Review
Original Research
Now WHO experts annually formulates references on structure of both the 3rd, and 4 valent vaccines against influenza applied worldwide.
The purpose of work was the assessment of averted costs due to influenza vaccination with trivalent and quadrivalent vaccines in different age groups.
Material and methods. The analysis was carried out by a modeling from a societal perspective taking into account epidemiological data on the Russian Federation.
Results. According to data on structure of the allocated influenza viruses in the Russian Federation for 2006-2015, at vaccination coverage of 40% of the population, replacement of trivalent vaccines with quadrivalent vaccines could prevent in addition during the season on average 604 cases of influenza per 100 thousand children aged up to 3 years, 736 cases per 100 thousand children at the age of 3–6 years, 613 cases per 100 thousand children aged from 7 up to 14 years, 106 cases per 100 thousand citizens at the age of 15– 64 years, 19 cases per 100 thousand citizens at the age of 65 years and older. In the whole population replacement of trivalent vaccines with quadrivalent vaccines would allow to prevent during the season on average 181 cases of influenza per 100 thousand citizens in addition.
The averted cost is the greatest at vaccination of children of preschool and school age.
In general, the volume of the costs averted when replacing trivalent vaccines with quadrivalent vaccines against influenza could be increased for 2006–2015 on average by 15,0%, and during separate seasons this increasing could be more.
Replacement of a trivalent vaccines with quadrivalent vaccines could cause decrease in number of cases of influenza during the season by 265,8 thousand, and the costs averted could make 2,498 billion rubles.
Conclusions. Influenza vaccination with quadrivalent vaccines can increase clinical effectiveness and costs averted in comparison with trivalent vaccines. Replacement of trivalent vaccines with quadrivalent vaccines can be the most significant at vaccination of children of preschool and school age, and also in adults from risk groups and elderly people. Economic and clinical advantages of quadrivalent vaccines in comparison with the trivalent vaccines depend on a share in the general structure of a case rate of the strains of influenza B which aren’t relating to the line included in the trivalent vaccine.
Objective: determine grade of DNA damage in lymphocytes and the levels of 8-hydroxy-2-deoxyguanosine (8- OHdG) and 8-nitroguanine (8-NO2G), total antioxidant activity (TAA) in the blood serum of patients with chronic viral hepatitis C (HCV), B (HBV).
Materials and methods. The study included 100 people with HCV, 50 with HBV and 43 volunteers. DNA damage was evaluated by comet assay. Level 8-NO2G and 8-OHdG were determined in serum samples using ELISA kits. TAA determined according to the standard ABTS method. All statisticalcalculations were performed and the graphs were plotted using STATISTICA 10.0 software.
Results. There was a tendency to increase the level of DNA damage with progression of the liver fibrosis stage in HCV and HBV. Significant differences from the norm of 8-NO2G in the F1, F2, F3 groups with HCV and in the groups F2, F3, F4 (ρ <0,05) with HBV were found. In the groups with HCV and in F2 and F4 with HBV, the level of 8-OHdG is higher in comparison with the control group (ρ = 0,0001). Correlations are shown between the stage of hepatic fibrosis and the level of 8-NO2G and 8-OHdG, respectively (r = 0,786620 and r = 0,625844; ρ <0,05) with CVHC and CVHB (r = 0,573933 and r = 0, 478849; ρ <0,05). In the study of OAA, the tendency towards its depletion with the development of fibrotic changes was noted in patients, however, significant differences in comparison with the control were only at the stage of F3 and F4 fibrosis in CVHC, and F2, F4 (ρ <0,05) with CHBV.
Conclusion. Revealed the genotoxic effect of hepatitis B and C on the DNA of lymphocytes. An increasing degree of DNA fragmentation with the progression of liver fibrosis. The correlation between fibrosis and biochemical markers of DNA damage and decrease shown decompensated TAA serum in advanced stages of liver fibrosis.
Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.
Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.
Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.
Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists). The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness.
