Methods for review

We consulted original manuscripts to minimize mistakes in translation. Detailed historical, serological, parasitological, clinical and genetic information on T. gondii infections in humans and other animals are summarized in tables throughout the review.

Most of the reports on toxoplasmosis relate to serological surveys with no uniformity with respect to tests used and cut-off values. In Table 1, information on serological assays used in Turkey is summarized and noted throughout the paper where applicable.

Table 1.

Details of serological tests used for the seropositivity of T. gondii in humans and animals in Turkey

^a IgG ve IgM antibodies (Cobas Core, Roche), IgA antibodies (ETI-TOXOK-A reverse); IgG Avidity EIA Well-RADIM.

Serological prevalence in the general population

The seropositivity of T. gondii antibodies in the general population, including 15–40 years old women and those pregnant is summarized in Tables 2 and 3, respectively; seroprevalence varied between 18–100%.

Table 2.

Serological prevalence of T. gondii in the general human population of different regions in Turkey

^a 15–50 year old.

Table 3.

Seroprevalence of T. gondii in pregnant women tested in hospital from different regions in Turkey

^a Pregnancies with abortion (412), normal pregnancies (828).

Most of these serological studies were retrospective and based on convenience samples. There were no data on children less than 14 years of age. Notable among these surveys are reports that assayed more than 7,000 sera from different regions of Turkey. A study found T. gondii IgG antibodies in 28.8% and IgM antibodies in 1.9% of 10 295 patients from the Marmara region (Alver et al., Reference Alver, Göral and Ercan2014). Another study reported T. gondii IgG antibodies in 21.3% of 4,048 and IgM antibodies in 1.2% of 13 605 patients from Bolu province in the Black Sea region (Aydın Türkoğlu et al., Reference Aydın Türkoğlu, Karabörk, Çakmak, Orallar, Yaman and Ayaz2018). From the Central region of Turkey, IgG antibodies were found in 29.5% and IgM antibodies in 2.4% of the 7051 hospital patients (Maçin et al., Reference Maçin, Fındık, Demircan, Arslan and Türk Dağı2018). The prevalence of T. gondii antibodies in pregnant women varied a great deal (Table 3). In the largest sample of 30 863 women tested, IgG antibodies were detected in 25.5% and IgM antibodies were present in 0.3% (Çelen et al., Reference Çelen, Sargın, Çitil, Saygan, Ünlü, Danişman and Seçkin2013). Several authors emphasized the need to use multiple serological tests for diagnosis of acute infection and serological conversion during pregnancy (Tanyuksel et al., Reference Tanyuksel, Guney, Araz, Saracli and Doganci2004; Bahar et al., Reference Bahar, Karaman, Kirdar, Yilmaz, Celiloglu and Mutlu2005; Ertug et al., Reference Ertug, Okyay, Turkmen and Yuksel2005; Doğan et al., Reference Doğan, Kafkaslı, Karaman, Atambay, Karaoğlu and Colak2012; Uysal et al., Reference Uysal, Cüce, Taner, Uysal, Atalay, Göl and Köse2013; Karacan et al., Reference Karacan, Batukan, Cebi, Berberoglugil, Levent, Kir, Baksu, Ozel and Camlibel2014; Dinçgez et al., Reference Dinçgez Çakmak, Dündar, Bayram and Özgen2018).

Limited risk factor analysis data indicated that eating raw meat (Tekay and Özbek, Reference Tekay and Özbek2007; Doğan Toklu, Reference Doğan Toklu2013; Gencer et al., Reference Gencer, Cevizci, Saçar, Vural, Cakir Güngör, Uysal, Hacivelioglu, Çelik, Duru and Cosar2014), contact with soil (Doğan Toklu, Reference Doğan Toklu2013; Gencer et al., Reference Gencer, Cevizci, Saçar, Vural, Cakir Güngör, Uysal, Hacivelioglu, Çelik, Duru and Cosar2014), and consumption of raw eggs (Gencer et al., Reference Gencer, Cevizci, Saçar, Vural, Cakir Güngör, Uysal, Hacivelioglu, Çelik, Duru and Cosar2014) were the main factors associated with seroprevalence. One study found seroprevalence of T. gondii IgG in 64.6% of 84 Syrian refugees (Bakacak et al., Reference Bakacak, Serin, Aral, Ercan, Köstü, Kireçci, Bostanci and Bakacak2015).

