Seroprevalence of Toxoplasma gondii in the Iranian general population: a systematic review and meta-analysis.

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Contents lists available at ScienceDirect

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Review

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Seroprevalence of Toxoplasma gondii in the Iranian general population: A systematic review and meta-analysis夽

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Ahmad Daryani a , Shahabeddin Sarvi a,∗ , Mohsen Aarabi b , Azadeh Mizani c , Ehsan Ahmadpour c , Azar Shokri c , Mohammad-Taghi Rahimi c , Mehdi Sharif a a

Toxoplasmosis Research Center, Mazandaran University of Medical Science, Sari, Iran Health Science Research Center, Mazandaran University of Medical Science, Sari, Iran c Parasitology and Mycology Department, Sari Medical School, Mazandaran University of Medical Science, Sari, Iran b

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a r t i c l e

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a b s t r a c t

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Article history: Received 8 November 2013 Received in revised form 17 May 2014 Accepted 25 May 2014 Available online xxx

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Keywords: Toxoplasma infection Toxoplasma gondii Iran General population Systematic review Meta-analysis

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Contents

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1. 2.

Toxoplasma gondii is one of the most common protozoan parasites with widespread distribution globally. It is the causative agent of Toxoplasma infection, which is prevalent in human and other warm-blooded vertebrates. While T. gondii infection in healthy people is usually asymptomatic, it can lead to serious pathological effects in congenital cases and immunodeficient patients. We sought to identify the seroprevalence rate of Toxoplasma infection in the Iranian general population to develop a comprehensive description of the disease condition in Iran for future use. Electronic databases (PubMed, Google Scholar, Science Direct, and Scopus) and Persian language databases (Magiran, Scientific Information Database [SID], Iran Medex, and Iran Doc) were searched. Furthermore, graduate student dissertations and proceedings of national parasitology congresses were searched manually. Our search resulted in a total of 35 reports published from 1978 to 2012.These include 22 published articles, 1 unpublished study, 8 proceedings from the Iranian conference of parasitology, and 4 graduate student dissertations, resulting in 52,294 individuals and 23,385 IgG seropositive cases. The random errors method was used for this meta-analysis. The result shows that the overall seroprevalence rate of toxoplasmos is among the general population in Iran was 39.3% (95% CI = 33.0%–45.7%). There was no significant difference in the seroprevalence rate between male and female patients. A significant linear trend of increasing overall prevalence by age was noted (P < 0.0001). In addition, the data indicates that there are high seroprevalence in groups who have direct contact with cats, consume uncooked meat and raw fruits or vegetables, in farmers and Housewife, individuals who have a low level of education, and live in rural areas. To the best of our knowledge, this is the first systematic review of T. gondii infection seroprevalence in Iran, which shows a high prevalence of Toxoplasma infection (more than one third). We highly recommend further study for the purposes of aiding patient management and developing more efficient diagnostic tests and effective prevention approaches. © 2014 Published by Elsevier B.V.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Data extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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夽 This article is the first systematic review and meta-analysis of Toxoplasma seroprevalence and its related risk factors in Iranian general population. ∗ Corresponding author at: Toxoplasmosis Research Center, Mazandaran University of Medical Science, PC 48168-95475, Sari, Iran. Tel.: +98 151 3241031; fax: +98 151 3543249. E-mail addresses: [email protected] (A. Daryani), [email protected] (S. Sarvi), mohsen [email protected] (M. Aarabi), a mizani [email protected] (A. Mizani), [email protected] (E. Ahmadpour), Azar [email protected] (A. Shokri), [email protected] (M.-T. Rahimi), [email protected] (M. Sharif). http://dx.doi.org/10.1016/j.actatropica.2014.05.015 0001-706X/© 2014 Published by Elsevier B.V.

Please cite this article in press as: Daryani, A., et al., Seroprevalence of Toxoplasma gondii in the Iranian general population: A systematic review and meta-analysis. Acta Trop. (2014), http://dx.doi.org/10.1016/j.actatropica.2014.05.015

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Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction

Toxoplasma gondii is a cosmopolitan obligate intercellular pro35Q2 tozoan parasite that can infect humans and a wide range of animals 36 (Garcia and Bruckner, 1997). Seroprevalence of Toxoplasma infec37 tion widely varies between 30% and 60%in both developed and 38 developing countries (Flegr et al., 2003). Human T. gondii infection 39 is one of the most important public health problems that affects 40 one-third of the human population (Tenter et al., 2000; Miller et al., 41 1972). Humans acquire the infection by either accidental ingestion 42 of contaminated food, water, or soil contaminated with oocysts 43 from a cat’s feces, or eating raw meat contaminated with tissue 44 cysts (Fayer et al., 2004). 45 Although most cases of Toxoplasma infection in healthy indi46 viduals are asymptomatic or mild, exposure to T. gondii during 47 pregnancy can lead to vertical transmission to the embryo result48 ing in serious pathological complications such as hydrocephalus, 49 microcephaly, blindness, spontaneous abortion, and fetal death. 50 Antibody screening in pregnant women and non-immune girls of 34

9,256 Papers from 8 databases (Pubmed, Google Scholar, Science Direct, Scopus, Maggiran, SID, Iran Doc and IranMedex) were identified.

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childbearing age can help in the control and prevention of congenital disease (Montoya et al., 2010; Boyer et al., 2004; Lindst¨roma et al., 2006). Given the increasing number of immunocompromised individuals such as HIV positive patients, cancer patients, and organ transplant recipients, T. gondii as an opportunistic parasite can lead to life-threatening conditions for those patients (Brinkman et al., 1998; Goebel et al., 2007; Singh et al., 1996).Moreover, after congenital infection, acute disease, reactivation, and ocular infection can occur (Montoya and Liesenfeld, 2004). Q3 Certain factors such as parasite strain and virulence, number of ingested organisms, immunity status, sex, and genetic background of the host are crucially important in the progress of infection (Montoya and Liesenfeld, 2004). In addition, Toxoplasma infection has serious socioeconomic effects on humans. Families incur many costs while caring for sick children, especially those with mental retardation and blindness (Roberts and Frenkel, 1990; Roberts et al., 1994). In Iran, most of the studies on T. gondii have focused on highrisk groups such as pregnant women, premarital women, neonates,

Proceedings of Iranian parasitology congresses and graduate student dissertations were searched manually.

9,234studies which not dealing with seroprevalence of toxoplasmosis in general population and duplicate paperswere excluded. 8 parasitology congress articles, 4 graduate student dissertations and 1 unpublished paper were added. 22 studies were selected based on topics.

Finally35 articles which met our eligibility criteria were approved in the current review and meta-analysis. Fig. 1. Flow diagram describing the study design process.


