Toxoplasmosis Symptoms

Toxoplasmosis is a disease, a protozoal infection caused by the obligate intracellular protozoan Toxoplasma gondii, which has a complex development cycle. This infection is characterized by a tendency to chronic flow with the development of lymphadenopathy, hepatosplenomegaly, lesions of the central nervous system, myocardium and eyes. How to treat this ailment with folk remedies, look here.

The final owner of toxoplasm can be a domestic cat, as well as wild representatives of the cat family. When a cat is infected by an alimentary method, parasites enter the epithelial cells of the intestine, where after several asexual generations, macro- and microgametes are formed. The sexual process is completed by the formation of oocysts, which are excreted into the external environment. Man is an intermediate host of the parasite, but does not isolate the causative agent into the external environment and does not pose an epidemic threat to others. In the human body, toxoplasm multiplies only asexually and go through two stages of development:

The main way of infection with toxoplasmosis is oral( the use of raw meat, vegetables and berries contaminated with soil through dirty hands when contacting cats).However, for clinical practice, the congenital pathway of infection is equally important - intrauterine infection of the fetus from the pregnant woman through the placenta. It is proved fetal infection only from women with a primary infection acquired during this pregnancy. When a woman is infected in the first trimester of pregnancy, congenital toxoplasmosis in a child is recorded in 15-20% of cases, it is severe. When infected in the third trimester of pregnancy, 65% of the newborns are infected. In women with chronic or latent toxoplasmosis, the transmission of the causative agent to the fetus is not proven.

Etiology. The causative agent of toxoplasmosis - Toxoplasma gondii - belongs to the protozoa( Protozoa), the class of sporoviks( Srotozoa), the coccidia( Coccidia), the genus Toxoplasma. An intracellular intracellular parasite that affects any nuclear cells, predominantly a histophagocytic system. Toxoplasma have a complex cycle of development with a change of host. The final owner is the cat and other animals of the cat family, in the intestine of which the sexual cycle of development occurs, which ends with the formation of immature cysts released into the external environment with feces. In the soil after 3-7 days oocysts are formed, which persist for 1.5-2 years. Man is an intermediate host, in the body of which T. gondii undergoes asexual development, which includes 2 stages - tachyzoites( breeding parasites) and bradizoites( persistent in cysts).Trophozoites are characteristic of the acute stage, tissue oocysts are for the chronic stage of the disease.

The parasite size in the trophozoite stage is 4-7 x 2-4 μm. Cysts have a rounded shape, up to 100 μm in diameter, containing up to 3,000-5,000 parasites.

Cysts and oocysts are resistant to chemotherapeutic agents, physico-chemical factors, high and low temperatures, well retained in the soil.

Trophozoites are sensitive to pyrimethamine, spiramycin, sulfonamides, tetracycline. Quickly die with drying, heating, under the influence of disinfectants.

Toxoplasma possesses tropism to the three groups of organs, which determines the specificity of the clinical picture of the disease:

• to lymphoid tissue - lymph nodes, liver, spleen;

• to muscle tissue - skeletal muscles, myocardium;

• to organs "forbidden" for the immune system, - to the central nervous system, to the eyes.

Epidemiology. Toxoplasmosis is an anthropozoonotic infection.

The source is domestic and farm animals:

• cats and other members of the cat family, in the gut of which there is sexual reproduction of the pathogen with the release of oocysts with feces into the environment;

• pigs, cows, sheep, etc., in the muscle tissue of which toxoplasm are in the form of cysts.

Transmission pathways:

1. The alimentary route is carried out when the oocyst enters the intestine with soil contaminated by the feces of cats, and when eating meat is not enough heat-treated meat of infected animals.

2. The parenteral route is described in case of infection of workers in meat processing plants, blood transfusion, organ transplantation, intralaboratory infection.

3. The vertical pathway is realized mainly with the primary infection during pregnancy( the risk of infection of the fetus is 30-40%).In recent years, cases of vertical transmission of pathogens in HIV-infected women with reactivation of chronic toxoplasmosis have been described.

Modern ideas about the pathogenesis of toxoplasmosis provide for the presence of two forms of the disease: congenital and acquired.