The purpose of the work is the development of an informationally significant mathematical and statistical model for predicting the development of functional disorders of the gastrointestinal tract in children after a norovirus infection.
55 children with norovirus infection aged 1 to 7 years (mean age 2,8±0,2 years, boys – 25, girls – 30) in a hospital and within 12 months after acute infection were observed due to development of a mathematical discriminant model of the prognosis for the formation of functional disorders of the gastrointestinal tract (FDGIT) with the purpose of their subsequent prevention. Statistically significant differences in the prognosis «probability of development of FDGIT» and «the lack of probability of FDGIT» were found on the following grounds: duration of preservation of norovirus infection symptoms (p=0,056), detection of opportunistic microorganisms in the intestinal microbiota in titles not less than 5 lg CFU/g (p=0,02), detection of bacterial overgrowth syndrome in the small intestine (p=0,001). These signs can be considered as a determinant of the probability of development of FDGIT. This model based on the available definition of informative clinical and laboratory signs characterizing the severity of the disease and the state of the intestinal microbiota of patients with norovirus infection. The information capacity of a statistically significant model (p<0.01) is 86,8%.
The study presents the results of comparing the social status and the efficiency of TB treatment in pregnant women with or without HIV treated in Krasnoyarsk Regional TB Clinic № 1 in the years 2010–2014. It is based on a retrospective analysis of health cards of 133 pregnant TB patients divided into groups: Group 1 (TB), n=109; Group 2 (TB and HIV), n=24. More than a half of the women (51,3% and 54,1% accordingly) were new TB patients, the others had been previously treated for TB. A moderate immunodeficiency was more often detected in co-infected pregnant women (mean CD4+ lymphocyte count being 387 cells/ml), although in 4 patients the CD4 count was lower than 200 cells/ml. The registered rates of bacterioexcretion and lung disintegration were practically the same (57,7% and 58,3% versus 53,2% and 54,1% accordingly); MDR TB was diagnosed in 51,1% in Group 1 and in 60,0% in Group 2.
Results: Patients of both groups had various social problems. However, the most aggravating medico-social factor among the co-infected women was active drug abuse during pregnancy (proved in 37,5%). The clinical course of TB in patients with HIV was severer, they more often developed acute forms of the disease. Preterm delivery was more frequent in TB/HIV cases (46,1% vs. 12,3%, p<0,01). Children born by the women with HIV co-infection showed signs of prematurity and intrauterine growth retardation more often than those born by HIV-negative patients (50,0% vs. 12,3%, p<0,01). Treatment efficiency for TB was authentically less in co-infected cases (33,4% vs. 58,7%, p<0,01). TB recurrence was more often registered in HIV-positive patients (25,0% vs. 3,1%, p<0,01). As for chemotherapy tolerance, treatment adherence or lethality rate, no authentic differences between the groups have been revealed.
Aim. To determine the prevalence of hepatitis C virus (HCV) in different age groups of the conditionally healthy population of Russia.
Materials and methods. Total 4764 serum samples from a conditionally healthy population of five regions of Russia (Moscow, Rostov, Sverdlovsk regions, Tyva Republic, and Sakha Republic (Yakutia) were tested. The study included persons of 10 age groups: < 1 year, 1–4 years, 5–9 years, 10–14 years, 15–19 years, 20–29 years, 30–39 years, 40–49 years, 50–59 years old, ≥ 60 years. Anti-HCV was determined in ELISA with commercial test systems. Anti-HCV positive samples were tested for HCV RNA by RT-PCR. The genotype of HCV was determined based on the analysis of the nucleotide sequences of the core and NS5B regions of the viral genome.