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Table 1 Baseline characteristics of included studies. Province

Total individuals

IgG positive Cases

Seroprevalence %

Reference

Fars Around Caspian sea West Azerbaijan/Khuzestan Tehran Fars Khuzestan Fars Hamedan Gilan 12 province Isfahan Khuzestan Khuzestan Gilan Alborz Markazi Kerman Ardebil Kermanshah Fars Golestan Tehran Mazandaran Isfahan Tehran Tehran Isfahan East Azerbaijan East Azerbaijan Chaharmahal va Bakhtiyari Isfahan/Mazandaran Sistan va Baluchestan Tehran Khorasan Razavi Mazandaran

300 1770 3370 4792 1804 2902 225 917 400 13,018 2080 2364 600 975 2017 1299 690 909 1837 87 1250 1552 600 120 1187 180 599 200 171 990 160 182 119 787 1832

88 991 432 3150 715 1688 48 375 170 6743 1057 277 191 841 917 459 324 166 668 24 175 606 190 35 812 61 248 82 60 339 111 37 43 240 1018

29 55.7 12.8 65.7 36.9 60.95 21.3 41.3 42.5 51.8 50.8 12 31.9 86.3 45.5 35.3 46.9 18.3 36.3 27.6 14 39 31.66 29.16 68.4 33.9 41.4 41 35.1 34.2 51.25/87.5 22.7 36 31.6 55.5

Sedaghat et al. (1979) Ghorbani et al. (1979) Ghorbani et al. (1981) Hafizi et al. (1990) Sarkari et al. (1992) Hoghooghi-Rad and Afraa (1993) Shad-Del and GhaffariSarvestani (1993) Shahmoradi et al. (1995) Reza-Zadeh (1996) Assmar et al. (1997) Arbabi et al. (1997) Amir-Zargar (1997) Amin-Zadeh and Asmar (1997) Shahmoradi et al. (1998) Keshavarz-Valian et al. (1998) Chegini et al. (1998) Keshavarz-Valian et al. (2000) Sultan-Mohammad-zadeh et al. (2003) Mansoori et al. (2003) Razavi et al. (2003) Dehbashi (2003) Keshavarz et al. (2004) Dehgani et al. (2008) Torkan et al. (2008) Salahi-Moghadam and Hafizi (2009) Abbasian et al. (2010) Mostafavi et al. (2011) Davoodi et al. (2012) Jafari et al. (2012) Manouchehri-Naeini et al. (2012) Pirali-Kheirabadi et al. (2012) Etemadi et al. (2012) Mohammad-Ali Gol and Neyeb-Zadeh (2012) Shamsian et al. (2012) Sharif and Daryani (2011)

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and children. Presently there is little information on the seroprevalence of T. gondii infection in the general population. Therefore, the objective of this systematic review and meta-analysis was to review papers on human Toxoplasma infection in order to estimate the prevalence of this parasite in the Iranian general population and to evaluate risk factors associated with infection.

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2. Methods

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2.1. Search strategy

70 71 72 73 74

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Four English language databases (PubMed, Science Direct, Scopus, and Google Scholar) and four Persian databases (Magiran, Scientific Information Database, Iran Medex, and Iran Doc) were searched for articles published from 1978 to 2013. All scientific publications with T. gondii infection were sought (full texts, abstracts, national conference proceedings, and graduate student dissertations). Fig. 1 illustrates the search process. Search terms included were “toxoplasmosis”, “Toxoplasma gondii”, “T. gondii”, “Iran”, “Islamic Republic of Iran”, “general population”, and “seroprevalence”. The search was restricted to English and Persian language articles.

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2.2. Study selection

78 79 80 81 82 83 84 85 86 87

90 91 92 93 94 95 96

Cross-sectional studies that estimated the seroprevalence of T. gondii infection in the Iran general population were included in this review. The criteria for diagnosis of T. gondii infection were based on serological methods. All identified studies from the searches were independently assessed for eligibility and inclusion by 2 different authors. Discrepancies were resolved by discussion and consensus. In

addition to duplications, studies with non-random sampling methods and those with specific populations (pregnant women, HIV-positive individuals, and immunocompromised patients) were also excluded. 2.3. Data extraction Papers marked for inclusion were investigated carefully and information regarding the year of publication, first author, study location, total sample size, number of male and female participants, number of subjects with positive test results, age distribution, and T. gondii diagnostic methods were extracted using a data extraction form. Information on risk factors such as cat contact, raw meat, fruit or vegetable consumption, fruit and vegetable washing methods, occupational group, place of residence, and education level was also collected. 2.4. Statistical analysis Point estimates and their 95% confidence intervals (CI) of seroprevalence of all included studies were calculated. An overall seroprevalence and group-specific seroprevalence were calculated by age groups (0–19, 20–30, and ≥40 years), gender (male and female), and geographical region. A forest plot was used to visualize the heterogeneity among the studies. The heterogeneity was expected in advance, and statistical methods, I2 and Cochrane Q statistics (P-value < 0.1) were used to quantify the variations. For the purpose of meta-analysis, we assumed that the included studies were a random sample from a population of studies, and thus a random effects model was employed. Forest plots presented proportions of individual studies and overall seroprevalence. The meta-analysis was performed with the trial version of StatsDirect statistical software (www.statsdirect.com).


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Sedagat- 1978-Fars-IFA

0.29 (0.24, 0.35)

Ghorbani-1978- Around caspian sea- IFA

0.56 (0.53, 0.58)

Gorbani- 1981 - Azerbaijan and khuzestan- IFA

0.13 (0.12, 0.14)

Hafizi- 1990- Tehran- IFA

0.66 (0.64, 0.67)

Sarkari- 1991- Fars- IFA

0.40 (0.37, 0.42)

Hoghooghirad- 1993- Khuzestan- IFA

0.58 (0.56, 0.60)

Shad- Del- 1993- Fars- IFA

0.21 (0.16, 0.27)

Shahmoradi- 1995- Hamedan- IFA

0.41 (0.38, 0.45)

Reza Zadeh- 1996- Gil an- IFA

0.43 (0.38, 0.48)

Asmar - 1997- 12 Provinces- IFA

0.52 (0.51, 0.53)

Arbabi- 1997- Isfahan- IFA

0.51 (0.49, 0.53)

Amir Zar gar- 1997- Khuzestan- IFA

0.12 (0.10, 0.13)

Amin Zadeh- 1997- khuzestan- ELISA

0.32 (0.28, 0.36)

Shahmoradi- 1998- Gilan- IFA

0.86 (0.84, 0.88)

Keshavarz- 1998- Alborz- IFA

0.45 (0.43, 0.48)

Chegini- 2001- Markazi- IFA

0.35 (0.33, 0.38)

Keshavarz-2001- Kerman- IFA

0.47 (0.43, 0.51)

Soltanmohammad Zadeh- 2003- Ardebil- IFA

0.18 (0.16, 0.21)

Mansouri- 2003- Kermanshah- ELISA

0.36 (0.34, 0.39)

Razavi- 2003- Fars- IFA

0.28 (0.19, 0.38)

Dehbashi- 2003- Gorgan- IFA

0.14 (0.12, 0.16)

Keshavarz- 2004- Tehr an- IFA

0.39 (0.37, 0.42)

Dehguni - 2008- Mazandaran- IFA

0.32 (0.28, 0.36)

Torkan- 2008- Isfahan- ELISA

0.29 (0.21, 0.38)