Mother to foetus transmission of T. gondii and congenital toxoplasmosis

There are no firm data with respect to transmission of T. gondii during pregnancy. Toxoplasma gondii DNA was detected in amniotic fluid in one of 300 foetuses tested between 15^th and 18^th week of gestation (Gunel et al., Reference Gunel, Kalelioglu, Ermis, Has and Aydinli2012). Evidence of recently acquired infection (based on low-avidity antibodies) in one of 4651 women tested during the first trimester (Uysal et al., Reference Uysal, Cüce, Taner, Uysal, Atalay, Göl and Köse2013). The intrauterine growth of the foetus was retarded with deficient amniotic fluid; there was no follow up. Chorioretinitis was diagnosed in one of the seven babies born to mothers that had IgM antibodies.

One study followed the outcomes of pregnancy in 13 women who had seroconverted to T. gondii infection during pregnancy; all were given anti-T. gondii therapy (Samanci et al.,Reference Samanci, Ovali, Dagoğlu, Yüksel and Bengisu1995). One of the childrens had classical symptoms of congenital toxoplasmosis: chorioretinitis, intracerebral calcification and hydrocephalus at birth. Thus, the authors estimated the risk of foetal infection at 7.1% (1 of 13), based only on symptoms; there was no confirmation of congenital toxoplasmosis.

Evidence was presented that spiramycin therapy during pregnancy can reduce congenital transmission of T. gondii (Avci et al., Reference Avci, Arslan, Çiftçi, Ekiz, Tüten, Yildirim and Madazli2016). Of the 61 women who acquired T. gondii infection during pregnancy, 55 (90.2%) received spiramycin prophylaxis while six (6.6%) refused it. Obvious lesions of congenital toxoplasmosis were evident by ultrasonographic examination of foetuses of two mothers who refused spiramycin therapy. Both foetuses had intracranial calcification, enlarged ventricles and hepatomegaly. Pregnancy was terminated in foetuses from four of the six mothers who refused treatment; autopsy was not permitted. In summary, there are no estimates of the rate of congenital toxoplasmosis in Turkey.

There are only two proven cases of congenital toxoplasmosis, as documented by the isolation of viable T. gondii. The first report by Ekmen et al. (Reference Ekmen, Altay and Altıntaş1974) was discussed earlier in the history section. The second case of congenital toxoplasmosis was a child who had bilateral chorioretinitis, hepato-splenomegaly and jaundice at birth and died 2 weeks later (Döşkaya et al., Reference Döşkaya, Caner, Ajzenberg, Değirmenci, Dardé, Can, Erdogan, Korkmaz, Üner, Güngör, Altintas and Gürüz2013). The CSF collected from the baby at postmortem was inoculated intraperitoneally into mice and viable tachyzoites were found in the peritoneal fluid. This highly mouse-virulent strain was designated Ege-1 strain. Retrospectively, T. gondii IgG and IgM antibodies were found in serum samples of the child and mother; low-IgG avidity in mother serum indicating recent infection. Additionally, T. gondii DNA was detected by the polymerase chain reaction (PCR) in CSF. There was no screening for T. gondii antibodies in mother before or during pregnancy.