Results. The overall prevalence of anti-HCV in 5 regions of Russia was 2,6% (126/4764), and the proportion of people with HCV RNA was 1,1% (50/4764). The highest anti-HCV positivity rate was observed in Tyva and Yakutia (3,3% in both regions), in other regions its prevalence varied from 1,7% (Moscow region) to 3,0% (Sverdlovsk region). The highest frequency of HCV RNA detection was observerd in Tyva Republic and Rostov region (1.3% in both regions). No positive for HCV RNA cases was detected among persons aged 0–19 years in any region, except for Tyva Republic (1,0% (1/98) in age group 15–19 years). Peak positivity rates of HCV RNA were detected in the age groups 20–29 years and 30–39 years in the Rostov Region (3,9% and 3,0%, respectively); in Yakutia – in the group of 30–39 years (3,7%), in Tyva – in the group of 40–49 years (3,6%), in the Moscow region – in the groups of 20–29 and 30–39 years (2,9% and 2,5%, respectively).
Conclusion. The results obtained indicate a high degree of HCV infection in virtually all age groups in the interval from 20 years to ≥60 years. Specific age cohorts that might benefit from inclusion in regional HCV screening programs were identified in each region.
The rotavirus is the leading etiologic factor of intestinal infections. Epidemiological studies confirm the high prevalence of rotavirus gastroenteritis in children up to 5 years. WHO recommends the inclusion of routine vaccination against rotavirus infection in the national immunization programs of all countries with 2009. The article presents the experience and results of the introduction of vaccination against tear among children on the territory of Achinsk in Krasnoyarsk region.
Objective: to evaluate the effectiveness of the regional program of immunization of children on the territory of Achinsk in Krasnoyarsk region, with pentavalent rotavirus vaccine (PVRVV) (Merck, Sharp & Dohme Corp., USA, LP- 001865 dated 10/01/2012).
Methods.1267 children were immunized with PVRVV (80,0% of the newborn cohort) in the period July 2015 – June 2016: V1 – 1267; V2 – 918; V3 – 815. The vaccine was introduced, both independently and simultaneously with other vaccines of the Russian National Immunization Calendar (NIC), except for BCG (BCG-m). The immunization effect was evaluated in 2016 compared to 2014 (doubtingly period): reduction of IIs hospitalizations among 0-3 years old cohort, and reduction of IIs outpatient visits among pediatric and adult patients.
Results. Demonstrated safety and good tolerability of PVRVV, the overall rate of adverse events constituted 6,4±0,7, the possibility of combination with other vaccines of the NIC, no side effects with self-administration, reduction of IIs hospitalizations in 0–12 months years old group of vaccinated by 39,1%; among children not subject to vaccination (12–36 months) by 26,5%; the reduction of IIs outpatient visits both among pediatric and adult population.
Conclusion. Our study confirms numerous global observations of the fact that the RVI vaccination is one of the best ways to control the RVI incidence rate, thereby improving the socio-economic population well-being through preservation of life and health in children.
Aim. Study cases virologic failure ART HIV-1 in children.
Materials and methods. The blood plasma samples of 6 patients with HIV infection were used, identified under 1 year of life, from the North-West Federal District of the Russian Federation, received in 2014–2016. Presented in a group of patients were aimed at identifying drug resistance in the virus and correction of ART due to virological failure. In the present study we used genotyping by direct sequencing of the site of the polymerase gene (pol) length of 1285 nt., The gene encoding the protease (PR) length of 465 nt. and a portion of the reverse transcriptase (RT) gene length of 820 nt.
Results. In all cases, I was diagnosed with HIV-1 subtype A1, the so-called IDU-A, which is the most common form of HIV-1 in the Russian Federation. Among the obtained isolates of HIV have been identified typical drug resistance mutations to NRTI and NNRTI. Detected multiple natural polymorphic variants from the land of the nucleotide sequences. Thus, all samples show protease mutation M36I, R41K, H69K, and L89M, five samples E35D, four samples I13V. Only one among the surveyed our children with combined variant protease gene mutations L63T + V77I + I93L and reverse transcriptase gene V35I + K166R, despite ongoing therapy and absence of significant drug resistance mutations, according to Stanford University-based data showed high viral load – 2.03×107 copies/ml. The importance of the influence of natural polymorphisms in the drug resistance of the virus is discussed.