Acquired toxoplasmosis occurs when the infection is transmitted by alimentary or parenteral routes. Getting into the human body, pathogens through the lymphatic channels penetrate into the regional lymph nodes. With sufficient barrier mechanisms, the disease does not develop, the pathogens die. Immunodeficiency promotes the multiplication of parasites, their entry into the blood and hematogenous spread through various organs. Parasitemia, as a rule, is short. Toksoplazms settle in the liver, spleen, bone marrow, lymph nodes, nervous system, myocardium, skeletal muscles, eyes and multiply in them. Infectious granulomas are formed, consisting of epithelioid cells, macrophages, plasma cells, lymphocytes, eosinophils and other elements. In the nervous system, eyes, skeletal muscles, it is possible to develop foci of necrosis with the subsequent deposition of calcium salts. With the development of the immune response( 7 to 12 days), the death of free and active intracellular parasites occurs. Only toxoplasm remains in the cysts. As a result of repeated ingestion of toxoplasma products, sensitization of the body begins and a specific allergy is developed, which is detected with the help of an intradermal test with toxoplasmin.

In the human body, toxoplasm in the form of cysts can persist indefinitely, mainly in the tissues of the brain, eyes, internal organs. In the future, they die, calcify, resolve. With the development of IDS, the cyst shells are destroyed and the released parasites, multiplying, affecting a number of located cells, can enter the bloodstream, which explains the recurring course of chronic toxoplasmosis.

Features of the pathogenesis of congenital toxoplasmosis are determined by a number of factors. The frequency of vertical transmission toxoplasm depends on the gestation period. In connection with the "aging" of the placenta, its permeability increases, so the infection rate of the fetus increases from 10% in the first trimester to 60% in the third trimester of pregnancy. On the other hand, an important role is played by the intensity of organogenesis, the maturation of the immune system and the inflammatory reaction of the fetus. In case of infection in the first trimester, in half of the children the disease has a clinical manifestation, and with infection in the third trimester, congenital toxoplasmosis almost always proceeds in an erased or subclinical form.

It is known that the inflammatory reaction of the fetus ripens during ontogeny. In the first trimester of pregnancy, the alterative component of inflammation predominates, and the intensity of organogenesis is quite high. In this regard, infection in the first two weeks of pregnancy leads to the death of the fetus or to blastopathy - a systemic pathology similar to a genetic disease. Infection with a gestation period of 15-75 days is accompanied by its interruption or the formation of embryopathy - the true malformations at the organ and cell level. Further, the intensity of organogenesis decreases, the proliferative component of the inflammatory reaction ripens. When infected with toxoplasma during pregnancy 76-180 days, it is possible to interrupt or develop early fetopathy - a generalized inflammatory reaction with an outcome with fibro-sclerotic deformation of the organs( false vices).In the third semester of pregnancy, the fetus forms an exudative component of inflammation. Infection after the 180th day of pregnancy is accompanied by the development of late fetopathy - the generalized lesion of various systems and organs( hepatitis, encephalitis, chorioretinitis, carditis, pneumonia, etc.).The defeat of the central nervous system and eyes with congenital toxoplasmosis occurs at a later date than the pathology of other organs. When infected shortly before childbirth a child is born with a clinic of acute congenital toxoplasmosis. When infecting in the middle of the third trimester of pregnancy, the acute phase of the disease passes in utero, and symptomatology of the CNS and eye lesions dominates in clinical symptoms( subacute congenital toxoplasmosis).When infected in the second trimester, acute and subacute stages end before the birth of the child, and congenital toxoplasmosis proceeds in a chronic form with a clinical manifestation in the form of hydrocephalus, calcifications in the brain and chorioretinitis with optic nerve atrophy. At infection in even earlier terms of pregnancy the child is born with a clinic of the residual form of congenital toxoplasmosis, which is represented by gross residual phenomena.

There is no generally accepted classification of toxoplasmosis, therefore, in practical work, we recommend using the working variant of the disease classification( Table).

Table

Classification of toxoplasmosis in children

The incubation period of acquired toxoplasmosis is from several days to 3 weeks.

The acquired acute and chronic toxoplasmosis can occur with the predominant lesion of the lymph nodes( lymphonodular form), the nervous system( meningoencephalitic form), the eye( eye form), the heart( myocarditis), the lungs( pulmonary form), the liver( icteric form), gastrointestinal(intestinal form), skin rashes( exanthema form).It is possible to form a generalized form with involvement of visceral organs and the nervous system. Often there are erased, subclinical, latent asymptomatic forms.

The disease often begins with prodromal phenomena: malaise, general weakness, headache, loss of appetite, fever, muscle and joint pain. In the future, the symptoms associated with the predominant localization of the infectious process appear first.

