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Development of a Reagent Kit for the Quantitative Determination of Hepatitis B Virus (HBV) DNA in Clinical Material by PCR with Hybridization-Fluorescence Detection PCR -杂交-荧光法定量检测临床材料中乙型肝炎病毒DNA试剂盒的研制
Q4 Medicine Pub Date : 2023-09-21 DOI: 10.31631/2073-3046-2023-22-4-86-94
O. N. Zhigaleva, S. G. Mardanly, T. Yu. Gashenko, I. I. Ermolaev
Relevance. Hepatitis B virus (HBV) is one of the most common viral infections affecting people worldwide and can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Currently 3% of the world's population are infected with hepatitis B virus and are at risk of developing life-threatening liver disease. Immunological and molecular biological methods of detection of HBV are currently used in laboratory diagnostics. The polymerase chain reaction (PCR) is currently the most sensitive method for the detection and quantification of HBV. HBV DNA quantification is widely used to monitor the antiviral treatment of HBV infection. Aim. To develop a real-time PCR kit for the quantification of HBV DNA. Materials and methods. A total of 200 plasma and serum samples positive and negative for HBV were used in the development. The performance of the developed kit was compared with the use of other commercially registered HBV diagnostic kits in Russia. Additionally, the nucleotide sequences of all existing virus genotypes analysed for the selection of primers using GeneBank system. Results and discussion. Comparison analysis of the results of quantitative determination by real-time PCR in 200 clinical serum and blood plasma samples showed that the diagnostic sensitivity of the developed kit was 100% and specificity 100%. The primers developed specific to the POL gene region. The kit is capable of detecting all types of virus genotypes. Conclusions. The developed reagent kit allows detection of hepatitis B virus and determination of its quantity within 70 minutes. In addition to a large number of genotypes and subgenotypes, the virus is characterized by mutational changes in the genome, which complicates its diagnosis and, as a consequence, the ongoing therapy with drugs. Conservative regions for primer and probe selection taken into account in the development, and the sequencing results obtained are applicable to all HBV genotypes. The reagent kit is designed to monitor HBV infected patients and will allow the analysis of different HBV viral loads.
的相关性。乙型肝炎病毒(HBV)是影响全世界人群的最常见病毒感染之一,可导致慢性肝炎、肝硬化和肝细胞癌。目前,世界上3%的人口感染了乙型肝炎病毒,并有发展为危及生命的肝脏疾病的危险。免疫和分子生物学方法检测HBV目前用于实验室诊断。聚合酶链反应(PCR)是目前检测和定量HBV最灵敏的方法。HBV DNA定量被广泛用于监测HBV感染的抗病毒治疗。的目标。目的:研制一种用于HBV DNA定量的实时PCR试剂盒。材料和方法。该研究共使用了200份HBV阳性和阴性的血浆和血清样本。将开发的试剂盒的性能与俄罗斯其他商业注册的HBV诊断试剂盒的使用进行了比较。此外,利用GeneBank系统分析所有现有病毒基因型的核苷酸序列,选择引物。结果和讨论。对200份临床血清和血浆标本的实时荧光定量PCR检测结果进行对比分析,试剂盒的诊断敏感性为100%,特异性为100%。这些引物是针对POL基因区域开发的。该试剂盒能够检测所有类型的病毒基因型。结论。开发的试剂盒可以检测乙型肝炎病毒,并在70分钟内确定其数量。除了大量的基因型和亚基因型外,该病毒的特点是基因组发生突变变化,这使其诊断复杂化,并因此影响了正在进行的药物治疗。开发过程中考虑了引物和探针选择的保守区域,获得的测序结果适用于所有HBV基因型。该试剂盒旨在监测HBV感染患者,并允许分析不同的HBV病毒载量。
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引用次数: 0
Organization of Mass Vaccine Prevention in the Conditions of a Modern Megapolis 现代大都市条件下的大规模疫苗预防组织