Clinical toxoplasmosis in adults

Ocular disease is a common sequelae of toxoplasmosis but definitive diagnosis is difficult. There are several reports of ocular toxoplasmosis in Turkey (Ozcan, Reference Ozcan1975; Küçükerdönmez et al., Reference Küçükerdönmez, Akova and Yilmaz2002; Atmaca et al., Reference Atmaca, Simsek and Batioglu2004; Tanyuksel et al., Reference Tanyuksel, Guney, Araz, Saracli and Doganci2004; Tugal-Tutkun et al., Reference Tugal-Tutkun, Corum, Otük and Urgancioglu2005; Avkan Oguz et al., Reference Avkan Oguz, Koçak, Köse, Unek, Ozbilgin, Karademir and Kaynak2012; Celebi et al., Reference Celebi, Kilavuzoglu, Altiparmak, Cosar and Ozkiris2015; Oray et al., Reference Oray, Ozdal, Cebeci, Kir and Tugal-Tutkun2015; Türkcü et al., Reference Türkcü, Şahin, Yüksel, Çınar, Cingü, Altindağ, Deveci, Özkurt and Çaça2017). However, most of these reports were based on lesions and the presence of T. gondii antibodies in the serum. One of the shortcomings of serological diagnosis is that chronically infected patients have low-antibody titers, not different than in the general population; a negative serological test, however, rules out ocular toxoplasmosis. Among the reports of ocular toxoplasmosis, two studies are discussed here. Atmaca et al. (Reference Atmaca, Simsek and Batioglu2004) reported 189 cases of ocular toxoplasmosis from 1972 to 1999; 140 (74%) were considered congenital toxoplasmosis and 49 (26%) acquired toxoplasmosis. At the first examination, 65 active lesions were detected in 65 eyes. Lesions were seen in macula of 59%. Manifestations of congenital toxoplasmosis included were: strabismus in 15%, nystagmus in 9.2%, microphthalmia in 2.6%, optic nerve atrophy in 3.1% and lens opacities in 1%. The second study (Tugal-Tutkun et al., Reference Tugal-Tutkun, Corum, Otük and Urgancioglu2005) reported on 109 consecutive patients with active ocular disease in the Department of Ophthalmology, Istambul Faculty of Medicine in the last decade. The patients had IgG but no IgM antibodies to T. gondii. Retino-choroidal scars were present in 90 (83%) of 189 patients. Bilateral lesions, suggestive of congenital toxoplasmosis, were seen in 21 patients and active lesions were detected in 55 patients. All patients were treated with anti-T. gondii drugs with favourable prognosis.

Confirmatory tests, such as the detection of T. gondii antibodies in aqueous humour or T. gondii DNA, were not used in any reports on ocular toxoplasmosis.

Lymphadenitis, dermal rash, fever, headaches, myalgia, hepatitis and chorioretinitis are some of the common symptoms of acquired toxoplasmosis. A 46-year old woman who had a history of eating undercooked meat developed maculopapular rashes, hepatomegaly and elevated liver enzymes (Atilla et al., Reference Atilla, Aydin, Demirdöven and Kiliç2015). She had both IgG and IgM T. gondii antibodies, and T. gondii-like bodies were seen in histological sections of liver biopsy.

Reactivation of chronic T. gondii infection in patients with human immunodeficiency virus (HIV) has been reported worldwide, but rarely from Turkey. We are aware of only two reports of toxoplasmosis in HIV-infected patients in Turkey. Cerebral toxoplasmosis was diagnosed in a 29-year-old woman with HIV infection who had fever, vomiting, headache, weakness of the right side and seizure (Yapar et al., Reference Yapar, Erdenizmenli, Avkan Oğuz, Çakır and Yüce2005). Cranial MRI revealed four mass lesions in the cerebellar cortex. The patient had T. gondii IgG antibodies but no IgM antibodies. She was treated with clindamycin and antiviral therapy. After 2 months, the neural lesions were resolved.

The second patient, a 37-year-old male, who had neurological signs, cranial MRI revealed multiple cerebral lesions and the diagnosis of toxoplasmosis was confirmed by brain biopsy (Midi et al., Reference Midi, Çalışkan, Toktaş, Sav and Günal2008). Despite antitoxoplasmosis, antiretroviral and antidopaminergic treatments, the patient died because of bacterial septicemia.

There is only limited information concerning toxoplasmosis in patients with other immunosuppressive disorders or transplant recipients. Possible toxoplasmosis was reported in five of 170 allogenic haematopoietic stem cell transplant patients, based on MRI, response to treatment with anti-T. gondii therapy and the PCR on CSF (Hakko et al., Reference Hakko, Ozkan, Karman and Gulbas2013). Two of these patients died of toxoplasmosis; postmortem was not performed.