The lymphonodular form of is characterized by an increase in occipital, cervical, less often - axillary and inguinal lymph nodes. Mesenteric lymphadenitis with pains in the abdomen, lesion of bronchopulmonary nodes are described. Lymph nodes reach sizes from 1.5 to 3.5 cm in diameter, painless, elastic consistency, mobile, not soldered to surrounding tissues and to each other. Often the liver and spleen are enlarged at the same time. Possible manifestations of acute tonsillitis. In a number of patients, the glandular form proceeds with relapses, which are characterized by an increase and soreness of the lymph nodes, symptoms of intoxication.

Meningoencephalitic form. Toxoplasmosis can be the cause of acute, subacute and chronic diseases of the nervous system. It leads to severe lesions, both organic and functional.

The following forms of acquired neurotoxoplasmosis are distinguished: cerebral( encephalitis, meningoencephalitis, leptomeningitis, vasculitis, pseudotumorous meningoencephalitis), common( meningo-cephalopolyradiculoneuropathy, diencephalitis), spinal( myelopathy), peripheral nerves( mono- and polyneuropathy).

In the clinic of toxoplasma meningoencephalitis, there are signs of cerebrospinal fluid hypertension, damage to the soft meninges, brainstem and cerebellum. The nature of the inflammation is serous. The hypertensive-hydrocephalic syndrome is rapidly growing, which serves as an erroneous basis for suspicion of the brain tumor.

Chronic acquired toxoplasmosis is often accompanied by damage to the arachnoid of the brain. Toxoplasma leptomeningitis is usually diffuse, however, it is possible and a predominant lesion of the posterior cranial fossa, the bridge-cerebellar angle.

In the clinic, there are attacks of intracranial hypertension, it is possible to involve the ventricles in the process of ependyma with the development of the adhesion process on the basis of the brain and subsequent hypertensive crises.

Organic damage to the vascular wall and impaired innervation of the cerebral vessels lead to the development of cerebral vasculitis, manifested by vascular crises, dynamic disorders of cerebral circulation.

Toxoplasma diencephalitis is characterized by irritable weakness, mental hyperesthesia, sleep disturbances, pronounced adynamia, endocrine and vascular disorders.

Spinal form( myelitis) is rare, the course of the disease is subacute. Perhaps the prevalent lesion of the posterior columns of the spinal cord.

Peripheral nerves are affected in most patients with neurotoxoplasmosis. Patients are concerned about pain and paresthesia in the limbs, painfulness along the roots and peripheral nerves, positive symptoms of tension, peripheral disorders of pain sensitivity, vegetative-trophic disorders( cold snap, cyanosis, hypertrichosis, hyperkeratosis, trophic nail abnormalities) are objectively revealed.

The defeat of the vegetative system is observed in the chronic course of acquired toxoplasmosis and is manifested by acrocyanosis, the "marble pattern" of the skin, and the hyperhidrosis of the skin. Possible attacks of tachycardia, dizziness, sweating.

The eye form proceeds according to the type of chorioretinitis and granulomatous uveitis. The disease has a chronic recurrent course and is often accompanied by other clinical signs of infection - lymphadenopathy, changes in the heart, nervous system. The ability of parasites to persist for a long time in the retina causes the possibility of multiple relapses. Initially, the changes can proceed according to the type of retinitis, and only with repeated relapses the vascular envelope is involved in the process. As a rule, one eye is first affected, and then the other. Changes in both eyes usually proceed in the same way. Chronic recurrent course can lead to atrophy of the optic nerve and retina disc with partial or total loss of vision.

Heart attack occupies one of the leading places in frequency among pathologies of internal organs. Develop focal or diffuse myocarditis, pericarditis. Patients are concerned about weakness, fatigue, shortness of breath, palpitation, chest pain. Objectively, the expansion of the heart boundaries, deafness of tones, systolic murmur are revealed. Atrial fibrillation is possible. On the ECG, there are conduction disorders, expansion of the PQ complex, negative or biphasic T.

. Respiratory damage, of the gastrointestinal tract, liver, kidneys often develops in patients with a generalized form of the disease.

The generalized form of is accompanied by fever, chills, muscle and joint pain. In the first 3-4 days in the process involved myocardium, liver, kidneys, intestines, nervous system. The symptoms of intoxication are sharply expressed. Often there is a patchy-papular rash. The disease is characterized by a severe course, an unfavorable outcome is possible.

Acquired toxoplasmosis in some patients has an acute course, but often the process acquires a chronic course. In patients with chronic toxoplasmosis, in addition to intoxication and subfebrile body temperature, lymphadenopathy, hepatosplenomegaly, nervous system damage( chronic leptomeningitis), eye( chorioretinitis), liver( chronic hepatitis), and heart( myocarditis) are detected.