Salahi -Moghaddam- 2009- Tehran- IFA

0.68 (0.66, 0.71)

Abbasiyan- 2010- Tehran- ELISA

0.34 (0.27, 0.41)

Pirali kheir Abadi- 2010- Isfahan- Mazandaran- ELI

0.69 (0.62, 0.76)

Mostafavi- 2011- Isfahan- ELISA

0.41 (0.37, 0.45)

Davoodi- 2012- East Azerbaijan- CLIA

0.41 (0.34, 0.48)

Jafari- 2012- East Azer baijan- ELISA

0.35 (0.28, 0.43)

Manoochehri- 2012- Chaharmahal and Bakhtiyari- 201

0.34 (0.31, 0.37)

Shamsiyan- 2012- Razavi Khorasan- ELISA

0.30 (0.27, 0.34)

Etemadi- 2012- Sistan and Baluchestan- ELISA

0.20 (0.15, 0.27)

Mohammad Ali Gol- 2012- Tehran- IFA

0.36 (0.28, 0.45)

Sharif(Unpublished)- 2012- Mazandaran- ELISA

0.56 (0.53, 0.58)

combined

0.39 (0.33, 0.46) 0.0

0.3

0.6

0.9

propor tion (95% confidence interval) Fig. 2. Forest plot diagram of 35 studies showing IgG seropositivity rates of Toxoplasma infection in Iranian general population (first author, year and province of study and laboratory method).

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3. Results Out of 9256 studies from the literature search, 35 records were eligible for inclusion in the systematic review and meta-analysis. Table 1 shows the results of the literature search. In total, 52,294

individuals and 23,385 IgG seropositive cases were included for meta-analysis. There was a wide variation in the seroprevalence estimates among the different studies, and the Q statistic was very large (Q = 7319.1, df = 34, P < 0.0001; I2 = 99.5%). The pooled


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Fig. 3. Seroprevalence of Toxoplasma infection in Iranian general population in different provinces according to IgG antibody seropositivity.

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seroprevalence of T. gondii infection among the Iranian general population using the random-effects model meta-analysis was 39.3% (95% CI = 33.0%–45.7%). The forest plot diagram of this review is shown in Fig. 2. Three different serological diagnostic tests were used in the included studies. The number of papers utilizing indirect fluorescent antibody test (IFA), enzyme-linked immunosorbent assay (ELISA), and chemiluminescence enzyme immuno assay (CLIA)were 23, 11, and 1, respectively (Table 3). Results of the meta-analysis showed that male and female patients had similar seroprevalence rates (44% versus 42%, respectively; P > 0.05). Considering age, IgG seropositive rate in the age groups of 0–19, 20–39, and ≥40 years were 29%, 44%, and 55%, respectively (P < 0.0001). The peak prevalence was seen in the ≥40 years age group. The prevalence of T. gondii infection was significantly higher among individuals who had direct contact with cats; individuals who consume raw meat, fruits, or vegetables; individuals with a low level of education; farmers; and housewives (Table 2). The seropositivity rate of T. gondii in several provinces is shown in Fig. 3. Infection was more common in warmer climates than in mountainous and colder regions. It was also more common in humid climates than in more arid climates.

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4. Discussion

135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156

159 160 161 162 163 164 165 166 167 168 169 170 171

It is crucially important to understand the status of Toxoplasma infection in the general population. This systematic review and meta-analysis estimates the seroprevalence of T. gondii infection rate in the Iranian general population, using the documented data from the literature review, which have been collected from different provinces. This study was conducted using 8 databases, 35 records, 52,294 individuals, and 23,385 IgG seropositive cases. Our results show that the seroprevalence of Toxoplasma infection in Iran is 39%. While Latin America, Central and Eastern Europe, and Southeast Asia have the highest seroprevalence of T. gondii infection (75%–85%), North America and Northern Europe report low seropositivity rates of T. gondii (Ruiz Fons et al., 2006; Bobic et al., 1998; Song et al., 2005;

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Jones et al., 2003; Cunningham et al., 1997). In our neighboring countries, Pakistan and Qatar, the overall seroprevalence rate of infection were found to be 29.45% and 29.8%, respectively (Tasawar et al., 2012; Abu-Madi et al., 2008). In China and India, seroprevalence estimates were 12.5% and 30.9%, respectively (Xiao et al., 2010; Meisheri et al., 1997). In the Mexican general population, the seroprevalence of T. gondii infection was found to be 20.26% (95%CI = 18.78%–19.36%), lower than that in the Iranian population (Galvan-Ramirez et al., 2012). Global Toxoplasma infection variations and disease distribution have been associated with various risk factors. These risk factors include geographical climate, abundance of cats (and sometimes other pets), nutritional behavior (consumption of uncooked meat, raw vegetables, and contaminated drinking water) and location of residence (El-Deeba et al., 2012). Although any of these risk factors on their own may have little effect on the epidemiological situation, together they can change the epidemiologic pattern of disease in different regions. One of the main variables is geographical climate. Although Iran has an arid climate, the weather condition is subject to variability. Some provinces such as Tehran, Kerman, Khuzestan, and Fars have climates that vary widely due to geographic location and elevation. Epidemiologic investigation in these provinces and territories is much more difficult to carry out. Our study results reveal that there is a high prevalence rate of Toxoplasma infection (54%)in the Northern part of Iran (near the Caspian Sea), which has high humidity. In contrast, cold mountainous provinces (e.g., Ardebil) and hot provinces (e.g., Sistan va Baluchestan) were found to have lower seropositivity rates of 18.3% and 22.8%, respectively. This situation may depend upon the appropriate conditions for sporulation and oocysts survival in the environment. Oocysts maturation and transmission to a new host is more rapid at mild and wet climates (Dubey and Beattie, 1988). Presently in metropolitan cities such as Tehran, migration from rural regions to urban areas occurs as a result of the favorable economic and financial situation. In emigrants who have been exposed to the disease, IgG antibody titers persist throughout the remainder of one’s life that lead to a more complicated interpretation. Abundance of cats is the second variable that can affect T. gondii infection distribution in many regions. Domestic cats are one of the major sources of infection. They can excrete millions of oocysts after ingestion of even 1bradyzoite or 1 tissue cyst (Hill and Dubey, 2002; Dubey and Frenkel, 1972; Dubey, 2001). Sporulated oocysts can survive for months and even for years in moist soil. On the other hand, earthworms, beetles, and flies can spread oocysts from the soil and transmit it to food. With regards to oocysts abundance in the environment, prey animals may become infected, which could be lead to increased infection among cats (Dubey and Beattie, 1988). In our study, seroprevalence of toxoplasmosis in individuals keeping cats in the house was higher than that in individuals who did not house cats. The condition of cat maintenance within ahouse such as feeding behavior, place of keeping cat (indoor or outdoor), medical surveillance for the presence of Toxoplasma infection or other diseases, and good handling and disposal of cats fecal material should be considered. In urban areas, cats and other pets can be kept inside houses or flats, and fed dry, canned, and cooked meat with continuous medical surveillance. Cat owners can also remove pet feces from the residence daily, and prevent their pets from hunting. In rural areas, cats and other pets roam in and out houses and farms easily. They may be infected with tissue cysts during the hunting of small mammals. Cats may shed a large amount of oocysts via feces indoors and outdoors. Water, gardens, farms, and food may be contaminated with cats’ oocysts; hence, cat owners and other animals may be at risk. Our study data indicate that the prevalence rate of T. gondii is different among various occupational groups. Certain occupations have more contact than others with Toxoplasma, either directly


