger's test indicated publication bias.
Conclusions:
This updated synthesis demonstrates that cryptosporidiosis remains a substantial health burden in HIV/AIDS patients, with notable genetic diversity reflecting both anthroponotic and zoonotic transmission routes. The strong association with immunosuppression, as evidenced by low CD4 counts and diarrheal symptoms, underscores its clinical relevance. These findings highlight the urgent need for improved surveillance, molecular epidemiology, and preventive interventions to mitigate the impact of Cryptosporidium spp. in vulnerable populations.
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