Intrauterine infection

Intrauterine infection is a fetus and newborn disease that occurs as a result of an ante- and / or intranatal infection, manifested in the intrauterine period or in the first days (months) after birth.

The frequency of intrauterine infection among sick newborns is 3-5%.

[1], [2], [3],

What causes intrauterine infection?

Previously, intrauterine infection was termed "TORCH infection" in the first letters of the names of nosologies: toxoplasmosis - toxoplasmosis, other - others, rubella - rubella, cytomegalia - cytomegalia, herpes - herpes.

Currently, congenital, or intrauterine infection - numerous diseases of different etiologies.

Among the pathogens of this group of diseases, the most significant viruses are able to pass through the placenta easily due to their small size. These include representatives of the families Herpesviridae [cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2], Retroviridae [human immunodeficiency virus (HIV)], Parvoviridae (viruses of group B), Togaviridae (Rubella virus), Paramyxoviridae measles), Hepadnoviridae (hepatitis B virus), Flaviviridae (hepatitis C virus), Picornaviridae (enteroviruses). The causative agents of acute respiratory viral diseases are etiologically not so important, since they are quite large in size, which do not allow penetration through the placenta, and also because of the presence of specific antibodies in the mother are eliminated from the body.

In second place in importance in the etiological structure of these diseases are the simplest, toxoplasm, and a representative of the family Treponematoceae, pale treponema. An even smaller role is assigned to listeria and pathogenic fungi.

So, the etiology of intrauterine infections looks like this.

Viruses:

• family Herpesviridae (CMV, HSV types 1 and 2);
• family Retroviridae (human immunodeficiency virus);
• family Parvoviridae (viruses of group B);
• the Togaviridae family (rubella virus);
• family Paramyxoviridae (measles virus);
• family Hepadnoviridae (hepatitis B virus);
• family Flaviviridae (hepatitis C virus);
• family Picomaviridae (enterovirus).

The simplest (toxoplasm).

Bacteria:

• streptococcus groups B and D;
• staphylococci;
• pale treponema;
• chlamydia;
• Mycoplasmas (mycoplasmas and ureaplasma);
• Listeria. 

Pathogenic fungi (representatives of the genus Candida).

Pathogenesis and ways of infection of the fetus and the newborn

• Depending on the gestational age at which the infectious factor is affected, different outcomes are possible.
• In the period of embryogenesis, in response to the effect of the pathological factor, there is an alteration in the rudiments of the organs, which causes the disturbance of morphogenesis. An infectious agent can have a double effect.
• Embryotoxic mechanism: damage to the endothelium, occlusion of the lumen of the vessels, leading to hypoxia of the embryo. As a result, the development of the embryo is slowing down to its death. Diagnose frozen pregnancy or miscarriages in the early stages.
• Teratogenic mechanism: violation of the laying of organs and tissues, leading to malformations (VPR); Miscarriages are possible (both early and late).

Thus, the effect of the infectious agent in the embryonic period (16-75 days) may result in the formation of VLF, frozen pregnancy, miscarriages.

In the period of early fetogenesis (76-180th day), the fetus has an inflammatory reaction in response to the action of damaging agents. The reaction is imperfect, since it is non-specific, and consists in the alteration and excessive development of the mesenchyme, leading to the formation of fibrotic changes in the organs. In the case of severe disease, the fetus is killed (late miscarriage, stillbirth). In a mild course, there may be changes in the organs of the fetus. In this case, you can expect several outcomes.

Formation of congenital malformations of inflammatory genesis due to proliferation of connective tissue. For example, with transferred hepatitis, as a result of compression of the bile ducts, atresia of the bile ducts occurs. When the encephalitis is transferred, there is an underdevelopment of gray matter, gliosis of the brain and, as a consequence, microcephaly.

With a very light course of the inflammatory reaction, only a slowdown in the increase in mass and length of the fetal body can be observed, as a result, a delay in intrauterine development (FTD) is noted.

When the infectious agent contacts the fetal tissues before the 12th week of gestation, when the antigen is not recognized by the immune system and is not eliminated (the formation of immunological tolerance); there is a slow infection, which can occur at a later age.

Thus, the effect of the infectious agent in the period of early fetogenesis can result in stillbirth, ZVUR, the formation of VLP, immunological tolerance.

When infected in the III trimester of pregnancy, the fetus produces antibodies (Th-2-response). Th-1-the immune system response is poorly expressed. It underlies the elimination of any antigen, and if it were not for the placenta, the fetus would be rejected during pregnancy.

That is why the immune reaction of the fetus is formed mainly in the Th-2 type, which is more associated with humoral immunity, which is also at the basis of the atopic response. There is more sensitization than protection of the fetus.

The consequences of an intrauterine infection will depend on the severity of the infection process.

In severe infectious process, fetal death and stillbirth are possible.

With moderate severity, fetal disease develops, i.e. Intrauterine infection.

With a light course, it is possible to have an ESRD, and mainly on a hypotrophic (asymmetric) type.

