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A systematic review and meta-analysis of protozoan parasite infections among patients with mental health disorders: an overlooked phenomenon

Gut Pathogens volume 16, Article number: 7 (2024) Cite this article

Abstract

Background

Patients with mental disorders have a high risk of intestinal parasitic infection due to poor hygiene practices. Hence, to better clarify this overlooked phenomenon, the current study is conducted to determine the global prevalence of protozoan parasite infections in patients with mental disorders and investigate the associated risk factors.

Methods

Several databases (PubMed, Scopus, Web of Science, ProQuest, and Google Scholar) were searched for papers published until December 2022. The fixed effect meta-analysis was used to estimate the overall odds ratio (OR) and pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI).

Results

Totally, 131 articles (91 case–control and 40 cross-sectional studies) met the eligibility criteria. Patients with mental disorders were significantly at higher risk for protozoan parasites than healthy controls (OR: 2.059, 1.830–2.317). The highest pooled OR (2.485, 1.413–4.368) was related to patients with neurodevelopmental disorders, and the highest pooled prevalence was detected in patients with neurodevelopmental disorders (0.341, 0.244–0.446), followed by bipolar and related disorders (0.321, 0.000–0.995). Toxoplasma gondii was the most prevalent protozoan parasite (0.343, 0.228–0.467) in cross-sectional studies and the highest pooled OR was related to Cyclospora cayetanensis (4.719, 1.352–16.474) followed by Cryptosporidium parvum (4.618, 2.877–7.412).

Conclusion

Our findings demonstrated that individuals afflicted with mental disorders are significantly more susceptible to acquiring protozoan parasites in comparison to healthy individuals. Preventive interventions, regular screening, and treatment approaches for parasitic diseases should be considered for patients with mental disorders.

Background

Over the past few decades, protozoan parasites have been recognized as significant potential agents to cause waterborne and foodborne disease [1, 2]. Enteric protozoa of public health importance are associated with diarrheal illnesses, contributing to severe morbidity and mortality in both humans and animals globally [3]. Approximately 3.5 billion people in the world are infected by enteric protozoan parasites, which are responsible for 1.7 billion annual diarrhea cases [4]. Intestinal parasitic infections are a highly prevalent and significant health concern worldwide, particularly in developing countries. The diarrhoea caused by these pathogens can be chronic or severe, with clinical symptoms including abdominal cramps, nausea, vomiting, anorexia, weight loss, fatigue, and a mild fever [5].

Mental disorders are common health issues affecting people of all ages worldwide [6, 7]. According to WHO, in 2019, 970 million people were living with a mental disorder globally [8]. Psychiatric diseases, also called mental diseases are psychological and behavioural syndromes that account for 30% of the global disease burden. They cover many mental health conditions but mainly refer to disorders influencing emotions, thinking, and behavior. Depression, anxiety and hypochondriasis disorders, dementia, schizophrenia, autism spectrum disorders, and personality disorders are examples of mental disorders [9].

Patients with mental disorders can be more susceptible to infections due to a combination of factors that influence their immune system, lifestyle, and overall health. The conditions associated with mental diseases might lead to neglect of personal hygiene, a lack of motivation to seek medical care, or limited healthcare access. Furthermore, mental disorders can affect the functions of the immune system (e.g., due to malnutrition, sleep disruption, chronic stress, medication side effects, neuroendocrine effects, and chronic inflammation), leading to dysregulation and diminished immune responses, making individuals more susceptible to infections [10, 11].

Mental disorders are considered risk factors leading to parasitic infections because the lack of hygienic behaviours in psychiatric patients. Keeping these patients in close contact with each other as the condition occurs through institutionalization can intensify the risk of acquiring a disease, primarily when the environment is confined and the sanitation level is poor [12, 13].

