Toxoplasma gondii is an ubiquitous pathogen. Toxoplasmosis is considered a rare opportunistic infection in people with immune deficiencies and, as a rule, it is caused by the reactivation of a latent infection. In humans, T.gondii is an unprecedented danger only for pregnant women, because in 40% of cases, it means vertical transmission of the pathogen to the fetus with subsequent severe lesions in most between them. However, the prevalence of toxoplasmosis among various groups of immunodeficient people and its clinical significance need to be re-examined. The development of new laboratory diagnostic methods (in particular PCR) allows us to assess a large number of patients (mainly in multicenter studies, because the number of patients in each center is low). Due to the growing interest in the problem of toxoplasmosis, ESCMID has created a research group on toxoplasmosis, the main activities of which are:

The agent responsible for toxoplasmosis Toxoplasma gondii belongs to the type of protozoa (Protozoans), to the class of sporozoans (Sporozoa), to the 'coccidia order (Coccidia)) Toxoplasmas are mobile and have the shape of an arc, an arc or resemble a slice of orange. There are also oval and round shapes. The type of movement in the toxoplasm is in movement.

Representatives of the cat family are the final owners, in their body there is a sexual cycle of development of pathogens, leading to the formation of oocysts, which are excreted in the external environment with excrement, where they persist for a long time. The walls of tissue cysts that have entered the body of the cat when eating raw meat, infected rodents, are destroyed by the action of proteolytic enzymes from the stomach and small intestine with the release of the phase of slow division of toxoplasmas - bradyzoites. These enter the epithelial cells of the small intestine and give rise to the formation of a large number of male and female gametes (gametogony, asexual stage of development). After the fusion of male and female cells, a zygote is formed, non-sporulated oocysts are formed, which are excreted with excrement in the external environment.

Further development occurs when an intermediate host enters the body, one of which is a person. A person is infected either by eating poorly heat-treated meat containing tissue cysts, or when oocysts enter the digestive tract through contaminated hands. In the intestine, oocysts turn into active sporozoites, among which there are two forms. Tachyzoites are a proliferative form that occurs during the active period of infection and are characterized by rapid asexual reproduction. Along with the blood flow, they are transported throughout the body. With the development of the immune response, tissue cysts appear, most often formed in the striated muscles and brain, consisting of slowly dividing bradyzoites. The multiplied parasites fill the cells affected by them, adjusting closely to each other. These clusters are called pseudocysts. They do not have their own shell. Affected cells are destroyed, the released parasites enter healthy cells, where pseudocysts form again.

In chronic toxoplasmosis, real cysts can form in the internal organs. They undergo calcification or are destroyed by the release of toxoplasmas and their penetration into healthy cells, which leads to a relapse of the disease. If the mother is infected during pregnancy, transplacental transmission of the infection to the fetus is possible. The number of cases of congenital toxoplasmosis varies from 1 in 1,000 to 1 in 10,000 live births. At the same time, toxoplasmosis can be transmitted through the blood and during organ transplantation, which is facilitated by deep immunosuppression. Cases of damaged skin infection are described [3].

In 70 to 90% of cases of congenital toxoplasmosis, newborns have no symptoms, the disease begins to manifest itself over the months and years. Symptoms of congenital toxoplasmosis at birth may be a maculopapular rash, generalized lymphadenopathy, hepatomegaly, splenomegaly, jaundice, thrombocytopenia. As a result of intrauterine meningoencephalitis, microcephaly, hydrocephalus, choreoretinitis, convulsive syndrome and deafness develop. Foci of calcification in the brain can be detected by radiography, ultrasound, computed tomography.

In 1985, the United States spent more than $ 221 million on the treatment, education and upbringing of these children (approximately 3,300 people). In 2000, this amount already exceeded one billion dollars. It has been shown that the introduction in Finland of a national extended screening program to determine the probability of having a baby with congenital toxoplasmosis could save up to $ 2.1 million per year [3].

Infection acquired after birth is generally asymptomatic. The incubation period varies from 4 to 21 days and is on average 7 days. In a small percentage of cases, the development of an active process is possible, manifested by non-specific symptoms such as fever, malaise, myalgia, lymphadenopathy. In addition, patients may present with mononucleosis-like syndrome in association with a maculopapular rash and hepatosplenomegaly. The clinical course is favorable, as a rule, this symptomatology is resolved without treatment. Complications such as myocarditis, pericarditis, pneumonitis rarely occur.

Ocular toxoplasmosis often develops with a congenital form of the disease, but is also seen in a small percentage of infections during life. The signs of ocular involvement in the infectious process are blurred vision, characteristic retinal infiltrates which develop in 85% of young people after congenital toxoplasmosis. Ocular toxoplasmosis can reactivate several years after the initial infection.