Conclusion. The high frequency of natural polymorphic variants of the protease and reverse transcriptase genes of the virus in clinical samples submitted. The number of such mutations, apparently does not depend on the number of treatment regimens, but found some correlation with adherence to treatment.
Aim. To determine of the prevalence of viral hepatitis A, E, B, C and D markers in migrant workers.
Materials and methods. Blood serum samples from 1,333 migrant workers recently arrived in Russia from Uzbekistan (n = 464), Tajikistan (n = 415), Ukraine (n = 308) and Moldova (n = 146) were analyzed. Anti-HAV IgG, anti-HEV IgM and IgG, HBsAg, anti-HBV and anti-HCV were tested using commercial ELISA tests.
Results. The frequency of HBsAg detection was significantly higher among migrants from Tajikistan and Uzbekistan (5,3% and 5,2%, respectively) compared to migrants from Ukraine (1,0%) and Moldova (3,4%). No anti-HDV was detected in any positive HBsAg sample. The rate of anti-HCV detection was high regardless of the country of origin: 4,5% (Uzbekistan), 4.8% (Tajikistan), 3,9% (Ukraine), 4,8% (Moldova). Anti-HEV IgG was significantly higher in migrants from Uzbekistan and Tajikistan compared to those from Ukraine and Moldova (25,4% and 43,1%, vs. 7,8% and 12,3%, respectively, p <0,05). Anti-HEV IgM, indicative of current or recent infection, was detected in migrants from Uzbekistan, Tajikistan, Ukraine and Moldova with similar frequency – 3,9%, 7,8%, 5,8% and 6,8%, respectively. AntiHAV IgG positivity rate was significantly lower in migrants from Ukraine compared to those from Moldova, Uzbekistan and Tajikistan (70,1% versus 91,8%, 98,7%, 99,8%, respectively, p <0,05).
Conclusion. The high prevalence of hepatitis B and C serologic markers in labor migrants, as well as anti-HEV IgM, suggests a high probability of the importation of HCV, HBV and HEV in the Russian Federation. Thus, inclusion of hepatitis B, C and E testing into routine screening of labor migrants might be beneficial.
Epidemiology
Objective: studying of dynamics, level, structure, features of territorial distribution of a mortality of patients with HIVinfection in the Siberian Federal District in 2015.
Materials and methods: observation descriptive and estimated epidemiological research of these forms of federal statistical observation of subjects of the Siberian Federal District (SFD).
Results: in the Siberian Federal district for the period of 2006–2015 dynamics of mortality of HIV-infected individuals was characterized by a high rate of growth (9,21%). For the entire period of study HIV infection in the region died 31772 patients, of whom 19,3 percent in 2015. The mortality rate of HIV-infected persons died from various causes in 2015 was 31.9 per 100 thousand population (6153). Male mortality is 2.6 times higher than the mortality of women (47,8 and 17,9 per 100 thousand population, respectively). More than 80% of persons died from HIV- infection were urban residents, 99,6 percent were over the age of 18 years. 43.9% of the deceased persons had the HIV-infection as a direct cause of death, they were under medical observation in 2015 (11,2 on 100 thousand population), of which 98.4% of the dead had late stage of HIV-infection. 47,4% of HIV-infected persons, who died from various causes, had coinfection of tuberculosis, mortality from tuberculosis in the later stages of HIVinfection was 12,9 per 100 thousand population. The distribution of mortality of HIV-infected persons in the territory of the Siberian Federal district was characterized by unevenness in the range from 1,3 in the Republic of Tuva to 52,2 in the Kemerovo region.
Conclusion. The presence of a clear trend of increasing mortality of people living with HIV on the territory of the Siberian Federal district on the background of high prevalence of infection indicates the need of optimization of preventive measures and epidemiological surveillance system of HIV infection.