In addition, possible rejection of the fetus, miscarriage and premature birth. This is due to the fact that as a result of the infectious process, the release of interferons, which in turn induce an immune response in the Th-1 type. The pregnant also increases the Th1-1 immune response, which increases the probability of rejection.

When the infectious pathogen enters the fetus, intrauterine infection occurs. This is not a disease, and various outcomes are possible:

• absence of intrauterine disease of the fetus (in the presence of natural resistance to the causative agent, for example, anthrax);
• the formation of immunological tolerance (depends on the timing of infection in the period of fetogenesis);
• infectious process, i.e. Disease.

Infection of the fetus can occur both in the antenatal and in the intranatal period. In the antenatal period, two routes of infection are possible: transplacental and ascending. The first is more typical for viruses that are able to penetrate through an intact placental barrier. However, under the influence of other microorganisms (listeria, chlamydia, ureaplasma, etc.), placental development and infection of the fetus are possible. With ascending infection, the integrity of the amniotic membranes is broken and the infectious agent comes in aspiration of infected amniotic fluid and / or secretion of the mother's birth canal. Contact path of infection through the affected skin is possible. Intranatal infection occurs during labor and can be realized with all kinds of pathogens.

The source of infection for the fetus is in most cases the mother. But the widespread use in recent years of invasive methods of prenatal diagnosis and treatment, as well as the prolongation of pregnancy with premature rupture of amniotic membranes, creates conditions for iatrogenic intrauterine infection.

Symptoms of intrauterine infection

Almost all intrauterine infections are characterized by a similar clinical picture, which includes the following symptom complexes:

• ZVUR;
• changes on the skin of a different nature, jaundice;
• hepatosplenomegaly (possibly in combination with hepatitis);
• defeat of the central nervous system from minimal manifestations to a picture of meningitis or meningoencephalitis;
• defeat of the respiratory tract;
• cardiovascular disorders;
• kidney damage;
• hematological abnormalities in the form of anemia, thrombocytopenia or hyperthrombocytosis, neutropenia, blood clotting disorders.

Congenital cytomegalovirus infection

One of the most frequent intrauterine infections (0.2-0.5%). The high frequency of intrauterine infection with CMV is due to its wide spread in the human population, depending on age, social status, level of material well-being and sexual activity of 20-95%.

The source of infection is a sick person or a virus carrier. Transmission is carried out mainly by contact, less often - airborne and alimentary. Congenital cytomegalovirus infection develops as a result of antenatal (transplacental) or intranatal infection. In most cases of intrauterine infection, the source of the pathogen is the mother, ailing CMV. Transfusion transfer of the causative agent is possible with the introduction of fetal blood products infected with CMV. The greatest risk of intrauterine infection of the fetus of CMV and the development of severe forms of the disease is noted in cases when the pregnant woman is sick with primary CMV. The incidence of primary diseases during pregnancy is approximately 1%. Intrauterine infection of the fetus occurs in 30-50% of cases. At the same time, 5-18% of infected children are marked with a manifest form of intrauterine infection with severe course and, often, lethal outcome.

If the secondary infectious disease develops (reactivation of latent-transmitting CMVI or infection with a new virus strain of women seropositive for CMV), the risk of infection of the fetus and development of severe forms of congenital cytomegalovirus infection is significantly lower (less than 2%), which is caused by the formation of specific immunity.

Causes

The causative agent of this intrauterine infection is Cytomegalovirus hominis. It is a DNA-containing virus of the Herpesviridae family, belonging to the group "Human Herpesvirus-5".

Pathogenesis

In the fetal organism, the virus spreads unimpeded, penetrates into cells where it actively replicates and forms daughter virus particles. The daughter virions, having left the infected cell, hit adjacent intact cells. Affected CMV cells are hypertrophied, their nuclei increase in size. Such a cell with a large nucleus and a narrow band of protoplasm is called the "owl eye". The degree of damage to the fetus depends on the intensity of reproduction of the virus. In this case, both minimal manifestations of the disease (asymptomatic, subclinical forms) and severe lesions are possible: embryo and fetopathy, generalized inflammatory changes.

Classification

Generalized form.

Localized forms:

• cerebral;
• hepatic;
• pulmonary;
• renal;
• mixed.

Asymptomatic form.

Symptoms

With antenatal infection, the clinical picture of the disease can manifest itself from birth. Observe the symptoms:

• thrombocytopenic purpura (76%);
• jaundice (67%);
• hepatosplenomegaly (60%);
• microcephaly (53%);
• hypotrophy (50%);
• prematurity (34%);
• hepatitis (20%);
• interstitial pneumonia;
• encephalitis;
• chorioretinitis.

In rare cases, when a secondary cytomegalovirus infection in a pregnant woman is accompanied by intrauterine infection of the fetus, congenital CMVI is asymptomatic. However, in the future, 5-17% of children may develop such neurological changes as neurosensory deafness, delayed psychomotor development, small brain dysfunction, etc.