In patients with chronic immunodeficiency, including HIV infection, reactivation of a chronic infection can lead to encephalitis, pneumonia, and generalized toxoplasmosis. Newborn babies born to mothers infected with HIV or with another immunodeficiency state and with a chronic infection caused by T.gondii may acquire toxoplasmosis in utero following reactivation of maternal infection [2].

The main diagnostic method is serological. Immunoglobulins G (determined by an indirect fluorescence reaction or an enzyme immunoassay) reach a concentration peak 1 to 2 months after infection and remain positive indefinitely. In patients with seroconversion or a four-fold increase in IgG titer, a specific IgM should be determined to confirm acute infection. The presence of IgM confirms an acute or recent infection. The enzyme linked immunosorbent assay is more sensitive in determining IgM. IgM is determined 2 weeks after infection, reaching a peak after 1 month, and generally disappears after 6 to 9 months, but may persist in some cases for more than 2 years, which makes it difficult to distinguish between infections acute and previous infections. The determination of IgA and IgE, the level of which grows faster than IgM, is useful for the diagnosis of congenital toxoplasmosis and the examination of patients, in particular pregnant women, for whom information on the duration and stage of infection processes are extremely important.

The diagnosis of congenital toxoplasmosis can be made before birth in the study of fetal blood or amniotic fluid (determination of IgM and IgA, DNA T.gondii by PCR). On ultrasound, an increase in the size of the lateral ventricles is an indirect sign of infection.

If toxoplasmosis is suspected in newborns, a study of the visual, auditory and nervous systems, lumbar puncture and CT scan of the head should be performed. You should also try to isolate the pathogen from the placenta, umbilical cord, and blood by mouse infection. An alternative may be the isolation of the pathogen from the cerebrospinal or amniotic fluid using PCR. Transplacental IgG ceases to be detected after 6 to 12 months. In patients with HIV infection, the variability of the IgG titer and the absence of IgM are possible, therefore, with seroconversion and an increase in the IgG titer by 4 times, an active infection should be diagnosed. In people infected with HIV who are seropositive for toxoplasm, the diagnosis of encephalitis is established clinically and only if treatment with T.gondii is ineffective, antigens or DNA must be extracted biopsy material or cerebrospinal fluid [2].

It is possible to isolate the pathogen during infection in laboratory animals, but the conclusion that toxoplasmas are found in this drug does not carry any positive information, except that this patient has been infected. In addition, the absence of pathogens in the preparation cannot serve as a basis for excluding toxoplasmosis, as it simply could not penetrate the test material [3].

In 1948, J. Frenkel proposed using an evaluation of the response to intradermal administration of toxoplasmin for the diagnosis of toxoplasmosis (a complex of cell wall structures of toxoplasm, mainly SAG1). The principle of reaction and its accounting are similar to the tuberculin test. It is proven that the test is very specific, it is not positive for other diseases. In foreign countries, this method is not used due to the difficulty of standardizing the drug [3].

Most cases of infection acquired in immunocompetent individuals are resolved without specific treatment. In the case of chororetinitis or damage to the vital organs, a combination of pyrimethamine and sulfadiazine is prescribed. An alternative may be a combination of pyrimethamine and clindamycin with poor tolerance to sulfadiazine. In the treatment of choreoretinitis and CNS damage, glucocorticoids are used. HIV-infected patients with encephalitis should receive lifelong suppressive therapy to avoid recurrence of the infection.

In case of severe and asymptomatic congenital infection, a combination of pyrimethamine with sulfadiazine and folic acid is recommended as an initial treatment. Therapy is generally long, sometimes up to 1 year. Treatment of toxoplasmosis that occurs during pregnancy, including in women infected with HIV, should be done with spiramycin. When a woman is infected during the third trimester or the fetus is infected after 17 weeks of gestation, a combination of pyrimethamine and sulfadiazine is used [2].

High activity of telithromycin in vitro compared to T.gondii (M. Kilinc, M. Hokelek, M. Erturk) has been shown [1].

Animal studies have shown that atovaquone in combination with pyrrolidine dithiocarbamate causes tachyzoites to convert to the stage of tissue cysts (O. Djurkovic-Djakovic, A. Nikolic , B. Bobic, I. Klun) [1].

Pregnant women with unknown or HIV-negative status should avoid contact with the ground and other objects that may be contaminated with cat feces, or wear gloves and wash their hands after work. Domestic cats, in order to avoid infection, should not eat raw meat or captured rodents. Sufficient heat treatment of meat is necessary, washing vegetables and fruits, washing hands and cooking surfaces after contact with raw meat, vegetables and fruits [2].