Abstract
Background: Cyclospora cayetanensis, an opportunistic protozoan parasite, poses significant risks to immunocompromised patients, including those with cancer, transplants, or on hemodialysis. The aim of this study was to determine the pooled prevalence of C. cayetanensis in immunocompromised individuals (cancer, transplant, and hemodialysis) and assess the associated risk factors compared to nonimmunocompromised controls.
Methods: A comprehensive search of international databases was conducted for studies published up to October 18, 2024, focusing on cross-sectional and case–control studies that reported Cyclospora cayetanensis prevalence in immunocompromised patients. Comprehensive meta-analysis (CMA) software was used to calculate pooled prevalence and odds ratios (ORs), with random-effects models applied to account for heterogeneity based on statistical thresholds. Sensitivity analysis was performed to assess the robustness of pooled prevalence and weighted ORs. Meta-regression analysis was used to evaluate associations between prevalence and variables such as publication year, sample size, and the Human Development Index (HDI). Subgroup analyses were conducted based on geographical regions, publication years, sample sizes, HDI values, income levels, and patient types. This systematic review included 19 studies/22 datasets, comprising 2084 immunocompromised patients and 954 controls across eight countries.
Results: The pooled prevalence of C. cayetanensis in immunocompromised patients was 4% (95% CI: 2.1%–7.2%), significantly higher than the 1.2% (95% CI: 0.4%–3.4%) in controls, resulting in an OR of 5.4 (95% CI: 2.6–10.8, p < 0.001). Transplant recipients exhibited the highest pooled prevalence of C. cayetanensis at 5%, indicating the importance of targeted screening and preventive measures for this high-risk group.
Conclusions: Despite the relatively low pooled prevalence of C. cayetanensis infection in immunocompromised patients, its notable occurrence compared to controls and its opportunistic nature underscore the need for enhanced surveillance and targeted prevention strategies, especially in high-risk populations and regions with higher exposure.
Keywords: cancer, Cyclospora cayetanensis, hemodialysis, immunocompromised patients, prevalence, transplant
1. Introduction
Cyclospora cayetanensis, an apicomplexan protozoan, causes cyclosporiasis, a gastrointestinal (GI) illness transmitted through contaminated food and water [1]. Unlike some coccidian parasites, C. cayetanensis oocysts require environmental sporulation to become infectious, preventing direct person-to-person transmission and highlighting produce and water contamination as the main infection route [2]. Outbreaks have been linked to fresh fruits and vegetables like berries, cilantro, basil, and lettuce in multiple countries [2, 3].
A recent meta-analysis estimated the global prevalence of C. cayetanensis in humans at 3.4%, with rates varying from negligible in high-income countries (0.4%) to higher rates in low-income regions, particularly Africa (5.9%), and underserved populations (over 7%) [4].
Immunocompromised individuals, including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), transplant recipients, cancer patients on chemotherapy, and dialysis patients, face a significantly increased risk of infection [5–8]. Prevalence among HIV-positive individuals has varied widely (0%–48%) [9]. A global systematic review and meta-analysis estimated a pooled prevalence of 3.89% (95% CI: 2.62–5.40) in people living with HIV/AIDS, with diarrhea and low CD4 counts identified as risk factors in immunosuppressed individuals [10].
Cyclosporiasis in immunocompetent individuals typically presents as self-limited diarrhea with abdominal discomfort, nausea, fatigue, low-grade fever, and weight loss, resolving within weeks. Immunocompromised patients, however, often suffer chronic, relapsing, or prolonged diarrhea, leading to malnutrition, dehydration, and increased morbidity. Limited evidence suggests that C. cayetanensis can exacerbate conditions like HIV-related GI mucosal damage [10–12].
Despite this, existing data on prevalence and risk factors in high-risk groups remain fragmented, with heterogeneous diagnostic methods (microscopy vs. PCR), small study sizes, and diverse geographic coverage [9]. No comprehensive synthesis has yet integrated data across different immunocompromised populations to assess disease burden, subgroup differences, or regionally relevant trends. Understanding the true prevalence of C. cayetanensis in immunosuppressed populations is critically needed: it informs clinical guidelines (screening, diagnosis, prophylaxis), directs public health and food-safety interventions (especially given the environmental route of transmission), and allows identification of the most vulnerable subgroups, such as patients with cancer, transplant recipients, and dialysis patients.
Therefore, this systematic review and meta-analysis aim to synthesize available evidence on the prevalence and risk factors of C. cayetanensis infection in immunocompromised populations (those with cancer, organ transplantation, and hemodialysis) and immunocompetent controls. By consolidating existing studies, we aim to clarify the epidemiological patterns and burden in these high-risk groups, addressing important knowledge gaps and supporting more effective health policy and clinical practice.
2. Methods
2.1. Ethical Considerations
This study involved secondary analysis of data extracted exclusively from the previously published peer-reviewed literature and did not involve direct interaction with human participants. Therefore, informed consent and individual ethical approval were not required. However, the research protocol was reviewed and approved by the Ethics Committee of Qazvin University of Medical Sciences (Approval No. IR.QUMS.REC.1403.498). The ethical approval pertained to the appropriate handling, management, citation, and synthesis of published data in accordance with responsible research practices and academic integrity standards.
