Вакцинопрофилактика пневмококковой инфекции у детей

Pneumococcal infection remains one of the leading reasons for infant mortality from vaccine-preventable infections. Today vaccination is the most effective way to prevent diseases caused by antibiotic-resistant pneumococci. In the article, authors present current approaches to vaccinal prevention of pneumococcal diseases. The plan of action for carrying out active immunoprophylaxis of pneumococcal infection is explained in detail for both healthy children and patients from risk groups for severe pneumococcal diseases development. The published work is based on key points of the guidelines of the Ministry of Health of the Russian Federation on vaccinal prevention of pneumococcal infection (developed and approved by the professional association of pediatricians «The Union of Pediatricians of Russia»).Пневмококковая инфекция остается одной из ведущих причин детской смертности от вакциноуправляемых инфекций. Вакцинация на сегодняшний день является наиболее эффективным направлением профилактики заболеваний, вызываемых устойчивыми к антибактериальным препаратам пневмококкам. В статье коллективом авторов представлены актуальные подходы к вакцинопрофилактике болезней пневмококковой этиологии. Подробно разъяснен алгоритм действий при проведении активной иммунопрофилактики пневмококковой инфекции как здоровых детей, так и пациентов из групп риска по развитию тяжелых форм пневмококковых заболеваний. Публикация основана на ключевых позициях методических рекомендаций Министерства здравоохранения РФ по вакцинопрофилактике пневмококковой инфекции (разработанных и утвержденных профессиональной ассоциацией детских врачей «Союз педиатров России»).КОНФЛИКТ ИНТЕРЕСОВАвторы статьи подтвердили отсутствие конфликта интересов, о котором необходимо сообщить

Ротавирусная инфекция у детей — нерешенная проблема. Обзор рекомендаций по вакцинопрофилактике

These clinical guidelines were developed by the professional association of pediatric specialists «Union of Pediatricians of Russia» and approved by the Association’s Executive Committee at the Congress of Pediatricians of Russia «Actual Problems of Pediatrics». Clinical guidelines are devoted to the problem of rotavirus infection, the relevance of which is determined by the high prevalence level and significant contribution of infectious diarrhea to the mortality pattern of children in the first 5 years of life. We present epidemiological data and detailed information on the infectious agent and pathogenesis of rotavirus infection progression. A detailed picture of clinical manifestations as well as extraintestinal complications is presented. The approach to specific prophylaxis has been reasoned. Practical recommendations for immunization as well as various regimens for administering the vaccine, depending on the age and condition of the patient, are given.Данные клинические рекомендации разработаны профессиональной ассоциацией детских специалистов «Союз педиатров России» и утверждены Исполкомом ассоциации на Съезде педиатров России «Актуальные проблемы педиатрии». Клинические рекомендации посвящены проблеме ротавирусной инфекции, актуальность которой определяется высоким уровнем распространенности и значительным вкладом инфекционной диареи в структуру смертности детей первых 5 лет жизни. Приводятся эпидемиологические данные, подробно описаны особенности возбудителя, патогенез развития ротавирусной инфекции. Представлена развернутая картина клинических проявлений, а также внекишечных осложнений. Обоснована тактика специфической профилактики. Даны практические рекомендации по проведению иммунизации, а также различные схемы введения вакцины в зависимости от возраста и состояния пациента

Evaluation of the Cost-Effectiveness of Vaccination of Children with 5-valent Vaccine against Rotavirus Infection in the Russian Federation

One of the main causes of the incidence of intestinal infections in children under 5 years infection is rotavirus. Vaccines against rotavirus infection substantially reduce morbidity.The objective of this study is to analyze cost-effectiveness of vaccination of children with 5-valent vaccine against rotavirus infection in the Russian Federation.Methods. The evaluation was carried out using modelling on the  basis of published data on the effectiveness of vaccines and  epidemiological data for the Russian Federation. In the base case analysis was performed from the position of the society as a  whole. During the sensitivity analysis cost-effectiveness was also  evaluated from the position of the health system. The evaluation was performed on the period of survival of vaccinated children. The costof therapy corresponded to the rates of OMS in St. Petersburg in 2017, the price of 1 dose of vaccine accounted for in the calculationof 1450 rubles. Costs and life expectancy with regard to quality were discounted at 3.5% per year.Results. Taking into account the accepted assumptions, the mass  vaccination will prevent the vaccinated population in the average  4675 RVI outpatient cases and 1732 RVI cases requiring  hospitalization per 100 thousand children the first year of life, with  90% coverage. In unvaccinated populations will be prevented 4128  outpatient cases and 1212 RVI cases requiring hospitalization. The  projected amount of avoided costs in general — 2.94 thousand RUB  per 1 child (54% in the vaccinated cohort, 46% in unvaccinated  population). Cost-effectiveness will be in the evaluation from the  perspective of society as a whole of 260.1 thousand RUB counting on an quality adjusted life year (QALY), and the evaluation from the perspective of the health system — 653.0 thousand roubles/QALY. Thus, in both cases, costeffectiveness of rotavirus vaccination per 1  QALY will not exceed the generally accepted threshold willingness-to- pay equal to three times the gross domestic product in Russia (2016  — 1.76 million RUB). The projected economic efficiency of selective  vaccination 4.94 times lower than one of mass vaccination.Conclusions. Mass vaccination of children with 5-valent vaccine against RVI will not only reduce the incidence in the Russian  Federation, but, given the adopted assumptions, may also be  considered as a cost-effective intervention