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Table 2 Risk factors associated to seropositivity for Toxoplasma gondii in Iranian general population. Demographic factors

Total individuals

Positive cases

Overall prevalence (%)

Sexes

Male Female Age

7143 11,519

0–19 y 20–29 y ≥40 y Contact with cat

6591 5606 2278

Yes No Raw meat consumption

1423 3416

Yes No Raw vegetable/fruit consumption

3061 2181

Yes No Washing vegetable/fruit

3415 389

Water Detergent Residence

903 441

2619 5119

1843 2700 1292

717 1837

1876 999

1385 121

637 309

P-value

References

P > 0.05

Sedaghat et al. (1978), Ghorbani et al. (1981), Reza-Zadeh (1996), Shahmoradi et al. (1998), Keshavarz et al. (1999), Chegini et al. (2001), Keshavarz et al. (2001), Mansoori et al. (2003), Razavi et al. (2003), Arbabi et al. (2007), Dehgani et al. (2008), Torkan et al. (2008), Salahi-Moghadam and Hafizi (2009), Mostafavi et al. (2011), Pirali-Kheirabadi et al. (2012), Manouchehri-Naeini et al. (2012), Mohammad-Ali Gol and Neyeb-Zadeh (2012), Sharif and Daryani (2011)

P < 0.0001

Ghorbani et al. (1978), Ghorbani et al. (1981), Shahmoradi et al. (1998), Keshavarz et al. (1999), Sultan-Mohammad-zadeh et al. (2003), Mansoori et al. (2003), Razavi et al. (2003), Dehgani et al. (2008), Torkan et al. (2008), Salahi-Moghadam and Hafizi (2009), Mostafavi et al. (2011), Manouchehri-Naeini et al. (2012), Sharif and Daryani (2011)

P < 0.05

Shahmoradi et al. (1998), Keshavarz et al. (1999), Razavi et al. (2003), Dehgani et al. (2008), Jafari et al. (2012), Manouchehri-Naeini et al. (2012)

P < 0.0001

Shahmoradi et al. (1998), Keshavarz et al. (1999), Arbabi et al. (2007), Jafari et al. (2012)

P < 0.05

Keshavarz et al. (1999), Dehgani et al. (2008), Jafari et al. (2012), Manouchehri-Naeini et al. (2012)

P > 0.05

Shahmoradi et al. (1998), Davoodi et al. (2012), Jafari et al. (2012)

44.08 (95% CI = 34.5–53.9) 42.06(95% CI = 32.04–52)

29 (95% CI = 17.3–42.4) 44.2 (95% CI = 33.1–55.6) 55.4 (95% CI = 39.7–70.6)

49.4 (95% CI = 34.7–64.1) 44.1 (95% CI = 23.6–65.7)

58 (95% CI = 35.7–78.8) 49.5 (95% CI = 36.4–62.7)

38.6 (95% CI = 31–46.4) 31.2 (95% CI = 26.7–35.9)

58.2 (95% CI = 24.9–87.7) 52.4 (95% CI = 0.93–93.3) Chegini et al. (2001), Dehgani et al. (2008), Davoodi et al. (2012), Mostafavi et al. (2011), Manouchehri-Naeini et al. (2012)

Urban Rural Educational

2011 1675

Primary school Junior high school Senior high school University Illiterate Occupational group

2832 911 1545 1142 2056

Unemployed Employee Self-employment Housewife Student Farmer Worker

347 987 891 4499 1893 331 224

726 592

1297 458 744 482 1040

128 455 416 2342 542 180 114

34.8 (95% CI = 29.2–40) 41.9 (95% CI = 32.7–51.4)

P > 0.05 p < 0.0001

Shahmoradi et al. (1998), Keshavarz et al. (1999), Chegini et al. (2001), Arbabi et al. (2007), Dehgani et al. (2008), Mostafavi et al. (2011), Davoodi et al. (2012), Manouchehri-Naeini et al. (2012)

p < 0.0001

Shahmoradi et al. (1998), Keshavarz et al. (1999), Sultan-Mohammad-zadeh et al. (2003), Mansoori et al. (2003), Arbabi et al. (2007), Dehgani et al. (2008), Davoodi et al. (2012), Manouchehri-Naeini et al. (2012)

47.7 (95% CI = 37–58.5) 52.4 (95% CI = 30.8–73.5) 47.7 (95% CI = 32–63.6) 42.1 (95% CI = 30.6–54.1) 53.8 (95% CI = 38.6–68.6)

36.9 (95% CI = 31.9–42) 42.5 (95% CI = 29.5–56) 46.8 (95% CI = 32.2–61.8) 49.5 (95% CI = 36.1–63) 31.9 (95% CI = 19.5–45.8) 52.8 (95% CI = 36.2–69) 46.7 (95% CI = 40.5–52.9)




7

Table 3 Diagnostic methods.

238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269

Authors

Method

Cut off value (antibody titer)

Kit/manual

Sedaghat et al. (1979) Ghorbani (1979) Ghorbani (1981) Hafizi (1990) Sarkari (1992) Hoghooghi-Rad and Afraa (1993) Shad-Del and GhaffariSarvestani (1993) Shahmoradi et al. (1995) Reza-Zadeh (1996) Assmar et al. (1997) Arbabi et al. (1997) Amir-Zargar (1997) Amin-Zadeh and Asmar (1997) Shahmoradi et al. (1998) Keshavarz-Valian et al. (1998) Chegini (1998) Keshavarz-Valian et al. (2000) Sultan-Mohammad-zadeh et al. (2003) Mansoori et al. (2003) Razavi et al. (2003) Dehbashi (2003) Keshavarz et al. (2004) Dehgani et al. (2008) Torkan et al. (2008) Salahi-Moghadam and Hafizi (2009) Abbasian et al. (2010) Mostafavi et al. (2011) Davoodi et al. (2012) Jafari et al. (2012) Manouchehri-Naeini et al. (2012) Pirali-Kheirabadi et al. (2012) Etemadi et al. (2012) Mohammad-Ali Gol and Neyeb-Zadeh (2012) Shamsian et al. (2012) Sharif and Daryani (2011)

IFA IFA IFA IFA IFA IFA IFA IFA IFA IFA IFA IFA ELISA IFA IFA IFA IFA IFA ELISA IFA IFA IFA IFA ELISA IFA ELISA ELISA CLIA ELISA ELISA ELISA ELISA IFA ELISA ELISA