The clinical picture of congenital toxoplasmosis depends on the gestational age at which the fetus has become infected.

Infection of the fetus with toxoplasma after the completion of organogenesis in the last months of pregnancy leads to the birth of a child with symptoms of acute generalized form. The disease is characterized by a general severe condition, pronounced intoxication, high body temperature, abundant polymorphous rash( roseoseous, spottypapular, hemorrhagic), hepatosplenomegaly, icteric skin color and sclera, generalized lymphadenopathy. Possible development of hemorrhagic syndrome, pneumonia, myocarditis, dyspeptic disorders. The course of acute congenital toxaplasmosis is severe, a lethal outcome is possible.

Subacute form is observed in case of infection of the fetus in the last months of pregnancy and development of the generalized acute form in utero. By the time of birth, acute toxoplasmosis is replaced by a subacute form. Clinically diagnosed toxoplasma meningoencephalitis or encephalitis. Very characteristic of the defeat of the eyes( chorioretinitis, optic nerve atrophy).Attention is drawn to progressive hydrocephalus. Vlivore detect lymphocytic pleocytosis, high protein content, protein-cell dissociation, xanthochromia. Calciocytes are revealed on the craniogram.

When the fetus is infected during the first 3 months of pregnancy, during embryogenesis, the acute generalized stage of the infectious process can result in abortion or the birth of a child with manifestations of chronic toxoplasmosis. A triad of chronic congenital toxoplasmosis is described: hydrocephalus, intracranial calcifications, chorioretinitis. There are lag in physical and mental development, spastic paralysis, convulsive syndrome, hepatosplenomegaly, often prolonged jaundice, anemia. With age, the child develops hydrocephalus, optic nerve atrophy.

In 75-80% of patients, congenital toxoplasmosis occurs in a latent form. The consequences of slow toxoplasma encephalitis may occur later, in children older than 5-7 years of life. Hypothalamic syndrome as a manifestation of congenital toxoplasmosis is diagnosed in puberty and prepubertal age and manifests itself mainly as neuroendocrinal disorders. The body weight of children exceeds the normal ratio with growth by 25-40%.Obesity is uniform. The development of the skeleton is harmonious. In boys, there are changes in the external genital organs according to the type of hypogenitalism. Girls are more likely to have external signs of premature ripening. The intellect of these children almost always corresponds to the age, but there are pronounced violations in the emotional-volitional sphere.

Congenital neurotoxoplasmosis can be the cause of diencephalic epilepsy, which manifests itself at the age of 13-15 years. Attacks of diencephalic epilepsy join the pre-existing pathological symptoms: urinary incontinence, visual hallucinations, night terrors, prolonged fever, lymphadenopathy. Intellect in these patients corresponds to age, but emotional lability is expressed, working capacity is reduced. With objective examination, symptoms of vascular innervation are revealed, especially at the time of the diencephalic crisis.

In patients with recurrent meningoencephalopoliradiculoneuropathy, unlike other forms of congenital neurotoxoplasmosis, eye damage and calcification on the radiograph of the skull are rarely observed. Symptoms of damage to the nervous system are combined with signs of damage to internal organs( myocarditis, hepatocholecystitis, generalized lymphadenopathy).Among the patients, girls from 7 to 14 years old prevail. The disease begins both acute and subacute, and is characterized by the presence of meningeal syndrome, microsymptomatology of the damage to the brain substance, peripheral nerves, vegetative-trophic disturbances in the distal parts of the extremities.

Diagnosis of toxoplasmosis is based on epidemiological history, clinical symptoms of the disease and laboratory examination.

In the hemogram, leukopenia, neutropenia, relative lymphocytosis, increased eosinophils, normal ESR are detected.

In the liquorgram, patients with toxoplasma meningoencephalitis are diagnosed with xanthochromia, lymphocytic pleocytosis, and an increase in protein content.

The radiograph of the skull of a patient with toxoplasmosis shows an increase in the vascular pattern, finger impressions, widening of the interosseous sutures, and the presence of intracranial calcifications. Calcifications are located mainly in the occipitoneal parietal region. They have a size from 1-2 to 3-4 mm, round, oval or irregular shape, are arranged one by one or in the form of a chain, a broken line.

There are three groups of methods for laboratory diagnosis of toxoplasmosis.

1. Methods aimed at direct detection of toxoplasm, their antigens and DNA:

• Culture method.