2.2. Study Design and Search Strategy
This systematic review and meta-analysis was conducted following the PRISMA 2020 guidelines [13]. A comprehensive literature search was carried out to identify all relevant studies reporting the prevalence of C. cayetanensis in immunocompromised populations and their immunocompetent controls. The following electronic databases were searched from inception through October 18, 2024: PubMed, Web of Science, Scopus, ScienceDirect, and ProQuest. These databases were selected to maximize the coverage of both biomedical and interdisciplinary literature and to minimize publication bias. In addition, Google Scholar was searched for gray literature. Gray literature includes sources not found in official scientific databases. These sources may include papers, theses, and/or dissertations. The reference lists of all included studies and relevant systematic reviews were manually screened for additional eligible articles. The search strategy combined Medical Subject Headings (MeSH) and free-text keywords related to the target population and the pathogen. The main search terms included (“Cyclospora cayetanensis” OR “Cyclospora” OR “cyclosporiasis”) AND (“prevalence” OR “frequency” OR “occurrence” OR “epidemiology”) AND (“immunocompromised” OR “immunosuppressed” OR “cancer” OR “transplant” OR “hemodialysis”). Boolean operators (AND/OR), truncation, and database-specific syntax were used to tailor the searches to each platform. No language restrictions were applied. Duplicate records were removed using EndNote (version 7), and titles and abstracts were independently screened by two reviewers.
2.3. Eligibility Criteria
This review included cross-sectional and case–control studies of immunocompromised patients (cancer, organ transplant, and hemodialysis) and immunocompetent controls with confirmed C. cayetanensis infection or colonization, without time or language restrictions. Excluded were studies focused solely on other immunocompromised groups, general population studies, reviews, editorials, case reports, and studies lacking extractable prevalence data for meta-analysis.
2.4. Data Extraction and Quality Assessment
Two independent reviewers screened titles, abstracts, and full texts of potentially eligible articles using a standardized form. Disagreements were resolved through discussion or consultation with a third reviewer. Extracted data included author name, implementation and publication years, country, continent, World Health Organization (WHO) region, Human Development Index (HDI), country income level, sample size, study design, diagnostic method, and patient type. The quality of studies was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence studies [14]. Scores of > 6 were classified as high quality, 4–6 as moderate quality, and those with a score of ≤ 3 rate as low quality.
2.5. Statistical Analysis
A meta-analysis was conducted using comprehensive meta-analysis (CMA) v3 software and a random-effects model to address between-study heterogeneity. Prevalence estimates were presented as proportions with 95% confidence intervals (CIs). Heterogeneity was measured using the I2 statistic, with values exceeding 50%, indicating substantial heterogeneity. The link between C. cayetanensis infection and immunocompromised patients was evaluated using weighted odds ratios (ORs) from case–control studies. Subgroup analyses were performed to identify the prevalence and potential sources of heterogeneity based on publication year, country, continent, WHO region, patient type (cancer, transplant, hemodialysis), HDI value, country income level, and sample size. Income classifications were determined according to the World Bank's country income groups (low, lower-middle, upper-middle, and high income) based on gross national income (GNI) per capita (https://blogs.worldbank.org/en/opendata/world-bank-country-classifications-by-income-level-for-2024-2025). HDI values and categories (low, medium, high, very high) were obtained from the United Nations Development Program (UNDP) Human Development Reports (https://hdr.undp.org/). A sensitivity analysis was conducted by excluding individual studies to reassess the pooled prevalence and weighted OR, confirming the robustness of the findings against potential biases. Meta-regression was employed to assess the potential association between C. cayetanensis prevalence in immunocompromised patients and quantitative variables, including publication year, sample size, and HDI value. Publication bias was assessed via funnel plot inspection and Egger's test. A p-value of < 0.05 indicated statistical significance for all analyses, with all statistical tests being two-tailed.
3. Results
3.1. Study Selection and Characteristics
A comprehensive literature search was conducted across five major electronic databases up to October 18, 2024. The number of records identified from each database was as follows: PubMed (n = 1287), Scopus (n = 1945), Web of Science (n = 1376), ScienceDirect (n = 934), and ProQuest (n = 671), yielding a total of 6213 records. After removing duplicates and screening titles and abstracts, 54 studies were selected for full-text assessment. Of these, 25 studies initially met the eligibility criteria. However, six studies were excluded during data extraction due to the following reasons: irrelevant study population or outcomes (n = 3), incomplete or nonextractable data (n = 2), and unclear methodology or reporting (n = 1). Consequently, 19 studies/22 datasets were included in the final qualitative synthesis and meta-analysis that met the inclusion criteria [5, 7, 8, 15–30] (Figure 1). These studies included 2084 immunocompromised patients and 954 controls across eight countries and four continents. The majority were case–control studies (13 datasets), with the rest being cross-sectional designs (nine datasets). Patient categories included cancer patients (11 datasets, 1099 individuals), organ transplant recipients (seven datasets, 653 individuals), and hemodialysis patients (four datasets, 332 individuals). Diagnostic methods used were microscopic examination (18 datasets) and polymerase chain reaction (PCR) (four datasets) (Table 1). Based on the JBI checklist, nine studies were rated as high quality and 10 studies as moderate quality (Supporting Table 1).
Figure 1.
The PRISMA 2020 flow diagram depicting the process of included studies in the present systematic review.
Table 1.
Data from 19 articles/22 datasets on the prevalence of C. cayetanensis infection in immunocompromised patients and immunocompetent controls.
