Problem of differential diagnostics of granulematous diseases remains actual till nowadays. Despite the use of modern radiological, microbiological, immunological and routine morphological methods they don’t allow always to formulate correct diagnosis. Use of immunechistochemistry frequently reveals the pathogen, this is very important to elaborate the tactic of patients treatment. In the paper are clinically characterized 17 cases in which clinical and laboratory data allowed to exclude tuberculosis and sarcoidosis. Are presented morphological data concerning mycoplasmosis (4) and chlamydiosis (4). As an example are given the details related to the first in the literature observation of respiratory granulematous chlamydiosis.

Cellular immune response plays a central role in control of intracellular pathogens like viruses, some bacteria and parasites. Evaluation of presence, specificity and strength of cellular immune response can be done by investigation of reaction of immune cells to specific stimulus, like antigen. The major cellular reactions to antigen stimulation are production of cytokines, proliferation and cytotoxicity. This review is focused on interferon-gamma as one of the central Th1 cytokines: its biology, immunological role and application as marker of cellular immune response.

Interest in acute respiratory viral infections (ARVI) in children does not tend to decrease and is determined by their high prevalence, relatedness to «uncontrollable infections» in most cases and presence of age limits in the use of antiviral drugs. Presently, focus on the use of national drugs is made in the RF clinical practice. An innovative drug Anaferon for children was developed by the Russian pharmaceutical company OOO «NPF «Materia Medica Holding» and registered in Russia in 2002.

The summary purpose is to classify and analyze national and international publications on the results of non-clinical and clinical investigation of Anaferon for children efficacy and safety in ARVI and other viral infections.

Study method: exploratory and analytical.

Results: the summary presents the data of non-clinical studies justifying the drug mechanism of action at molecular level ensuring its combined antiviral and immunomodulating efficacy. The results obtained in the experiment were verified by clinical studies and are reflected in numerous scientific publications including international ones. The summary contains analysis of the results of clinical studies of the drug in children with ARVI including influenza. Anaferon for children was found to reduce duration of the main clinical symptoms of ARVI and influenza, incidence of bacterial complications, it is well-tolerated and has high safety profile. The open-label randomized comparative study of Anaferon for children efficacy and safety vs. Oseltamivir in influenza demonstrated clinical efficacy of these drugs. Numerous publications evidence that Anaferon for children exerts antiviral effect against most viruses causing acute respiratory viral infections as well as herpes viruses, viruses causing intestinal infections and tick-borne encephalitis. The list of scientific publications on the drug consists of approximately 800 references including more than 50 articles in foreign languages, particularly in journals with high citation index.

Neopterin is a specific marker of cellular immunity and monocytes/macrophages activation. Correlation between serum neopterin levels and clinical features of herpes zoster is unknown.

The objective of the study was to determine the concentration of serum neopterin in patients with herpes zoster.

Methods: 55 patients with herpes zoster (30 HIV-positive and 25 HIV-negative) were included. Serum neopterin levels were measured three times during the observation period (before onset of treatment with acyclovir, on the 3rd day of treatment and after healing of skin lesions). The clinical course and dynamics of laboratory data were also evaluated.

Results: The study showed that elevated serum neopterin levels were found in all patients with herpes zoster. Neopterin concentrations were significantly reduced during acyclovir treatment (from 30 (17; 32) to 12 (11; 27) nmol/L) (p = 0,0000001), but remained above the upper limit of normal by the time skin lesions were healed in most patients. Neopterin levels before and after treatment weren’t associated with HIV-status. Neopterin concentration was slightly higher in patients with HIV infection on the third day of observation only, that could reflect the abnormal immunoreactivity of this host. Neopterin levels in patients with varicella zoster viremia were higher compared to patients without viremia on the third day of treatment with acyclovir (23.5 (12,7; 30,0) and 12 (4,2, 24,5) nmol/L, respectively, p = 0,037).

Conclusions: These results suggest that the dynamics of serum neopterin could be a marker of effectiveness of immune response in herpes zoster.

Objective: To evaluate relationships between virological and morphological data in patients with chronic hepatitis B in phase immune control and reactivation.

Materials and methods: The study involved 46 patients with chronic hepatitis B, indicators defined were content of surface antigen and hepatitis B virus DNA in the peripheral blood, the level of covalently closed circular HBV DNA in liver tissue and fibrosis stage and histological activity index (METAVIR).