• Microscopy of blood smears, cerebrospinal fluid centrifugation, lymph node biopsy specimens of other organs and tissues when stained by Romanovsky-Giemsa or silvering.

• Immunofluorescence reaction - an express method for detecting toxoplasm in smears -prints of the brain, centrifuges.

• Polymerase chain reaction - detection of DNA toxoplasma in blood and CSF.

• Bioassay for infecting a laboratory animal.

Factor limiting the effectiveness of direct toxoplasm detection methods for intravital diagnosis of the disease is the short-term presence of pathogens in biological fluids that are accessible to research.

2. Methods that characterize a specific humoral immune response. Traditional serological reactions( RNIF, RAC) in paired sera are currently rarely used. High sensitivity and specificity is possessed by the method of I FA, which allows separate detection of antibodies of classes IgM and IgG.At present, test systems have been developed that make it possible to determine antibodies of IgA class and avidity of IgG antibodies.

• IgM antibodies appear from the first-second week after the primary infection and peak at the end of the first month. Later, their titre decreases. In 70% of patients, IgM antibodies disappear by the third month after infection, 10% by the 12th month. This makes it difficult to determine the timing of infection, which is especially important when examining pregnant women. It should be remembered that with exacerbation of chronic toxoplasmosis IgM class antibodies are not synthesized. When reinfected in patients with chronic or latent toxoplasmosis, antibodies of IgM class may reappear in the blood.

• IgG antibodies are beginning to be synthesized from the second week after the primary infection. Their titre increases within two to three months. Over the next 12 months, the IgG titer stabilizes at a high level, further decreases and has a wavy character. When reactivated, the IgG content of antibodies may increase, but this is not observed in all patients, especially in chorioretinitis in children and adolescents with congenital toxoplasmosis. Of great importance nowadays is the study of avidity of antibodies of IgG class( strength and binding with antigen).At the primary infection antibodies with low avidity are first synthesized( indexedness 30-50%).After 1-7 months, highly antibodies of IgG class with an avidity index of more than 50% begin to be produced. Their appearance indicates the end of the acute phase of the disease.

• For the diagnosis of toxoplasma encephalitis, test systems have now been developed that allow the determination of intrathecal synthesis of anti-toxoid IgG antibodies.

• Antibodies of class JgA with a short half-life( 4-5 days) are a marker of the activity of the infectious process. Antibodies of this class do not penetrate the placenta. They begin to be synthesized 10-14 days after the primary infection. During the first three months, their titer increases, then remains stable for 3-6 months. Later they disappear, usually later than antibodies of IgM class. However, in some patients, IgA antibodies are detected 4 years after the registered seroconversion. When reactivating toxoplasmosis, IgA reappear in the blood. The disappearance of IgA on the background of antitoxic-plasma therapy testifies to its effectiveness.

• Immunoblot - serological method, which allows to determine antibodies to individual antigens of toxoplasm. The markers of the active phase of toxoplasmosis are antibodies to MAGI( p65), SAG1( pZO), indicators of the inactive phase - antibodies to GRA7( p29), GRA8( p35).The immunoblot is recommended to be used to confirm the diagnosis in pregnant women and in patients with IDS.

3. Hypersensitivity of the delayed type to toxoplasm is detected by means of an intradermal test with toxoplasmin.0.1 ml of toxoplasmine is injected into the anterior surface of the forearm. The reaction is evaluated after 48 hours. The sample is considered positive for hyperemia and infiltration more than 10 mm. It becomes positive at the 4-5th week after the primary infection and persists throughout life. In children of the first two years of life, a test with toxoplasmin can be false-negative. To distinguish the inactive and active phases of chronic toxoplasmosis, a sample with diluted toxoplasmine( 1: 10) is recommended. A positive test indicates an active phase of the infection process.

It is necessary to distinguish between toxoplasmic( carrier) infection from toxoplasmosis proper( disease), so the most important thing in laboratory diagnostics is not the fact of detection of a positive immune response( AT), but a clarification of the nature of the course of the process - carriage or illness. The complex definition of AT classes IgM and IgG makes it possible to quickly confirm or deny the diagnosis. The main method at present is ELISA, which allows detecting ATM classes of IgM and IgG.

AT-class IgM to toxoplasma in serum is normal.