| Author, year | Patient type | Time tested | Country | Cases | Controls | Study type | Methods | ||
|---|---|---|---|---|---|---|---|---|---|
| Total no. | Prevalence (%) | Total no. | Prevalence (%) | ||||||
| Baiomy et al., 2010 [5] | Cancer | UC | Egypt | 40 | 5 | 20 | 0 | C-C | MIC |
| Al-Qobati et al., 2012 [25] | Cancer | 2011–2012 | Yemen | 206 | 5.3 | —a | —a | C-S | MIC |
| Ballani et al., 2012 [27] | Cancer | UC | India | 100 | 0 | 50 | 0 | C-C | MIC |
| Jiménez-Cardoso et al., 2013 [16] | Cancer | 2010–2011 | Mexico | 77 | 0 | — | — | C-S | MIC, MOL |
| Sanad et al., 2014 [19] | Cancer | UC | Saudi Arabia | 54 | 51.9 | 42 | 13.1 | C-C | MIC |
| Saad et al., 2015 [8] | Transplant | 2011–2013 | Egypt | 50 | 6 | 25 | 0 | C-C | MIC |
| Yadav et al., 2016 [20] | Transplant | 2011–2013 | India | 88 | 2.3 | — | — | C-S | MIC |
| Agholi et al., 2016 [21] | Transplant | 2009–2014 | Iran | 124 | 0 | — | — | C-S | MIC, MOL |
| Agholi et al., 2016 [21] | Cancer | 2009–2014 | Iran | 187 | 0 | — | — | C-S | MIC, MOL |
| Berenji et al., 2017 [22] | Transplant | 2015–2016 | Iran | 71 | 2.8 | 71 | 0 | C-C | MIC |
| Mahmoudvand et al., 2019 [18] | Cancer | 2017–2018 | Iran | 87 | 3.5 | — | — | C-S | MIC |
| Ismail and Fadl, 2019 [28] | Transplant | 2018–2019 | Egypt | 50 | 10 | — | — | C-S | MIC |
| Shehata et al., 2019 [7] | Hemodialysis | 2014–2016 | Egypt | 120 | 1.7 | 100 | 0 | C-C | MIC |
| Elsayad et al., 2020 [30] | Hemodialysis | UC | Egypt | 50 | 0 | 50 | 0 | C-C | MIC |
| Bağci et al., 2021 [23] | Transplant | 2016–2019 | Turkey | 119 | 17.6 | — | — | C-S | MIC |
| Bağci et al., 2021 [23] | Cancer | 2016–2019 | Turkey | 51 | 19.6 | — | — | C-S | MIC |
| El-Mawgood et al., 2022 [17] | Hemodialysis | 2020 | Egypt | 100 | 10 | 100 | 0 | C-C | MIC |
| Ghoshal et al., 2022 [29] | Cancer | 2007–2019 | India | 61 | 1.6 | 170 | 0 | C-C | MIC |
| Ghoshal et al., 2022 [29] | Transplant | 2007–2019 | India | 151 | 3.3 | 170 | 0 | C-C | MIC |
| Moawad et al., 2022 [24] | Hemodialysis | 2018–2019 | Egypt | 62 | 1.6 | 39 | 0 | C-C | MIC |
| Gezici et al., 2023 [26] | Cancer | 2017–2018 | Turkey | 100 | 1 | 100 | 0 | C-C | MIC |
| Siti Farah Norasyikeen et al., 2024 [15] | Cancer | UC | Malaysia | 134 | 2.2 | 17 | 0 | C-C | MIC, MOL |
Note: UC: unclear, C–C: case–control design, C-S: cross-sectional design, MIC: microscopic detection, and MOL: molecular detection.
aThe dashed line (—) indicates that these studies did not have a control group.
3.2. Weighted Prevalence of C. cayetanensis in Immunocompromised Patients and Controls
The pooled prevalence of C. cayetanensis was 4% (95% CI: 2.1%–7.2%) in immunocompromised individuals (Figure 2), while it was only 1.2% (95% CI: 0.4%–3.4%) in nonimmunocompromised controls (Figure 3). This resulted in an OR of 5.4 (95% CI: 2.6–10.8, p < 0.001), indicating a significantly higher susceptibility of immunocompromised individuals to C. cayetanensis infections (Figure 4). The country-based prevalence of C. cayetanensis among immunocompromised patients is illustrated in Figure 5. The heterogeneity of prevalence data was assessed using the I2 statistic, which revealed substantial heterogeneity among cross-sectional (I2 = 86.8%, p < 0.001) and case–control (I2 = 57%, p < 0.05) studies.
Figure 2.
Forest plot showing the prevalence of C. cayetanensis infection among immunocompromised patients. Each horizontal black line represents the 95% confidence interval (CI) for the prevalence reported in an individual study. The red circles indicate the point estimate (event rate) for each study, with the size of the circle proportional to the study's weight in the meta-analysis. The vertical solid line at 0 represents the null value (no events), while the vertical dashed line represents the overall pooled prevalence estimated from the random-effects model. The diamond at the bottom summarizes the pooled prevalence and its 95% CI, with the center indicating the point estimate and the horizontal tips representing the CI limits. ∗Due to software limitations, studies with 0% prevalence were assigned a minimal value (e.g., 1%) for the analysis. This may lead to a slight overestimation of the pooled prevalence. Readers are advised to consider this methodological limitation when interpreting the pooled prevalence results.
Figure 3.
Forest plot showing the prevalence of C. cayetanensis infection among nonimmunocompromised controls. Each horizontal black line represents the 95% confidence interval (CI) for the prevalence reported in an individual study. The red circles indicate the point estimate (event rate) for each study, with the size of the circle proportional to the study's weight in the meta-analysis. The vertical solid line at 0 represents the null value (no events), while the vertical dashed line represents the overall pooled prevalence estimated from the random-effects model. The diamond at the bottom summarizes the pooled prevalence and its 95% CI, with the center indicating the point estimate and the horizontal tips representing the CI limits.
Figure 4.
Forest plot showing the weighted random-effects odds ratio (OR) with 95% confidence intervals (CIs) for C. cayetanensis infection in immunocompromised patients compared with nonimmunocompromised controls. Each red square represents the OR for an individual study, with the size of the square proportional to the study's weight in the meta-analysis. Horizontal lines indicate the 95% CI for each study; wider intervals reflect lower precision due to smaller sample sizes or few positive cases. The vertical solid line at OR = 1 denotes the null value (no association). The black diamond at the bottom represents the pooled OR and its 95% CI. OR values to the right of the vertical line indicate increased odds of infection in immunocompromised patients (risk factor), while values to the left indicate a potential protective effect. The x-axis is plotted on a logarithmic scale.
