卷 25, 编号 1 (2020)

Background: The physiological course of pregnancy is largely determined by immunological processes, the violation of which in the perinatal period can cause various congenital pathologies. The course of influenza during pregnancy largely depends on the level of physiological adjustment of the immune response. It is known that in severe cases of influenza A (H1N1), excessive production of a number of pro-inflammatory cytokines, the “cytokine storm”, is observed, with the development of endothelial necrosis.

Aim: To determine the nature of the cytokine response to influenza A (H1N1) against the background of pregnancy and to clarify its relationship with the development of intrauterine neonatal pathology.

Materials and methods: A total of 94 pregnant women were treated at the special clinical infectious diseases hospital of the Ministry of Health of the Krasnodar Region for influenza A (H1N1) during the epidemic recovery from December 2015 to February 2016. The diagnosis of influenza is confirmed by the isolation of RNA of influenza A (H1N1) virus by PCR in a nasopharyngeal scraping. Influenza occurred in the first trimester in 20 (21.3%), in the second trimester in 36 (38.3%) and in the third trimester in 38 (40.4%) women. The outcomes of pregnancy were traced, and a retrospective analysis of 91 neonatal observation cards in the maternity hospital was conducted. The comparison groups were as follows: 25 women with physiological pregnancy, 16 pregnant women with chronic placental insufficiency and intrauterine infection, and a control group of 20 healthy, non-pregnant women of reproductive age. The levels of IL-2, IL-4, IL-10, IFN-α, and IFN-γ cytokines in blood serum were studied using the enzyme immunoassay with Vector-Best reagent kits (Novosibirsk) at a sensitivity of 1 pg/ml. The study of cytokine status was conducted at the height of the flu on the first day of admission to the hospital.

Results: In pregnant women with influenza compared with physiological pregnancy, there are considerable decreases in the levels of IL-4 and IL-10, whereas IFN-α and IFN-γ do not change significantly but have a wide range of indicators. Against the background of altered immunoreactivity in pregnancy, the immunosuppressive effects of the influenza virus, in blocking the production of type I interferons, exert a more pronounced negative effect. In pregnant women with influenza and those with chronic placental insufficiency combined with intrauterine infection, unidirectional changes in the levels of IL-4 and IL-10 against physiological pregnancy were detected. The level of IFN-α in chronic placental insufficiency combined with intrauterine infection was significantly higher than the figures reported by other groups. The level of IFN-γ in chronic fetoplacental insufficiency and intrauterine infection was reduced. A significant increase in the IFN-γ/IL4 coefficient was associated with the development of intrauterine infection of the fetus. The level of IFN-α was maximally reduced in women with influenza in the first trimester of pregnancy, whose newborns subsequently had developmental defects in the cardiovascular system. A decrease in the level of IFN-α may reflect the onset of failure of the compensatory mechanisms of immunological regulation of pregnancy.

Conclusion: Determination of the level of interleukins in the acute period of influenza in pregnant women makes it possible to assess the threat of development of the pathology of newborns. The determination of the levels of IL-4, IFN-γ, and IFN-α is of diagnostic value. A high risk of intrauterine infection can be predicted with an increase in the IFN-γ/IL-4 coefficient. Prognostically unfavorable for the development of newborn malformations is a decrease in the level of IFN-α in the development of influenza in women who are in early gestation.

Background. Today, according to the WHO, in Russia 15% of couples do not have children. Opportunistic infections in adults are pathological processes that occur and develop against the background of a reduced immune response and often cause infertility.

Aim. To study the ratio of opportunistic infection markers in women with various types of infertility who are treated with IVF to create a model for predicting treatment outcomes.