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy adults

Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18–75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632)

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy infants, children, and adolescents

Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV), which can result in bacterial superinfection, central nervous system complications, and hospitalization. Stage 2 of this Phase 3 open-label study (ClinicalTrials.gov identifier: NCT03843632) enrolled 100 healthy infants, children, and adolescents (12 months–6 years, n = 37; 7–12 years, n = 33; 13–17 years, n = 30) without a clinical history of varicella. Participants aged 12 months–12 years were administered 1 dose of VARIVAX™ 0.5 mL (Varicella Virus Vaccine Live [Oka/Merck]) and adolescents aged 13–17 years were administered 2 doses 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immunosorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and VZV antibody geometric mean titers 6 weeks after the final dose. For participants who were VZV seropositive at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by antibody titer geometric mean fold rise and percentage of participants with ≥4-fold rise in antibody titer 6 weeks after the final dose. A Vaccine Report Card was used to report solicited and unsolicited adverse events through 42 days post-vaccination. After series completion among seronegative participants across age groups (n = 74), 98.6% demonstrated seroconversion 6 weeks post-vaccination; among seropositive participants (n = 26), 65.4% had ≥4-fold rise in antibody titer 6 weeks post-vaccination. No new safety signals were observed. Administering VARIVAX to infants, children, and adolescents resulted in an acceptable immune response with a safety profile consistent with the licensed product

Preservation of Postvaccinal Immunity to Measles, Rubella, Parotitis, Hepatitis B and Diphtheria in Patients With Juvenile Idiopathic Arthritis Who Undergone Planned Immunization Under the Age of Two: Preliminary Results of Cross-Sectional Study

Background. Patients with juvenile idiopathic arthritis (JIA) can have low levels of antibodies to vaccine antigens due to immunologic features of the main disease, disruptions in vaccination schedule and immunosuppressive drugs administrationObjective. The aim of the study was to examine the status of postvaccinal immunity and determine the factors associated with preservation of protective level of antibodies in patients with JIA.Methods. This cross-sectional study included patients with JIA at the age from 2 to 17 years old vaccinated under the age of two (before JIA) against measles, rubella, parotitis, hepatitis B and diphtheria. Levels of IgG to vaccine antigens were measured by enzyme immunoassay. The minimum protective level of anti-measles IgG was esteemed as 0.18 IU/ml, antibodies to rubella — 10 IU/ml, for parotitis — COI &gt; 1.0, for hepatitis B — 10 mIU/ml, antibodies to diphtheria — 0.09 IU/ml.Results. The study included 90 patients with JIA (71% of girls) at the age (median) 11.3 (7.5; 14.9) years. The age of JIA manifestation was 6.0 (4.0; 8.0) years, disease duration — 4.0 (2.0; 7.3) years. Glucocorticosteroids administration in anamnesis or at study entry was recorded in 24/88 (27%) patients, methotrexate — 81/88 (92%), genetically engineered biologic drugs — 54/89 (61%). Protective level of antibodies to measles virus was revealed in 45 (50%) children with JIA, to rubella virus — in 88 (98%), to parotitis — in 68 (76%), to hepatitis B — in 49 (54%), to diphtherial anatoxin — in 45 (50%). The decrease of postvaccinal immunity level was associated with JIA duration and glucocorticosteroids administration (against diphtheria) duration, as well as drop-out immunization (against measles).Conclusion. Major part of children with JIA have no protection against measles, parotitis, hepatitis B or diphtheria. High risk of progression of such vaccine-preventable diseases in these children demands development of individual programs of immunization

Cost-Effectiveness of Quadrivalent Human Papillomavirus Vaccination in Adolescent Girls in Russian Federation