Figure 5.
The distribution and prevalence of C. cayetanensis infection in immunocompromised patients by country.
3.3. Pooled Prevalence of C. cayetanensis Based on Patient Type
Transplant recipients showed the highest pooled prevalence of C. cayetanensis infection among immunocompromised groups at 5% (95% CI: 2.1%–11%), followed by cancer patients at 3.5% (95% CI: 1.2%–10.3%) and individuals undergoing hemodialysis at 3% (95% CI: 0.8%–10.6%) (Figure 6).
Figure 6.
Forest plot showing the prevalence of C. cayetanensis infection among immunocompromised patients by patient types. Each horizontal black line represents the 95% confidence interval (CI) for the prevalence reported in an individual study. The red circles indicate the point estimate (event rate) for each study, with the size of the circle proportional to the study's weight in the meta-analysis. The vertical solid line at 0 represents the null value (no events), while the vertical dashed line represents the overall pooled prevalence estimated from the random-effects model. The diamonds summarize the pooled prevalence and its 95% CI in each group, with the center indicating the point estimate and the horizontal tips representing the CI limits.
3.4. Sensitivity Analysis and Subgroup-Based Prevalence
Removing individual studies did not significantly alter the pooled prevalence estimates (Supporting Figure 1). Furthermore, sensitivity analyses excluding studies reporting ORs showed no meaningful change in the overall OR, reinforcing the robustness of our findings. These results confirm that immunodeficiency is a significant and specific risk factor for C. cayetanensis infection, beyond the general susceptibility of immunocompromised patients to infections (Supporting Figure 2). Table 2 outlines the pooled prevalence of C. cayetanensis infections by publication year, country, continent, WHO region, country income level, HDI value, and sample size (Supporting Figures 3–9).
Table 2.
Subgroup analysis of C. cayetanensis infection in immunocompromised patients by publication year, continent, WHO region, country, HDI value, country income level, and sample size.
| Subgroup variable | Prevalence % (95% CI) | Heterogeneity (Q) | df (Q) | I 2 (%) | p value |
|---|---|---|---|---|---|
| Publication year | |||||
| 2010–2017 | 2.9 (0.8–10.2) | 103.7 | 9 | 91.3 | p < 0.05 |
| 2018–2024 | 4.8 (2.5–8.8) | 52.1 | 11 | 78.9 | p < 0.05 |
| Continent | |||||
| Africa | 5.3 (2.8–9.5) | 10.9 | 6 | 45.3 | p > 0.05 |
| Asia | 2.8 (0.9–8.6) | 121.1 | 10 | 91.7 | p < 0.05 |
| Europe | 11.7 (4.5–27.1) | 9.2 | 2 | 78.3 | p < 0.05 |
| Central America | 0.6 (0–9.4) | 0 | 0 | 0 | p > 0.05 |
| WHO region | |||||
| AMR | 0.6 (0–9.4) | 0 | 0 | 0 | p > 0.05 |
| EMR | 4.2 (1.7–9.9) | 109 | 12 | 89 | p < 0.05 |
| EUR | 11.7 (4.5–27.1) | 9.2 | 2 | 78.3 | p < 0.05 |
| SEAR | 2.5 (1.3–4.8) | 1.9 | 3 | 0 | p > 0.05 |
| WPR | 2.2 (0.7–6.7) | 0 | 0 | 0 | p > 0.05 |
| Country | |||||
| Egypt | 5.3 (2.8–9.5) | 10.9 | 6 | 45.3 | p > 0.05 |
| India | 2.5 (1.3–4.8) | 1.9 | 3 | 0 | p > 0.05 |
| Iran | 1.8 (0.6–5.1) | 4.5 | 3 | 33.1 | p > 0.05 |
| Malaysia | 2.2 (0.7–6.7) | 0 | 0 | 0 | p > 0.05 |
| Mexico | 0.6 (0–9.4) | 0 | 0 | 0 | p > 0.05 |
| Saudi Arabia | 51.9 (38.7–64.7) | 0 | 0 | 0 | p > 0.05 |
| Turkey | 11.7 (4.5–27.1) | 9.2 | 2 | 78.3 | p < 0.05 |
| Yemen | 5.3 (3–9.4) | 0 | 0 | 0 | p > 0.05 |
| HDI value∗ | |||||
| High | 3.4 (1.8–6.1) | 23.9 | 11 | 54 | p < 0.05 |
| Low | 5.3 (3–9.4) | 0 | 0 | 0 | p > 0.05 |
| Medium | 2.5 (1.3–4.8) | 1.9 | 3 | 0 | p > 0.05 |
| Very high | 11.6 (3.7–31.1) | 55.1 | 4 | 92.7 | p < 0.05 |
| Country income level | |||||
| High | 51.9 (38.7–64.7) | 0 | 0 | 0 | p > 0.05 |
| Low | 5.3 (0.3–9.4) | 0 | 0 | 0 | p > 0.05 |
| Lower middle | 3.9 (2.3–6.6) | 19.2 | 10 | 47.9 | p > 0.05 |
| Upper middle | 3.1 (1.1–8) | 49.1 | 8 | 83.7 | p < 0.05 |
| Sample size | |||||
| ≤ 100 | 4.4 (1.9–9.8) | 108.9 | 14 | 87.1 | p < 0.05 |
| > 100 | 3 (1.1–7.8) | 41.1 | 6 | 85.4 | p < 0.05 |
Note: World Health Organization (WHO) region. Df (Q): This column represents the degrees of freedom associated with the heterogeneity test (Q statistic). It indicates the number of independent comparisons used to assess the heterogeneity among studies. The value provides context for interpreting the Q statistic and the I2 metric, helping determine if the variability between studies is greater than what would be expected by chance alone. I2 for heterogeneity: The I2 statistic quantifies the percentage of total variation across studies due to heterogeneity rather than chance. It provides a clearer understanding of the degree of consistency among study results, where values closer to 0% suggest low heterogeneity and values closer to 100% indicate high heterogeneity. In this study, heterogeneity was measured using the I2 statistic, with values exceeding 50% indicating substantial heterogeneity. Threshold for interpretation: The threshold for interpreting heterogeneity, such as a p value threshold (typically < 0.05), helps determine whether the heterogeneity observed is statistically significant.