Q4 Medicine Pub Date : 2023-09-21 DOI: 10.31631/2073-3046-2023-22-4-95-105
A. V. Starshinin, T. N. Elagina, Yu. B. Novikova, G. N. Gribanovskaya, N. N. Kamynina, O. I. Nechaev
Relevance. Thanks to decisions taken at the national level, many countries have managed to significantly increase coverage with preventive vaccination and reduce mortality from vaccine-preventable diseases. However, the COVID-19 pandemic has recaptured the relevance of organizing mass vaccination. Based on the current epidemiological situation, characteristics of the population, peculiar features of infrastructure, available resources in individual country, and individual city, various organizational vaccination solutions have been developed and implemented. The Moscow-based experience of vaccinating against influenza at mobile vaccination sites near the Moscow metro stations in 2016 became the starting point in the development of new organizational forms and technologies for mass vaccination in a megapolis, that have been successfully adapted to the new conditions of the COVID19 pandemic. Aims. is to summarize foreign and Russian (exemplified by Moscow) experience in organizing mass vaccination. Material and methods. The study is based on the publication search results in Google and PubMed. The authors selected materials published in 2017– 2023. The implemented analysis of the long-term dynamics in the influenza incidence in the Russian Federation, the Central Federal District (CFD) and Moscow was based on data of the Federal State Statistical Observation Form No. 2 «Information on infectious and parasitic diseases» for 2013–2019. Results and discussion. The analysis of foreign experience shows that the development and implementation of new forms of mass vaccination cannot become a "standard project". In each region of the world, it is organized with due regard to the local economic, legal, social, medical, organizational and even cultural conditions. Vaccination of the population against influenza at mobile vaccination sites near the Moscow metro stations contributed to a 42.3% decrease in the incidence of influenza (from 24.6 in 2016 to 14.2 per 100,000 population in 2017). In 2019, the incidence of influenza in Moscow was 28.8% lower than the CFD one and 62.2% lower than the Russian rate. The recognized successful experience of deploying mobile vaccination sites near the metro stations has been significantly expanded to control the COVID-19 pandemic with mobile teams, vaccination sites in shopping centers, etc. Conclusion. The conducted research and literature data substantiate the deployment of additional vaccination sites to ensure the necessary coverage with vaccination within a short period of time.
的相关性。由于在国家一级作出的决定,许多国家已设法大大提高了预防性疫苗接种的覆盖率,并降低了疫苗可预防疾病的死亡率。然而,2019冠状病毒病大流行再次凸显了组织大规模疫苗接种的重要性。根据当前流行病学情况、人口特点、基础设施特点、各国和各城市现有资源,制定并实施了各种组织性疫苗接种解决方案。2016年在莫斯科地铁站附近的流动疫苗接种点进行流感疫苗接种的经验,成为在大城市开发大规模疫苗接种的新组织形式和技术的起点,这些组织形式和技术已成功适应了covid - 19大流行的新情况。目标是总结国外和俄罗斯(以莫斯科为例)组织大规模疫苗接种的经验。材料和方法。这项研究是基于Google和PubMed上的出版物搜索结果。作者选择2017 - 2023年出版的材料。对俄罗斯联邦、中央联邦区和莫斯科流感发病率长期动态的分析基于2013-2019年联邦国家统计观察表第2号“传染病和寄生虫病信息”的数据。结果和讨论。国外经验分析表明,开发和实施新形式的大规模疫苗接种不能成为“标准项目”。在世界每一个区域,教育的组织都适当考虑到当地的经济、法律、社会、医疗、组织甚至文化条件。在莫斯科地铁站附近的流动疫苗接种点接种流感疫苗,将流感发病率降低了42.3%(从2016年的每10万人24.6人降至2017年的每10万人14.2人)。2019年,莫斯科的流感发病率比CFD低28.8%,比俄罗斯低62.2%。在地铁站附近部署移动疫苗接种点的公认成功经验已被大大扩展,以移动团队、购物中心疫苗接种点等方式控制COVID-19大流行。结论。开展的研究和文献数据证实部署了更多的疫苗接种点,以确保在短时间内实现必要的疫苗接种覆盖。