There are several mental symptoms with unknown aetiologies, which may be due to microbial pathogens. Many infectious diseases are often connected with severe behavioral problems, including depression, decreased physical and social activities, hyposomnia or hypersomnia, anorexia, malaise, fatigue, and cognitive disturbances [9]. Based on a review, mental illnesses are common in low and middle-income countries, with a pooled prevalence of 17.6% (15.5–20.0%) [14]. There are neurotropic parasitic diseases including malaria, toxoplasmosis, African human trypanosomiasis, Chagas disease, cysticercosis, and human toxocariasis [15, 16].

Parasitic diseases with neurological effects are regarded as public health issues widely prevalent in developing countries, where more than 25% of population encounters the development of one or multiple mental or behavioral disorders in their lifetime [17].

Despite the high number of reports with regard to parasitic infections in mentally ill patients, studies focused on the association of mental illnesses with parasitic diseases are limited in the world. The public health significance of parasitic infections in these populations lies in the intricate interplay between mental health and physical well-being. Addressing parasitic infections in mentally ill patients is crucial as these infections can further compromise their overall health, exacerbate their mental health conditions, and lead to more challenging treatment courses. Moreover, the socio-economic and behavioral factors associated with mental illnesses, such as hygiene neglect, limited access to healthcare, and compromised immune responses, contribute to an increased risk of parasitic infections.

Therefore, in the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to evaluate the worldwide status of infections caused by protozoan parasites in patients with mental health diseases. We further conducted a comprehensive investigation regarding the association between mental disorders and protozoan parasite infection.

Methods

Search strategy

The present study complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist [18]. Multiple databases (PubMed, Scopus, Web of Science, ProQuest, and Google Scholar) were explored to obtain papers published from 2000 until December 2022 without a lower date limit. Search terms related to mental disorder, mental illness, mental disabilities, neurotic disorder, psychiatric disorders, psychiatric illness, protozoan parasites, protozoan pathogens, protozoan infections, protozoan diseases, prevalence, frequency, proportion, worldwide, global, using AND and/or OR Boolean operators. The duplicate papers were omitted automatically using the EndNote software X9 version. The references list was hand-searched to find further relevant studies that were not accessible through a database search. Two authors independently searched, evaluated titles and abstracts, and reviewed the full texts.

Inclusion and exclusion criteria

Full-text articles were regarded eligible if they met the inclusion criteria described below:

  1. 1.

    Case–control and cross-sectional studies reporting the protozoan parasites among patients with mental disorders.

  2. 2.

    Peer-reviewed original articles.

  3. 3.

    Availability of full-text and abstract in English.

  4. 4.

    Availability of total sample size and the exact number of positive subjects.

Case series, case reports, letters, editorials, publications with non-original data, review articles, articles with unclear or ambiguous findings, non-English-language papers, and the papers that reported protozoan parasites in samples related to subjects other than humans were excluded from the analyses of the present study. Microsoft Excel® version 2016 was employed to separately collect the following information from the included papers: author’s name, year of publication, annual precipitation, humidity, annual rainfall, average temperature, WHO region, income level, type of protozoan parasite, and diagnostic method (Tables 1, 2, 3, 4, 5, 6).

Table 1 Main characteristics of the included case–control studies reporting the prevalence of protozoan parasitic infections among patients with mental disorders
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Table 2 Sub-group analysis based on annual precipitation, humidity, annual rainfall, average temperature, WHO regions, income level, and diagnostic method in included case–control studies
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Table 3 Sub-group analysis based on type of protozoan parasites in case–control studies
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Table 4 Main characteristics of the included cross-sectional studies reporting the prevalence of protozoan parasitic infections among patients with mental disorders
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Table 5 Sub-group analysis based on annual precipitation, humidity, annual rainfall, average temperature, WHO regions, income level, mean age, and diagnostic method in included cross-sectional studies
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Table 6 Sub-group analysis based on type of protozoan parasites in cross-sectional studies
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Quality assessment

A Newcastle–Ottawa Scale was applied to assess the study quality (Additional file 1: Table S1 and Additional file 2: Table S2) [19, 20]. Scoring was according to the items and score ranges as follows: (1) Selection (maximum of 5 stars), (2) Comparability (maximum of 2 stars), and (3) Outcome (maximum of 3 stars).

