The thesis is devoted to the study of clinical features of the course, the diagnostic value of biomarkers for the diagnosis of sepsis and the determination of genetic predictors of the latter in children aged 1 month to 18 years. The goal was studied by determining the diagnostic value of the levels of CRP, TNF-α, procalcitonin, presepsin and the role of the single-site mutation of the promoter site of the TNF-α gene at point 308. We carried out a bacteriological study of various biological fluids (blood, liquor and urine), wound fluids, smears from the mucous membranes (nose, throat), washes from tracheobronchial tree, drainage tubes, peripheral and central catheters in the children of the main group and the comparison group.
In sepsis detection of a causative agent was seen in 24 children (51.0 %), in the comparison group - 10 children (14.7 %), which coincides with the data of the literature. Not large number of cases of purulent pathogen isolation in children with localized purulent infection in comparison with the group of children with sepsis is due to a single examination from one environment, while in the case of sepsis the bacteriological examination was carried out from several environments and several times.To diagnose sepsis from laboratory biomarkers we used a determination of the level of CRP (47 children from the main group and 68 groups of comparison), procalcitonin (31 children with sepsis, 54 children with localized bacterial infection and 30 children from the control group), TNF-α (31 children - the main group, 54 children - the comparison group and 30 children - the control group) and the level of presepsin (16 children with sepsis, 14 children with localized bacterial infection and 26 children from the control group). Thus, in localized bacterial infections, the level of CRP, TNF-α, PTC and presepsin was: 28.3 mg / L CI 95 % [22.4-34.2], 186.5 pg / ml CI 95 % [163.1-209, 9] 0.86 ng / ml CI 95 % [0.77-1.03] and (m) 313.5 pg / ml (IQR 208-376 pg / ml), respectively. In case of sepsis indicators of CRP, TNF-α, PCT and presepsin were significantly higher (44.7 mg / L CI 95 % [35 -54.3], 280.3 pg / ml CI 95 % [243.9-316 7], 4.06 ng / ml CI 95 % [2.34-5.69], (m) 1887.5 pg / ml (IQR 505.5-3702.5 pg / ml)) and the difference was statistically significant compared to those with localized bacterial inflammation. In this case, the highest specificity (96 %) and sensitivity (97 %) were detected in presepsin for the diagnosis of bacterial infection and 92 % of sensitivity and 93 % of specificity for the differential diagnosis of sepsis and localized infection.
The replacement of guanine by alanine in the promoter site of the TNF-α gene at the 308 point increases the risk of sepsis in children at 5 times. We found that the substitution of guanine for alanine increases the level of synthesis of TNF-α: in children with genotype 308 G / G, its level was 201.9 pg / ml [CI 95% 168.6-235.2 pg / ml], with the allele variant at the 308 G / A point was 460.6 pg / ml [95% 379.2-541.9 pg / ml], the difference was statistically significant (p <0.001), and between these indicators there is a direct medium-strength correlation link (r-0,66, p = 0,0002), which explains the pathogenetic cause of the development of genetic predisposition for the development of sepsis in this mutation in children.
