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Iranian Journal of Parasitology logoLink to Iranian Journal of Parasitology
. 2022 Oct-Dec;17(4):443–457. doi: 10.18502/ijpa.v17i4.11271

Toxoplasma gondii Infection in Immunocompromised Patients in Iran (2013–2022): A Systematic Review and Meta-Analysis

Aref Teimouri 1, Fatemeh Goudarzi 2, Kimia Goudarzi 1, Rasoul Alimi 3, Keivan Sahebi 4, Hassan Foroozand 4, Hossein Keshavarz 2,5,*
PMCID: PMC9825698  PMID: 36694563

Abstract

Background:

Toxoplasma gondii infection (toxoplasmosis) has the potential to cause a serious disease in immunocompromised patients and can be fatal in this population. We conducted a systematic review and meta-analysis to assess comprehensively the pooled seroprevalence of toxoplasmosis among immunocompromised patients including HIV/AIDS patients, cancer patients, and transplant recipients in Iran.

Methods:

PubMed, Web of Science, Scopus, Embase, and Google Scholar databases (international) and Scientific Information Database (SID), Magiran, IranMedex, and IranDoc databases (national) were systematically searched for all reports that possibly contained data for T. gondii prevalence in different immunocompromised populations in Iran between 2013 and 2022.

Results:

Overall, IgG seroprevalence rate of toxoplasmosis in Iranian immunocompromised patients was 45.1% (95% confidence interval (CI), 37.4–52.9). IgG seroprevalence rate of toxoplasmosis in 12 studies that included 2279 cancer patients, 19 studies that included 2565 HIV/AIDS patients and in 3 studies that included 200 transplant recipients was 43.6% (95% CI, 30.2–57.0), 45.9% (95% CI, 34.8–57.1) and 45.8% (95% CI, 32.5–59.0), respectively. Moreover, IgM seroprevalence rate in the 26 studies was 2.6% (95% CI, 1.4–3.7).

Conclusion:

Our findings represent a high seroprevalence rate of Toxoplasma IgG among immunocompromised patients. Health improvement and education toward prevention of toxoplasmosis is of great importance for these susceptible populations.

Keywords: Toxoplasma gondii, Immunocompromised patients, HIV, Aids, Cancer patients, Transplant recipients, Iran

Introduction

Toxoplasmosis, one of the most common parasitic infections worldwide, is caused by an opportunistic protozoan parasite Toxoplasma gondii (1). Humans acquire the infection through consumption of tissue cysts in raw or un-cooked meat or via ingestion of contaminated water, food or soil with oocysts from environment or infected cats’ faeces (2,3). Other routes of transmission include vertical transmission, blood transfusion and transplantation (4–6).

Although the infection with T. gondii in healthy individuals appears to be asymptomatic or presents as a self-limited febrile disease, it can cause a serious condition and even be life threating in immunocompromised patients including HIV positive patients, organ transplant recipients, cancer patients and any candidates of immunosuppressive therapies (7–9).

The prevalence of the infection in humans varies greatly in different parts of the world, ranging from 16–40% in United States and United Kingdom to 40–80% in Central and South Europa, tropical areas of Africa and Latin America (8, 10). In Iran, the seroprevalence rate of T. gondii was estimated to be 39% in general population and 50% in immunocompromised patients which is considerably significant (11,12).

Toxoplasmosis has the potential to cause a serious disease in immunocompromised patients and can be fatal in this population (13). More commonly, the infection in immunocompromised patients occurs because of reactivation of the latent infection rather than an acutely acquired one. The most common manifestation of the infection with T. gondii in immunocompromised patients is toxoplasmic encephalitis (TE), which causes fever, headache, ataxia, seizures and decreased level of consciousness as well as loss of memory (14,15). Transplanting an organ from a sero-negative donor to a seropositive recipient can lead to reactivation of the latent infection in recipient due to immunosuppressive therapies. Moreover, transplantation of an infected organ from a seropositive donor to a sero-negative recipient receiving immunosuppressive drugs can initiate the infection. The latter appears to be more dangerous and fatal (16).