Purpose of the study. Epidemiological characteristics of hepatitis E in the territory of the Central European region of Russia (on the example of the Nizhny Novgorod region) for the scientific justification of the system of epidemiological monitoring and surveillance of this infection.
Materials and methods. Samples of blood sera from patients with a diagnosis of hepatitis (n=860); «сonditionally healthy» population, livestock keepers (n=3108); migrants from the republics of Central Asia (n=160). Twelve years of dynamic monitoring of the prevalence of antibodies to the hepatitis E virus among an adult «conditionally healthy» population (n=1359). To resolve the issue of the prescription period for infection, the avidity of IgG antibodies to the hepatitis E virus (n=37) was determined by an experimental series of the test system produced by «Diagnostic Systems». Serological markers of hepatitis E virus infection was determined by ELISA using commercial test kits. For the detection of HEV RNA in faeces samples of pigs analyzed by PCR using an experimental set of «Interlabservice».
Results. Manifestations of the epidemic process the hepatitis E in Russia Central European region are characterized by: substantially higher than the conventional parameters, the intensity of the manifest (from 0,9±0,20 /0000 to 6,9±1,70 /0000), and the latent components (from (1,03±1,0% to 9,3±2,2%); a high proportion of the hepatitis E (from 8,3±2,3% to 13,0±2,9%) in the etiological structure of acute viral hepatitis; low manifestation; active involvement of the epidemic process in persons aged 30-49 years, workers of livestock farms (from 6,4±1,3% to 31,1±0,4%) and enterprises in the meat industry (from 9,1±3,8% to 19,1±2,9%) and migrants from regions with high activity of epidemic process (31,9±3,7%). Workers of cattle-breeding complexes and the enterprises of meat processing industry in areas of temperate climate are at high risk of hepatitis E infection. A significant prevalence of hepatitis E in the human population non-endemic regions may be due not only to importation of infection from endemic areas, but also by contact with animals and/or possible ingestion of insufficiently cooked meat that in the conditions of sporadic morbidity is indicative of mainly zoonotic nature of hepatitis E in the framework of realization of fecal-oral mechanism of transmission.
Conclusion. The conducted research allowed to characterize the epidemiological features of hepatitis E in the territory of the Central European region of Russia and served as the basis for developing a system of epidemiological supervision and control for this differentiated nosology.
Pharmacoeconomics
Interferon-free therapy for genotype 1 hepatitis C are preferable from the point of view of clinical effectiveness and safety.
The purpose of work was the assessment of costs and costeffectiveness of regimens for the treatment of HCV (1 genotype) at the treatment-naive patients.
Methods. The assessment was carried out from the payer perspective. In base case the analysis of costs of the drugs included and recommended for inclusion in the List of VED was carried out on the basis of a median of the registered prices including VAT and the average wholesale extra charge taking into account population in the Russian Federation.
Besides, the scenario with the assessment on the basis of the prices of all drugs (which both are included, and not included in the List by VED) revealed in auctions for 2016 is analysed.
Results. In the base case cost of paritaprevir/ombitasvir/ dasabuvir/ritonavir (PTV/OBV/DSV/r) therapy in patients without cirrhose is 12,2-26,6% less compared with simeprevir with pegylated interferon alfa and ribavirin (PegIFN/RBV/ SMV) at a full course of the last (12 weeks) at all patients. In scenario with refusal of inefficient therapy with PegIFN/ RBV/SMV after 4 weeks, PTV/OBV/DSV/r is characterized by the comparable volume of expenses – from decrease by 15,5% to increase by 3,2%.
The analysis on the basis of the prices of auctions has shown that in comparison with the PegIFN/RBV/SMV (without refusal of inefficient therapy with PegIFN/RBV/SMV after 4 weeks) and daclatasvir and asunaprevir, economy at therapy by a PTV/OBV/DSV/r will make 4,1-19,8% and 28,3%, respectively. In comparison with PegIFN/RBV/SMV (with refusal of therapy in the absence of effect in 4 weeks) PTV/OBV/DSV/r is characterized by the comparable volume of expenses (from decrease by 7,5% to increase by 12,8%). In genotype 1b costs of PTV/OBV/DSV/r are 24,6% higher compared with narlaprevir in a combination with ritonavir, peginterferon and ribavirin.