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引用次数: 0
Influenza and Pneumococcal Vaccination of Healthcare Workers during a Pandemic Reduces the Risk and Severity of COVID-19 in Vaccinated 大流行期间卫生保健工作者接种流感和肺炎球菌疫苗可降低接种者感染COVID-19的风险和严重程度
Q4 Medicine Pub Date : 2023-09-21 DOI: 10.31631/2073-3046-2023-22-4-56-66
M. P. Kostinov, N. Yu. Nastaeva, A. E. Vlasenko, A. M. Kostinova, K. V. Mashilov, E. G. Simonova
Background. Individuals who were vaccinated against seasonal influenza or had a history of pneumococcal vaccination were found to be less likely to become infected and tolerate COVID-19 more easily. However, it has not been sufficiently studied how vaccination against these infections, carried out during the pandemic period, can affect the incidence of COVID-19. Aims. The purpose of the investigation: to study the effect of vaccination against influenza and pneumococcal infection carried out during the pandemic of a new coronavirus infection on the susceptibility and course of COVID-19 in healthcare workers. Materials and methods. In August- Setempber 2020, after the first rise in the incidence of COVID-19, out of 547 employees (aged 18 to 70 years) of a medical organization (MO), 266 (49%) were vaccinated against influenza (group II, n = 98), pneumococcal infection (group III, n = 60) and combined vaccination (group IV, n = 108), while 281 (51%) remained unvaccinated (group 1). Follow-up period: from September 2020 to March 2021 with the registration of the incidence of acute respiratory infections (ARI) according to primary medical records and the use of PCR methods for SARS-CoV-2, epidemiological and statistical analysis. Results. Two months after the start of the study, the proportion of cases of COVID-19 in the 1st group (unvaccinated) was 5% versus 1% in the 4th group (persons vaccinated with two vaccines), after 4 months – 15% and 5%, respectively, and at the end of observation (166 days) – 16% and 8%, respectively. That is, among unvaccinated individuals, the risk of getting COVID-19 was higher by HR = 2.1 [95% CI: 1.0÷4.7] times. The time between the start of observation and a positive test for COVID-19 in study participants was significantly higher in the 4th group compared to the group I: 106 [60–136] days versus 47 [17–75] days. The distribution of patients with COVID-19 according to the severity of viral pneumonia showed that in unvaccinated patients in most (64%) cases, pneumonia had a moderate to severe course, while in the 4th group of patients with combined vaccination in 100% of cases, mild (p = 0.04 for the entire sample). Conclusions. During the COVID-19 epidemic rises, vaccination against respiratory infections remains relevant, reducing the number of cases, the severity of the coronavirus infection and preventing the occurrence of co-infections.