Given the increase in the prevalence of immunocompromised patients, it is critical to gather information regarding the prevalence of T. gondii in this population in order to properly diagnose and manage the infection. Therefore, we conducted a systematic review and meta-analysis to investigate the prevalence of T. gondii in immunocompromised patients in Iran between 2013 and 2022.

Methods

Search strategy and selection criteria

The present study is in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement (17). Five international databases of PubMed, Web of Science, Scopus, Embase and Google Scholar and four national databases including Scientific Information Database (SID), Magiran, IranMedex, and IranDoc, were respectively searched for English and Persian publications between January 1, 2013 and July 5, 2022, for all reports that possibly contained data for T. gondii prevalence in different immunocompromised populations. The databases were searched using the Key words “toxoplasmosis”, “Toxoplasma gondii”, “T. gondii”, “cancer”, “malignancies”, “transplant”, “HIV”, “AIDS”, “acquired immune deficiency syndrome”, “immunocompromised”, “immuno-deficiency”, “immune deficiency”, “Iran”, “Islamic Republic of Iran”, and “seroprevalence” (alone or combined). Papers written in Persian and English were included. Studies were excluded if they were reviews, repeated studies, or animal studies. All identified titles and abstracts were carefully screened by two independent experienced systematic reviewers (AT and FG) to find relevant articles. The full text of articles considered as potentially relevant based on title and abstract were independently examined by the same two reviewers. Any disagreements with the selected studies were resolved by discussion and involvement of another two authors (RA and KS).

Data extraction and quality assessment

The information that was extracted from the relevant articles included year of publication, province, region, patient group, design of the study, sample size, seroprevalence of IgG and IgM positive cases (Table 1, 2). Two reviewers (FG and AT) independently extracted the data and reached a consensus after discussing controversial literatures. The quality of the included publications was assessed based on the criteria (18, 19). These criteria were created based on the Grading of Recommendations Assessment, Development and Evaluation method (20), and including the diagnostic approach of T. gondii infection and matching of case and control subjects. Quality assessment of the included studies was carried out using the Joanna Briggs Institute (JBI) critical appraisal instrument for studies reporting prevalence data (21).

Table 1:

Baseline characteristics of included studies (based on IgG assessment)