Data synthesis and statistical analysis

The overall pooled odds ratio (OR), and pooled prevalence reporting on protozoan parasites among patients with mental disorders at the global scale were calculated with a 95% confidence interval (95% CI). A Freeman-Tukey double arcsine transformation for the random-effects model was used to estimate the pooled prevalence. Begg’s rank test was applied to specify the possible publication bias. Furthermore, publication bias was determined based on the Luis Furuya-Kanamori (LFK) index and the Doi plot [21]. An LFK index within the range of outside ± 2, ± 2, and ± 1 is regarded as significantly/major asymmetrical, slightly/minor asymmetrical, and asymmetrical symmetrical (absence of publication bias), respectively. Furthermore, Cochrane’s Q test and inconsistency index (I2 statistics) was used to evaluate the magnitude of heterogeneity among included studies, considering I2 values of 0–25% as low, 25–50% as moderate and 50–75% as high heterogeneity [22]. A p-value less than 0.05 was defined as statistically significant. All procedures of statistical analyses were performed via meta and metasens packages in R version (3.6.1) [23].

Results

Characteristics of included studies

The initial database search yielded a total of 12,875 articles (Fig. 1). After screening and excluding duplicates, 131 articles (91 case–control and 40 cross-sectional studies) were found to be eligible and are included in this systematic review and meta-analysis. There were 91 case–control studies involving 18,626 cases and 18,312 controls (Tables 1 and 2), and 40 cross-sectional studies with 19,994 participants (Tables 4 and 5).

Fig. 1
figure 1

Flow diagram of the study design process

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The odds ratio/pooled prevalence

The analysis based on case–control studies found a significant association between protozoan parasites and mental disorders (OR: 2.059, 95% CI 1.830–2.317) (Fig. 2, Table 2). The random-effects model for cross-sectional studies showed that the overall prevalence of protozoan parasites in patients with mental disorders was 0.252 (95% CI 0.189–0.320) (Fig. 3, Table 5). The heterogeneity was significant for both case–control (I2 = 74%; τ2 = 0.247; p < 0.001) and cross-sectional studies (I2 = 98%; τ2 = 0.063; p < 0.001) (Tables 2 and 5).

Fig. 2
figure 2

Forest plot of odds rations for relationship between prevalence of protozoan parasites and mental disorders in case–control studies

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Fig. 3
figure 3

Forest plots for random-effects meta-analysis of the global prevalence of protozoan parasites among patients with mental health disorders based on cross-sectional studies (The boxes indicate the effect size of the studies (prevalence) and the whiskers indicate its confidence interval for corresponding effect size. There is no specific difference between white and black bars, only studies with a very narrow confidence interval are shown in white. In the case of diamonds, their size indicate the size of the effect, and their length indicate confidence intervals

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Subgroup analysis

The odds ratio/pooled prevalence based on WHO regions

According to the WHO regions, our analyses of case–control studies revealed that the highest pooled OR was related to the Eastern Mediterranean Region (OR: 2.289, 95% CI 1.868–2.805) with heterogeneity (I2 = 79%; τ2 = 0.299; p < 0.001) (Table 2). The analyses of cross-sectional studies showed that protozoan parasitic infections were most prevalent in patients with mental disorders in the European Region (0.386, 95% CI 0.150–0.656) with heterogeneity (I2 = 98%; τ2 = 0.047; p < 0.001) (Table 5).

The odds ratio/pooled prevalence based on the type of the parasite

Subgroup analysis based on the type of protozoan parasite revealed the pooled OR of the higher risk of these parasites in patients with mental disorders in case–control studies (OR: 2.069, 95% CI 1.841–2.326) with heterogeneity (I2 = 73%; τ2 = 0.260; p < 0.001). However, the pooled OR of Cyclospora cayetanensis (4.719, 95% CI 1.352–16.474), followed by Cryptosporidium parvum (4.618, 95% CI 2.877–7.412) revealed a significantly higher risk of these parasites in patients with mental disorder compared to controls (Table 3).