Toxoplasmosis was detected in four of 40 liver transplants in a transplant service in Turkey (Caner et al., Reference Caner, Döşkaya, Karasu, Degirmenci, Guy, Kiliç, Zeytunlu, Francis, Bozoklar and Gürüz2008). Both the donors and the recipients were seropositive to T. gondii. Toxoplasmosis was suspected when symptoms of fever, headaches and nausea were noted. Diagnosis was supported by positive DNA detection in blood of patients using PCR and anti-T. gondii therapy; all four patients recovered.

A rare case of spinal cord arachnoiditis was reported by Cosan et al. (Reference Cosan, Kabukcuoglu, Arslantas, Atasoy, Dogan, Ozgunes, Kebabci and Tel2011). Toxoplasma gondii-like tachyzoites and bradyzoites were said to be detected but images are too low power to be convincing.

There are several reports of higher T. gondii serological prevalence in patients with schizophrenia (Cetinkaya et al., Reference Cetinkaya, Yazar, Gecici and Namli2007; Tamer et al., Reference Tamer, Dundar, Yalug, Caliskan, Yazar and Aker2008; Dogruman et al., Reference Dogruman, Aslan, Yalcin, Kustimur and Turk2009; Tanyüksel et al., Reference Tanyüksel, Uzun, Araz, Koru and Babür2010; Çelik et al., Reference Çelik, Kartalci, Aytaş, Aral Akarsu, Gözükara and Ünal2015; Cevizci et al., Reference Cevizci, Celik, Akcali, Oyekcin, Sahin and Bakar2015; Karabulut et al., Reference Karabulut, Bilgiç, Gürok and Karaboğa2015; Yuksel et al. Reference Yuksel, Alpay, Babur, Bayar, Saribas, Karakose, Aksoy, Aslan, Mehmetali, Kilic, Balcioglu, Hamanca, Dirican, Kucukbasmaci, Oner, Mamal Torun and Kocazeybek2010) and patients with chronic renal failure (Yazar et al., Reference Yazar, Demirtaş, Yalçin, Yaman, Tokgöz, Utas and Sahin2003; Ocak et al., Reference Ocak, Duran, Eskiocak and Aytac2005), neoplastic disorders (Yazar et al., Reference Yazar, Yaman, Eser, Altuntas, Kurnaz and Sahin2004), cirrhosis (Ustun et al., Reference Ustun, Aksoy, Dagci and Ersoz2004; Atilla et al., Reference Atilla, Aydin, Demirdöven and Kiliç2015), chronic heart failure (Yazar et al., Reference Yazar, Gur, Ozdogru, Yaman, Oguzhan and Sahin2006), reactive arthritis (Sert et al., Reference Sert, Ozbek, Paydas and Yaman2007), idiopathic Parkinson's disease (Celik et al., Reference Celik, Kamisli, Babür, Cevik, Oztuna and Altinayar2010), Alzheimer's disease (Kusbeci et al., Reference Kusbeci, Miman, Yaman, Aktepe and Yazar2011) and Multiple Sclerosis (Koskderelioglu et al., Reference Koskderelioglu, Afsar, Pektas and Gedizlioglu2017); however, the sample size and appropriate controls were lacking for cause effect relationship.

Companion animals

Cats

Cats are key in the epidemiology of T. gondii because they are the only hosts that can excrete environmentally resistant oocysts. Seroprevalence varied with age and life style of the cat (Table 4). Viable T. gondii was isolated from homogenates of hearts and brains in 20 of 100 cats by bioassay in mice (Can et al., Reference Can, Döşkaya, Ajzenberg, Özdemir, Caner, Iz, Döskaya, Atalay, Çetinkaya, Ürgen, Karaçali, Ün, Dardé and Gürüz2014). Additionally, T. gondii DNA was detected in tissues of 12 additional cats. These 32 T. gondii strains were used for genotyping – (see molecular epidemiology and genotyping analysis section).

Table 4.

Serological prevalence of T. gondii at cats in different regions of Turkey

^a The seropositivity of T. gondii in cats older than 1 year (47.8%) was more about three times than cats less than a year old (13.6%). The seropositivity in indoor cats was 23.1% by IFAT and 30.8% by SFDT. The seropositivity in stray cats was 41.7% by IFAT and 52.8% by the SFDT. The presence of antibodies was significantly related to outdoor access.