Year Province Patient group Number of cases IgG-positive cases Sero-prevalence (%) Age range Serological test Design Ref
2013 Tehran HIV 100 65 65 >15 ELISA Case-control (26)
2013 Khouzestan HIV 42 31 73.81 18–54 ELISA Case-control (27)
2013 Tehran Transplant 50 27 54 Different ELISA Cross-sectional (28)
2013 Khouzestan Renal Transplant 100 34 34 16–80 ELISA Case-control (29)
2014 Tehran Cancer 535 208 38.88 Children ELISA Comparative study (30)
2014 Kordistan HIV 94 18 19.15 >18 ELISA Cross-sectional (31)
2015 Mazandaran Cancer 66 57 86.36 20–50 ELISA Cross-sectional (32)
2015 Mazandaran HIV/AIDS 82 79 96.34 Different ELISA Cross-sectional (33)
2016 Bushehr Malignancy 86 21 24.42 Different ELISA Cross-sectional (34)
2016 Qom/Isfahan Transplant 50 26 52 Different ELISA Case-control (35)
2017 Markazi HIV/AIDS 49 10 20.41 NA ELISA Cross-sectional (36)
2017 Tehran/Alborz Leukemia 170 96 56.47 10–60 ELISA Cross-sectional (37)
2017 Isfahan HIV 20 10 50 Different ELISA Cross-sectional (38)
2017 Qom/Isfahan Cancer 112 70 62.5 Different ELISA Cross-sectional (38)
2017 Fars/Yazd HIV 90 19 21.11 20–58 ELISA Cross-sectional (39)
2017 Khouzestan Cancer 372 155 41.66 Children ELISA Cross-sectional (40)
2018 Fars HIV 251 39 15.54 14–83 ELISA Cross-sectional (41)
2018 Mazandaran Blood cancer 101 37 36.63 <18 ELISA Case-control (42)
2018 Kermanshah HIV 358 157 43.85 3–68 ELISA Cross-sectional (43)
2018 Fars HIV 246 51 20.73 Different ELISA Retrospective study (44)
2018 Khouzestan AIDS 379 131 34.56 NA ELISA Cross-sectional (45)
2019 Tehran Cancer 106 44 41.51 NA ELISA Cross-sectional (46)
2019 East Azerbaijan HIV 124 47 37.90 Different Chemiluminescence Cross-sectional (47)
2019 Kohgiluye & Boyer-Ahmad Cancer 100 13 13 Different ELISA Cross-sectional (48)
2019 Tehran HIV 149 69 46.31 18–74 ELISA Cross-sectional (49)
2019 Yazd HIV 84 44 52.38 Different ELISA Cross-sectional (50)
2019 Alborz HIV 102 44 43.14 20–60 ELFA Cross-sectional (51)
2020 Tehran HIV/AIDS 108 95 87.96 5–60 ELISA Cross-sectional (52)
2020 Mazandaran HIV 102 70 68.63 Different ELISA Cross-sectional (53)
2021 Khouzestan Cancer 127 9 7.1 Different ELISA Cross-sectional (54)
2021 Sistan & Baluchestan Malignancy 154 61 39.61 16–72 ELISA Cross-sectional (55)
2021 Mazandaran Cancer 350 264 75.43 17–86 ELISA Cross-sectional (56)
2021 Guilan HIV/AIDS 121 72 59.50 7–74 ELISA Cross-sectional (57)
2022 Kohgiluye & Boyer-Ahmad HIV 64 11 17.19 NA ELISA Case-control (58)
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*

NA: not available

Table 2:

Baseline characteristics of included studies (based on IgM assessment)

Year Province Patient group Number of cases IgM-positive cases Seroprevalence (%) Age range Serological test Design Ref
2013 Tehran Transplant 50 2 4 Different ELISA Cross-sectional (28)
2013 Khouzestan Renal Transplant 100 18 18 16–80 ELISA Case-control (29)
2014 Tehran Cancer 535 51 9.53 Children ELISA Comparative study (30)
2015 Mazandaran Cancer 66 5 7.57 20–50 ELISA Cross-sectional (32)
2015 Mazandaran HIV/AIDS 82 0 0 Different ELISA Cross-sectional (33)
2016 Bushehr Malignancy 86 0 0 Different ELISA Cross-sectional (34)
2016 Qom/Isfahan Transplant 50 0 0 Different ELISA Case-control (35)
2017 Markazi HIV/AIDS 49 1 2.04 NA ELISA Cross-sectional (36)
2017 Tehran/Alborz Leukemia 170 10 5.88 10–60 ELISA Cross-sectional (37)
2017 Khouzestan Cancer 372 24 6.45 Children ELISA Cross-sectional (40)
2018 Fars HIV 251 3 1.19 14–83 ELISA Cross-sectional (41)
2018 Mazandaran Blood cancer 101 0 0 <18 ELISA Case-control (42)
2018 Kermanshah HIV 358 10 2.79 3–68 ELISA Cross-sectional (43)
2018 Khouzestan AIDS 379 11 2.9 NA ELISA Cross-sectional (45)
2019 Tehran Cancer 106 0 0 NA ELISA Cross-sectional (46)
2019 East Azerbaijan HIV 124 2 1.61 Different Chemiluminescence Cross-sectional (47)
2019 Kohgiluye & Boyer-Ahmad Cancer 100 2 2 Different ELISA Cross-sectional (48)
2019 Tehran HIV 149 4 2.68 18–74 ELISA Cross-sectional (49)
2019 Alborz HIV 102 0 0 20–60 ELFA Cross-sectional (51)
2020 Tehran HIV/AIDS 108 1 0.92 5–60 ELISA Cross-sectional (52)
2020 Mazandaran HIV 102 0 0 Different ELISA Cross-sectional (53)
2021 Khouzestan Cancer 127 2 1.57 Different ELISA Cross-sectional (54)
2021 Sistan & Baluchestan Malignancy 154 0 0 16–72 ELISA Cross-sectional (55)
2021 Mazandaran Cancer 350 9 2.57 17–86 ELISA Cross-sectional (56)
2021 Guilan HIV/AIDS 121 6 4.96 7–74 ELISA Cross-sectional (57)
2022 Kohgiluye & Boyer-Ahmad HIV 64 5 7.81 NA ELISA Case-control (58)
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*