The analysis based on cross-sectional studies showed that the pooled prevalence of different types of protozoan parasites was as follows: T. gondii (0.343, 95% CI 0.228–0.467) with heterogeneity (I2 = 99%; τ2 = 0.064; p < 0.001), Cryptosporidium spp. (0.087, 95% CI 0.005–0.242) with heterogeneity (I2 = 95%; τ2 = 0.032; p < 0.001), Blastocystis hominis (0.085, 95% CI 0.047–0.132) with heterogeneity (I2 = 93%; τ2 = 0.018; p < 0.001), Entamoeba coli (0.083, 95% CI 0.050–0.123) with heterogeneity (I2 = 92%; τ2 = 0.018; p < 0.001), Cystoisospora belli (0.076, 95% CI 0.022–0.156), Cyclospora cayetanensis (0.075, 95% CI 0.042–0.116), E. histolytica / dispar (0.064, 95% CI 0.011–0.151) with heterogeneity (I2 = 97%; τ2 = 0.067; p < 0.001), Giardia lamblia (0.062, 95% CI 0.040–0.088) with heterogeneity (I2 = 89%; τ2 = 0.008; p < 0.001), Dientamoeba fragilis (0.029, 95% CI 0.000–1.000) with heterogeneity (I2 = 95%; τ2 = 0.023; p < 0.001), Endolimax nana (0.029, 95% CI 0.006–0.067) with heterogeneity (I2 = 88%; τ2 = 0.017; p < 0.001), Iodamoeba butschlii (0.024, 95% CI 0.013–0.037) with heterogeneity (I2 = 53%; τ2 = 0.001; p < 0.001), Chilomastix mesnili (0.021, 95% CI 0.001–0.058) with heterogeneity (I2 = 77%; τ2 = 0.005; p < 0.001) (Table 6).

The odds ratio/pooled prevalence based on climatic variables

The estimates of pooled OR based on climatic variables showed that the highest rate was related to an annual precipitation range of 300–650 (OR: 2.297, 95% CI 1.700–3.103), humidity levels of 40–75% (OR: 2.194, 95% CI 1.917–2.510), annual rainfall of < 400 mm (OR: 2.256, 95% CI 1.844–2.761), and average temperatures of > 20 ℃ (OR: 2.281, 95% CI 1.850–2.811) (Table 2).

Moreover, our analyses of studies with cross-sectional design revealed that the highest pooled prevalence was observed for an annual precipitation of < 300 (0.270, 95% CI 0.192–0.355), humidity levels of < 40% (0.303, 95% CI 0.218–0.394), annual rainfall of < 400 mm (0.331, 95% CI 0.249–0.418), and the average temperatures of < 10 ℃ (0.448, 95% CI 0.398–0.499) (Table 5). The heterogeneity related to analyses based on each climatic variable in both study designs is presented in Tables 2 and 5.

The odds ratio/pooled prevalence based on diagnostic method

In terms of case–control studies, the highest rate of OR was related to studies that utilized a combination of EIA and Western blot methods (OR: 5.818, 95% CI 1.490–22.715) (Table 2).

Regarding cross-sectional studies, the highest pooled prevalence was associated with the combination of direct smear & PCR (0.708, 95% CI 0.618–0.783) (Table 5).

The odds ratio/pooled prevalence based on mean age and income level

The analyses of cross-sectional studies showed that protozoan parasites were most prevalent in patients with a mean age ranging from 15–20 years old (0.664, 95% CI 0.594–0.724) (Table 5).

According to our estimates regarding income level, the pooled OR (2.190, 95% CI 1.823–2.632) with heterogeneity (I2 = 77%; τ2 = 0.263; p < 0.001) and pooled prevalence (0.285, 95% CI 0.201–0.378) of protozoan parasitic infections was found to be highest in patients in lower-middle income regions with heterogeneity (I2 = 98%; τ2 = 0.060; p < 0.001) (Tables 2 and 5).