Results: The study found a direct correlation between the level of covalently closed circular DNA in liver puncture biopsies (number of copies per cell) and quantitative content of HBsAg in serum (r = 0,51, p = 0,03) in patients with chronic hepatitis B in phase immune control. Also in the immune control phase a direct correlation between the HBV DNA and the level of HBsAg in serum (r = 0.79, p = 0.0001) is shown. The level of covalently closed circular HBV DNA in liver puncture biopsy specimens did not differ in patients with chronic hepatitis B in the phase of immune control in the phase of reactivation (1,02 ± 0,01 copies / cell and 1,03 ± 0,03 copies / cell, p = 0.72). The index of histological activity and fibrosis were not correlated with any of the investigated virological indicator.

Conclusion: Results of the study emphasized the complexity and ambiguity of the relationships between both virological and morphological indicators in patients with chronic hepatitis B, determined the direction for further study (in particular the assessment of the epigenetic regulation of the synthesis of circular covalently closed DNA), as well as set the stage for improving the principles of dynamic observing the patients with chronic hepatitis B in a phase of immune control.

Objective: improving the efficiency of pharmacotherapy of drug-induced liver injury in tuberculosis by clarifying pharmaco-epidemiological, clinical and laboratory features.

Materials and Methods: A retrospective analysis of primary medical records of 250 patients with pulmonary tuberculosis, patients «Volgograd Regional Clinical TB Dispensary № 1». We evaluated the dynamics of biochemical parameters characterizing the development of hepatic cytolytic syndrome, examined the impact of gender and age on the incidence of liver damage, we investigated the relationship of clinical tuberculosis and chemotherapy regimen with the incidence of drug-induced liver injury, examined the clinical manifestations of liver disease.

Results: Drug-induced liver injury as a complication of a specific anti-TB treatment was diagnosed in 67 patients (26,8%). In 170 patients (68,0%) showed increase in alanine aminotransferase and asparaginaminotrasferazy. Hepatotoxicity significantly more common in patients with disseminated tuberculosis with the collapse of the lung tissue, smear, and a high degree of disease severity. Risk factors for drug liver damage were female gender and age older than 50 years. Women develop liver disease at an earlier date, and displays it harder than men. The earliest and most informative routine biochemical tests, reflecting the state of the liver in the dynamics are ALT and AST. It was found that the mode of the standard anti-TB treatment determines the type of liver injury: the first, 2a and 3rd modes prevails cytolytic hepatocellular type, with 2b mode – combined (mixed) type 4th – type of cholestatic liver damage. It was found that repeated, after the development of hepatotoxic reactions, the appointment of anti-TB drugs without gepatoprotektsii in 94% of patients leads to repeated drug-induced liver damage. Cancel specific therapy against the background of cytolytic syndrome promotes the formation of drug-resistant forms of mycobacteria, and reduces the effectiveness of treatment for tuberculosis.

Aim of work: to prove necessity and safety of antiviral treatment with nucleoside analogues for severe form of acute hepatitis B.

Materials and methods: The study involved 137 patients with severe form of acute hepatitis B, established by results of the identification of markers of hepatitis B virus. In 75 patients (54%) recorded the initial signs of acute hepatic encephalopathy, which were indications of hospitalization in intensive care unit. The treatment of 25 patients included nucleoside analog: telbivudine (600 mg/day) or entecavir (0,5 mg/day) – the main group. The method of «case – control» matched 25 patients in the comparison group who did not receive antiviral drugs. Monitoring of clinical and biochemical parameters were carried out once a week, the viral load – at the start of antiviral therapy and 4 weeks later.

Results: In the main group noted rapid relief of major clinical symptoms of the disease (within 3–6 days). ALT levels in the main group was significantly decreased after a week of antiviral therapy, after four – reached 43,6 ± 18,7 U/L. The concentration of bilirubin in three weeks of therapy in the main group became significantly lower (p ≤ 0,05), than in the comparison group (38,0 ± 15,0 and 130,3 ± 105,1 mmol / L, respectively). After four weeks of antiviral therapy viral load decreased twice (p = 0.0001). Adverse events were not marked.

