Articles
Jubilee
Lead article
Vaccination against pneumococcal infections by 13-valent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality.
The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection.
Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system.
The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level.
In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given.
The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018.
Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided.
Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively).
In the 15-year-horizon noting the distribution of 65-yearolds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively.
Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.
Problem article
There is introduced the analysis of molecular-genetic mechanisms of tropical malaria pathogenesis and P. falciparum virulence. It is shown, that pathogenesis of tropical malaria is associated with the properties of red blood cells membrane surface (RBCs or erythrocytes) that are infected by P. falciparum. There are «knobs structures» on membrane surface infected RBCs. Knobs structures contains a complex of P. falciparum proteins – PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1). PfEMP1 is associated with virulence of P. falciparum. Complex PfEMP1 has difficult polymorphous structure. Domains of PfEMP1 are able to associate with different cell receptors. Virulence`s individual components of the main factor are selectively sensitive to different tissues and organs. The severity of the clinical malaria infection course depends on the complex structure PfEMP1 of malaria parasites. Composition of polypeptide PfEMP1 is determined by var-complex. Nowadays there are 60 variants of var-complex. Regulation of gene expression, forming part of the var-complex, is carried out on a molecular-genetic level, cellular level, tissue level. Modern research in this area are aimed to explore genes polymorphism of the virulence`s main factor, to identify mechanism of its differential expression. Search of molecular – genetic markers is relevant to develop methods of gene diagnostic and malaria vaccine.
Review
Original Research
Objective: to study the features of the clinical and epidemiological characteristics of whooping cough in children in the Samara region.
Materials and methods: 389 cases of pertussis in the Samara region for 2015–2016 were analyzed.
Results: it is shown that in spite of 95–98% vaccination coverage, in recent years there has been an increase in the incidence of whooping cough. Seasonality of morbidity remains. Among the children observed, the youngest children were not vaccinated against pertussis. The clinical picture of the disease remains typical with the classic course of catarrhal and spasmodic periods. Moderately severe forms of the disease predominate. Complications were noted mainly in unvaccinated children of the first year of life. The most frequent complications were pneumonia and apnea. There is a hypodiagnosis of pertussis in outpatient conditions. Infection often occurs under the mask of ARVI, while the sensitivity of the bacteriological method of diagnosis is zero. Of the methods for confirming the diagnosis, the most reliable is ELISA and PCR.
Conclusion: these epidemiological and clinical features of pertussis current testify to the need to further improve methods of early diagnosis, especially express methods, etiopathagenetic treatment, specific prevention, antiepidemic measures in the foci of infection.
The purpose was to study the clinical and epidemiological features of respiratory syncytial virus infection in hospitalized children the first year of life with lower respiratory tract diseases in different regions of the Russian Federation (Russia) during the 2015–2016 epidemic season.
Materials and methods: in the original study data of a multicentre observational study conducted on the basis of children’s hospitals in St. Petersburg, Arkhangelsk, Kazan, and Saratov are presented. Etiology of acute respiratory viral infections were confirmed by examination of smears from the posterior pharyngeal wall by polymerase chain reaction. The study sample included 991 child’s first year of life with lesions of the lower respiratory tract.
Results. In the etiological structure of the surveyed children in the season of 2015-2016, RSVI ranged from 14% to 46,2%, an average of 33%. RSVI dominated in the Centers of St. Petersburg (38,3%), Arkhangelsk (36.2%) and Kazan (42.5 per cent).RSVI significantly more often (p<0.01) leads to the development of bronchiolitis (29.4% against 16.3% and 10.0%, with rhinovirus infection and parainfluenza, respectively. Patients with RSUI often develop pneumonia (23,5%) vs 20.6% and 20,0% with rhinovirus infection, and parainfluenza. Patients with RSVI often suffer severe forms of the disease require oxygen support (13,8%) and treatment in the departmentof intensive care (15,9%).Seasonal peaks of hospitalization due to RSVI in all Centres were recorded in December-April 2015 and 2016. Regional differences in monthly intensity of hospitalization of children with RSVI were established.
Thus, the high prevalence of RSVI among children in the first year of life, especially with heavy and complicated forms of lower respiratory tract disorders requiring intensive care benefits, represents a socially important issue, which requires monitoring for effective prevention in children at risk.