NA: not available

Statistical analysis

Preliminary analyses including summations, subtractions, divisions, multiplications and estimation of percentages were conducted using Microsoft Excel. Statistical and meta-analyses were carried out using STATA statistical software v.14 (Stata Corp, College Station, TX, USA). Overall pooled prevalence of T. gondii infection in immunocompromised patients (95% confidence interval, CI) was calculated, using random-effects model, and presented as a forest plot (22). Statistical heterogeneity of results was appraised using a x2 -based Q-test and I2 statistic. I2 values of 0, 25, 50, and 75% were considered as ‘no’, ‘low’, ‘moderate’, and ‘high’ heterogeneities respectively (23). The fixed effects model was used when literature heterogeneity not existed; otherwise, the random-effects model was employed.

Publication bias, sensitivity and meta-regression analyses

Publication bias was assessed using Egger’s regression asymmetry test and visual inspection of the funnel plot (24). A sensitivity analysis was carried out using random-effect model through systematic omitting of a single study to evaluate robustness of the pooled prevalence estimate (25).

Results

Literature Search

As shown in Fig. 1, the literature search yielded 1926 relevant studies, which included 1499 duplicates. After a careful examination of each article’s title and abstract, 34 studies were found eligible for the final analysis (Fig. 1).

Fig. 1.

Fig. 1

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Flow diagram describing the study design process

Characteristics of the eligible studies

Table 1 presents the characteristics of the 34 eligible studies meta-analyzed. In brief, 19 publications described T. gondii infection in HIV/AIDS patients, 12 articles investigated T. gondii infection in cancer/malignancy patients, whereas 3 studies reported T. gondii infection in transplant recipients. The identified studies were conducted in Iran. In terms of epidemiological design, 26 of the included publications were cross-sectional studies, 6 were case-control studies, 1 comparative and 1 retrospective study (Table 1). Regarding the risks of bias assessments, 29 studies (85%) had low risks of bias, 3 studies (9%) included medium risks of bias, and two study (6%) included high risks of bias.

Pooled prevalence of T. gondii infection (IgG) in immunocomprised patients

The IgG seroprevalence rates of T. gondii in immunocompromised patients from Iran was 45.1% (95% CI, 37.4–52.9). The Cochrane Q test was 1981.48; I2=97.68% and P<0.0001.

The pooled seroprevalence in 12 studies that included 2279 cancer patients were 43.6% (95% CI, 30.2–57.0) (Fig. 2). In this group, the Q statistic was 683.39 (P<0.0001) with inconsistency (I2=98.15%).

Fig. 2:

Fig. 2:

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Forest plot diagram of studies showing IgG seropositivity rates to T. gondii in cancer patients from Iran

The pooled seroprevalence in 19 studies that included 2565 HIV/AIDS patients were 45.9% (95% CI, 34.8–57.1) (Fig. 3). In this group, the Q statistic was 1267.87 (P<0.0001) with inconsistency (I2=97.89%).

Fig. 3:

Fig. 3:

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Forest plot diagram of studies showing IgG seropositivity rates to T. gondii in HIV/AIDS patients from Iran

The pooled seroprevalence in 3 studies that included 200 Transplant recipients were 45.8% (95% CI, 32.5–59.0) (Fig. 4). In this group, the Q statistic was 7.67 (P=0.022) with inconsistency (I2=71.63%). Subgroup analysis based on geographical area is shown in Fig. 5. The highest IgG seroprevalence rates is related to region 1 (61.2% (95% CI, 49.8–73.3)) and the lowest is related to region 2 (20.6% (95% CI, 13.5–27.8)).