With intranatal infection, the course of the disease is largely determined by the features of the premorbid state of the newborn (maturity, fullness, perinatal lesions, the degree of manifestation of functional changes during the adaptation period, etc.). At the same time, preterm weakened children with a burdened perinatal anamnesis have a clinical manifestation of CMVI already by the 3rd-5th week of life. Most often, interstitial pneumonia is noted, prolonged jaundice, hepatosplenomegaly, anemia and other hematologic disorders are possible.

Diagnostics

Virological methods. Molecular - the detection of the genome of CMV by DNA hybridization and PCR. The material for research can be any biological environment of the body (blood, saliva, urine, tracheal washings, cerebrospinal fluid, etc.).

Serological (ELISA) is used to detect anti-CMV antibodies, to determine the avidity of antibodies.

Absolute criteria for the verification of the diagnosis of "congenital CMVI" is the detection in the blood of the causative agent (viremia), its genome (DNA) or antigens. Detection of the genome of CMV in the blood and CSF can be interpreted as a sign of an active period of intrauterine CMV. If the DNA of the virus is found in the cells of other biological media, then it is impossible to judge the period of the disease unequivocally.

Serologic markers of this intrauterine infection are less reliable. But the detection of antibodies of IgM class in cord blood, as well as in the blood of the newborn is one of the important diagnostic criteria. The confirmation of the active period of congenital CMV is also the detection, along with anti-CMV IgM, of a rise in the low-like anti-CMV titre

The detection of specific anti-CMV IgM, as well as the detection of a 4-fold increase in titre in anti-CMV paired sera or the detection of low-avidity indicates an active (acute) period of infection.

Treatment

Indication for the conduct of etiotropic treatment is the active period of the manifest form of the disease.

Because of the high toxicity, the use of virostatic drugs (ganciclovir, valganciclovir) in neonates is unacceptable.

The drug of choice for the etiotropic treatment of intrauterine infection is the human immunocorticine antitcitomegalovirus (NeoCytotect). Form release: 10 ml in a vial, solution ready for use. Neocystect can not be mixed with other drugs.

Method of administration: intravenously with a perfusion pump. Single dose is 1 ml / kg every 48 hours until the disappearance of clinical symptoms (usually 3-5 infusions). Initial infusion rate of 0.08 ml / (kghh), after 10 min, with a good tolerance of the drug, a gradual increase in the rate of maximum to 0.8 ml / (kghh) is possible.

Contraindications:

• intolerance to human immunoglobulin;
• hereditary immunodeficiency conditions, accompanied by a lack or a sharp decrease in the concentration of IgA. The issue of the need for etiotropic treatment of newborns
• with the asymptomatic course of congenital CMV is not completely resolved.

Features of care and feeding:

• to care for a child with congenital CMVI should not be allowed seronegative pregnant women;
• It is not allowed to feed a seronegative newborn with donor milk from a seropositive woman;
• In case of CMVI, a seropositive woman should not stop breastfeeding the baby.

[4], [5], [6], [7], [8], [9], [10]

Dispensary supervision

Children with congenital CMVI, as well as children at risk, are subject to follow-up. The risk group consists of newborns from infected mothers and women with a history of obstetric anamnesis. The district pediatrician and neurologist, and other specialists, if necessary, carry out the medical examination.

Children with this intrauterine infection are observed throughout the year, with a chronic form - for 3 years, with a residual form, when they detect developmental anomalies, before going to a teenage room. Multiplicity of examinations: at birth, at 1, 3, 6 months, later - every 6 months.

For children at risk, dispensary observation is carried out during the year, with examinations at birth, at 1, 3, 6 and 12 months of life.

Clinical and laboratory surveillance includes neurological and audiological research, ultrasound of the brain and parenchymal organs, assessment of hematological parameters, biochemical blood test, determination of specific antibodies to CMV, immunogram examination.

Preventive vaccinations for children with CMV are not recommended for a year.

[11], [12], [13], [14], [15], [16], [17], [18], [19], [20]

Congenital herpetic infection

The frequency of neonatal herpes ranges from 1/2500 to 1/60 000 newborns with the spread of herpetic infection among the adult population of 7-40%. Clinical symptoms of genital herpes are observed only in 5% of infected. In preterm births, congenital herpetic infection (VGI) occurs 4 times more often than in term infants. The highest risk of developing a herpetic infection in a newborn is observed in cases of manifestation of genital herpes in a pregnant woman shortly before birth (within 1 month).

The source of this intrauterine infection for a pregnant woman is a patient or a virus carrier. Transmission ways: contact, sexual and airborne. Probably antenatal (about 5% of cases), more often - intranatal infection in contact with secretions from the genital tract of the mother. Women with a primary clinical episode of herpes less than 6 weeks before delivery should be resolved by caesarean section. The incubation period with intranatal infection is 3-14 days.

Causes

This intrauterine infection is caused by HSV 1 (labial) or 2nd (genital) type. Of great importance in the etiologic structure is HSV type 2, and the share of the 1st is about 10-20%.