Materials and methods. The main sample consisted of 711 patients, aged 20 to 46 years, who were treated for infertility with IVF methods at the Clinic of the Kuban State Medical University from 2016 to 2018. The study group consisted of 431 patients with pregnancy according to ultrasound. Depending on the outcome of pregnancy, two groups were considered: group 1 - 167 women with preterm birth or termination of pregnancy at different gestational periods; Group 2 - 264 women who gave birth to healthy children on time. The first and second groups were divided into subgroups depending on the type of infertility: primary and secondary. Before pregnancy planning (IVF), all women were examined for opportunistic infections by ELISA and PCR. Antibodies to herpetic infection (At HSV IgM and G), cytomegalovirus infection (At CMV IgM and IgG) and toxoplasmosis (At TOXO IgM and IgG) were determined.

Results. Among the studied group of women with signs of a latent course of opportunistic infections, positive IVF results were noted in 40%. Upon successful completion of IVF with an urgent delivery, there are more often markers for only herpes viruses of type I-II, and less often markers for cytomegalovirus infection are recorded. In contrast, with premature birth or miscarriage, infection markers by several opportunists are determined. In secondary infertility in the group with failed IVF outcomes, infection with several opportunistic infections was detected in 87.7 ± 3.85% of cases.

Conclusion. The combination of several opportunistic infections, including those with a latent course, can have a negative impact on the effectiveness of IVF, leading to a decrease in the percentage of positive results. Secondary infertility is characterized by the presence of markers of several opportunistic infections. Screening for opportunistic infections is a necessary part of preparing a woman for an IVF procedure.

Bacterial vacuolated intracellular parasites, such as Salmonella spp. and Brucella spp., possess the ability to cause persistent, long-life chronic infection during which the microbe continues to replicate inside the host organism in spite of the development of an immune response. Such bacteria develop a strategy to evade the immune response, which plays a key role in the development of chronic infection. The implementation of this strategy is aimed at inhibiting the action of factors of innate immunity. In brucella, this process is mediated by the noncanonical structure of lipopolysaccharide (LPS), as a result of which the pathogen is not recognized by the cells of innate immunity, as well as by the functioning of T4CC, the effector proteins of which block the development of the inflammatory response. The strategy of S. Typhi is realized via the expression of genes of pathogenicity island 7 encoding Vi-antigen and genotoxin. Vi-antigen inhibits recognition of the microbe by cells of the innate immune system. Typhoid genotoxin causes the death of immune cells. Brucella realizes this strategy via the noncanonical structure of LPS and T4SS, effector proteins of which block the development of inflammation. Alternative activated macrophages appear during chronic infection caused by both pathogens. These microbes are able to regulate the metabolism of macrophages according to their needs while persisting in them. A review of the sources of information on this problem allows us to conclude that both the causative agent of typhoid fever S. Typhi and the causative agents of brucellosis use the same strategies for the development of a chronic infectious process, but the implementation of these strategies is carried out specifically.

Nervous forms of listeriosis are observed in 5%–10% of persons suffering from this disease and in 75% of children with bacteriologically confirmed listeriosis as well. The most widespread clinical variant is Listeria meningitis, making up 15% of all cases of bacterial and serous meningitides. The mortality rate at neurolisteriosis reaches 30%–40%. A case of acute meningoencephalitis associated with Listeria monocytogenes 4b in a 37-year-old immunocompetent woman is described. The disease was characterized by subacute onset, manifested intoxication, long-lasting and high-grade fever, cerebral coma, bulbar syndrome, right-side hemiparesis, bilateral hypertonus of the wrist flexors, strabism, anisocoria, manifested leukocytosis with leukocyte formula stab shift, ESR 45–59 mm/hour. Cerebrospinal fluid test: cytosis – 663 сells in 1 mcl, neutrophils – 79%, lymphocytes – 21%, protein – 1451 mg/l, glucose – 3.8 mmol/l. Diagnosis had been confirmed with detection of IgM against Listeria monocytogenes 4b in liquor using the indirect immunofluorescence reaction and Listeria monocytogenes by means of PCR. Antibacterial therapy had been conducted using Meropenem, Ampicillinum, endolumbal administration of 4 mg once daily of Gentamycinum combined with intravenous administration of 24 million of units/day of Penicillin. On day 50, she was transferred for rehabilitation treatment to the Department of Neurology.