Fig. 4:

Fig. 4:

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Forest plot diagram of studies showing IgG seropositivity rates to T. gondii in transplant recipients from Iran

Fig. 5:

Fig. 5:

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Forest plot diagram of studies showing IgG seropositivity rates to T. gondii in immunocompromised (country divisions of provinces) patients from Iran (Region 1: Provinces of Tehran, Qazvin, Mazandaran, Semnan, Golestan, Alborz, Qom, Region 2: Provinces of Isfahan, Fars, Bushehr, Chaharmahal Bakhtiari, Hormozgan, Kohkiluyeh & Boyer-Ahmad, Region 3: Provinces of East Azerbaijan, West Azerbaijan, Ardabil, Zanjan, Guilan, Kurdistan, Region 4: Kermanshah, Ilam, Lorestan, Hamedan, Markazi, Khuzestan, Region 5: Provinces of Razavi Khorasan, South Khorasan, North Khorasan, Kerman, Yazd, Sistan & Baluchestan)

Pooled prevalence of T. gondii infection (IgM) in immunocomprised patients

Table 2 presents the characteristics of the 26 eligible studies meta-analyzed. The IgM sero-prevalence rates of T. gondii in immunocompromised patients from Iran was 2.6% (95% CI, 1.4–3.7). The Cochrane Q test was 123.99; I2=84.82% and P<0.0001.

The pooled seroprevalence in 11 studies that included 2167 cancer patients was 3.1% (95% CI, 1.0–5.1) (Fig. 6). In this group, the Q statistic was 60.68 (P<0.0001) with inconsistency (I2=84.61%).

Fig. 6:

Fig. 6:

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Forest plot diagram of studies showing IgM seropositivity rates to T. gondii in cancer patients from Iran

The pooled seroprevalence in 12 studies that included 1889 HIV/AIDS patients was 1.3% (95% CI, 0.06–2.1) (Fig. 7). In this group, the Q statistic was 22.13 (P=0.023) with inconsistency (I2=41.85%).

Fig. 7:

Fig. 7:

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Forest plot diagram of studies showing IgM seropositivity rates to T. gondii in HIV/AIDS patients from Iran

The pooled seroprevalence in 3 studies that included 200 Transplant patients was 7.1% (95% CI, 0.00–17.5) (Fig. 8). In this group, the Q statistic was 14.09 (P=0.001) with inconsistency (I2=87.98%). Subgroup analysis based on geographical area is shown in Fig. 9. The highest IgM seroprevalence rates is related to region 4 (4.5% (95% CI, 0.2–8.8) and the lowest is related to region 5 (0.0% (95% CI, 0.0–2.0).

Fig. 8:

Fig. 8:

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Forest plot diagram of studies showing IgM seropositivity rates to T. gondii in transplant recipients from Iran

Fig. 9:

Fig. 9:

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Forest plot diagram of studies showing IgM seropositivity rates to T. gondii in immunocompromised (country divisions of provinces) patients from Iran (Region 1: Provinces of Tehran, Qazvin, Mazandaran, Semnan, Golestan, Alborz, Qom, Region 2: Provinces of Isfahan, Fars, Bushehr, Chaharmahal Bakhtiari, Hormozgan, Kohkiluyeh & Boyer-Ahmad, Region 3: Provinces of East Azerbaijan, West Azerbaijan, Ardabil, Zanjan, Guilan, Kurdistan, Region 4: Kermanshah, Ilam, Lorestan, Hamedan, Markazi, Khuzestan, Region 5: Provinces of Razavi Khorasan, South Khorasan, North Khorasan, Kerman, Yazd, Sistan & Baluchestan)

Publication bias

The funnel plots showed no publication bias, which was also confirmed from Egger’s test which revealed that publication bias might not have a significant influence on overall prevalence estimates.