≥1:16 ≥1:20 ≥1:20 ≥1:20 ≥1:20 ≥1:20 1:64–1:1024 ≥1:20 ≥1:20 ≥1:20 ≥1:20 ≥1:20 >50 IU/ml ≥1:20 ≥1:20 ≥1:20 ≥1:16 ≥1:20 >1.1 IU/ml ≥1:16 ≥1:20 ≥1:20 ≥1:20

Manual Manual Manual Manual Manual Manual Manual Manual Manual Manual Manual Manual Kit Manual Manual Manual Manual Manual Kit Manual Manual Manual Manual Toxoplasma IgG/IgM ELA Manual Kit Dia-Pro, Milan, Italy Diasorin, USA Euro-immune, Germany DIA Pro Diagnostic Bioprobes, Srl, Italy Kit Kit Manual Viroimmune Euro Immune, Germany

or indirectly. The data reveals that housewives and farmers are 2 groups with high seroprevalence of T. gondii in Iran. Our results are compatible to those of studies done in Saudi Arabia and the United States, which indicate a high prevalence in those groups (Al-Qurashi, 2004; Al-Qurashi et al., 2001; Jones et al., 2001). Traditionally, housewives take care of pets, spend more time cooking at home, handle and chop meat without wearing gloves, taste uncooked meat during meal preparation, clean vegetables, and engage in gardening, especially in some rural regions. Farmers are the second highest occupational risk group of T. gondii infection. Oocysts can easily be dispersed via rain, water, and wind in environments such as farms. Livestock are infected via straw or hay contaminated with cat feces, and farmers may come in contact with T. gondii during the daily activities involving these fomites. Exposure to contaminated soil through gardening is another route of infection for farmers. In Iran, published data reveal that by increasing the level of education, Toxoplasma seroprevalence can be reduced; Jones et al. (2001) and Moschen et al. (1991) show the same results. While the highest seroprevalence are observed in illiterate group, people with academic education show lower seroprevalence. The authors suggest that the high prevalence rate among this group mainly depends on their socioeconomic activities. Lack of awareness of disease as a source of infection, as well as hygiene, route of transmission, and ignorance of the disease are important factors in the risk of infection. Actually, one of the most important sources of Toxoplasma infection is the consumption of meat from domestic animals that contain tissue cysts. Transmission of T. gondii via meat depends on nutritional and cultural habits of people in special regions or countries (Tenter et al., 2000; Dubey and Jones, 2008). While in Europe, America (Tenter et al., 2000), and some parts of Asia, pork is the major

≥1:10 >11 IU/ml IgG > 8.8 IU/ml IgM > 8 IU/ml >11 IU/ml >50 IU/ml

≥1:20 >10% >15.95 IU/ml

source of infection, because of religious beliefs predominant in Iran, eating animals such as pig, dog, rabbit, and horse is forbidden. In contrast, consumption of lamb, beef, birds, and fish is common in Iran. Our study results show that there is a high seropositivity rate in the group that consumes raw meat or vegetables. Meat is the main ingredient in almost all kinds of Iranian foods; thus, consumption of undercooked meats is a major source of Toxoplasma transmission. Eating meat products such as sausages, due to their special preparation process, serves as another route of disease transmission. On the other hand, consumption of raw fruits and vegetables contaminated with T. gondii oocysts can lead to infection. The seropositivity rate of T. gondii infections in the group that consumed raw vegetables was higher than that in other group. Our data show that Toxoplasma seroprevalence in villagers was higher than that in people living in cities. However, because of the nature and habits of their lifestyle (contact with soil, livestock, pets, etc.), a high seroprevalence of T. gondii in people in rural areas are predictable. The prevalence of infection varies by age and gender. Seroprevalence tended to increase with age. Fan et al. (2007) showed that the older age group (≥45 years) had significantly higher seroprevalence (80%) than the younger age group (20%). Our findings reveal that serological positive cases increase with age too. IgG positivity is predominantly observed in the older age group ≥40 years (55%) than the younger age groups 0–19 years (29%) and 20–39 years (44%). Other studies reported similar results (Shin et al., 2009; AlvaradoEsquivel et al., 2011). The reason why seroprevalence rate is higher in older age groups is not clear yet, but it might be due to their longer exposure to the risk factors and one of the transmission routes. The data revealed that the seroprevalence rate is a little higher in male (44%) than in female (42%) individuals. However, there


270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301

G Model ACTROP 3386 1–10 8 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367


is no significant difference in Toxoplasma seroprevalence between the two sexes. Lee et al. (2000) indicated that the positive rate in women (7.2%) was slightly higher than that in men (6%), but the difference was not significant. Serological methods for the detection of T. gondii humoral antibodies include the Sabin–Feldman test (SFT), IFA, the direct agglutination test (DAT), the latex agglutination test (LAT), ELISA, the immunosorbent agglutination assay test (ISAGA), and the IgG avidity test (Montaya et al., 2005; Moghazy et al., 2011; Zhu et al., 2012). Between 1978 and 2009 in Iran, the most common method used for T. gondii detection was IFA. Although the latter test is safe, inexpensive, and manageable, ultraviolet light microscopy is necessary (Roman et al., 2005; Araujo et al., 1971). From 2010 until present, ELISA has been used in epidemiologic surveys for the screening of T. gondii infection. As ELISA is a quantitative, inexpensive, and sensitive method (Moghazy et al., 2011), it is used widely in epidemiological studies and screening of T. gondii antibodies in Iran. Although CLIA is an automated method that performs in a short period of time, it is not a routine method used in either private or public laboratories in Iran (Gharavi et al., 2008). Our data revealed that IFA and ELISA techniques are the most common used tests for seroepidemiological studies. Although IFA method was performed manually, ELISA used as commercially. Table 3 summarizes the cut off value of each test in several studies that are in different variety. Albeit, sensitivity and specificity for ELISA were between 98 and 100%, they have not been determined for IFA. Most of the epidemiological surveys in Iran are based on IgG titers. IgG antibody positive titers can be detected in 2–3 weeks after infection, reaching a maximum titer within 2 months. It then declines to a baseline level that persists throughout the remainder of one’s life. In contrast, IgM titers appear within a few days after infection and reach a maximum level within 4 weeks. It is necessary to detect both the IgG and IgM antibodies at the same time to establish chronic or acute phase of infection (Meisheri et al., 1997). Our findings show heterogeneity across the studies as illustrated by the forest plot. Differences in sample size, sensitivity and specificity of laboratory methods, nutritional habits, and regional climate conditions can cause this heterogeneity. Prevention and control of this disease depend on sufficient information about its epidemiology (Moghazy et al., 2011). Awareness of Toxoplasma seroprevalence, risk factors, disease complications, and prevention methods could lead to effective incidence reduction (Rieman, 1974; Schnurrenberger et al., 1964; McCulloch et al., 1963). This systematic review has certain limitations. Little is known about the seroepidemiology of T. gondii in the general population of Iran. The major limitations include: (1) absence of studies in certain regions of Iran, (2) different methods without similar sensitivities and specificities, and (3) the heterogeneous epidemiological results of the available data. The above-mentioned points affect the overall seroprevalence rate in our study. These skewed factors might have biased the overall estimate of Toxoplasma infection in the Iranian general population. For instance, use of various laboratory methods with different sensitivities and specificities has a high impact on the results of these studies. Therefore, we propose to design a reliable test with high sensitivity and specificity in order to achieve accurate results in various surveys in our county. For analysis of the epidemiological pattern of disease in this group, it is necessary to know the seroepidemiology of the parasite in all parts of the country. In addition, some studies fail to evaluate some of the risk factors discussed above. In conclusion, to the best of our understanding, this is the first systematic review and meta-analysis that provides a comprehensive view of the seroepidemiology of T. gondii in the Iranian general population. More than one third of Iranian people have been infected with T. gondii. Therefore, two thirds of the population