Abbreviation: HDI, Human Development Index.
∗HDI values above 0.800 are classified as very high, those between 0.700 and 0.799 as high, from 0.550 to 0.699 as medium, and below 0.550 as low.
3.5. Meta-Regression
Our meta-regression analysis found no statistically significant association between the prevalence of C. cayetanensis infection in immunocompromised patients and quantitative variables like publication year (regression coefficient: −0.0039, p > 0.05), sample size (regression coefficient: −0.0090, p > 0.05), and HDI value (regression coefficient: 3.5684, p > 0.05). Therefore, the year of study, sample size, and HDI value did not account for variability in C. cayetanensis infection rates among immunocompromised patients (Figure 7).
Figure 7.
Bubble plots from meta-regression assessing the association between the logit-transformed prevalence of C. cayetanensis infection in immunocompromised patients and continuous moderators: (a) year of publication, (b) sample size of the included studies, and (c) Human Development Index (HDI) value of the study location. Each circle represents one study, with circle size proportional to the study's weight in the meta-analysis. The solid line shows the fitted meta-regression slope, and the shaded area represents the 95% confidence interval. No statistically significant associations were observed for any moderator (p > 0.05). The “logit event rate” corresponds to the logit-transformed proportion of infected individuals, calculated as the natural log of the odds (log[p/(1 − p)]) of infection in each study.
3.6. Publication Bias
Visual inspection of the funnel plot and Egger's regression test indicated a degree of asymmetry, suggesting the presence of publication bias (p < 0.05) (Figure 8).
Figure 8.
Funnel plot illustrating publication bias in the current systematic review and meta-analysis. The x-axis represents the logit event rate, while the y-axis displays the standard error. The plot's symmetry is an indicator of the potential publication bias, with smaller studies being dispersed at the bottom and larger studies toward the top. The triangles represent the expected distribution of studies under the assumption of no bias. Any asymmetry observed may suggest selective reporting or missing studies, potentially affecting the validity of the findings.
4. Discussion
The findings of the present study align with those of previous research, confirming that C. cayetanensis infection remains relatively uncommon, even among high-risk populations. The weighted prevalence of 4% (95% CI: 2.1%–7.2%) observed in immunocompromised patients (cancer, transplant, and hemodialysis) is comparable to the 3.9% (95% CI: 2.6%–5.4%) reported by Ramezanzadeh et al. [10] in HIV/AIDS patients. This suggests that various forms of immunosuppression may contribute similarly to susceptibility to C. cayetanensis infection.
In the current study, the pooled prevalence of C. cayetanensis was 4% (95% CI: 2.1%–7.2%) in immunocompromised individuals, compared to 1.2% (95% CI: 0.4%–3.4%) in control groups, indicating a notable disparity in infection rates. The calculated OR (5.4, 95% CI: 2.6–10.8, p < 0.001) further highlights a substantially increased risk of infection among immunocompromised individuals, suggesting that immune dysfunction significantly contributes to both the acquisition and prolonged persistence of C. cayetanensis. However, the relatively wide confidence interval observed for the OR indicates variability across the included studies and underscores the need for cautious interpretation. This heterogeneity may reflect differences in diagnostic methods, population characteristics, or regional exposures. Although immunocompromised individuals are generally more susceptible to infections, the risk of C. cayetanensis appears to be influenced by specific factors such as the degree of immune suppression, exposure to contaminated food or water, poor hygiene and nutrition, and limited access to timely diagnosis and care [31, 32]. These findings emphasize the importance of implementing targeted prevention strategies beyond routine infection control, particularly in endemic areas and among high-risk subgroups, through seasonal screening, improved food safety practices, and broader access to reliable diagnostic tools.
Subgroup analyses revealed that transplant recipients exhibited the highest pooled prevalence of C. cayetanensis infection among immunocompromised groups, followed by cancer patients and those undergoing hemodialysis. The higher pooled prevalence of C. cayetanensis infection observed in transplant recipients and cancer patients likely reflects the profound immunosuppression caused by their treatments, which can compromise mucosal barriers and reduce the host's ability to eliminate the pathogen [33]. However, pathogen-specific factors may also contribute to this susceptibility. For instance, the prolonged environmental viability of C. cayetanensis oocysts, the need for a minimal infectious dose, and its resilience in food and water sources may disproportionately affect individuals with impaired immune responses [2]. In contrast, the relatively lower prevalence in hemodialysis patients might be explained by differences in the nature of their immune dysfunction, more frequent clinical monitoring, and potentially lower environmental exposure. These findings suggest that both host-related and pathogen-specific characteristics must be considered when assessing infection risk in immunocompromised populations.
The sensitivity analysis confirmed the absence of influential outliers in studies reporting the prevalence and ORs of C. cayetanensis infection among immunocompromised individuals, indicating the robustness of the association between immunodeficiency and the likelihood of infection. The ORs specifically reflect the comparative odds of C. cayetanensis infection in immunocompromised patients versus immunocompetent controls. Although this increased risk should be more consistently observed in longitudinal and well-controlled studies, the overall pattern supports a meaningful association across diverse patient subgroups, suggesting that immunosuppression, regardless of its cause, may elevate susceptibility to infection by compromising the host's ability to clear the parasite.