Sensitivity tests

The sensitivity tests indicated that all single-study omitted estimates lay within the 95% CI of the respective overall effect. This suggested that the pooled effect was not substantially influenced by any single study. The stability of such results validated the rationality and reliability of our analysis.

Discussion

Considering the importance of toxoplasmosis in immunocompromised population, the present systematic review and meta-analysis was carried out. The overall seroprevalence of toxoplasmosis among Iranian immunocompromised patients from 2013 to 2022 was investigated, which demonstrated a noticeable seroprevalence of 45.1%. The prevalence is comparable with the similar previous meta-analysis in Iran among the same population from 1997 to 2013 (50.01%) (59). Given the global prevalence of T. gondii in immunocompromised individuals (35.9%) (60), new measurements are essential for better management of the disease in our country.

Our meta-analysis of 2565 HIV/AIDS patients in Iran showed that less than half (45.9%) of them were estimated to be seropositive for T. gondii, as the previous meta-analysis of published studies from 1997 to 2013 in Iran had reported a similar prevalence (50.05%), as well (59). However, considering global and regional studies, HIV/AIDS patients in North Africa and the Middle East have the highest seroprevalence (60.7%) among all other regions (61), with a pooled worldwide seroprevalence of 35.8 to 42.1% (60, 61). The lowest global seroprevalence of HIV positive individual co-infected with T. gondii was found in Asia and the Pacific (25.1%) (61). Included studies of the present review from north of Iran, for example Mazandaran and Tehran provinces, have reported co-infection of T. gondii and HIV as high as 96.3 and 88% (33, 52), while in the central and south Iran, 20.7 and 15.5% co-infection, were reported respectively (41, 44). Similarly, in previous studies in Iran, the highest prevalence of HIV and T. gondii co-infection was in Mazandaran (77.4%) and Tehran (65%) provinces and lowest prevalence (18.2%) was in Fars provinces (26,62,63). These studies support the fact that the seroprevalence of antibodies to T. gondii among patients with HIV/AIDS follows the regional patterns of seropositivity in the general population. Moreover, most of HIV/AIDS patients have been infected previously in sometime, probably before they become immunocompromised (7). This was depicted by our meta-analysis of 1889 HIV/AIDS patients tested for IgM anti-Toxoplasma antibody, a marker of acute infection. We showed that the majority of HIV/AIDS patients have been infected previously, while only a very small percentage of them (1.3%) were infected recently. Comparing to cancer patients and organ transplant recipients, HIV positive individual had the lowest positive IgM seroprevalence in our study.

Serological evidence of T. gondii infection among patients with all types of cancers is 26 to 30.8% worldwide (61, 64). However, our results of meta-analysis in Iran indicated that 43.6% of patients with cancer are seropositive for Toxoplasma, which is the lowest seroprevalence among the studied immunocompromised populations of the present study. Two previous meta-analysis in Iran reported 45% and 51% seroprevalence in these patients (59, 64). A number of studies have stated that patients with different cancers from similar geographic areas had significantly different seropositivity rates for toxoplasmosis. For instance, in a 2019 worldwide meta-analysis, positive serology for toxoplasmosis was as high as 81% in breast cancer patients, as compared to those with liver cancer (24.1%) (60). Similarly, in North Iran (Mazandaran), 88.24% of the patients with leukemia were seropositive for T. gondii, while patients with colon cancer showed 67.6% seropositivity (56). Therefore, it could be hypothesized that apart from regional and geographic patterns, the seroprevalence of Toxoplasma among cancerous patients may be affected by the patient’s immune system state, which is in turn determined by the type of cancer, its clinical stage and treatment regimens. By taking immune system-related factors as well as lifestyle and environmental risk factors into account, future studies may be able to estimate a more accurate seroprevalence and uncover possible risk factors in these patients. Interestingly, the prevalence of recently infected cancerous patients with Toxoplasma, which was assessed by the presence of IgM antibody, was higher than that of HIV/AIDS patients (3.1% vs. 1.3%). However, determining risk factors of this higher prevalence of acute infection among patients with cancer is difficult. Analysis of geographic distribution of IgM seroprevalence as well as age, sex, immune system state, dietary and environmental risk factors between HIV/AIDS and cancerous patients may be helpful, although the majority of the studies lack enough data regarding most of these variables.