ATM IgM appear in the acute period of infection( in the first week in the titer 1:10), peak within a month( 2-3 weeks after infection) and disappear after 2-3 months( at the earliest - after 1 month).They are detected in 75% of congenital infected newborns and in 97% of infected adults. Negative results of the determination of AT IgM allow to exclude an acute infection lasting less than 3 weeks, but do not exclude an infection of a longer duration. When reinfection, the titer of Ig Ig again rises( in the presence of immunodeficiency does not increase, in such cases, a computer or magnetic resonance imaging of the brain that reveals multiple dense rounded foci is shown for diagnosis).The presence of rheumatoid factor and / or antinuclear AT in the blood of patients can lead to false positive results of the study. In persons with immunodeficiency of Ig IgM in an acute period of infection, there are usually no.

Early diagnosis of toxoplasmosis is especially important for pregnant women due to the risk of intrauterine infection of the fetus, which can lead to fetal death( spontaneous abortion) or the birth of a child with serious lesions. Specific treatment of women in the early stages of the infectious process reduces the risk of fetal damage by 60%.Because IgM class antibodies do not penetrate the placenta, detection of them in the blood of the newborn indicates an innate infection.

АТ class IgG appear in the period of convalescence and have recovered for up to 10 years. Definition of AT class IgG is used for diagnostics of the period of convalescence of toxoplasmosis and evaluation of the intensity of post-vaccination immunity. False positive results can be obtained from patients with SLE and rheumatoid arthritis.

Persons with positive AT titers for toxoplasmosis are recommended to re-conduct serological tests 10-14 days later to establish the dynamics of the disease. The absence of an increase in AT titers indicates a chronic toxoplasmosis. The increase of titers by 3-4 dilutions of serum testifies to the active course of the invasion.

Indications for the appointment of serological tests for toxoplasmosis:

• Weighed obstetrical anamnesis - spontaneous abortions, stillbirths, threat of termination of pregnancy, gestosis, infectious diseases during pregnancy.

• Contact pregnant woman with cats, eating insufficiently thermally processed meat, tasting fresh minced meat.

• Long-term febrile or subfebrile fever and symptoms of intoxication in a child.

• CNS lesion - encephalitis, meningoencephalitis, arachnoiditis, hydrocephalus, microcephaly, calcification in the brain.

• Eye damage - chorioretinitis, uveitis, microphthalmia, atrophy of the optic nerve.

• Hepatosplenomegaly, jaundice, generalized lymphadenopathy.

• Myocarditis.

• Polymorphic exanthema.

• Prematurity, intrauterine growth retardation, lag in physical development.

• Detection of specific antibodies of IgM class, IgA, growth of IgG class titer, detection of DNA toxoplasma in blood and CSF by PCR method.

• epidemiological anamnesis - contact with cats, eating insufficiently thermally processed products of animal origin;

• anamnestic data - frequent infectious diseases accompanied by fever, increased lymph nodes, liver, joint and muscle pain, rash, anemia;

• clinical criteria - involving a number of organs and systems, including lymph nodes( their enlargement), the liver( its enlargement, icteric staining of the skin and sclera), the heart( myocarditis), the nervous system( asthenic syndrome, emotional and vascularlability, sensitivity disorders like "gloves" and "socks", diencephalic disorders, etc.), eye damage( chorioretinitis, uveitis, iridocyclitis);

• characteristic changes on the neurosonogram, radiograph of the skull( calcinates);

• positive allergic intradermal tests with toxoplasmin;

• detection of specific antibodies by ELISA;

• detection of toxoplasm in the blood, CSF.

Treatment of toxoplasmosis in infants and young children with severe and complicated forms of the disease is carried out in a hospital, in older patients with erased and subclinical forms - in outpatient settings. Patients are shown a balanced diet.

Drugs used for etiotropic therapy only act on vegetative forms of toxoplasm( tachyzoites) and are ineffective against parasites in cysts. The drugs of choice are pyrimethamine, spiramycin( rovamycin), clarithromycin( fromilide).Pyrimethamine is a folic acid antagonist. The effectiveness of the drug increases with its combination with sulfonamides( sulfadimezinom, sulfadiazinom, etc.).When taking pyrimethamine, side effects often occur, such as oppression of bone marrow hematopoiesis, headache, dizziness, pain in the heart and abdomen, nausea, vomiting, diarrhea, etc. To prevent them simultaneously with pyrimethamine, calcium folinate( leucovorin) or beeryeast. High antitoxoplasma activity is possessed by the macrolide antibiotic spiramycin( rovamycin).

Indications for prescribing etiotropic therapy:

• Children younger than 3 months with proven congenital toxoplasmosis, and if it is impossible to exclude this disease, regardless of the severity of clinical manifestations.