Cost-effectiveness of PTV/OBV/DSV/r is higher at patients without cirrhosis in comparison with all analysed alternatives, except for a narlaprevir in a combination with ritonavir, peginterferon and ribavirin (genotype 1b).
At patients with cirrhosis the analysis on the basis of the registered prices has shown that at a full cycle of therapy decrease in costs of a PTV/OBV/DSV/r ± RBV will make 8,4% in comparison with the PegIFN/RBV/SMV, but at refusal of PegIFN/RBV/SMV in 4 weeks in the absence of the response, additional expenses on PTV/OBV/DSV/r ± RBV will make 5,6%.
In the analysis on the basis of the prices of auctions PTV/ OBV/DSV/r ± RBV will allow to lower expenses at patients with cirrhosis on average by 11,9% in comparison with the daclatasvir and asunaprevir. In comparison with PegIFN/ RBV/SMV PTV/OBV/DSV/r ± RBV or it doesn’t influence expenses (at a full course of a simeprevir at all patients), or it increases them by 15,2% (at refusal of therapy in the absence of the response in 4 weeks). The cost-effectiveness of PTV/ OBV/DSV/r ± RBV surpasses all comparators at patients with cirrhosis, as well as at patients without cirrhosis. The sensitivity analysis has shown high reliability of the received results.
Conclusions. Costs of PTV/OBV/DSV/r ± RBV at treatment-naive patients with HCV (1 genotype) without cirrhosis and with the compensated cirrhosis, are comparable to costs of a PegIFN/RBV/SMV at higher clinical and economic effectiveness.
Taking into account the need for repeated courses of therapy to treatment-naive patients with the compensated cirrhosis, now purpose of a PTV/OBV/DSV/r ± RBV in the first line of therapy is the most preferable economically.
History
The article deals with the history of formation of virology laboratory since 1963 after the resolution of the Academy of Medical Sciences of the USSR and the Ministry of Public Health on the expansion of virology investigation in the USSR.
The results of the research work on studying various infections in children, developing new modified approaches to etiological express-diagnostics of the diseases, including those introduced into practice of the laboratory and regional medical centers are generalized. The laboratory got the name of the Department of Etiological Diagnostics Methods due to the basic direction of the research work. The primary goal of the department is to develop the methods and diagnostic algorithms for definite verification of infectious forms and the prognosis of the development of pathological process that allows determining the direction of further therapeutic approach to improve the disease outcome. In 2008 the Department of Etiological Diagnostics Methods began its «golden age» characterized by cardinal re-equipment and strengthening of the staff. There appeared the devices of expert class which completely replaced the manual testing process, the work connected with interpretation of serous meningitis outbreaks in Russia and the near abroad became more active.
Now the department is a hi-technology scientific and practical center on studying viral and invasive forms of diseases with a priority direction of further innovations in laboratory diagnostics.
Clinical Case
This is the case of encephalitis associated with chlamydia infection of central nervous system. The diagnostic protocol of the patient included: a careful observation of somatic and neurological status, laboratory tests of blood and cerebrospinal fluid, neurovisualization. The results of the diagnostic protocol suggest that laboratory tests blood and cerebrospinal fluid possess low sensitivity and specificity. The MRI study has revealed the localization and inflammatory character of the changes in brain tissue; it has also helped to choose the most favorable area for the stereotaxic biopsy. The obtained tissue was evaluated by means of light (immunohistochemistry) and electronic microscopy. The active chlamydia infection was estimated. The subsequent antibacterial etiotropic therapy resulted in the regression of the neurologic symptoms and remission.
The intravitalpathomorphology study of the brain could be recommended for the management of the severe encephalitis of the unknown origin.