Introduction
Toxoplasmosis is one of the most common communicable human and animal infections caused by the infection of the intracellular parasite called Toxoplasma gondii [1]. The life cycle of toxoplasmosis involves two stages, sexual and non-sexual. In the sexual phase, the parasite is matured in the cat's intestines and the cats that host it, creating an oocyte that is excreted through the cat's feces. The non-sexual phase that occurs in the body of homeothermy animals and humans has two distinct stages, the acute phase, which is the rapid growth of the parasite, and the creation of tachyzoite, and the chronic phase that produces a bradyzoite tissue. The parasite invasion to the host mediate cell leads to an immune response, and as a result, the tachyzoite is converted to bradyzoites that are cysts and remain in the host for a long time [2].
Human may become infected with acquired or congenital form. The most important ways to develop toxoplasmosis, is eating raw meat containing parasite cysts, using water and herbs infected with oocyte parasites, contacting with contaminated soil, contaminated blood infusion, needle and syringe [3].
In congenital infections, the disease (tachyzoite) is transmitted from mother to fetus through the placenta [4]. Infection with Toxoplasma has been reported worldwide, but the prevalence of infection varies by age, geographical location, and food habits in different parts of the world and is reported to be up to 75% [5]. The infection is more prevalent in hot and humid areas and is significantly related to the quality of drinking water in the area and health care [6]. Some studies have found that cats are at home is associated with an increased risk of infection [7]. In areas where high prevalence of infection is observed, pregnant mothers who are negative for their serum tests are at risk for the acquisition of toxoplasmic infections and, consequently, their transmission to the fetus [1]. The purpose of this study was to review the general aspects of the disease, prevention methods, and methods for the diagnosis and treatment of Toxoplasma infection in pregnant women.
In this research, referring to reliable scientific databases such as Science Direct, PubMed and Elsevier, specific research conducted with the keywords of Toxoplasma infection, Congenital Toxoplasmosis and Toxoplasma infection during pregnancy, and related issues were investigated.
 
Clinical symptoms
Acquired toxoplasmosis is more common in healthy subjects without clinical symptoms or nonspecific symptoms including brief fever and swollen lymph nodes [8, 9], but in patients with immune deficiency, it causes acute symptoms such as central nervous system attacks, Seizures, cerebral calcification, pneumonia, etc. [10]. People who use immunosuppressive drugs for various reasons, such as organ transplants, are prone to recurrence. The recurrence of infection in these people causes severe complications such as meningitis, encephalopathy, myocarditis, etc., and can even lead to death [11]. If the mother gets toxoplasmic infection for the first time during pregnancy, it is possible to transfer the parasite from mother to fetus. The risk of transmission of toxoplasma as well as congenital toxoplasmosis symptoms depends on the time of the infection [12]. The probability of transmission of infection in the first trimester of pregnancy is lower, but in case of transmission, it can lead to severe complications such as neurological or ocular damage, mental retardation, microcephaly, hydrocephalus, abdominal ascites, hepatocellular ulcers, severe intrauterine growth or even death [2]. Therefore, the timely diagnosis of the onset of primary infection in pregnant women is important.
 
Prevention
In most parts of the world, the consumption of half-cooked meat containing parasitic cysts is the most important way of transmitting contamination. Also, in areas where water and food is not sanitized, there is a potential for contamination [13]. Therefore, the best way to prevent is health education to avoid having to deal with the parasite. Many countries have implemented educational programs to prevent congenital toxoplasmosis [14]. The most important ways to prevent are the not using milk, eggs, and raw or half-cooked meat [15]. Freezing meat at -20 ° C can eliminate parasite cysts. Wearing gloves during gardening and cleaning the cats is mandatory. Washing hands before and after contact with soil, cat and raw meat, lack of contact of hands with the face and eyes when cooking and not drinking water that can be contaminated with parasite oocytes are another means of preventing infection. [16]. Given the fact that once contamination with disease develops permanent immunity, the vaccine is an achievable target [17]. Research has shown that with the use of recombinant antigens, an effective vaccine can be obtained for human immunization, but this goal has not yet been achieved [18, 19]. As it has been said, the incidence of congenital toxoplasmosis varies from one geographical point to another and is estimated to be between 0.1 and 3 per 1,000 pregnancies [20]. Screening for Toxoplasmosis is a subject in which there is no consensus. Screening pregnant mothers using serological methods allows the identification of recent cases of infection and prevente the congenital infection or its complications in the infant. Screening for pregnant women is currently restricted to some countries, such as France and Australia, and screening for infants is done in some states in the United States [21, 22]. In societies with low prevelence of the parasite, screening for pregnant mothers is not cost-effective. On the other hand, it has not confirmed that treatment during pregancy can prevent the congenital toxoplasmy. For this reason, neonatal screening may be more effective [23]. The author suggests that women who may be exposed to toxoplasmic gonii should perform screening tests for toxoplasmosis if they decide to become pregnant. This group includes those who hold cats, those who are directly exposed to sand and soil, such as gardening, people who travel to another country or the places with prevalent toxoplasmy, and who are accustomed to eating half-cooked meat. .
 