• Children aged 3 to 12 months with newly diagnosed congenital toxoplasmosis in the presence of clinical and laboratory indicators of the active phase of the disease.

• Children over one year of age with a documented acute stage of the disease, regardless of the severity of clinical symptoms, as well as during an exacerbation of chronic toxoplasmosis.

Etiotropic therapy for congenital toxoplasmosis. In the generalized form of congenital toxoplasmosis, triterapy( pyrimethamine + sulfadiazine + calcium folinate) is recommended. Pyrimethamine in the first 2 days is prescribed at a dose of 2 mg / kg / day in 2 divided doses, then at a dose of 1 mg / kg / day in 2 divided doses for 2-6 months. Later on they switch to a dose of 1 mg / kg / day in 2 divided doses 3 times a week. At the same time, sulfadiazine is prescribed at 50 mg / kg / day in 2 divided doses and calcium folinate( leucovorin) 10 mg 3 times a week. The total duration of treatment is 12 months.

Given the frequent side effects with pyrimethamine, alternate four-week courses of triterapy with spiramycin( rovamycin) at a dose of 300 thousand units / kg / day in 2-3 oral administration or monotherapy with this drug. The total duration of treatment is 12 months.

With erased and subclinical forms of congenital toxoplasmosis in children less than 3 months old and with newly diagnosed congenital toxoplasmosis in children aged 3 to 12 months with clinical and laboratory indicators of the active phase of the disease, spiramycin is used for 2-4 weeks.

Etiotropic therapy of acquired toxoplasmosis. In acute toxoplasmosis and exacerbation of chronic toxoplasmosis in children aged 1 to 9 years, spiramycin at a dose of 150-300 thousand units / kg / day in 2-

3 oral administration is used for 14 days. Patients over 9 years of age and simultaneously with spiramycin are prescribed doxycycline( on the first day of 200 mg, then 100 mg once inside) and metronidazole( 250-500 mg / day in 3 divided doses) for 10 days. With the development of chorioretinitis, the course of antiprotozoal therapy is 4 weeks. In patients with chronic toxoplasmosis at the age of more than 5 years after the course of etiotropic therapy, it is recommended to conduct specific immunotherapy with toxoplasmin. The effectiveness of two-stage treatment is more than 90%.

Pathogenetic therapy includes measures aimed at eliminating the leading pathogenesis pathways of the disease. Important importance is currently attached to toxoplasmotherapy. This method is indicated for children older than 5 years of life with an active form of chronic toxoplasmosis. Use working dilutions of the drug, with intradermal administration of which the diameter of hyperemia and infiltration of the skin is 5 to 10 mm, and the general reactions are poorly expressed( usually dilutions 1: 10,000 - 1: 100,000, sometimes 1: 10,000,000).On the first day, toxoplasmine is administered intracutaneously in 0.1 ml to 3 points of the palmar surface of the forearm. Subsequently, the number of injection points is increased by one per day, bringing up to 10 points on the eighth day of treatment. As the local reaction decreases, dilution of toxoplasmin is reduced. Simultaneously, a general UFO is administered, the dose of which is increased from 1/4 of the bio-dose in the first 2 days of therapy to 1 biodoside in the last 2 days of treatment. With chorioretinitis toxoplasmic therapy is carried out 4-6 months after the relief of acute manifestations of the disease or exacerbation of the chronic process on the fundus. The course is repeated after 12 months( the relapse rate is less than 1%).

Pathogenetic therapy should include the appointment of antihistamines, as well as immunomodulators( thymalin, tactivin, thymogen, imunofan, polyoxidonium, lycopide, derinat, sodium nucleate, IRS-19, ribomunil, bronchomunal, immunomax, etc.) and cytokine preparations( leukinferon, roncoleukinand others) under the control of the immunogram. For prophylaxis of a dysbacteriosis probiotics( bifiform, bifidumbacterin-forte, probibor, lineks, etc.) are used. Disintoxication therapy is carried out: in case of mild and moderate forms, abundant drinking is prescribed, with severe and complicated forms - intravenous drip infusions of glucose-salt solutions. Assign multivitamins, vitamin-mineral complexes, preparations of metabolic therapy( riboksin, kokarboksilaza, cytochrome, elkar, etc.), plant adaptogens( ginseng, eleutherococcus, etc.), enterosorbents( smecta, filterum, polyphepan, enterosgel, etc.).According to the indications, protease inhibitors( countercrasal, trasanol, gordox), vasoactive drugs( cavinton, actovegin, cinnarizine, pentoxifylline, etc.), hepatoprotectors, oxygen therapy are used. If necessary, prescribe physiotherapy: UFO, D'Arsonval currents, diadynamic currents, diathermy, paraffin applications, aeroionotherapy, etc. Treatment of individual nosological forms( hepatitis, encephalitis, etc.) is carried out according to general principles.