^b Seropositivity in male cats (48.6%) was lower than in female cats (51.4%).

^c Tissues of 100 cats were used to isolate viable T. gondii (shown in the text).

^d No significant differences for the seropositivity between 20 (44.4%) of 45 males and 25 (43.9%) of 57 females.

^e Nested PCR was positive for four cats (8.2%). Foetal toxoplasmosis was diagnosed in one cat.

To our knowledge, there is only one report dealing with prevalence of T. gondii-like oocysts in cats from Turkey. Toxoplasma gondii-like oocysts measuring 9–14 µm in size were found in faeces of three of 36 (8.3%) cats from farms, however, results were not confirmed by bioassay or by PCR (Muz et al., Reference Muz, Altuğ and Karakavuk2013).

There are three reports of clinical toxoplasmosis in cats from Turkey. The first report concerns three cats (one, 8-month old male necropsied in 1988, one 3-month old female and one 6 month old female, both necropsied in 1984) (Haziroglu et al., Reference Haziroglu, Altınsaat, Atasever and Akın1988; Haziroglu, Reference Haziroglu1993). All three cats had disseminated toxoplasmosis and T. gondii was detected in multiple tissues of these cats histologically and by transmission electron microscopy.

Histologically confirmed disseminated toxoplasmosis was detected in a 2.5 year-old queen and her two kittens (Atmaca et al., Reference Atmaca, Dincel, Macun, Terzi, Uzunalioglu, Kalender and Kul2013). The queen was hospitalized because of dystocia. Ultrasound examination revealed that three of five kittens had died in utero. After cesarean section, the queen and the two live kittens died. The queen had pneumonia and hepatitis. The presence of T. gondii was confirmed by both immunohistochemical examination and PCR testing in the kittens and the queen, thus, confirming transplacental toxoplasmosis.

Dermal toxoplasmosis was diagnosed in 2-year old female immunocompetent Angora cat (Kul et al., Reference Kul, Atmaca, Deniz and Süer2011). The cat had an antibody titer of 1:256 using the dye test and diagnosis was confirmed immunohistochemically and by PCR testing. The dermal lesions resolved after treatment with azithromycin.

Dogs

Serologic reports are summarized in Table 5. Viable T. gondii was isolated from lungs of a dog (Ekmen and Altıntaş, Reference Ekmen and Altıntaş1970) but details of the dog's condition are missing. Clinical toxoplasmosis was diagnosed postmortem in a dog owned by an American visitor to Turkey (Akcay et al., Reference Akcay, Pamukçu and Baran1950); in retrospect it is not clear if the dog had toxoplasmosis or neosporosis (Dubey et al., Reference Dubey, Hemphill, Calero-Bernal and Schares2017).

Table 5.

Serological prevalence of T. gondii in dogs from different regions of Turkey

Toxoplasmosis in livestock

Sheep and goats

Serological surveys indicate widespread exposure to T. gondii in sheep and goats in Turkey (Tables 6 and 7). Although toxoplasmosis is a major cause of abortion in sheep and goats worldwide (Dubey, Reference Dubey2010), there is little information from Turkey. Toxoplasma gondii-associated abortion cannot be diagnosed alone by serological testing of ewes; a negative serology rules out toxoplasmosis but positive result does not establish aetiology because seroprevalence is high in general population and antibodies can remain elevated in the next pregnancy (Dubey, Reference Dubey2010). To our knowledge, there is no confirmed report of T. gondii-associated abortion in sheep or goats from Turkey. Although T. gondii DNA was found in five of 20 sheep tissues (Ergin et al., Reference Ergin, Ciftcioglu, Midilli, Issa and Gargili2009), there is no report of isolation of viable T. gondii from sheep and goats in Turkey.

Table 6.

Serological prevalence of T. gondii in sheep in different regions of Turkey

^a 25.5% seropositivity of 259 aborted sheep with titers of 1:64–1:256.