In the current study, the visual inspection of the funnel plot and Egger's regression test suggests a degree of asymmetry, potentially suggesting publication bias. However, this visual pattern may reflect true heterogeneity rather than selective reporting, as most included studies (17 out of 22) reported low or zero prevalence (< 10%), and only a small number of studies showed high prevalence (> 10%). Meta-regression analyses were performed to explore whether publication year, sample size, or HDI of the study location explained variability in the reported prevalence of C. cayetanensis among immunocompromised patients. None of these moderators showed a statistically significant association with prevalence estimates (all p > 0.05). This suggests that the between-study heterogeneity is unlikely to be explained by these factors alone and may instead reflect differences in study design, diagnostic methods, or population characteristics. Although some funnel plot asymmetry was observed, it is more likely attributable to variations in study settings and sample sizes rather than systematic publication bias. Consequently, the pooled prevalence estimate appears reasonably robust; however, it should still be interpreted with caution.
The limited number of studies and regional disparities restricted definitive statistical conclusions, preventing the identification of a clear trend in C. cayetanensis prevalence among immunocompromised patients. Interestingly, pooled prevalence appeared higher in studies published after 2017 (4.8%) compared to those published before that year (2.9%). This increase raises concerns about potential shifts in environmental factors, food and water safety regulations, or improved diagnostic methodologies. Additionally, the geographic distribution of studies suggests that regional epidemiological factors might play a critical role.
Notably, the highest pooled prevalence of C. cayetanensis in immunocompromised patients was observed in Europe and the WHO EUR region (11.7%, 95% CI: 4.5%–27.1%), with Saudi Arabia [19] and Turkey [23, 26] reporting the highest national prevalence rates at 51.9% (95% CI: 38.7%–64.7%) and 11.7% (95% CI: 4.5%–27.1%), respectively. These findings highlight the need for further investigations into the environmental, public health, and sociocultural determinants contributing to these high infection rates. Factors such as water quality, agricultural practices, and food handling procedures likely play a significant role in facilitating transmission, as previously discussed in the literature [2, 32, 34].
Interestingly, countries with very high HDI value and high-income levels reported the highest pooled prevalence of C. cayetanensis infection among immunocompromised patients, despite having implemented advanced food safety regulations. This paradox may be explained by several factors. First, greater diagnostic capacity and surveillance systems in high-income countries likely lead to more accurate detection and reporting of infections. Second, immunocompromised patients in these settings may still be exposed to the parasite through the consumption of imported fresh produce or contaminated water sources, as C. cayetanensis oocysts are resilient to common disinfection methods and can survive in various environmental niches. Third, behavioral and dietary habits, such as increased consumption of raw fruits and vegetables, may contribute to ongoing exposure despite overall food safety improvements. Thus, while food safety measures reduce the general population's risk, immunosuppressed individuals remain vulnerable due to their impaired immune defenses and potential exposure routes that are not fully controlled by current safety practices.
A notable trend observed in this study was the inverse association between the sample size and prevalence estimates, with larger studies (sample size > 100) reporting a lower pooled prevalence of C. cayetanensis infection (3%) in immunocompromised individuals. While this highlights the importance of adequate sample size in improving the precision and reliability of epidemiological estimates, other contributing factors must also be considered. For example, studies with small sample sizes were often conducted in high-exposure settings or among subpopulations with severe immunosuppression, which could inflate prevalence figures. Additionally, variation in diagnostic methods, such as the use of PCR versus conventional microscopy can affect detection rates. Geographic differences, local sanitation conditions, and study design quality may also play substantial roles. Therefore, while sample size influences the stability of prevalence estimates, heterogeneity in methodological and contextual factors across studies necessitates cautious interpretation. These findings reinforce the need for standardized, multicenter studies using sensitive diagnostic tools to provide more generalizable and accurate prevalence data.
Despite the strengths of this meta-analysis, such as the inclusion of recent data, rigorous statistical methodologies, sensitivity analyses, meta-regression, and publication bias, the study has several limitations. The small number of included studies, limited geographic diversity, relatively small sample sizes, the restricted scope of variables included in the meta-regression analysis, and reliance on single studies/datasets for some analyses pose challenges to generalizability. Furthermore, the lack of age- and gender-specific data constrains the ability to explore demographic risk factors. Future research should focus on expanding geographical representation, increasing study sample sizes, and incorporating additional demographic variables to provide a more comprehensive understanding of C. cayetanensis epidemiology in immunocompromised populations.
5. Conclusion
This study highlights a significantly higher pooled prevalence of C. cayetanensis infection among immunocompromised individuals compared to immunocompetent controls, with over a fivefold increase in infection risk. Transplant recipients, cancer patients, and individuals undergoing hemodialysis were identified as particularly vulnerable subgroups. These findings underscore the opportunistic nature of C. cayetanensis and the need for heightened clinical awareness, especially in settings where foodborne exposure remains a concern. As the global population of immunosuppressed individuals continues to grow due to medical advances in oncology, transplantation, and chronic disease management, tailored prevention strategies, improved diagnostic access, and focused epidemiological surveillance are essential. Future research should further investigate host- and pathogen-related factors that drive infection risk and develop context-specific interventions to reduce the burden of cyclosporiasis in these high-risk populations.
Acknowledgments
The authors have nothing to report.
Contributor Information
Ali Asghari, Email: asghari3@yahoo.com.
Jalil Feizi, Email: feizi.j@gmail.com.
Data Availability Statement
The data that support the findings of this study are available in the supporting information of this article.
Ethics Statement
This study was approved by the Ethics Committee of Qazvin University of Medical Sciences, Qazvin, Iran (approval no. IR.QUMS.REC.1403.498).
Consent
The authors have nothing to report.
Disclosure
All the authors have read and approved the final manuscript.
Conflicts of Interest
The authors declare no conflicts of interest.