Pathogenesis

HSV when ingested, circulating in the blood, penetrates into erythrocytes and white blood cells. Actively multiplies in cells of internal organs, bypassing the barrier of capillaries by diapedesis. The virus has the property of causing tissue necrosis. Often the disease acquires a recurrent character with a long persistence of the pathogen in the body. In the absence of specific antiviral therapy in newborns, there is a high mortality: in generalized forms it is 80-90%, with a CNS lesion of 50%. The incidence of disability is up to 50%.

Classification

• Localized form with damage to the skin and mucous membranes of the mouth and eyes.
• Generalized form.
• Herpetic lesions of the central nervous system (meningoencephalitis, encephalitis).

Symptoms

The localized form with lesions of the skin and mucous membranes of the mouth and eyes occurs in 20-40% of patients with neonatal herpes and is characterized by the presence of single or multiple vesicular elements in various parts of the body in the absence of signs of a systemic inflammatory reaction. Most often they appear on the 5-14th day of life, but with antenatal infection, the elements are detected from birth. The reverse development of the vesicles and the process of their healing last 10-14 days.

Herpetic lesions of the eyes observe keratoconjunctivitis, uveitis, chorioretinitis, retinal dysplasia. Complications of herpetic infection of the eyes: corneal ulcer, optic nerve atrophy, blindness.

In the absence of specific treatment in 50-70% of newborns, a localized cutaneous form can lead to generalization of the process or to CNS damage.

The generalized form occurs in 20-50% of cases. Clinical signs appear usually on the 5th-10th day of life and earlier.

They note progressive deterioration of the child's condition, expressed disturbances of microcirculation. Characterized by damage to the liver and adrenal glands. Also noted increase spleen, hypoglycemia, hyperbilirubinemia, D BC syndrome. Herpetic meningoencephalitis occurs in 50-65% of cases. Specific rashes on the skin and mucous membranes appear on the 2-8th day from the onset of the disease, in 20% of patients there are no rashes.

Herpetic lesion of the central nervous system (meningoencephalitis, encephalitis) is about 30% of cases. Symptoms often appear on the 2-3 nd week of life. Characteristic of the rise in temperature, a decrease in appetite, lethargy, followed by episodes of increased excitability and tremor. Rapidly developing poorly docked focal and generalized seizures develop rapidly. The indices of the cerebrospinal fluid at the beginning can be within normal limits, then the increase in protein and cytosis of a lymphocytic or mixed character is observed.

In 40-60% of patients with this form there are no specific herpetic eruptions on the skin and mucous membranes.

Diagnostics

• Culture method - isolation of the virus from blood, cerebrospinal fluid, contents of vesicles. The sensitivity of the method is 80-100%, the specificity is 100%.
• Detection of HSV antigens by direct immunofluorescence method when examining the contents of vesicles, scrapings from suspicious areas of the skin.
• PCR (with blood samples and CSF) for the detection of the HSV genome. The sensitivity of the method is 95%, the specificity is 100%.
• ELISA to determine the antigens of the virus in the blood, cerebrospinal fluid, urine, the contents of the nasopharynx, and others.
• ELISA for the determination of specific antiherpetic antibodies in serum.

Treatment

With all forms of neonatal herpetic infection, specific antiviral therapy with acyclovir is indicated.

Preparation: Acyclovir.

• Method of administration: intravenous drip, slow infusion.
• Multiplicity of administration: 3 times a day every 8 hours.
• Doses: with a localized form - 45 mg / kghs); with generalized and meningoencephalitis - 60 mg / kghsut).
• The duration of treatment with a localized form is 10-14 days, with generalized and meningoencephalitis not less than 21 days.
• Multicentre studies conducted in recent years have shown the advisability of using a dose of 60 mg / kghs) and for the therapy of a localized form.

[21], [22], [23],

Features of feeding

With the development of the disease, a woman should continue to breast-feed, since even with a primary infection, the penetration of HSV into milk is unlikely. The only exception is when the herpetic eruptions are located on the mother's breast.

[24], [25], [26], [27], [28]

Outcomes

In the case of early administration of antiviral therapy for intrauterine infection, lethality in generalized forms is less than 50%, with meningoencephalitis 14%, the incidence of neurologic complications ranges from 10-43%, relapses of cutaneous manifestations in the first 6 months are observed in 46% of children.

[29], [30], [31]

Congenital rubella

The frequency of fetal lesions depends on the gestational age. In the period before the 8th week of gestation, the infectious process develops in 50-80% of the fetuses. If infection of the pregnant woman occurred in the second trimester, then no more than 10-20% are infected; In the third trimester, fetal damage occurs rarely.

A pregnant woman can get sick after contact with a sick person. The path of transmission of the virus is airborne. To the embryo or fetus, the virus gets transplacental.

Causes

The causative agent of intrauterine infection is the rubella virus, which belongs to togaviruses.

Pathogenesis

Cytodestructive action of the virus is manifested only in the lens of the eye and in the cochlea of the inner ear. In most organs and tissues affected by the rubella virus, no significant morphological changes are observed. These pathological manifestations are associated with the suppression of mitotic activity of cells and a slowing of the growth of cellular populations. Disturbance of cell growth occurs either with the direct action of the multiplying virus, or in the defeat of the genetic apparatus of the cell.