To evaluate the efficacy of therapy with sofosbuvir in combination with ledipasvir or daclatasvir, the results of treatment of 299 patients with chronic hepatitis C, including 128 non-responders to combined interferon plus ribavirin therapy, who have prognostically unfavorable single nucleotide polymorphisms 39743165T> G (rs8099917) and 39738787C> T (rs12979860) of interleukin-28B gene, were analyzed. 57 people had liver cirrhosis. 80,9% (242) had genotype 1 of hepatitis C virus, 5% (15) – genotype 2, 13,7% (41) – genotype 3, and 0,4% (1) – genotype 4.
All 299 patients, who adhered to the recommendations of the European Association for the Study of the Liver 2016 and the American Association for the Study of the Liver Disease 2017, achieved a sustained virologic response 12 weeks after the end of therapy. The clinical case of treatment failure, associated with the lack of confirmation of the elimination of hepatitis C virus by means of highly sensitive polymerase chain reaction methods and with the later identified amino acid substitution in position Y93H of NS5A (resistance to NS5A inhibitors), is shown.
It is necessary to carry out monitoring of effectiveness of therapy only by means of highly sensitive polymerase chain reaction (from 10 ME/ml). If the virus elimination delays in patients with advanced stages of liver fibrosis it is needed to use the prolonged schemes of treatment. Repeated treatment of patients with existence of a mutation of Y93H requires the use of new NS5A inhibitors or combined drugs.
In this work we investigated to which extent the evaluation results of the degree of hepatic fibrosis obtained by realtime elastography (RTE) method are compatible with the results of the transient elastography (TE) and with the APRI indexes. We also analyzed the factors which can influence the reliability of the fibrosis degree evaluation obtained by different methods.
Materials and methods. The study included 99 patients (60 women and 39 men) with HCV, examined in the polyclinic department of the Saint-Petersburg Botkin clinical infectious hospital in 2017. In 83 patients, the fibrosis degree in the liver tissue has been evaluated by the RTE method using HI VISION Preirus (Hitachi, Japan) with a linear sensor. In 67 patients, the evaluation has been performed by the TE method using Fibroscan (Echosens, France). Both methods have been applied to 51 patients.
Conclusions. The aplication results of the RTE and TE methods do not differ significantly for patients with a severe fibrosis. Usually, the degree of fibrosis in patients with CHC obtained by the RTE is higher than the one obtained by the TE in the same patient. Due to the possibility to visualize a larger area under study, the RTE method has clear advantages in evaluating the degree of fibrosis in liver tissue in patients with focal changes in the liver. If the results obtained by the RTE and TE methods differ significantly, alternative methods must be used, such as a liver biopsy and biochemical methods.
One of the serious negative consequences of the HIV infection epidemic is the involvement of women of reproductive age and children into the epidemic process. The problem of vertical HIV infection transmission does not lose its relevance and causes the need for continuous monitoring of measures to prevent the transmission of HIV from mother to child. The aim of the study is to evaluate the effectiveness of a set of measures to prevent the transmission of HIV infection from mother to child in the South of Russia.
Materials and methods. The common methods of variation statistics were used in the work to analyze the data from the reporting forms of monitoring by Rospotrebnadzor «Imformation on measures for the prevention of HIV infection, hepatitis B and C, detection and treatment of HIV patients» and federal reporting forms N 61 «Information on contingents of patients with a disease caused by a human immunodeficiency virus (HIV)» for 2016 and 2017, presented by the territorial Centers for Prevention and Control of AIDS of 15 RF subjects of the Southern Federal District and the North Caucasus Federal District.
Results. In 2017, compared to 2016, the decrease in the number of births in HIV-positive women was traced on the territory of the South of Russia. In 2017, target levels of mother-child coverage with chemoprevention of mother-to-child transmission of HIV during pregnancy (over 92%) and during childbirth (more than 93,5%) were achieved in the Southern Federal District and the North Caucasus Federal District. A high proportion of women with a detectable level of HIV replication before birth was revealed.
Conclusion. The implementation of the recommended by standards preventive measures and the provision of antiretroviral drugs allowed to significantly increase the coverage of HIV infected pregnant women and their newborns with antiretroviral prophylactic treatment by 2018 which prevented HIV infection transmission from mothers to 8840 children. The problems that prevent the implementation of the full range of measures for the prevention of the vertical transmission of HIV in the South of Russia are identified and approaches for their solution are suggested.
Study aims: The study purpose was to analyze the results of the clinical and laboratory monitoring of HBeAg-negative chronic hepatitis B patients after discontinuation of longterm nucleosides analogues antiviral therapy in order to determine further management.