Diagnosis
Since the clinical symptoms of Toxoplasmosis are nonspecific, the diagnosis of Toxoplasma infection is based primarily on direct evidence that the parasite (immunoproxidase) or its DNA (polymerase chain reaction method) is present in the tissue or body fluids. It is also detected by inoculation of tissues or body fluids into laboratory mice or cell culture and parasite isolation, or based on indirect evidence that shows the presence of antibodies against the parasite [11, 24]. Diagnosis during pregnancy can be done by serological tests, amniocentesis or evidence of abnormal findings in sonography [14]. Serologic tests, which are the first steps in diagnosis, measure the level of specific IgG and IgM antibodies to toxoplasmosis [16]. The most important point in diagnosing an infection during pregnancy is the ability to differentiate between acute and chronic infections, and usually the results of IgG and IgM tests can not easily be interpreted [1]. The presence of IgM antibodies can not be clearly indicative of acute infection. IgM antibodies start to rise about 5 days after the onset of an infection, and may remain high in blood for weeks or even months [15]. An IgM antibody reaches its highest level about one to two months after infection, and it is cleared faster than the IgG antibody. Although the IgM antibody is reduced after some time and even reaches an undetectable level by serological tests, cases have been reported that the level of this antibody remains high up to several years after the infection [25, 26]. The IgG antibody begins to rise somewhat after IgM (about one to two weeks after infection) and reaches its maximum level after 3 to 6 months. The presence of this antibody can be detected for many years and remains in blood until the end of life [27]. If the result of both IgG and IgM tests are negative, it is very recent that there is no infection or acute infection [28]. If the result of the IgG test is positive and the IgM is negative, it indicates an infection with a history of more than one year. If the result of both IgG and IgM tests is positive, it indicates a recent or false positive infection. If the results are somehow indicative of acute infection, the test should be repeated 2 to 3 weeks later [15]. If  in the second test, the level of IgG goes up to 4 times confirms the presence of the infection [24]. Serological diagnostic kits on the market can be unreliable and give false positive or negative results. Therefore, if the answer is yes, the results should be confirmed by the reference laboratories and this is very important [29]. In reference laboratories, certain tests are performed with higher precision for measuring the antibody level, such as the Sabinefeldman color test, or indirect fluorescent antibody test [30, 31]. Although, according to the author's information in Iran, there is no reference laboratory to confirm the diagnosis of toxoplasmosis,in the department of parasitology of the Pasteur Institute of Iran, the confirmatory tests are carried out for this purpose. It is important to know the time of infection during pregnancy in assessing the risk of transmission to the fetus, initiating antibiotic therapy and ensuring proper counseling. An appropriate strategy for differentiating the acute infection from chronic IgG test is to perform a specific IgG antibody test against toxoplasma [32]. Antibodies produced at the onset of the infection have a low affinity, but this affinity increases dramatically over time. If the avidity is high, it shows that infection has occurred at least 3-5 months before the test although it should be noted that low avidity does not indicate recent infection [33]. In these circumstances, more tests are needed to determine the exact infection [1]. The most common method for obtaining indirect evidence of infection is the Polymerase Chain Reaction (PCR) test, which has a sensitivity of over 80% and a specificity of over 95% [8]. If serological tests can not be performed to detect the acute toxoplasmosis infection, amniocentesis is suggested if the results of ultrasound show the probability of this infection. Amniocentesis is prescribed after consultation with a specialist for the diagnosis of congenital toxoplasmosis in order to finalize the infection by polymerase chain reaction [14]. Therefore, amniocentesis should not take place before the 18th week of pregnancy, as it is likely to produce false positive and negative results. It should also be past at least 4 weeks from the time that the mother is likely to develop toxoplasmic infections [14]. According to researches, the sensitivity of PCR depends on the use of amniotic fluid in the gestational age. The most susceptibility in the second trimester of pregnancy was shown in weeks 17 to 21 of pregnancy compared to before or after this date [10, 34]. The blood sample (from the umbilical cord), which used to be the best way to diagnose fetal infection, is no longer recommended as a diagnostic method, as the PCR test performed on amniotic fluid is equally as accurately as possible. Also, the risk of sample preparation from the umbilical cord is very high [14].
Treatment
Maternal treatment during pregnancy is aimed at preventing congenital toxoplasmosis. There are two basic medicines to treat, depending on whether the infection has been transmitted to the fetus or not. If the mother is infected, but the fetus is not infected, spiramycin is used to prevent the release of the organism, passing through the placenta and transferring to the fetus [35]. Spiramycin is an antibiotic that does not cross the placenta, therefore it is not usable for embryo therapy and is only used to prevent the direct transmission of parasite to embryo and is recommended by a large number of European and American researchers. If the amniotic fluid polymerase chain reaction has been reported to be negative, it is given as an oral regimen every 8 hours for the entire period of pregnancy [35, 36]. However, if the embryo is confirmed to be infected or likely to be infected, for treatment , Pyrimethamine and sulfadiazine are prescribed. Of course, this drug should not be used in the first trimister, because it is potentially teratogenic. Pyrimidamine is a folic acid antagonist that acts synergistically with sulfanamide. Since this drug, depending on the used dose, causes reversible weakness in the bone marrow, it should be prescribed with folic acid. Co-administration of pyrimethamine and sulfadiazine significantly reduces the severity of the disease [35, 37]. Some studies have shown that the treatment of pregnant mothers with acute infection does not reduce the risk of transmission of infection, but in the case of infected embryo, the severity of the disease decreases. However there is still no consensus on this issue [14, 15, 23]. In general, there is not enough research in this area and more research is needed to determine the most effective way to treat pregnant mothers and congenital toxoplasmosis [16, 23].
 