Conclusion: Inclusion in the basic therapy antiviral agents allows halving the duration of stay of the patient in the intensive care unit, to prevent death, to achieve a significant improvement in laboratory parameters, in the absence of adverse events.

Purpose of the study: study of the circulation, isolation and antigenic analysis of influenza viruses A and B in St.-Petersburg in the children aged 0–18 in the seasons 2013–2015.

Materials: nasal swabs from children-inpatients from Saint-Petersburg.

Methods: virus isolation in MDCK cell culture and chicken embryos, antigenic analysis with the hemagglutination inhibition (HAI) test with the set of hyper-immune rat antisera to the epidemic and reference strains, antigenic cartography.

Results: The epidemic seasons 2013–2015 were characterized by the co-circulation in children in St.-Petersburg of influenza sub-types А(H1N1)pdm09, A(H3N2), and B of Yamagata lineage (B yam). In the season 2014–2015 the low activity of epidemic process was observed with the predominant sub-type A(H3N2) and in the next season – 2014–2015 with the more pronounced epidemic activity – the pre-dominance of B yam viruses. Antigenic analysis of influenza viruses А(H1N1)pdm09 which circulated in children revealed their antigenic homogeneity and full correspondence with vaccine strain A/California/07/09. As for А(H3N2) viruses, two antigenic groups were established: strains similar to A/St.-Petersburg/80/14 (sub-clade 3C.2a) and strains similar to A/Switzerland/9715293/13 (sub-clade 3C.3a). А(Н3N2) strains of the season 2013-2014 were similar to the vaccine strain. However isolates of the season 2014-2015 did not fit to the vaccine strain because in the children were predominant strains similar to the evolution branch A/St.-Petersburg/80/14 while according the WHO recommendations the influenza vaccine contained the strain A/Texas/50/12. Antigenic analysis of influenza viruses B showed their homogeneity and all they were B/Phuket/3073/13-like. Influenza strains B also incompletely corresponded to the vaccine strain – B/Massachusetts/2/12 belonging to the different genetic sub-clade. That might be the reason of enhanced morbidity of children with influenza B in the last season.

Conclusion: The obtained results stress the urgency for the wide coverage of human population with the epidemic studies, virus isolation in different time periods and geographic regions and their etiological studies with the modern techniques. Only in these conditions we can assure high efficiency of flu seasonal vaccines.

The objective: to describe clinical and epidemiological picture of Yersinia infection in the Kirov region.

Materials and methods: the study included 40 patients, ranging in age from 17 to 69 years: 36 patients with a diagnosis of yersiniosis, 4 – pseudotuberculosis. The diagnosis was confirmed by the method of indirect hemagglutination Yersinia and pseudotuberculosis diagnosis.

Results of research: Yersinia infection in the Kirov region in all cases was accompanied by intoxication. Catarrhal syndrome and rash was detected in 2/3 of patients. Generalized form of the disease was characterized by liver disease in most patients. Almost half of the patients had lesions of the musculoskeletal system and the effects of gastroenteritis were recorded in 35% of cases. Factor for the development of chronic Yersinia infection is burdened premorbid background.

Conclusion: For the prevention of adverse outcomes Yersinia infection requires a comprehensive approach to the treatment of patients with severe premorbid background. Such patients should be allocated to risk group. Subsequent clinical supervision must be exercised within a period of 1 year with doctors of other specialties.

There is presented the analysis of the mortality of children aged up to one year in Sverdlovsk region from 2008 to 2013. The dynamics of infantile mortality indicators in Sverdlovsk region is given taking into account various reasons and in comparison with similar indicators in the Russian Federation. The increase of specific load of infectious diseases is shown in the structure of infantile mortality due to viral infections. The negative tendency of the increase in infant death cases at home due to infectious causes is marked in combination with unfavourable social factors. Infectious diseases composed 25,0% in the structure of child mortality at home among children aged up to one year. In 2013 unidentified infections (41,4%), Herpes virus infection (20,7%), intestinal viral infections (3,4%), and cytomegalovirus infections (3,4%) had the highest numbers.