The odds ratio/pooled prevalence based on the type of the mental disorder

In terms of case–control studies, the association between different mental disorders and protozoan parasitic infections was as follows: neurodevelopmental disorders (OR: 2.485, 95% CI 1.413–4.368), bipolar and related disorders (OR: 2.163, 95% CI 1.436–3.260), schizophrenia spectrum and other psychotic disorders (OR: 2.088, 95% CI 1.807–2.412), obsessive–compulsive disorder (OCD) and related disorder (OR: 1.893, 95% CI 0.908–3.947), depressive disorder (OR: 1.876, 95% CI 1.311–2.683), neurocognitive disorders (OR: 1.534, 95% CI 0.899–2.616), and trauma and stressor related disorders (OR: 1.757, 95% CI 0.493–6.261) (Fig. 2).

Moreover, the analysis of cross-sectional studies revealed that the pooled prevalence based on the type of mental disorders was as follows: 0.341 (95% CI 0.244–0.446) in neurodevelopmental disorder with heterogeneity (I2 = 97%; τ2 = 0.051; p < 0.001), 0.321 (95% CI 0.000–0.995) in bipolar and related disorders with heterogeneity (I2 = 99%; τ2 = 0.399; p < 0.001), 0.213 (95% CI 0.127–0.314) in schizophrenia spectrum and other psychotic disorders with heterogeneity (I2 = 98%; τ2 = 0.062; p < 0.001), 0.134 (95% CI 0.100–0.171) in depressive disorder with heterogeneity (I2 = 67%; τ2 = 0.001; p < 0.001), 0.119 (95% CI 0.082–0.170) in trauma and stressor-related disorders with, and 0.083 (95% CI 0.049–0.137) in neurocognitive disorders (Fig. 3).

Publication bias

Substantial publication bias was detected in case–control studies, as indicated by Egger’s funnel plot (t = 1.03, p = 0.306) and Begg’s test (t = 1.02, p = 0.308). Additionally, the Doi plot test revealed no asymmetry (LFK index: 0.43) (Fig. 4). Substantial publication bias was detected in cross-sectional studies, as indicated by Egger’s funnel plot (t = 2.24, p = 0.025) and Begg’s test (t = 3.07, p = 0.004). Additionally, the Doi plot test revealed a major asymmetry (LFK index: 2.74) (Fig. 5).

Fig. 4
figure 4

Egger's funnel plot and Begg's funnel plot to assess publication bias in studies evaluating of protozoan parasites among patients with mental health disorders based on case—control studies (Colored circles represent each study. The middle line is the effect size and the other two lines are the corresponding confidence ranges) (A, B). Doi plot for the global prevalence of intestinal protozoan parasites among patients with mental health disorders. A Luis Furuya -Kanamori (LFK) index 0.43 indicates no asymmetry (C)

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Fig. 5
figure 5

Egger's funnel plot and Begg's funnel plot to assess publication bias in studies evaluating of protozoan parasites among patients with mental health disorders based on cross-sectional studies (Colored circles represent each study. The middle line is the effect size and the other two lines are the corresponding confidence ranges) (A, B). Doi plot for the global prevalence of intestinal protozoan parasites among patients with mental health disorders. A Luis Furuya—Kanamori (LFK) index 2.74 indicates major asymmetry (C)

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Meta-regression

The results of the meta-regression analysis demonstrated that among all moderators, only annual rainfall, significantly affected the OR and the prevalence in studies with estimates of (slop = 0.6507, p < 0.0001) for a cross-sectional design and (slop = 0.8326, p < 0.0001) for a case–control studies (Figs. 6 and 7).