^b Pregnant 56, aborted 57 in the previous year, aborted 41 within the period of the study. Inactivating temperature for the ovine complement was 56 °C. Ovine sera should be heated to 60°C to inactivate complement (Dubey, Reference Dubey2010).

^c Healthy ewes 827, ewes aborted 283 (10.16%). No significant difference between the two groups for the presence of antibody titers.

^d 5 of 10 aborted sheep were seropositive for T. gondii.

^e 63 sheep older than one year of age were tested. SFDT was accepted as a reference test. The specificity and sensitivity of LAT were 61.90 and 78.57%, respectively. The correlation between two tests was 73.01%.

^f The seropositivity of 0–1 year old was 58.34% and >1 year age was 47.23%, respectively. The seropositivity of male (47.45%) and female (57.67%) and the seropositivity of Akkaraman breed (54.8%), Ivesi (55.71%) and Morkaraman (63.63%). No significant correlation between serum titers of age, sex and breed.

^g No dissimilarity between female (31.4%) and male ewes (30). The significant difference between 0.6–1 year age (12.5%) and >1 year age (41%),

^h Seropositivity of aborted 25 sheep was 96%. No significant difference between 2–4 year (96%) and 5–10 year (100%) sheep.

ⁱ Karaman, Konya provinces from Central region and Zonguldak province from Black Sea. Identify specific antibodies to T. gondii (rTgSAG2-ELISA).

^j The seropositivity 1 to 2 years sheep (11.53%) and 5 to 7 years (8.51%). No statistically significant differences between the two age groups. Toxoplasma gondii antibodies were detected in 18 (11.1%) out of 162 ewes, while there was no seropositivity in the 18 rams tested.

Table 7.

Serological prevalence of T. gondii in goats from different regions of Turkey

^a Mohair goats used for the production of mohair and blankets and Norduz are dairy breed.

^b 42.85% seropositive at 1:16, 27.55% at 1:64, 7.17% at 1:256 and 3.06% at 1:1024.

^c 38.33% seropositivity of 60 Saanen × Kilis goats at 1:16, 50% at 1:64, 6.67% at 1:256 and 5% at 1:1024. 36.5% seropositivity of 52 Angora goats at 1:16, 44.2% at 1:64, 11.53% at 1:256 and 7.7% at 1:1024.

^d 100% of the Shami goats were seropositive with titers of 1:16 in 40 of 53, 12 at 1:64 and 1 at 1:256. 90.38% of Kilis goats were seropositive with titers of 1:16 in 36 of 52, 10 at 1:64 and 1 at 1:256.

Horses

Serologic data are summarized in Table 8. There is no report of clinical toxoplasmosis in horses.

Table 8.

Serological prevalence of T. gondii in horses in different regions of Turkey

Cattle

There is limited information concerning toxoplasmosis in cattle in Turkey (Table 9). Additionally, the dye test used in several surveys is nonspecific and gives erratic results with cattle sera (Dubey and Beattie, Reference Dubey and Beattie1988). Finding of T. gondii DNA in five of 10 beef samples (Ergin et al., Reference Ergin, Ciftcioglu, Midilli, Issa and Gargili2009) needs confirmation.

Table 9.

Serological prevalence of T. gondii in cattle in different regions of Turkey

^a 13 of 30 aborted cattle were seropositive for T. gondii.

^b Aborted 234, pregnant cows 323.

Various other animals

Serologic prevalence of T. gondii in miscellaneous animals is shown in Table 10. There is no confirmed report of clinical toxoplasmosis in animals, except in a zoo animal. Fatal toxoplasmosis was diagnosed in a captive kangaroo (Macropus sp.) from a zoo in Ankara (Kabak et al., Reference Kabak, Guvenc, Kul, Deniz and Gulbahar2011). Toxoplasma gondii DNA was demonstrated in the brain of a badger (Meles meles); indicating contamination of local waters by T. gondii (Karakavuk et al., Reference Karakavuk, Aldemir, Şahar, Can, Özdemir, Döşkaya, Gürüz and Döşkaya2018a).

Table 10.

Serological prevalence of T. gondii in miscellaneous animals in different regions of Turkey

^a The SFDT does not work with chicken sera (Dubey, Reference Dubey2010).