Symptoms

Characteristic of the classic syndrome of congenital rubella, Gregg's triad:

• deafness develops in 50% of newborns if the mother was ill during the first month of pregnancy, 14-25% - if in the second or third month of pregnancy and 3-8% - if at a later date;
• damage to the eyes (cataracts, microphthalmia);
• heart damage, congenital malformations (open aortic duct, pulmonary artery stenosis, aortic stenosis, septal defects).

In addition to the classic, there is an advanced rubella syndrome, which includes microcephaly, brain damage (meningoencephalitis), glaucoma, iridocyclitis, the presence of areas of depigmented retina, interstitial pneumonia, hepatosplenomegaly, hepatitis, etc. Typical petechial rash on the skin (due to thrombocytopenia), anemia.

Diagnostics

Virological method - isolation of the virus from a pathological material.

Conduct ELISA for the detection of specific antibodies. The material for PCR is amniotic fluid, chorionic villus tissue, blood of the umbilical vessels, and fetal tissue.

Treatment

Specific treatment of intrauterine infection does not exist. Symptomatic therapy is performed.

[32], [33], [34], [35], [36], [37], [38]

Congenital toxoplasmosis

The number of infected people, depending on the place of residence and age, varies between 10-90%. At the age of 18 to 25 years, according to different authors, 10-40% are infected. During pregnancy, about 1% of women are primarily infected with toxoplasmosis. In 30-40% of cases, they transmit the causative agent to the fetus. Thus, 1 out of 1,000 fruits is infected.

Infection of a person often occurs alimentary in the use of raw or insufficiently thermally processed meat of domestic and wild animals. More rarely - by contact (for example, from a cat). Also, infection with blood transfusion or organ transplantation is possible. Infection of the fetus occurs through the placenta. Cases of infection through mother's milk are described.

Causes

The causative agent of intrauterine infection is an intracellular parasite from the class Sporozoa, Toxoplazma gondii.

Pathogenesis

Infection of a woman with toxoplasmosis in the first 2 months of pregnancy does not lead to infection of the fetus, whereas the disease in the 3-6th months is accompanied by infection of the fetus in 40% of cases, and in the 6-8th months - in 60% of cases. When the fetus is infected on the 3rd month of gestation, the disease occurs in a clinically expressed form in 50% of cases, when it is infected in the 3-6th months - in 25%, and in the 6-9th months it practically always erases or subclinically. When the fetus enters the body, toxoplasma affects mainly the central nervous system: underdevelopment of the cerebral hemispheres with microcephaly, ependymal involvement, the emergence of an adhesion process with the development of hydrocephalus. They note the development of thrombovasculitis with foci of aseptic necrosis, in the place of which multiple cavities and cysts are formed during resorption. Occasionally, the calcification of inflammatory foci is observed with the formation of disseminated calcinates. In case of lesions of the eye, focal necrosis is noted, productive inflammation of the retina and vascular membrane. Characterized by liver damage in the form of interstitial hepatitis. The pathological process captures the spleen, lungs, lymph nodes and other organs.

Classification

• Acute generalized form with hepatosplenomegaly and jaundice.
• Subacute with the phenomena of encephalitis or meningoencephalitis.
• Chronic form, manifested by postencephalic defects.

Symptoms

Congenital toxoplasmosis is characterized by:

• prolonged jaundice;
• feverish conditions;
• skin rashes of different nature;
• hepatosplenomegaly;
• a picture of meningitis, meningoencephalitis;
• convulsions;
• hydrocephalus;
• microphthalmia, chorioretinitis, uveitis;
• calcification in the substance of the brain (with additional examination);
• lymphadenitis;
• cardiomyopathy of unknown origin.

Diagnostics

Direct detection of toxoplasma in stained blood smears, centrifugate of cerebrospinal fluid, in puncture smears or biopsy of lymph nodes.

Serological examination (ELISA) - detection of specific antitoxoplasma antibodies.

Treatment

• Drugs: a combination of pyrimethamine and sulfonamides. Doses: pyrimethamine 1 mg / kg xut).
• Sulfonilamidy short action: sulfadiazine 0.1 g / kghsut); sulfadimethoxin 25 mg / kght); sulfadimidine 0.1 g / kg xut).
• Multiplicity: pyrimethamine - 2 times a day; sulfadiazine - 2 times a day; sulfadimethoxin - once a day; sulfadimidine - 4 times a day.
• Scheme of application: pyrimethamine 5 days + sulfanilamide 7 days, 3 cycles with interruptions for 7-14 days. With exacerbation of chorioretinitis, chronic form with immunodeficiency state, the course is repeated after 1-2 months.

Alternative scheme

• Preparations: combined (sulfadoxine + pyrimethamine) - fansite.
• Doses: Calculation of pyrimethamine - 1 mg / kg xut).