Fig. 6
figure 6

A meta-regression graph for the global prevalence of protozoan parasites among patients with mental health disorders based on annual rainfall (A), and year of publication (B) in cross-sectional studies. The pink line is the regression line, which was plotted based on the intercept and the slope of the regression model. The different color bubbles represent the countries under study and their sizes indicate the effect size of each study

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Fig. 7
figure 7

A meta-regression graph for the global prevalence of protozoan parasites among patients with mental health disorders based on annual rainfall (A), and year of publication (B) in case—control studies. The pink line is the regression line, which was plotted based on the intercept and the slope of the regression model. The different color bubbles represent the countries under study and their sizes indicate the effect size of each study

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QGIS3 map

To demonstrate the prevalence of protozoan parasites in patients with mental disorders in various geographical locations of the world, a map was created using QGIS3 software (https://qgis.org/en/site/) based on the included cross-sectional and case–control studies (Figs. 8 and 9).

Fig. 8
figure 8

The prevalence of protozoan parasites among patients with mental health disorders based on cross-sectional studies in different geographical regions of the world

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Fig. 9
figure 9

The prevalence of protozoan parasites among patients with mental health disorders based on case—control studies in different geographical regions of the world

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Discussion

The present systematic review and meta-analysis is the first to investigate an overlooked phenomenon concerning the status of protozoan parasitic infections and associated risk factors in patients with mental disorders through a comprehensive evaluation of the available data. The findings of our study revealed a pooled prevalence of 25.2% for protozoan parasites among the investigated patients. Notably, we also demonstrated that patients with mental disorders were about twofold more at risk of parasitic protozoan infections compared to healthy individuals.

Our analysis based on cross-sectional studies showed that, T. gondii was the most prevalent protozoan parasite among patients with mental health disorder.

In addition, the estimated pooled OR showed that that patients with mental disorder have a significantly higher risk of C. cayetanensis and C. parvum compared to control groups.

In the recent decades, a significant association has been identified between toxoplasmosis and a wide range of mental health diseases. Especially, this relationship has been well-documented in patients with bipolar disorder and schizophrenia. T. gondii is a widespread intracellular protozoan parasite with a neurotropic nature, which links it to mental and behavioral disorders. The chronic infection caused by the parasite is associated with formation of intracellular cysts in neurons and glial cells. Although, latent toxoplasmosis is commonly asymptomatic in immunocompetent patients, it is evidenced that it can trigger behavioral changes in mice and humans [24,25,26,27].

The experimental research demonstrated that T. gondii latent cysts distribute throughout the brain tissue in murine models. This experiment can raise the hypothesis that cysts formed by the parasite may affect frontal and limbic regions in humans resulting in emotional and behavioral changes [28]. Similarly, our subgroup meta-analysis of cross-sectional studies based on the type of mental disorder indicated that, patients with neurodevelopmental disorder followed by patients with bipolar and related disorders had the highest prevalence rate of toxoplasmosis. Previous studies showed that the seropositivity rates of anti-Toxoplasma antibodies were significantly higher in patients with neurodevelopmental disorders than in controls [29,30,31,32]. Furthermore, a meta-analysis study on 4021 patients diagnosed with bipolar disorder and 8669 healthy controls indicated that this disorder was associated with 1.34-fold higher risk of seropositivity for toxoplasmosis than healthy individuals [33]. As well, findings of a research conducted by Frye et al. [34], revealed that the inflammation which occur during toxoplasmosis infection may be one of the factors that have a role in bipolar disorder. Furthermore, it has been shown that a diminished long-term antibody response against T. gondii is associated with bipolar disorder and its subphenotypes, especially bipolar type I, non-early disease onset, and manic psychosis (OR: 1.33) [34].

In a recent analysis by Sutterland et al. [35], statistically significant ORs of the risk of anti-T. gondii IgG antibody have been reported in patients with bipolar disorder (OR: 1.52), and OCD patients (OR: 3.4). The investigation on relations between T. gondii and schizophrenia found a significant effect of seropositivity before onset and zero intensity. These findings revealed a potential link between toxoplasmosis and various psychiatric disorders, especially in schizophrenia which latent toxoplasmosis could be reactivated [35]. A comprehensive worldwide review discussed that T. gondii has the capacity to impact certain metabolic and developmental pathways, resulting in a modified susceptibility to the disease as a consequence [36]. Our estimates showed that patients with schizophrenia spectrum and other psychotic disorders were twofold at higher risk of protozoan parasite infections compared to the control group (OR: 2.08).