Author Contributions
A.A. and A.G. conceived and designed the study. J.F., R.M., F.K., A.P., A.M., and K.K. had a role in data extraction and methodology. A.A. and A.G. performed the data analysis. A.A., R.M., and J.F. wrote the manuscript. F.K., A.P., and J.F. critically revised the manuscript. A.G. and R.M. contributed equally to this study.
Funding
The authors received no specific funding for this work.
Supporting Information
Additional supporting information can be found online in the Supporting Information section.
Figure S1: The sensitivity analysis to check for the influence of any single study on the pooled estimates.
Figure S2: The sensitivity analysis to check for the influence of any single study on the weighted ORs.
Figure S3: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on publication years. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S4: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on continents. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S5: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on WHO regions. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S6: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on countries. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S7: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on HDI values. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S8: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on country-income levels. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S9: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on sample sizes. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Table S1: JBI critical appraisal checklist applied for included studies.#
References
- 1.Mansfield L. S., Gajadhar A. A. Cyclospora cayetanensis, a Food-and Waterborne Coccidian Parasite. Veterinary Parasitology . 2004;126(1-2):73–90. doi: 10.1016/j.vetpar.2004.09.011. [DOI] [PubMed] [Google Scholar]
- 2.Ortega Y. R., Sanchez R. Update on Cyclospora cayetanensis, A Food-Borne and Waterborne Parasite. Clinical Microbiology Reviews . 2010;23(1):218–234. doi: 10.1128/cmr.00026-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Hadjilouka A., Tsaltas D. Cyclospora cayetanensis, Major Outbreaks From Ready to Eat Fresh Fruits and Vegetables. Foods . 2020;9(11):p. 1703. doi: 10.3390/foods9111703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Chen Y., Qin Z., Li J., Xiao L., Zhang L. The Global Prevalence of Cyclospora cayetanensis Infection: A Systematic Review, Meta-Analysis, and Meta-Regression. Acta Tropica . 2024;253:p. 107175. doi: 10.1016/j.actatropica.2024.107175. [DOI] [PubMed] [Google Scholar]
- 5.Baiomy A. M. S., Mohamed K., Ghannam M. A. M., Al-Razek S. A. Opportunistic Parasitic Infections Among Immunocom-Promised Patients. Journal of the Egyptian Society of Parasitology . 2010;40:797–807. [PubMed] [Google Scholar]
- 6.Aminu M., Yakubu Y. E. Prevalence of Asymptomatic Intestinal Coccidian Parasite Infections Among Non-Diarrhoeic HIV-Positive Children in Zaria, Nigeria: Research in Action. South African Journal of Science . 2008;104:348–350. [Google Scholar]
- 7.Shehata A. I., Hassanein F., Abdul-Ghani R. Opportunistic Parasitoses Among Egyptian Hemodialysis Patients in Relation to CD4+ T-Cell Counts: A Comparative Study. BMC Infectious Diseases . 2019;19:480–489. doi: 10.1186/s12879-019-4110-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Saad A.-G. E., Afifi A. F., Shendi S. S., Elkersh W. M., Hawash Y. Coccidian Parasitic Infections in Liver Transplant Recipients. Menoufia Medical Journal . 2015;28:635–641. [Google Scholar]
- 9.Mahdavi F., Pouryousef A., Mohammadi M. R., et al. Worldwide Epidemiology of Cyclospora cayetanensis in HIV/AIDS Patients: A Systematic Review and Meta-Analysis. Acta Parasitologica . 2025;70(4):p. 163. doi: 10.1007/s11686-025-01099-8. [DOI] [PubMed] [Google Scholar]
- 10.Ramezanzadeh S., Beloukas A., Pagheh A. S., et al. Global Burden of Cyclospora cayetanensis Infection and Associated Risk Factors in People Living With HIV and/or AIDS. Viruses . 2022;14(6):p. 1279. doi: 10.3390/v14061279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Giangaspero A., Gasser R. B. Human Cyclosporiasis. The Lancet Infectious Diseases . 2019;19(7):e226–e236. doi: 10.1016/s1473-3099(18)30789-8. [DOI] [PubMed] [Google Scholar]
- 12.Mathison B. A., Pritt B. S. Cyclosporiasis: Updates on Clinical Presentation, Pathology, Clinical Diagnosis, and Treatment. Microorganisms . 2021;9:p. 1863. doi: 10.3390/microorganisms9091863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Page M. J., McKenzie J. E., Bossuyt P. M., et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ . 2021;372:p. n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Munn Z., Moola S., Riitano D., Lisy K. The Development of a Critical Appraisal Tool for Use in Systematic Reviews Addressing Questions of Prevalence. International Journal of Health Policy and Management . 2014;3:123–128. doi: 10.15171/ijhpm.2014.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Siti Farah Norasyikeen S. O., Ngui R., Syaza Zafirah A. R., et al. Study on Intestinal Parasitic Infections and Gut Microbiota in Cancer Patients at a Tertiary Teaching Hospital in Malaysia. Scientific Reports . 2024;14(1):p. 13650. doi: 10.1038/s41598-024-59969-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Jiménez-Cardoso E., Eligio-García L., Cano-Estrada A., Cortés-Campos A., Medina-Sansón A., Molina-Martínez D. Frequency of Emerging Parasites in HIV/AIDS and Oncological Patients Stool by Coprological and Molecular Analysis. 2013.