Alternative scheme

• Preparations: macrolides (spiramycin, roxithromycin, azithromycin) - in the absence of CNS damage.
• Doses: spiramycin at 150 000-300 000 IU / kghsut); roxithromycin at 5-8 mg / kg xut); azithromycin 5 mg / kg xut).
• Multiplicity: spiramycin - 2 times a day; roxithromycin - 2 times a day; azithromycin - once a day.
• Scheme of application: spiramycin - 10 days; roxithromycin - 7-10 days; azithromycin for 7-10 days.

[39], [40], [41], [42], [43], [44], [45]

Congenital listeriosis

The incidence of congenital listeriosis is 0.1%. In the human population, listeria carries an average of 2.1%. Perinatal mortality from listeriosis ranges from 0.7 to 25%.

The causative agent is widely distributed in some types of soils. Especially in the areas of agricultural holdings. Soil is the source of the pathogen for animals that are infected through contaminated water and feed. In the human body, listeria is obtained predominantly alimentary through contaminated products (milk and dairy products, meat of animals and birds, vegetables, seafood, etc.). Listeria can multiply in products stored in the refrigerator.

Isolate the transplacental and intranatal ways of infection of the fetus.

Causes

Intrauterine infection is caused by Listeria monocytogenes - a gram-positive rod belonging to the family of corynebacteria.

Pathogenesis

In case of infection of the pregnant, listeria is infected with the fetus, inflammation is observed with the development of the septic-granulomatous process. With transplacental infection in the fetus, lung damage or a generalized form of intrauterine infection is noted. When intranatal infection is more often diagnosed as CNS damage. Specific granulomas are found in almost all organs.

Symptoms

Clinical symptoms of intrauterine infection appear on the 2-4th day of life (with transplacental infection) or after the 7th day (with intranatal infection). The general condition of children is severe. Characteristic manifestations of pneumonia, severe respiratory distress syndrome and meningitis or meningoencephalitis. Typical rashes on the skin of a different nature: nodules, papules, roseola, less often - hemorrhages. Similar elements can be in the throat; ulceration on the mucosa of the oral cavity is also determined. Possible jaundice, hepatosplenomegaly, cardiac dysfunction.

• Diagnostics
• Biological test. The material from the patients is infected with animals (at present, it is practically not used).
• Bacteriological method - sowing of amniotic fluid, blood of umbilical cord, meconium, liquor, blood of the newborn on nutrient media.
• Serological methods (RSK, RPGA) - determination of the titer of specific anti-listeriosis antibodies, study of titer in dynamics.
• The detection of Listeria monocytogenes RNA in biological fluids by PCR is a highly specific diagnostic method.

Treatment

• Preparations: ampicillin.
• Doses: 200-400 mg / kght).
• Multiplicity of administration: 3 times a day.
• Duration of therapy: 2-3 weeks.

In severe cases, ampicillin + aminoglycosides (gentamicin) are used.

• Doses: ampicillin at 200-400 mg / kght); gentamicin for 5-8 mg / kg xut).
• Multiplicity of administration: ampicillin - 3 times a day; gentamicin - 2 times a day.
• Duration of therapy: ampicillin for 2-3 weeks; gentamicin for 7-10 days.

Alternative scheme:

• Benzylpenicillin for 100 000-200 000 units / kgsut) + gentamycin at 7.5 mg / kg xut); azlotsillin at 50-100 mg / kght); Amoxicillin + clavulanic acid 25-35 mg / kg xut).
• Multiplicity of administration: benzylpenicillin - 4-6 times a day; azlotsillin - 2-3 times a day; amoxicillin + clavulanic acid - 2-3 times a day.
• Duration of therapy: 3-4 weeks.

Or:

• Preparations: macrolides (spiramycin, roxithromycin, azithromycin) - with CNS damage.
• Doses: spiramycin at 150 000-300 000 IU / kghsut); roxithromycin at 5-8 mg / kg xut); azithromycin at 5-10 mg / kg xut).
• Multiplicity: spiramycin and roxithromycin - 2 times a day; azithromycin - once a day.
• Duration of treatment: 3-4 weeks.

[46], [47], [48], [49]

Congenital Chlamydia

The causative agent of intrauterine infection is widespread in nature. Chlamydia infected 6-7% of children. Intrauterine fetal death due to congenital chlamydia is observed in 5.5-14.4% of cases. The frequency of infection of pregnant women is 10-40%.

Infection occurs mainly intranatally, rarely - antenatal in the last weeks of pregnancy. Probably, infection occurs when ingestion of amniotic fluid or when they get into the respiratory tract of the fetus.

Causes

The disease is caused by microorganisms; isolated in a separate order Chlamydiaceae, genus Chlamydia. The latter includes four types.

• Chlamydia psittaci usually causes a person to have pneumonia, encephalitis, myocarditis, arthritis, pyelonephritis.
• Chlamydia pneumonia causes acute respiratory infections in adults and a mild form of pneumonia.
• Chlamydia trachomatis occurs only in humans, 18 antigenic variants (serotypes) of the microbe have been identified. Serotypes A, B, C are causative agents of trachoma.
• Chlamydia resomorph - described in sheep, cattle. Has a similarity with Chlamydia psittaci. The role in the pathogenesis of human diseases is unknown.