Another group of immunocompromised patients is recipients of Hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT). Both of these scenarios place the patient at a great risk of toxoplasmosis, whether through reactivation of encysted parasites in a seropositive recipient after immunosuppression or graft transmission from a seropositive donor (65, 66). The global seroprevalence of toxoplasmosis in transplant patients is 42.1% (60). This prevalence was estimated to be 55.1% in Iran, by a meta-analysis of 702 patients from 1997 to 2013 (59). Our results from 2013 to 2022 showed 45.8% seropositivity for toxoplasmosis in Iranian transplant patients. Considering the infection source, HSCT recipients more commonly develop toxoplasmosis by reactivation of latent infection in their course of immunosuppression, while transmission through contaminated transplanted organ is primarily encountered in cases of SOT (65, 66).

By subgroup analysis of geographic areas, we demonstrated a widely regional variation in Toxoplasma seroprevalence. Due to better survival of the T. gondii oocytes in areas with lower altitudes, hot and humid climates (4), the highest IgG seroprevalence (61.2%) of the infection in immunocompromised population was seen in the North provinces (region 1) and the lowest one (20.6%) was observed in Central and South-Western provinces of Iran (region 2). Regarding the IgM seroprevalence, Western and Northeastern areas of Iran (region 4) have shown the highest seroprevalence. Since these prevalence rates reflect the general population seropositivity, the importance of environmental health promotion and educational measurements, especially in high prevalence areas, is highlighted.

This climate-dependent distribution of the infection, may at least in part be responsible for Iran’s higher seroprevalence for T. gondii (45.1%) in immunocompromised patients, compared to its worldwide seroprevalence (35.9%) (60). Aside from climate factors, another element, which possibly affected this geographical distribution and high prevalence of T. gondii in our country, is agriculture and animal husbandry (67). However regarding to this matter limited data are available and more investigations are required.

This meta-analysis has a number of limitations that could possibly affect the results of study. First, most of the identified studies lack important data regarding risk factors of toxoplasmosis. As an example, although demographic data such as age, sex, rural or urban residency and dietary and environmental risk factors have a dramatic effect on probability of getting infection, these factors were not investigated in the included studies. Thus, subgroup analysis based on these demographic data, except for geographic area, was not performed. Secondly, apart from the type of the cancer, its pathological grade and clinical stage, chemotherapy regimens and even radiotherapy may alter patient’s level of immunosuppression and hence affect greatly on the potential of the latent infection reactivation. Immunosuppressive drugs prescribed for transplant patients are also a relevant risk factor, which were missed in the identified studies. Finally, the gold standard in the diagnosis of toxoplasmosis is tissue biopsy and detection of the parasite under the microscope (68). However, the serological methods were the only tests to identify Toxoplasma infection in all of the included studies. Since antibody production in immunocompromised patients may be impaired (13), use of serological tests without clinical correlation and pathological studies, may underestimate the actual prevalence of toxoplasmosis in immunocompromised patients. Future studies should consider clinical and para-clinical parameters, as well as serological investigations.

Conclusion

The high seroprevalence of toxoplasmosis among immunocompromised patients necessitates routine and appropriate serological and clinical assessment, with provision of proper prophylaxis and treatments. Acute infection is relatively uncommon among immunocompromised patients and the geographic distribution of toxoplasmosis seroprevalence in these patients matches that of the general population. Thus, health improvement and education toward prevention of toxoplasmosis is of great importance.

Acknowledgments

We express gratitude to Tehran University of Medical Sciences for provision of free access to research databases and internet service.

Footnotes

Conflicts of interest

Non-declared

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