Nevertheless, the significance of intestinal parasites, particularly parasitic protozoa in patients with mental disorders, can not be underestimated. Our findings indicated the occurrence of intestinal parasitic infections, including both pathogenic and non-pathogenic types, among individuals diagnosed with mental disorders. Accordingly, our investigation found that Cryptosporidium spp., C. cayetanensis, C. belli, E. histolytica/dispar, and G. lamblia were among the pathogenic parasites in these patients. Several factors, including unhygienic lifestyle, common unhealthy behaviors (nail biting, improper food handling, and habits involving putting hands or objects into the mouth), unavailability of daily necessities and crowding (e.g., in mental health institutions/hospitals), pica, and mental disabilities, are considered to be contributing factors to this condition, which pose a greater risk of acquiring parasitic protozoan infections in patients with mental health disorders [37, 38].

Herein, we observed that parasitic protozoa were most prevalent in patients in lower-middle income regions with 2.1-fold higher risk of infection for mentally ill patients in these regions. Based on a review, mental illnesses are common in low and middle-income regions, with a pooled prevalence of 17.6% (15.5–20.0%) [14]. However, studies focused on the association of mental illnesses with parasitic diseases are limited in these countries.

Moreover, a geographical distribution in the prevalence of parasitic protozoa was observed in our meta-analysis. Accordingly, it has been shown that patients with mental disorders in the Eastern Mediterranean Region had a 2.28-fold higher risk of these parasites than healthy patients. In this region, there is a notable growth in population size, significant variations in socio-economic status between developed and developing nations, considerable migration trends, heightened demands for water resources, and a concerning degradation of ecosystems. The region is faced with the climate change issue, which elevates the likelihood of diseases transmitted through vectors, water, and food. Those facing the highest risk include individuals with lower socio-economic status, limited education, young children, the elderly, migrants, and those dealing with chronic health issues [39].

However, regarding cross-sectional studies, the highest pooled prevalence rate was detected in patients in European WHO region. This was similar to the finding of a global survey on the seroprevalence of toxoplasmosis in patients with mental and neurological disorders which found that the highest pooled prevalence of T. gondii IgG antibody was related to Europe (57%). Furthermore, this study showed that the overall global seroprevalence of T. gondii IgM antibody was higher in neuropsychiatric patients (6.78%) than in healthy controls (3.13%) [40].

In light of these reasons, comprehensive strategies that integrate both mental health and infectious disease management are imperative. These strategies should focus on raising awareness, improving healthcare access, addressing stigma, and promoting interdisciplinary collaboration between mental health professionals and infectious disease specialists. There is evidence regarding the significant relationship between climatic variables (particularly temperature, humidity, and rainfall) and the prevalence of intestinal protozoan diseases. The high temperatures and increased humidity in areas with humid and subtropical climates regarded as favorable conditions for the survival and transmission of protozoan parasites. Heavy rainfall can lead to water contamination and facilitate the spread of these parasites [5, 41]. Patients with mental disorders may be at higher risk of infection due to potential difficulties in maintaining personal hygiene and accessing healthcare, exacerbating their susceptibility. Understanding and addressing these relationships is crucial for the development of effective public health interventions and tailored care for this vulnerable group [12, 42].

Limitations

This study faced some limitations that should be discussed. First, the number of studies for some subsets of mental disorders was limited, and for some of mental illnesses, only one article investigated the prevalence of protozoan parasites. Second, the heterogeneity of studies was high, and therefore, designing further studies with larger sample sizes and low heterogeneity is required to determine the contributing relationship between protozoan parasites and mental disorders.