背景。研究发现,接种过季节性流感疫苗或有肺炎球菌疫苗接种史的个体感染COVID-19的可能性较小,并且更容易耐受COVID-19。然而,尚未充分研究在大流行期间开展的针对这些感染的疫苗接种如何影响COVID-19的发病率。目标调查目的:研究新型冠状病毒大流行期间开展的流感和肺炎球菌感染疫苗接种对医护人员COVID-19易感性和病程的影响。材料和方法。2020年8月至9月,在COVID-19发病率首次上升后,某医疗机构(MO)的547名员工(18至70岁)中,266人(49%)接种了流感疫苗(第二组,n = 98)、肺炎球菌感染疫苗(第三组,n = 60)和联合疫苗(第四组,n = 108), 281人(51%)未接种疫苗(第一组)。在2020年9月至2021年3月期间,根据基本医疗记录登记急性呼吸道感染(ARI)的发病率,并使用PCR方法对SARS-CoV-2进行流行病学和统计分析。结果。研究开始两个月后,第一组(未接种疫苗)的COVID-19病例比例为5%,而第四组(接种两种疫苗的人)的比例为1%,4个月后分别为15%和5%,观察结束(166天)时分别为16%和8%。也就是说,在未接种疫苗的个体中,感染COVID-19的风险高出HR = 2.1倍[95% CI: 1.0÷4.7]。与第一组相比,第4组研究参与者开始观察和COVID-19阳性检测之间的时间明显更长:106[60-136]天比47[17-75]天。按病毒性肺炎严重程度划分的COVID-19患者分布显示,未接种疫苗的大多数(64%)患者的肺炎病程为中度至重度,而联合接种疫苗的第4组患者的肺炎病程为轻度(全样本p = 0.04)。结论。在COVID-19流行加剧期间,预防呼吸道感染的疫苗接种仍然具有重要意义,可以减少病例数,降低冠状病毒感染的严重程度,并预防合并感染的发生。
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引用次数: 0
Molecular Surveillance of Natural Focal Diseases Causative Agents in the Stavropol Territory in 2016–2021 2016-2021年斯塔夫罗波尔领土自然局灶性疾病病原体分子监测
Q4 Medicine Pub Date : 2023-09-20 DOI: 10.31631/2073-3046-2023-22-4-24-34
E. V. Chekrygina, A. S. Volynkina, O. A. Zaitseva, Ya. V. Lisitskaya, I. V. Tishchenko, O. A. Gnusareva, D. V. Rostovtseva, E. I. Vasilenko, N. O. Tkachenko, O. V. Vasilyeva, K. A. Purmak, N. I. Solomashchenko, A. N. Kulichenko
Relevance. Molecular surveillance, aimed at obtaining up-to-date information on the genetic variants of pathogens circulating in the studied region, is an important element of the surveillance of natural focal infections (NFIs). The Stavropol Territory is one of the main recreational regions in the Russian Federation; it is endemic for a number of NFIs, including: Crimean-Congo hemorrhagic fever (CCHF), Q fever, tularemia, Lime disease, etc. The aim of the work is is genomic profiling of NFIs causative agents circulating in the Stavropol Territory in 2016-2021. Materials and methods. Microbial strains and samples of field and clinical material containing genomic DNA/RNA of pathogens were used as material for the study. Genetic typing of strains and isolates of DNA/RNA NFIs causative agents was performed by MLVA (Francisella tularensis and Coxiella burnetii) and genome fragment sequencing (Crimean-Congo hemorrhagic fever virus, West Nile virus, orthohantaviruses, Borrelia burgdorferii s.l., Ricckettsia sp.). Results. As a result of molecular genetic typing in the ST in 2016-2021 confirmed circulation of strains of F. tularensis of genetic subgroups B.I, B.III, B.VI, genetically identical strains of C. burnetii (VNTR-профиль 4-6-6-4-7-6-3-12-3-11), rickettsia belonging to 5 species: R. raoultii, R. aeschlimannii, R. slovaca, R. massiliae, R. helvetica , Borrelia belonging to the species: B. afzelii, B. garinii, B. miyamotoi, B. bavariensis, B. lusitaniae, B. valaisiana, RNA isolates of the CCHF virus of the Europe-1 and Europe-3 genetic lines, Tula orthohantaviruses, West Nile virus genotype 2. For the first time on the territory of the CT, in insectivore lung samples, RNA isolates of orthohantavirus genetically close to Camp Ripley virus (RLPV) were detected. Conclusions. New data have been obtained on the distribution of genetic variants of NFIs causative agents in the S, also in the recreation areas. Genetic structure of the population of NFIs causative agents in the ST in 2016-2021 did not change significantly, which indicates the relative stability of the natural foci of NFIs in the region.