The main epidemiological significance is Chlamydia trachomatis, less often Chlamydia pneumonie. At a microscopy chlamydia have a kind of small gram-negative cocci. They are not able to grow on artificial media, so bacteriological diagnostics of the disease is impossible. Chlamydia have an affinity for the cylindrical epithelium (urethra, cervical canal, conjunctiva, bronchi, lungs), as well as for cells of flat epithelium, lymphocytes, neutrophilic leukocytes.

Pathogenesis

When the fetal enters the body, chlamydia intensively multiply. Increased isolation of tumor necrosis factor (TNF), destruction of damaged epithelial cells, increased metabolism of arachidonic acid, a change in the synthesis of prostaglandins contribute to impaired microcirculation in the brain, lungs and other organs. Due to the nature of the biological cycle of chlamydia (the duration of the full cycle of reproduction is 48-72 hours) and the morphofunctional maturity of the newborn, the development of the local inflammatory reaction is often slow, only after 2-3 weeks of life.

Symptoms

Usually the symptoms of intrauterine infection appear on the 5th-10th day of life. In this case, the predominant airway disease is noted. Observe nasal congestion, difficulty in nasal breathing, ungrowth discharge from the nose of a mucous nature. Respiratory chlamydia can occur more often in the form of pneumonia, less often - atelectasis, bronchiolitis and croup. Lymphadenopathy and mucosal lesions are also characteristic. Common features of clinical manifestations of congenital chlamydia:

• bilateral pneumonia;
• pleurisy;
• purulent conjunctivitis;
• encephalopathy of vascular genesis;
• vulvovaginitis, urethritis;
• myocarditis;
• enteropathy.

Clinical manifestations do not disappear for a long time during conventional therapy schemes and increase with the age of the child. The general blood test is characterized by normochromic anemia, a tendency to thrombocytopenia, neutrophilic leukocytosis, monocytosis, eosinophilia.

Chlamydial conjunctivitis of newborns appears on the first, less often in the second week after birth and is manifested by gluing the eyelids after sleep, with an abundant purulent discharge from the conjunctival sac, redness and edema of the conjunctiva. In the absence of therapy, the disease acquires a protracted course with a change in the periods of attenuation and exacerbation of the inflammatory process.

Chlamydial pneumonia in newborns develops at the 1-4 th month of life. It proceeds without an increase in body temperature and is characterized by child lethargy, a violation of appetite, attacks of pertussis-like (convulsive, spasmodic) cough, dyspnea, cyanotic skin, the presence of wet and dry wheezing in the lungs. Often along with pneumonia, pleurisy develops. The disease has a prolonged course. In half of cases, pneumonia is combined with conjunctivitis.

Middle otitis media is an inflammation of the middle ear. In newborns, it is manifested by pain in the ear against a background of increased body temperature. Pain intensification occurs during sucking, which is manifested by sudden crying of the child during feeding. Acute otitis in newborns often occur imperceptibly for others, up to the appearance of suppuration from the external auditory canal. With severe otitis, the child does not sleep well, often wakes up, is restless, shouts, turns his head, and gives up breast.

The defeat of the gastrointestinal tract of Chlamydia nature in newborns is due to the ingestion of microorganisms when ingested infected amniotic fluid. After birth, children notice increased regurgitation of food, vomiting, bloating, the appearance of diaper rash.

Diagnostics

Conduct ELISA, PCR.

Treatment

Preparations: macrolides.

• Doses: spiramycin at 150 000-300 000 IU / kghsut); roxithromycin at 5-8 mg / (kilohsut); azithromycin at 5-10 mg / (kilogram); josamycin at 30-50 mg / (kilohsut); midekamycin at 30-50 mg / (kilohsut); clarithromycin at 7.5-15 mg / (kilogram).
• Multiplicity: spiramycin - 2 times a day; roxithromycin - 2 times a day; azithromycin - once a day; josamycin - 3 times a day; midecamycin - 2-3 times a day; clarithromycin - 2 times a day.
• Scheme of application: not less than 3 weeks.
• Combination with immunocorrecting therapy.

[50], [51], [52], [53]

Congenital mycoplasmosis

Currently, there are 6 known mycoplasmas that cause human diseases: Mycoplasma pneumoniae, Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma species, Ureaplasma urealyticum, Mycoplasma incognitus (isolated from AIDS patients). At present, the number of diseases caused by mycoplasmas has increased significantly. Mycoplasma genitalium has the most pronounced pathogenic potential. With the help of a special structure (organelle), mycoplasma cells attach to erythrocytes and other cells. In homosexuals, Mycoplasma genitalium is detected more often (30%) than in heterosexual men (11%). Mycoplasma hominis is less pathogenic, but it is much more common in infectious processes of the genitourinary system. It is much more often found in inflammatory processes in women than in men. Mycoplasma pneumoniae is the causative agent of primary human pneumonia, which causes intrauterine infection. Infection occurs ante- and intranatally. The causative agent is detected in pregnant women in 20-50% of cases.