is seronegative and thus susceptible to infection. As such, individuals at high risk should be monitored. There are several actions that will aid in the prevention and control of T. gondii infection. These include promotion of public educational programs, governmental inspection of food production industries, improvement of hygienic standards of abattoirs, and establishment of screening programs. It is necessary for the Ministry of Health to implement a screening program in all provinces using standardized methods to estimate the real prevalence of T. gondii infection and determine its risk factors in Iran. Uncited reference

368 369 370 371 372 373 374 375 376 377

Q4

Chegini et al. (2011). Acknowledgments We would like to thank Dr. Hamid Badali for improving the use of English in the paper and Dr. Hajar Ziaee for helpful comments on the manuscript. References Abbasian, L., Ranhbaran, M., Talebi-Meymand, F., Arab-Salmani, F., 2010. Survey on toxoplasmosis effect on patients referred to health centers of Tehran according to height and weight. In: Proceeding of the 7th National and 2end regional congress of parasitology and parasitic disease in Iran. Tehran University of Medical Science. Abu-Madi, M.A., Al-Molawi, N., Behnke, J.M., 2008. Seroprevalence and epidemiological correlates of Toxoplasma gondii infections among patients referred for hospital-based serological testing in Doha, Qatar. Parasites Vectors 1, 39. Al-Qurashi, A.R., 2004. Seroepidemiological study of toxoplasmosis in rural areas in the eastern region of Saudi Arabia. J. Egypt. Soc. Parasitol. 34, 23–34. Al-Qurashi, A.R., Ghandour, A.M., Obeid, O.E., Al-Mulhim, A., Makki, S.M., 2001. Seroepidemiological study of Toxoplasma gondii infection in the human population in the Eastern Region. Saudi Med. J. 22, 13–18. ˜ M., Alvarado-Esquivel, C., Estrada-Martínez, S., Pizarro-Villalobos, H., Arce Quinones, Liesenfeld, O., Dubey, J.P., 2011. Seroepidemiology of Toxoplasma gondii infection in general population in a Northern Mexican City. J. Parasitol. 97, 40–43. Amin-Zadeh, S., Asmar, M., 1997. A seroepidemiological survey of toxoplasmosis in Shadegan district, Khuzestan province by ELISA method. In: Proceeding of the 2end Congress of Medical Parasitology in Iran. Tehran University of Medical Science. Amir-Zargar, A.K., 1997. Seroepidemiological survey of toxoplasmosis in Ahwaz, Khuzestan province. In: Proceeding of the 2nd Congress of Medical Parasitology in Iran. Tehran University of Medical Science. Araujo, F.G., Barnett, E.V., Gentry, L.O., Remington, J.S., 1971. False-positive antiToxoplasma fluorescent-antibody tests in patients with antinuclear antibodies. J. Appl. Microbiol. 22, 270–275. Arbabi, M., Talari, S.A., Asmar, M., Rasti, S., 1997. Seroepidemiology of toxoplasmosis in Kashan, 1993. J. Kashan Univ. Med. Sci. 1, 29–37. Assmar, M., Amirkhani, A., Piazak, N., Hovanesian, A., Kooloobandi, A., Etessami, R., 1997. Toxoplasmosis in Iran. Result of seroepidemiological study. Bull. Soc. Pathol. Exot. 90, 19–21. Bobic, B., Jevremovic, I., Marinkovic, J., Sibalic, D., Djuerkovic-Djakovic, O., 1998. Risk factors for Toxoplasma infection in a reproductive age female population in the area of Belgrade Yugoslavia. Eur. J. Epidemiol. 14, 605–610. Boyer, K.M., Remington, J.S., McLeod, R., 2004. Toxoplasmosis. In: Feigin, R.D., Cherry, J.D., Demmler, G.J., Sheldan, K. (Eds.), Textbook of Pediatric Infectious Diseases. Saunders, Philadelphia, PA, pp. 2755–2761. Brinkman, K., Debast, S., Sauerwein, R., Ooyman, F., Hiel, J., Raemaekers, J., 1998. Toxoplasma retinitis/encephalitis 9 months after allogeneic bone marrow transplantation. Bone Marrow Transplant. 21, 635–636. Chegini, S., Asmar, M., Abadi, A.R., Bagheri-Yazdi, S.A., 2011. Toxoplasma infection in human and domestic animals, 1999. J. Babol Univ. Med. Sci. 3, 47–52. Cunningham, F.G., Macdonald, F.C., Gan, N.F., 1997. Williams Obstetrics, 20th ed. Appleton and Lange, Stamford, UK, pp. 309–310. Davoodi, J., Rasouli, S., Asadi, R., Jafary, K., 2012. Serologic seroprevalence of human toxoplasmosis in the Mianeh city by chemiluminescence’s method. J. Vet. Med. Q5 5 (14). Dehbashi, G.R., (dissertation) 2003. Seroepidemiological survey of Toxoplasma infection in Torkaman race of Agh-ghala, Golestan province. Tehran University of Medical Sciences, Iran, Tehran. Dehgani, N., Asmar, M., Honarmand, H.R., 2008. Seroepidemiology of toxoplasmosis in referents to medical diagnostic laboratories in Ramsar during the year 2007. J. Biol. Sci. 1, 35–44. Dubey, J.P., 2001. Oocyst shedding by cats fed isolated bradyzoites and comparison of infectivity of bradysoites of the VEG strain Toxoplasma gondii to cats and mice. J. Parasitol. 87, 215–219.