Materials and methods: A retrospective-prospective investigation was performed in 106 patients with diagnosis of HBeAg-negative chronic hepatitis B during the course of antiviral therapy using nucleosides analogues. Average treatment duration was 190,1±77,7 weeks. The therapy was discontinued for 29 patients in the period of time from two to five years of the treatment, they were followed up from 6 months to 6 years. The activity of aminotransferases, the levels of HBV DNA were evaluated, the liver elastometry was performed during the patients monitoring. The relapse of disease after the treatment discontinuation was considered when the viral load exceeded 2.0x103 IU / ml and/or alanine aminotransferase levels were above the reference values.
Results: The viral load varied from 4,0х102 IU/ml to 2,87 х 107 IU/ml at 86,2% cases after the 6 months of discontinuation of the treatment. However median levels of viral load were not higher than 2,5 х 103 IU/ml at different timepoints of observation. The VL was higher than 2,0 х 103 IU/ml in 62,1% patients and it matched to relapse criterion. Clinical relapse was not revealed in 13,8% cases at observational period from 6 months to 2 years. The second course of antiviral therapy was not required for 37,9% patients, at the same time it was necessary to consider it for the rest ones.
Conclusion: Regular medical checkups with periodical clinical, laboratory and instrumental examinations after antiviral treatment discontinuation are required for timely detection of relapse and decision regarding the next course of antiviral therapy.
Pharmacoepidemiology
Introduction. The overuse of antimicrobial agents, and poor adherence to infection control measures are leading factors in the development of bacterial resistance. Despite the existence of numerous guidelines for the management of patients with different sites of infections up to 50% of assignments of antimicrobial agents does not follow them.
Aim. The aim of the study is to evaluate the structure and dynamics of the consumption of antimicrobial agents for systemic use in the multidisciplinary hospitals of St. Petersburg in 2014–2015.
Materials and methods. From the database of IMS Health were selected information regarding the supply of antimicrobial agents for systemic use (ATC code J01) in hospitals of St.Petersburg in 2014–2015. The Number of purchased antimicrobial drugs (g) is translated into a number of Defined Daily Dose (DDDh) for each international non-proprietary name.
Results. The level of consumption of AMP in 2014 was 83,3 DDDh/100 bed-days. In 2015, this figure amounted to 50,5 DDDh/100 bed-days. 70% of consumption of antimicrobial drug for systemic use in multidisciplinary hospitals amounted to 3 groups: fluoroquinolones, cephalosporins and semisynthetic penicillins. In 2015, in comparison with the previous year absolute value of fluoroquinolones decreased by 58% in favor of cephalosporins (+15%) while reducing the total number of DDDs used system antimicrobial agents (-40,5%), which is probably connected with the introduction into clinical practice of Russian clinical guidelines for the treatment of infections of various localizations and the perioperative antibiotic prophylaxis. There was growth in the number of purchased carbapenems and macrolides (+21 and +7% respectively) and significant decrease in the absolute number of purchased aminoglycosides (61%), with significant reduction in the consumption of expensive drugs: tigecycline, polymyxin, daptomycin, cefoperazone/sulbactam.
Conclusion. The level and structure of consumption of antimicrobial agents corresponds to global data. The implementation of monitoring of antimicrobial therapy is an important factor influencing the volume and structure of consumption of antibacterial drugs.
Discussion Articles
History
Clinical Case
Purpose of issue is to show difficulties of detecting tuberculosis the general physician during epidemic of acute respiratory viral infection and flu, to show efficiency of modern methods of mycobacterial and HIV evaluation.
Materials and methods. Clinical case from general physician’s practice was discussed. All methods from primary healthcare were used.
Results. Possibilities of tuberculosis diagnostics by general physician during epidemic were shown. Tuberculosis was held under mask of flu. While carrying out diagnostic minimum negative results have been received. As a result of plane radiography dissemination was found. After analysis of social risk factors, analysis for HIV and «Diaskin-test» were made. Sputum also was sent for mycobacterium evaluation to antituberculosis center laboratory. Positive «Diaskintest» (8 mm), positive Gene-expert molecular-genetic test and BACTEC fluid growth were found. Diagnosis of tuberculosis was stated and patient was sent to specialized center.
Conclusion. During flu epidemic alertness of general practitioners about tuberculosis is needed especially in social risk groups. It is recommended to enlarge diagnostic minimum using molecular genetic methods. These actions can improve rate of tuberculosis proving.