Causes

Intrauterine infection is caused by mycoplasma, belonging to the Mollicutes class of the family Mycoplasmataceae. This family is divided into 2 genera: the genus Mycoplasma, which includes about 100 species, and the genus Ureaplasma, which includes 2 species (ureaplasma urealyticum, ureaplasma parvum).

Pathogenesis

When the fetus enters the body, mycoplasma affects almost all organs; specific changes are found in the central nervous system, lungs, liver, kidneys. Often a generalized process develops.

Symptoms

The disease is characterized by:

• interstitial bilateral pneumonia (cough, mild dyspnea, little physical data);
• hepatosplenomegaly;
• meningitis, meningoencephalitis;
• lymphadenopathy;
• fever.

Clinical signs manifest themselves as the child's age increases. In the general blood test, normochromic anemia, absence of leukocytosis and severe neutrophilia are noted, there may be eosinophilia, monocytosis, thrombocytosis,

Diagnostics

Isolation of mycoplasmas in material from pathological foci by light microscopy, phase-contrast microscopy or immunofluorescence. This method is highly accurate. However, the difficulty lies in the fact that the conditions for cultivation of mycoplasmas are rather complicated, a special nutrient medium is required. In addition, it is necessary not only to establish the presence of mycoplasma in the patient's body (in some quantities they are almost all), but to determine the type and amount of the pathogen, as well as the peculiarities of its effect on the organism of a particular person.

Serological reactions (ELISA, RSK, RPGA). A 4-fold increase in the titer is considered diagnostic.

Carry out PCR diagnostics.

Treatment

Mycoplasma hominis

• Doses: josamycin and midekamycin for 30-50 mg / (kghsut).
• Multiplicity: josamycin - 3 times a day; midekamycin - 2-3 times a day.
• Scheme of application: not less than 3 weeks.

Mycoplasma pneumoniae

Preparations: macrolides.

• Doses: erythromycin at 20-40 mg / (kilogram); spiramycin at 150 000-300 000 IU / kghsut); roxithromycin at 5-8 mg / (kilohsut); azithromycin 5 mg / (kilogram); josamycin at 30-50 mg / (kilohsut); midekamycin at 30-50 mg / (kilohsut); clarithromycin at 15 mg / (kilogram).
• Multiplicity: erythromycin - 4 times a day; spiramycin - 2 times a day; roxithromycin - 2 times a day; azithromycin - once a day; josamycin - 3 times a day; midecamycin - 2-3 times a day; clarithromycin - 2 times a day.
• Scheme of application: not less than 3 weeks.

When CNS is affected, fluoroquinolones are used according to vital indications.

[54], [55], [56], [57], [58], [59], [60], [61]

Diagnostics

Diagnosis of intrauterine infection is based on the isolation of the pathogen itself, the definition of its genome, antigens or specific antibodies.

The cultural method (virological, bacteriological) is the isolation of the pathogen from the pathological material and its identification. Virtually no use is made of the virological method due to the laboriousness and duration of research in practical activities. Identify the bacterial pathogen is not possible in all cases.

The immunofluorescence method is based on the use of luminescence to detect the "antigen-antibody" reaction that occurs on the surface of cells or tissue sections.

Direct immunofluorescence serves to detect antigens of the pathogen in the pathological material under study.

Indirect immunofluorescence is used to detect antibodies to the pathogen in the test material.

Serologic examination of the newborn should be done before the introduction of blood products with simultaneous serological examination of the mother by the method of paired sera with an interval of 14-21 days. Seroconversion is observed later in clinical manifestations of the disease and the appearance in the blood of direct markers of the pathogen (DNA or antigens). In the formation of immunological tolerance in the fetus to the antigens of the pathogen, an inadequate specific immune response is possible. The following methods are referred to serological.

Immunoenzyme analysis (ELISA) is the most promising, it is used to identify specific antibodies and acting as markers of the immune response. The detection of antibodies indicates an active course of the infectious process. Detection only does not allow us to characterize the period of the disease. Antibodies of this class, appearing after the acute phase of the infectious process, continue to be synthesized after recovery for a long time. In addition, they can penetrate the placental barrier and appear in the newborn. If the titre at birth corresponds to the mother tier or below its level, and when the study is repeated 3-4 weeks later, it decreases by 1.5-2 times, then the ones determined by the child most likely were maternal. ELISA is performed with a parallel definition of antibodies avidity, since the degree and degree of avidity can indirectly characterize the period and severity of the infectious process. The detection of low-visibility is indicative of the current or recent disease, and the detection of highly antibodies allows to exclude the active phase of the infectious process.

The complement fixation (RSK) reaction allows the antibody to be detected by a known antigen or antigen from a known antibody based on the ability of the antibodies included in immune complexes to bind complement.

Passive hemagglutination reaction (RPHA). For its formulation, use red blood cells or neutral synthetic materials on the surface of which antigens or antibodies are adsorbed. Agglutination occurs when appropriate serums or antigens are added.

Molecular methods. Detection of the genome of the pathogen by DNA hybridization and polymerase chain reaction (PCR).