378

379

380

381 382 383

384

385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440



441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526

Dubey, J.P., Beattie, C.P., 1988. Toxoplasmosis of Animals and Man. CRC Press, Boca Raton, FL. Dubey, J.P., Frenkel, J.K., 1972. Cyst-induced toxoplasmosis in cats. J. Protozool. 19, 155–177. Dubey, J.P., Jones, J.L., 2008. Toxoplasma gondii infection in humans and animals in the United States. Int. J. Parasitol. 38, 1257–1278. El-Deeba, H.K., Salah-Eldinb, H., Khodeerc, S., Abdu-Allahd, A., 2012. Prevalence of Toxoplasma gondii infection in antenatal population in Menoufia, governorate, Egypt. Acta Trop. 124, 185–191. Etemadi, S., Mullashahi, S., Mir, M., Sarani-Aliabadi, P., Bamedi, T., 2012. Seroepidemiology of toxoplasmosis in patients referred to Zahedan Health Center in 2011. In: Proceeding of the 1st International and 8th National Congress of Parasitology and Parasitic Disease in Iran, Kerman. Fan, C.K., Hung, C.C., Su, K.E., Chiou, H.Y., Gil, V., Ferreira, M.C.R., Tseng, L.F., 2007. Seroprevalence of Toxoplasma gondii infection among inhabitants in the Democratic Republic of Sao Tome and Principe. Trans. R. Soc. Trop. Med. Hyg. 101, 1157–1158. Fayer, R., Dubey, J.P., Lindsay, D.S., 2004. Zoonotic protozoa: from land to sea. Trends Parasitol. 20, 531–536. Flegr, J., Preiss, M., Klose, J., Havlicek, J., Vitakova, M., Kodym, P., 2003. Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii dopamine, a missing link between schizophrenia and toxoplasmosis? Biol. Psychol. 63, 253–268. Galvan-Ramirez, M.D.L.L., Troyo, L., Roman, S., Calvillo-Sanchez, C., Bernal-Redondo, R., 2012. A systematic review and meta-analysis of Toxoplasma gondii infection among the Mexican population. Parasites Vectors 5, 271. Garcia, S.L., Bruckner, A.D., 1997. Parasitic infections in the compromised host (Toxoplasma gondii). In: Garcia, S.L., Bruckner, A.D. (Eds.), Diagnostic Medical Parasitology. American Society for Microbiology, Washington, DC, pp. 423–424. Gharavi, M.J., Oormazdi, H., Roointan, E.S., 2008. A comparative study on sensitivity and specificity of conventional and unconventional IgG and IgM assays for diagnosis of Toxoplasmosis. Iran. J. Public Health 37, 42–45. Ghorbani, M., Edrissian, G.H., Afshar, A., 1981. Serological survey of human toxoplasmosis in mountainous regions of north-west and south-west parts of Iran. Trans. R. Soc. Trop. Med. Hyg. 75, 38–40. Ghorbani, M., Edrissian, G.H., Assad, N., 1978. Serological survey of toxoplasmosis in northern part of Iran, using indirect fluorescent antibody technique. Trans. R. Soc. Trop. Med. Hyg. 72, 369–371. Goebel, W.S., Conway, J.H., Faught, P., Vakili, S.T., Haut, P.R., 2007. Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient. Pediatr. Blood Cancer 48, 222–226. Hafizi, A., 1990. Seroepidemiological survey of toxoplasmosis in patients referred to health Centers of Tehran University of Medical Sciences. In: Proceeding of the 1st Congress of Medical Parasitology in Iran, Gilan. Hill, D., Dubey, J.P., 2002. Toxoplasma gondii: transmission, diagnosis and prevention. Clin. Microbiol. Infect. 8, 634–640. Hoghooghi-Rad, N., Afraa, M., 1993. Seroprevalence of toxoplasmosis in humans and domestic animals in Ahwaz, capital of Khuzestan Province, south-west Iran. Am. J. Trop. Med. Hyg. 96, 163–168. Jafari, R., Sadaghian, M., Safari, M., 2012. Seroprevalence of Toxoplasma gondii infection and related risk factors in Tabriz City, Iran, 2008. J. Res. Health Sci. 12, 119–121. Jones, J.L., Kruszon – Moran, D., McQuillan, G., Navin, T., MacAuley, J.B., 2001. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am. J. Epidemiol. 154, 357–365. Jones, J.L., Ogunmodede, F., Scheftel, J., Kirkland, E., Lopez, A., Schulkin, J., et al., 2003. Toxoplasmosis related knowledge and practices among pregnant women in the United States. Infect. Dis. Obstetr. Gynecol. 11, 139–145. Keshavarz, H., Nateghpour, M., Eskandari, S.E., 2004. A seroepidemiologic survey of toxoplasmosis in Islamshahr district of Tehran, Iran. Modares J. Med. Sci.: Pathobiol. 6, 111–119. Keshavarz-Valian, H., Nateghpour, M., Zibaee, M., 1998. Seroepidemiology of toxoplasmosis in Karaj district, Iran. J. Public Health 27, 73–82. Keshavarz-Valian, H., Mamishi, S., Daneshvar, H., 2000. Seroprevalence of toxoplasmosis in hospitalized patients of Kerman hospitals, Iran. J. Kerman Univ. Med. Sci. 7, 126–139. Lee, Y.H., Noh, H.J., Hwang, O.S., Lee, S.K., Shin, D.W., 2000. Seroepidemiological study of Toxoplasma gondii infection in the rural area Okcheon-gun, Korea. Korean J. Parasitol. 38, 251–256. Lindst¨roma, I., Kaddu-Mulindwa, D.H., Kironde, F., Lindh, J., 2006. Prevalence of latent and reactivated Toxoplasma gondii parasites in HIV-patients from Uganda. Acta Trop. 100, 218–222. Manouchehri-Naeini, K., Mortazaee, S., Zebardast, N., Kheiri, S., 2012. Seroprevalence and some of risk factors affecting Toxoplasma infection in Chaharmahal va Bakhtiyari province, Iran. J. Shahrekord Univ. Med. Sci. 13, 8–18. Mansoori, F., Hatami, H., Mahdavian, B., Hashemian, A.H., 2003. Epidemiology of toxoplasmosis in Kermanshah province. J. Kermanshah Univ. Med. Sci. 7, 12–19. McCulloch, W.F., Braun, J.L., Heggen, D.W., Top, F.H., 1963. Studies on medical and veterinary students’ skin tested for toxoplasmosis. Public Health Rep. 78, 689–698. Meisheri, Y.V., Mehta, S., Patel, U., 1997. A prospective study of seroprevalence of toxoplasmosis in general population and in HIV/AIDS patients in Bombay. Ind. J. Postgrad. Med. 43, 93–98.