Symptomatic therapy includes prescription according to the indications of antipyretic drugs and cardiac glycosides.

The timing, the frequency of follow-up and the amount of examination depend on the form of toxoplasmosis.

Children who have experienced acute toxoplasmosis, pediatrician and infectious diseases are examined once every 6 months for 10 years. Consultation of specialists( neuropathologist, oculist) is carried out once in 6 months for 10 years. Serological markers of toxoplasmosis by ELISA are examined once every 3-6 months.

Patients with chronic toxoplasmosis are examined by a pediatrician and infectious disease specialist 1 and 3 months after the start of treatment, then 1 time in 6 months. Consultation of specialists( neuropathologist, oculist) is carried out 1 and 3 months after the beginning of treatment, then 1 time in 6 months. Serological markers of toxoplasmosis by ELISA are examined once every 3-6 months.

Rehabilitation therapy includes the following activities:

1. Safety mode.

2. Health food.

3. Immunomodulators( thymalin, tactivin, thymogen, imunophane, lipoxidonium, lycopide, derinat, sodium nucleate, IRS-19, ribomunil, bronchomunal, immunomax, etc.) and cytokine preparations( leukinferon, roncoleukin) under the control of the immunogram.

4. Interferons( viferon, kipferon, reaferon-EC-lipint, etc.) and its inducers( neovir, cichopopher, amixin, anaferon, etc.).

5. Multivitamins courses for 1 month.

6. Vegetative adaptogens in 1 month courses.

7. Metabolic therapy( riboksin, limonar, elkar, etc.) - courses for 2-3 weeks.

8. LFK.

9. Massage.

10. Physiotherapy - UFO, D'Arsonval currents, diadynamic currents, diathermy, paraffin applications, aeroionotherapy.

11. Acupuncture.

12. Sanatorium treatment.

Specific prophylaxis of toxoplasmosis is not developed, so the main importance is attached to non-specific measures taking into account the pathways of transmission of the pathogen.

Important place is to observe personal hygiene, heat treatment of meat, restrict contact with cats, examine them for toxoplasmosis and treatment in case of illness.

Prophylaxis of congenital toxoplasmosis is performed at the pregravidar and gravidar stages. It is necessary to examine women of childbearing age, preferably 2 months before the planned pregnancy. When detecting the markers of the active phase of toxoplasmosis, it is treated. In the absence of antibodies with women, they are instructed to prevent toxoplasma infection.

At the gravitational stage, an early serological examination of pregnant women is required, preferably in the first 10-12 weeks of pregnancy. Seronegative women explain the measures for the prevention of toxoplasmosis and recommend a re-examination at the gestation period of 20-22 and 30-32 weeks. When high-antibodies of IgG class are detected, a woman is excluded from the risk group. When detecting classes of IgM, IgA and low-grade IgG, a repeated examination with an interval of 7-14 days is necessary, which allows diagnosing acute toxoplasmosis in a pregnant woman and determining the risk of infection of the fetus( Table).

In difficult cases, direct methods for detecting the pathogen and the use of the immunoblot are additionally recommended( the markers of the active phase are antibodies to the antigens MAG1 and SAG1).

When an acute toxoplasmosis is diagnosed, counseling the pregnant woman about the risk of congenital toxoplasmosis in a child is conducted and the issue of abortion is considered. When prolonging pregnancy, preventive treatment with spiramycin is prescribed and antenatal diagnosis of congenital toxoplasmosis in the fetus is recommended. To do this, use ultrasound, the detection of IgM antibodies in fetal blood taken during cordocentesis, and the detection of toxoplasma DNA by PCR in the amniotic fluid obtained in amniocentesis. In the absence of laboratory signs of congenital toxoplasmosis and in the event that its antenatal diagnosis was not performed, spiramycin treatment is continued until delivery. When the laboratory markers of congenital toxoplasmosis are found in the fetus, the issue of abortion is re-examined. In the case of prolongation of pregnancy in the third semester, the appointment of three-week courses of triterapy( pyrimethamine + sulfadiazine + calcium folinate) and spiramycin alternate. In the first and second trimesters of pregnancy, a combination of erythromycin and sulfadiazine is used instead of triterapy.