的相关性。分子监测是自然局灶性感染监测的一个重要组成部分,其目的是获取在研究区域传播的病原体遗传变异的最新信息。斯塔夫罗波尔领土是俄罗斯联邦的主要休闲地区之一;它是一些非传染性疾病的地方病,包括:克里米亚-刚果出血热(CCHF)、Q热、兔热病、莱姆病等。这项工作的目的是对2016-2021年在斯塔夫罗波尔领土流行的非传染性疾病病原体进行基因组分析。材料和方法。以微生物菌株和含有病原菌基因组DNA/RNA的野外和临床材料样品为研究材料。采用MLVA(土拉弗朗西斯菌和伯纳柯赛特菌)和基因组片段测序(克里米亚-刚果出血热病毒、西尼罗病毒、正汉坦病毒、伯氏疏螺旋体、立克次体)对NFIs病原体的菌株和分离株进行遗传分型。结果。通过2016-2021年ST分子遗传分型,确认了土拉螺旋体遗传亚群B.I、B.I、B.I、B.I、伯氏体遗传相同菌株(VNTR-профиль 4-6-6-4-7-6- 12-3-11)、立克次体属5种:拉乌尔蒂氏体、埃斯chlimannii、slovaca、马氏体、helvetica、伯氏体属5种:阿夫泽利布氏杆菌、加里尼布氏杆菌、宫莫托布氏杆菌、巴伐利亚布氏杆菌、卢西塔尼亚布氏杆菌、瓦莱西布氏杆菌、欧洲1号和欧洲3号遗传系CCHF病毒RNA分离株、图拉正汉坦病毒、西尼罗病毒基因2型。首次在CT范围内,在食虫动物肺样本中检测到遗传上接近雷普利坎普病毒(Camp Ripley virus, RLPV)的正汉坦病毒RNA分离株。结论。关于非传染性疾病致病因子的遗传变异在南部地区的分布已经获得了新的数据,也在娱乐区。2016-2021年ST地区nfi病原菌种群遗传结构无明显变化,表明该地区nfi自然疫源地相对稳定。
{"title":"Molecular Surveillance of Natural Focal Diseases Causative Agents in the Stavropol Territory in 2016–2021","authors":"E. V. Chekrygina, A. S. Volynkina, O. A. Zaitseva, Ya. V. Lisitskaya, I. V. Tishchenko, O. A. Gnusareva, D. V. Rostovtseva, E. I. Vasilenko, N. O. Tkachenko, O. V. Vasilyeva, K. A. Purmak, N. I. Solomashchenko, A. N. Kulichenko","doi":"10.31631/2073-3046-2023-22-4-24-34","DOIUrl":"https://doi.org/10.31631/2073-3046-2023-22-4-24-34","url":null,"abstract":"Relevance. Molecular surveillance, aimed at obtaining up-to-date information on the genetic variants of pathogens circulating in the studied region, is an important element of the surveillance of natural focal infections (NFIs). The Stavropol Territory is one of the main recreational regions in the Russian Federation; it is endemic for a number of NFIs, including: Crimean-Congo hemorrhagic fever (CCHF), Q fever, tularemia, Lime disease, etc. The aim of the work is is genomic profiling of NFIs causative agents circulating in the Stavropol Territory in 2016-2021. Materials and methods. Microbial strains and samples of field and clinical material containing genomic DNA/RNA of pathogens were used as material for the study. Genetic typing of strains and isolates of DNA/RNA NFIs causative agents was performed by MLVA (Francisella tularensis and Coxiella burnetii) and genome fragment sequencing (Crimean-Congo hemorrhagic fever virus, West Nile virus, orthohantaviruses, Borrelia burgdorferii s.l., Ricckettsia sp.). Results. As a result of molecular genetic typing in the ST in 2016-2021 confirmed circulation of strains of F. tularensis of genetic subgroups B.I, B.III, B.VI, genetically identical strains of C. burnetii (VNTR-профиль 4-6-6-4-7-6-3-12-3-11), rickettsia belonging to 5 species: R. raoultii, R. aeschlimannii, R. slovaca, R. massiliae, R. helvetica , Borrelia belonging to the species: B. afzelii, B. garinii, B. miyamotoi, B. bavariensis, B. lusitaniae, B. valaisiana, RNA isolates of the CCHF virus of the Europe-1 and Europe-3 genetic lines, Tula orthohantaviruses, West Nile virus genotype 2. For the first time on the territory of the CT, in insectivore lung samples, RNA isolates of orthohantavirus genetically close to Camp Ripley virus (RLPV) were detected. Conclusions. New data have been obtained on the distribution of genetic variants of NFIs causative agents in the S, also in the recreation areas. Genetic structure of the population of NFIs causative agents in the ST in 2016-2021 did not change significantly, which indicates the relative stability of the natural foci of NFIs in the region.","PeriodicalId":36064,"journal":{"name":"Epidemiologiya i Vaktsinoprofilaktika","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136376054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Prevalence of Genetic Determinants of Antibiotic Resistance, which are of Particular Epidemiological Consequences, in the Microbiota of the Oropharyngeal Swabs in Patients with Cystic Fibrosis 囊性纤维化患者口咽拭子微生物群中抗生素耐药性的遗传决定因素的流行病学影响