9

Miller, N.L., Frenkel, J.K., Dubey, J.P., 1972. Oral infections with Toxoplasma cysts and oocysts in felines, other mammals, and in birds. J. Parasitol. 58, 928–937. Mohammad-Ali Gol, S., Neyeb-Zadeh, H., 2012. Seroprevalence of Toxoplasma gondii infection in patients presenting to Pathobiology laboratory in Tehran, using Indirect Fluorescent antibody test (IFA). In: Proceeding of the 1st International and 8th National Congress of Parasitology and Parasitic Disease in Iran, Kerman. Moghazy, E.I., Kandil, F.M., Shaapan, R.M., 2011. Toxoplasma gondii comparison of some serological tests for antibody detection in sera and naturally infected pigs. World Zool. 6, 204–208. Montoya, J.G., Boothroyd, J.C., Kovaks, J.A., 2010. Toxoplasma gondii. In: Mandell, G.L., Bennett, J.E., Dolin, R. (Eds.), Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia, pp. 3495–3526. Montaya, J.G., Kovacs, J.A., Remington, J.S., 2005. Toxoplasma gondii. In: Mandel, G.L., Bennet, J.E., Dolin, R. (Eds.), Mandel, Douglas and Bennets. Principals and Practice of Infectious Diseases. , sixth ed. Churchill Livingstone, Philadelphia, pp. 3170–3198. Montoya, J.M., Liesenfeld, O., 2004. Toxoplasmosis. Lancet 363, 965–976. Moschen, M.E., Stroffolini, T., Arista, S., Pistopia, D., Giammanco, A., Azara, A., et al., 1991. Prevalence of Toxoplasma gondii antibodies among children and teenagers in Italy. Microbiologica 14, 229–234. Mostafavi, S.N., Ataei, B., Nokhdian, Z., Yaran, M., Babak, A., 2011. Seroepidemiology of Toxoplasma gondii infection in Isfahan province, central Iran: a population based study. J. Res. Med. Sci. 16, 496–501. Pirali-Kheirabadi, Kh., Tahmasebi, H., Monjii, H., Shafigh, Z., Amiri-Dehcheshmeh, J., 2012. Seroepidemiology of Toxoplasma gondii in Isfahan and Mazandaran provinces by ELISA method. In: Proceeding of the 7th National and 2nd Regional Congress of Parasitology and Parasitic Disease in Iran. Tehran University of Medical Sciences. Razavi, S.M., Esnaashari, H.R., Gheisari, H.R., 2003. Seroepidemiological survey of toxoplasmosis by IFA technique in the students of faculty of Veterinary Medicine, university of Shiraz. J. Vet. Res. 58, 163–167. Reza-Zadeh, F., (dissertation) 1996. Seroepidemiological survey of Toxoplasma gondii in Bandar-Anzali, Gilan province. Shahid Beheshti University of Medical Sciences, Iran, Tehran. Rieman, H.P., 1974. Antibodies to Toxoplasma gondii and Coxiella burneti among students and other personnel in veterinary colleges in California and Brazil. Am. J. Epidemiol. 100, 197–208. Roberts, T., Frenkel, J.K., 1990. Estimating income losses and other preventable costs caused by congenital toxoplasmosis in people in the United States. J. Am. Vet. Med. Assoc. 196, 249–256. Roberts, T., Murrell, K.D., Marks, S., 1994. Economic losses caused by foodborne parasitic diseases. Parasitol. Today 10, 419–423. Roman, E., Zamir, C.S., Rilkis, I., Ben-David, H., 2005. Congenital toxoplasmosisprenatal aspects of Toxoplasma gondii infection. Reprod. Toxicol. 21, 458–472. Ruiz Fons, F., Vicente, J., Vidal, D., Hofle, U., Villanua, D., 2006. Seroprevalence of six reproductive pathogens in European wild boar (Susscrofa) from Spain the effect on wild boar female reproductive performance. Theriogenology 65, 731–743. Salahi-Moghadam, A., Hafizi, A., 2009. A serological study on Toxoplasma gondii infection among people in south of Tehran, Iran. Korean J. Parasitol. 47, 61–63. Sarkari, B., (dissertation) 1992. Seroepidemiological survey of toxoplasmosis in individuals referred to clinics of Kazerun districts. Tarbiat Moddares University, Iran, Tehran. Schnurrenberger, P.R., Tjalma, R.A., Wentworth, F.H., Wentworth, B.B., 1964. An association of human reaction to intradermal toxoplasmin with degree of animal contact and rural residence. Am. J. Trop. Med. Hyg. 13, 281–286. Sedaghat, A., Ardehali, S.M., Sadigh, M., Buxton, M., 1979. The seroprevalence of Toxoplasma infection in southern Iran. J. Trop. Med. 81, 204–207. Shad-Del, F., GhaffariSarvestani, R., 1993. Seroprevalence of Toxoplasma infection in human and dog population in Shiraz, Iran. J. Appl. Anim. Res. 3, 83–89. Shahmoradi, A., Daryani, A., Haji-zadeh, A., 1998. Seroepidemiological survey of toxoplasmosis in individuals referred to Health Center of Roodsar, Gilan. J. Shahed Univ. 4, 7–12. Shahmoradi, A., Sardarian, K.H., et al., 1995. Seroepidemiological survey of toxoplasmosis in patients referred to health Medical Centers of Malayer district, Hamedan province. J. Shahed Univ. 2, 70–73. Shamsian, S.A., Soghandi, L., Fathimoghadam, F., 2012. The frequency of IgG and IgM anti-toxoplasmosis antibodies in patients referred to ACECR clinical laboratory in Neyshabour during 2011. In: Proceeding of the 1st International and 8th National Congress of Parasitology and Parasitic Disease in Iran, Kerman. Sharif, M., Daryani, A., (unpublished data) 2011. Seroepidemiology of Toxoplasma gondii in general population in Mazandaran province in 2011. Shin, D.W., Cha, D.Y., Hua, Q.J., Cha, G.H., Lee, Y.H., 2009. Seroprevalence of Toxoplasma gondii infection and characteristics of seropositive patients in general hospitals in Daejeon, Korea. Korean J. Parasitol. 47, 125–130. Singh, N., Gayowski, T., Marino, I.R., 1996. Toxoplasma gondii pneumonitis in a liver transplant recipient: implications for diagnosis. Liver Transpl. Surg. 2, 299–300. Song, K.J., Shin, J.C., Shin, H.J., Nam, H.W., 2005. Seroprevalence of toxoplasmosis in Korean pregnant women of congenital toxoplasmosis. Korean J. Parasitol. 43, 69–71. Sultan-Mohammad-zadeh, M., Keshavarz, H., Mohebali, M., Holakouie-Naieni, K., Arsh, S.H., 2003. Seroepidemiologic study of human Toxoplasma infection in residents of Meshkin-Shahr. J. Sch. Public Health Inst. Public Health Res. 1, 57–72.


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G Model ACTROP 3386 1–10 10 613 614 615 616 617 618 619


Tasawar, Z., Aziz, F., Lashar, M.H., Shafi, S.S., Ahmad, M., Lal, V., Sikandar Hayat, C., 2012. Seroprevalence of human Toxoplasmosis in Southern Punjab, Pakistan. Pak. J. Life Soc. Sci. 10, 48–52. Tenter, A.M., Heckeroth, A.R., Weiss, L.M., 2000. Toxoplasma gondii: from animals to humans. Int. J. Parasitol. 30, 1217–1258. Torkan, S., Momtaz, H., Abdi-Zadeh, R., 2008. Comparison of Toxoplasma infection in owner of domestic cats and individuals without contact with cat. J. Shahrekord Univ. Med. Sci. 10, 83–89.

Xiao, Y., Yin, J., Jiang, N., Xiang, M., Hao, L., Lu, H., Sang, H., Liu, X., Xu, H., Ankarklev, J., Lindh, J., Chen, Q., 2010. Seroepidemiology of human Toxoplasma gondii infection in China. BMC Infect. Dis. 10, 4. Zhu, C.H., Cui, L.L., Zhang, L.S., 2012. Commercial ELISA with the modified agglutination test for detection of Toxoplasma gondii antibodies in sera of naturally dogs and cats. Iran J. Parasitol. 7, 89–95.


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