- 17.El-Mawgood A. B. D., Ahmed A., El-Nazer M. M. A., Mohamed H. S., Gabalia M. R. Intestinal Parasites and Microsporidia in Patients With Chronic Kidney Disease, Sohag Governometal Hospitals. Journal of the Egyptian Society of Parasitology . 2022;52:311–316. [Google Scholar]
- 18.Mahmoudvand H., Sepahvand A., Khatami M., Moayyedkazemi A. Prevalence and Associated Risk Factors of Cystoisospora belli and Cyclospora cayetanensis Infection Among Iranian Patients With Colorectal Cancer. Journal of Parasitic Diseases . 2019;43(3):402–405. doi: 10.1007/s12639-019-01104-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Sanad M. M., Thagfan F. A., Al-Olayan E. M., et al. Opportunistic Coccidian Parasites Among Saudi Cancer Patients Presenting With Diarrhea: Prevalence and Immune Status. Research Journal of Parasitology . 2014;9(2):55–63. doi: 10.3923/jp.2014.55.63. [DOI] [Google Scholar]
- 20.Yadav P., Khalil S., Mirdha B. R. Molecular Appraisal of Intestinal Parasitic Infection in Transplant Recipients. Indian Journal of Medical Research . 2016;144(2):258–263. doi: 10.4103/0971-5916.195041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Agholi M., Shahabadi S. N., Motazedian M. H., Hatam G. R. Prevalence of Enteric Protozoan Oocysts With Special Reference to Sarcocystis cruzi Among Fecal Samples of Diarrheic Immunodeficient Patients in Iran. Korean Journal of Parasitology . 2016;54(3):339–344. doi: 10.3347/kjp.2016.54.3.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Berenji F., Imanfar H., Nazemian F., Vakili V., Fata A., Khorasani S. R. Investigating the Prevalence of Intestinal Parasitic Infections in Kidney Transplant Recipients. Journal of Research in Medical and Dental Science . 2017;5:p. 127. [Google Scholar]
- 23.Bağci Ö.U., Zorbozan O., Yetişmiş K., et al. Changes in the Prevalence of Coccidian Protozoa in Immunocompromised Patients over the Last Decade. Changes . 2021;10:p. 30. [Google Scholar]
- 24.Moawad H. S. F., AboZaid A. M., Ibrahim H. E., Etewa S. E., Mohammad S. M. Prevalence of Intestinal Parasitic Infections Among Egyptian Children with Chronic Kidney Diseases in Zagazig University Children’s Hospital. Zagazig University Medical Journal . 2022;28:1386–1397. [Google Scholar]
- 25.Al-Qobati S. A., Al-Maktari M. T., Derhim M., Derhim M. Intestinal Parasitosis Among Yemeni Patients With Cancer, Sana’a, Yemen. Journal of the Egyptian Society of Parasitology . 2012;42(3):727–734. doi: 10.12816/0006356. [DOI] [PubMed] [Google Scholar]
- 26.Gezici A., Cengiz Z. T., Yılmaz H., Aydemir S. The Significance of Opportunistic Parasitosis and Blastocystosis in Patients With Gastric Cancer: A Study With Control Group. Significance . 2023;47:220–223. doi: 10.4274/tpd.galenos.2023.33042. [DOI] [PubMed] [Google Scholar]
- 27.Ballani N., Shujatullah F., Khan H. M., Malik A., Ali M. S., Khan P. A. Intestinal Protozoa in Immunosuppression: A Medical Hassle. Journal of Bacteriology & Parasitology . 2012;3:p. 2. [Google Scholar]
- 28.Ismail M. A. M., Fadl H. O. Cyclospora Infection in Renal Transplant Recipien. Journal of the Egyptian Society of Parasitology . 2019;49(3):727–730. doi: 10.21608/jesp.2019.68083. [DOI] [Google Scholar]
- 29.Ghoshal U., Siddiqui T., Tejan N., Verma S., Pandey A., Ghoshal U. C. Cyclosporiasis in Immunocompetent and Immunocompromised Patients–A Twelve Years Experience from a Tertiary Care Centre in Northern India. Tropical Parasitology . 2022;12(2):94–98. doi: 10.4103/tp.tp_79_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Elsayad M. H. M., Maharem D. A. L. Y., Ali F. A. S., El-Latif N. F. A. B. D. Detection of Intestinal Protozoan Infections With Stress on Blastocystis, Microsporidia in Egyptian Chronic Kidney Disease Patients. Journal of the Egyptian Society of Parasitology . 2020;50(3):513–521. doi: 10.21608/jesp.2020.131079. [DOI] [Google Scholar]
- 31.Rossi F., Santonicola S., Amadoro C., Marino L., Colavita G. Food and Drinking Water as Sources of Pathogenic Protozoans: An Update. Applied Sciences . 2024;14(12):p. 5339. doi: 10.3390/app14125339. [DOI] [Google Scholar]
- 32.Almeria S., Cinar H. N., Dubey J. P. Cyclospora cayetanensis and Cyclosporiasis: An Update. Microorganisms . 2019;7(9):p. 317. doi: 10.3390/microorganisms7090317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Alkorta M., Manzanal A., Zeberio I. A Case of Severe Diarrhoea Caused by Cyclospora cayetanensis in an Immunocompromised Patient in Northern Spain. Access Microbiology . 2022;4(2):p. 000313. doi: 10.1099/acmi.0.000313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Ortega Y. R., Sterling C. R., Gilman R. H. Cyclospora Cayetanensis. Advances in Parasitology . 1998;40:399–418. doi: 10.1016/s0065-308x(08)60128-1. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: The sensitivity analysis to check for the influence of any single study on the pooled estimates.
Figure S2: The sensitivity analysis to check for the influence of any single study on the weighted ORs.
Figure S3: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on publication years. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S4: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on continents. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S5: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on WHO regions. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S6: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on countries. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S7: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on HDI values. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S8: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on country-income levels. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Figure S9: The pooled prevalence of C. cayetanensis infection in immunocompromised patients based on sample sizes. Red indicates the prevalence from each study, while black shows the overall weighted prevalence.
Table S1: JBI critical appraisal checklist applied for included studies.#
Data Availability Statement
The data that support the findings of this study are available in the supporting information of this article.