Conclusion
It is necessary to provide information on the prevention of toxoplasmic infections during pregnancy to all women who are pregnant or intend to become pregnant and screening for women exposed to Toxoplasma parasites. On the other hand, non-pregnant women who have been diagnosed with acute infection of the toxoplasma gonii are advised to wait up to 6 months before any pregnancy attempt although they should consult with a specialist individually. Given the possibility of transmission of infection late in pregnancy, but the complications of the infection transmitted earlier in pregnancy are more severe, the infection should be confirmed before any intervention by a laboratory test or by tests that are as accurate as possible. For three cases, for the detection of amniocentesis toxoplasma gonii, it is suggested that PCR is performed on amniotic fluid; first, if the mother's primary infection is diagnosed; secondly, the serological tests can not confirm or rule out the acute infection; and thirdly, if ultrasound abnormal symptoms such as calcification are seenseen. Of course, if a pregnant mother is suspected of acute infection, the test should be repeated 2 to 3 weeks later, and the treatment should begin immediately with spiramycin without waiting for the next test result, as infants born with clinical infection may have visual impairment and backwardness that can not easily be detected early in childhood. In other sources for mothers who have a highly suspected or confirmed embryo infection, the prescription of a combination of pyrimethamine, sulfadiazine and folic acid has been  suggested. Of course, wether the treatment of pregnant mothers with spiramycin or pyrimethamine-sulfadiazine, or both, reduces the risk of developing fetal infections or not, is still uncertain. It is also not clear whether the anti-parasite medication given to infants before birth is effective or not. However, there is a consensus that the infected infants should be treated with pyrimethamine and sulfadiazine for 6 to 12 months.

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Contribution of authors
Gita Saadat Nia (First author), all sections of the article is carried out by the author (100%).