The human papillomavirus (HPV) infection is one of the major risk factor of development of genital warts, a cervical dysplasia, a cervical cancer, and also some other oncologic diseases. The usage  of quadrivalent HPV vaccine in girls reduces the corresponding case  rate and the mortality significantly.The objective of this study is to analyze the cost-effectiveness of quadrivalent HPV vaccination cases of 12-year-old girls in Russian Federation.Methods. A Markov model is used on the basis of epidemiological data in Russian Federation. In base case the cost-effectiveness was  estimated from societal perspective. We assumed that the effect of  vaccination remains throughout all life. The analysis is performed for survival of 12-year-old girls. We considered only effect in the  vaccinated population. Costs for therapy of the diseases associated  with HPV infection corresponded to compulsory health insurance  rates across St. Petersburg for 2017. Costs and life expectancy have been discounted for 3.5% a year.Results. Quadrivalent HPV vaccination of 12-year-old girls in Russian Federation will allow to prevent counting on 100 000 the  vaccinated persons 2918 cases of genital warts, 5095 cases of  cervical dysplasia, 893 cases of invasive cervical cancer, 56 cases of  vulvar cancer, 18 cases of vaginal cancer, 13 cases of anal cancer, 7  cases of oropharyngeal cancer. The vaccination will provide cost  reduction, caused by HPV-associated diseases, for 453.9 million  rubles on 100 000 vaccinated, and 86.5% of the predicted prevented costs will be caused by decrease in incidence of cervical cancer, 9%  — cervical dysplasia, 2.9% — genital warts. The quadrivalent HPV vaccination is associated with an incremental cost-effectiveness ratio (ICER) of 247 560 rubles per quality adjusted life-year (QALY) and  334 200 rubles per life-year gained (LYG). Thus, in both cases, cost  effectiveness of rotavirus vaccination per 1 QALY will not exceed the  generally accepted threshold willingness-to-pay equal to three times  the gross domestic product in Russia (2016 — 1.76 million RUB).Conclusions. Quadrivalent HPV vaccination of girls prior to the beginning of sex life could be considered in Russian Federation as an economically effective technology for preventing HPV-associated diseases

Эффективность и безопасность вакцинации пациентов с ювенильным идиопатическим артритом

Background. Vaccination is the most effective method for reducing morbidity, disability, mortality from of various infections. However, there was a view for a long time that vaccines are ineffective and unsafe to use in people with rheumatological diseases, including juvenile idiopathic arthritis (JIA). Objective.The aim of the study is to analyze literature data on safety and efficacy of vaccination for JIA patients with live and non-live vaccines.Methods: literature analysis was based on data from medical databases PubMed and Google Scholar.Results. Both live and non-live vaccines are safe and immunogenic enough for children with JIA. Most studies confirm vaccination efficacy in patients with JIA when using glucocorticosteroids (GCS) and methotrexate, while therapy with disease-modifying antirheumatic drugs (DMARD) can reduce antibody titers over time. In general, antibodies levels preservation in previously vaccinated children with JIA is less than in global population. This indicates the need to administer booster doses for such patients. No adverse effects on the course of primary disease after vaccination and no post-vaccine complications were revealed.Conclusion. Vaccination of patients with JIA should be performed with reference to the therapy that the patient already receives, under the control of antibodies level. Booster doses should be implemented in case of titers decrease below the protective levels.Обоснование. Вакцинация является наиболее эффективным средством снижения заболеваемости, инвалидизации, смертности от ряда инфекций. Однако долгое время существовало мнение, что для людей с ревматологическими заболеваниями, в том числе с ювенильным идиопатическим артритом (ЮИА), вакцины могут быть неэффективны и небезопасны.Цель – проанализировать данные литературы о безопасности и эффективности вакцинации живыми и неживыми вакцинами пациентов с ЮИА.Материалы и методы: анализ литературы по данным, представленным в медицинских базах данных PubMed и Google Scholar.Результаты. Как живые, так и неживые вакцины являются достаточно безопасными и иммуногенными для детей с ЮИА. Большинство исследований подтверждают эффективность вакцинации пациентов с ЮИА при применении глюкокортикостероидов (ГКС) и метотрексата, в тоже время терапия болезнь-модифицирующим антиревматическими препаратами (БМАРП) может ускорить снижение титров антител с течением времени. В целом длительность сохранности уровня антител у ранее привитых детей с ЮИА меньше, чем в популяции, что свидетельствует о необходимости введения им бустерных доз. Не выявлено негативного влияния на течение основного заболевания после вакцинации или развития поствакцинальных осложнений.Выводы. Вакцинация пациентов с ЮИА должна осуществляться с учетом терапии, которую получает пациент, под контролем уровня антител и при снижении титров ниже защитных – решением вопроса о введении бустерных доз