The unsuccessful epidemiological situation on HIV infection with negative tendencies is observed in Chelyabinsk region (1034,1 on 100 thousand population). The big difference between estimated quantity of people living with HIV and the registered number of HIV-positive people increase (for 59,7% – in 2012, for 60,2% – in 2013, for 61,1% – in 2014). The cascade model of levels of medical care of people living with HIV of Chelyabinsk region is used in thearticle. Main «losses» of people living with HIV are noted at the following stages of the cascade in Chelyabinsk region: «HIV infection – Detection of HIV (-61,1%) With»; «Detection of HIV – statement on the dispensary account (-22,4%)»; «Medical examination – needs in the ART (-71,1%)». The cascade of delivery of health care in Chelyabinsk region is distinguished from data on the Russian Federation with big percent of losses (-32,7%) at the stage «receiving the ART-epidemiologically safe level of virus loading». Leaving of the patient from everyone «cascade steps» of delivery of health care reflect problems in the organization of medical care. Transition of epidemic from groups of risk in the general population, its feminization and generalization demands optimization of strategy of counteraction of epidemic of HIV infection. The cascade model reflecting «profile» of the organization of medical care in a period can be effectively used as an independent element of an information and analytical subsystem of epidemic supervision of HIV infection in regions of the Russian Federation.

Tularemia is a zoonotic disease. The pathogen (Francisella tularensis) is а gram negative bacteria virulent to humans and animals (rodents, hares, rabbits). The outbreak of tularemia had happened in 2013, in Khanty-Mansiysk Autonomous District, during which 1005 people became ill, including 157 children, of whom 152 people were treated at the Hospital District of Khanty-Mansiysk. The histories of inpatients and outpatients affected children had been analysed (n=152). Specialists have identified epidemiological and clinical features of children tularemia. There was ulceroglandular form of tularemia in 98.7% of cases. Purulent lymphadenitis has appeared in 5.9% of cases. 21,2% of affected children have been vaccinated and revaccinated against tularemia for 1–11 years before the disease.

The purpose: detection of morphological changes of fetoplacental complex in pregnant women with chronic hepatitis C.

Methods: The study involved 48 pregnant women , 38 of them with chronic hepatitis C and 10 – healthy pregnant women without complicated obstetric – gynecological history. Do all women was conducted morphological and histological study of their placentas. Placental tissue samples were fixed in 10% formalin solution. After fixation in 10% neutral formalin, the samples were subjected to histological wiring placentas by incubation in isopropyl alcohol and paraffin imbibition using the apparatus for automatic wiring histological samples gated Exelsior (Thermo, Germany) .Immunogistohimicheskie (IHC) studies were performed using a mouse monoclonal antibody NS3-antigen to hepatitis C virus (at a dilution of 1/80, Novocastra Lab., UK).

Results: chronic ( sub) compensated placental insufficiency often revealed by the presence of NS3-HCV in the placenta. In the presence of placental infection with hepatitis C virus ( HCV NS3 ) , the presence of more common detsiduita placenta.

Conclusions: Hepatitis C virus is one of the most important factors in the development of chronic placental insufficiency.

Updated HCV clinical guidelines placed direct acting agents (DAAs) as the preferable the first line regimens.

The objective of the study was PE assessment of HCV therapy among G1 naïve patients

Methods: Analysis is based on data of randomized clinical trials and average price of HCV medicines from state auctions placed in state procurement system in 2015.

Results: PTV/OBV/DSV/r cost is 30,5% lower vs PegIFN/RBV/SMV. In comparison with PegIFN/RBV/BCV combination PTV/OBV/DSV/r is cost saving by 10,6% at patients without cirrhosis and 36,2% at patients with cirrhosis. DCV/ASV combination is chipper PTV/OBV/DSV/r and it would be used for G1 naïve patient (cost saving is 9,4-10,4%). DCV/ASV and PTV/OBV/DSV/r SVR12 costs are comparable and significantly lower than PegIFN-based regimen: PegIFN/RBV/SMV and PegIFN/RBV/BCV. 4 weeks stop rules due to therapy inefficiency for PegIFN/RBV/SMV regimen could cut cost by 12,6% и 28,0% among patients without and cirrhosis accordingly. By way PTV/OBV/DSV/r is the most cost effective versus PegIFN/RBV/SMV. PTV/OBV/DSV/r as the first line therapy for PegIFN experienced patients provides budget saving 118,2 thousand RUB or 12,2% of budget.

Conclusion: Right now PTV/OBV/DSV/r regimen is the most cost effective the first line therapy for naïve patients.