Conclusion

The present systematic review and meta-analysis have shed light on an overlooked connection between protozoan parasitic infections and mental disorders. Our study indicated that patients with mental disorders are at significantly higher risk of acquiring protozoan parasites than healthy individuals. We also demonstared that T. gondii as one of the most frequently observed parasite, has been extensively linked to a range of mental health conditions, with a strong correlation established in patients with bipolar disorder and schizophrenia.

This meta-analysis strengthens the growing body of evidence linking protozoan parasitic infections, particularly T. gondii, to mental disorders. The intricate interplay between infectious agents and mental health underscores the need for a multidisciplinary approach in understanding and managing these complex conditions. Recognizing and addressing these associations could have substantial implications for improving the overall well-being and mental health of affected individuals.

Considering the implications for public health arising from our findings, the current epidemiological data highlights the need for further research to explore the mechanisms underlying these connections and to develop effective strategies for prevention and intervention. Preventive interventions, regular screening programmes, and treatment for parasitic infections should be included in clinical care approaches applied to psychiatric patients, especially in specialized clinical services. It would be also beneficial if healthcare sectors in the psychiatry field consistently provided education on hygiene practices to improve the overall health of their patients.

Availability of data and materials

All data generated or analyzed during this study are included in this manuscript and Supplementary Files.

Abbreviations

OR:

Odds ratio

CI:

Confidence interval

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

LFK:

Luis Furuya-Kanamori

I 2 :

Inconsistency index

EIA:

Enzyme Immunoassay

IFA:

Immunofluorescence assay

OCD:

Obsessive–compulsive disorder

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Acknowledgements

We sincerely thank personnel from the Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Funding

This work was supported by the Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran (contract no. IR.QUMS.REC.1402.150), and Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran.

Author information

Author notes

  1. Amir Abdoli, Aida Vafae Eslahi, Rasoul Samimi and Milad Badri have contributed equally to this work.

Authors and Affiliations

  1. Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran

    Amir Abdoli

  2. Department of Parasitology and Mycology, Jahrom University of Medical Sciences, Jahrom, Iran

    Amir Abdoli

  3. Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran

    Meysam Olfatifar

  4. Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

    Aida Vafae Eslahi, Rasoul Samimi & Milad Badri

  5. Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Zeinab Moghadamizad

  6. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Amin Habibi

  7. Clinical Research Development Center, Qom University of Medical Sciences, Qom, Iran

    Mohammad Amin Habibi

  8. Department of Clinical Psychology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Amir Sam Kianimoghadam

  9. University of Cologne, Medical Faculty and University Hospital, Cologne, Germany

    Panagiotis Karanis

  10. Medical School, Department of Basic and Clinical Sciences, Anatomy Centre, University of Nicosia, Nicosia, Cyprus

    Panagiotis Karanis

Authors
  1. Amir Abdoli
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  3. Aida Vafae Eslahi
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  4. Zeinab Moghadamizad
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  8. Milad Badri
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  9. Panagiotis Karanis
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Contributions

AVE, MB, and PK: designed the study. ZM, AA, MAH, RS, and AK: searched for primary publications, screened and appraised primary studies. ZM and MB: extracted the data. AVE, MB, and PK: wrote the study manuscript. MO, AVE and MB: contributed to data analysis and interpretation. PK: reviewed and edited the manuscript. All authors read the manuscript and participated in the preparation of the final version of the manuscript.

Corresponding authors

Correspondence to Milad Badri or Panagiotis Karanis.

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Supplementary Information

Additional file 1: Table S1.

Quality assessment using the Newcastle–Ottawa scale modified for case-control studies.

Additional file 2: Table S2.

Quality assessment using the Newcastle–Ottawa scale modified for cross-sectional studies.

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Abdoli, A., Olfatifar, M., Eslahi, A.V. et al. A systematic review and meta-analysis of protozoan parasite infections among patients with mental health disorders: an overlooked phenomenon. Gut Pathog 16, 7 (2024). https://doi.org/10.1186/s13099-024-00602-2

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Keywords

Gut Pathogens

ISSN: 1757-4749