Q4 Medicine Pub Date : 2023-09-20 DOI: 10.31631/2073-3046-2023-22-4-44-48
T. S. Skachkova, E. V. Kniazeva, E. N. Goloveshkina, T. V. Tronza, E. I. Kondratyeva, A. Y. Voronkova, V. G. Akimkin
Relevance. Antibiotic resistance of microorganisms can contribute to the chronicity of the inflammatory process, lead to an increase in the cost of treating patients and make it difficult to eradicate the pathogen. Patients with cystic fibrosis constantly require medical supervision, regular visits to medical institutions, and therefore there is a high risk of infection with nosocomial antibiotic- resistant strains. In addition, the necessary intake of antibacterial drugs provides an advantage for the reproduction of resistant microorganisms. Aim. Comparison of the frequency of detection of antibiotic resistance determinants in oropharyngeal swabs in children with cystic fibrosis and conditionally healthy children using molecular biological methods. Materials and methods. A PCR study of oropharyngeal discharge from 100 children with cystic fibrosis and 100 children from the control (healthy comparison subject) group was performed. Genetic antibiotic resistance locus: metallo-b-lactamases of the VIM, IMP and NDM groups; carbapenemase genes of the KPC and OXA-48 groups; extended-spectrum beta-lactamase genes of the CTX-M group and the mecA gene were detected by polymerase chain reaction (PCR) with hybridization-fluorescence detection. Results and discussion. As a result of the analysis, a statistically significant increase in the frequency of detection of genetic determinants of antibiotic resistance in the microbiota of the oropharyngeal discharge in children with cystic fibrosis was found compared with healthy children (p<0.001). The chances of detecting antibiotic resistance loci in the discharge of the oropharynx among children with cystic fibrosis are 38.5 times higher than among healthy children (95% CI: 5.1-289.5). In 28% of children with cystic fibrosis, DNA of the genetic determinants of antibiotic resistance was detected in the microbiome of the discharge of the oropharynx. A high percentage of the presence of genetic determinants of antibiotic resistance may be the reason for the ineffectiveness of antibiotic therapy. Conclusion. Due to the high occurrence in the microbiome of the oropharyngeal discharge of patients with cystic fibrosis of genetic antibiotic resistance locus that are of particular clinical and/or epidemiological significance, and the high risk of the spread of antibiotic-resistant strains outside medical institutions, it is necessary to include this group of patients in regular epidemiological monitoring.
的相关性。微生物的抗生素耐药性可能导致炎症过程的慢性,导致治疗患者的成本增加,并使病原体难以根除。囊性纤维化患者需要持续的医疗监督,定期到医疗机构就诊,因此存在院内耐药菌株感染的高风险。此外,必要的抗菌药物摄入为耐药微生物的繁殖提供了有利条件。的目标。分子生物学方法在囊性纤维化儿童和条件健康儿童口咽拭子中抗生素耐药决定因素检测频率的比较材料和方法。对100例囊性纤维化患儿和100例健康对照患儿的口咽分泌物进行PCR检测。遗传耐药位点:VIM、IMP和NDM组的金属-b-内酰胺酶;KPC组和OXA-48组碳青霉烯酶基因;采用聚合酶链反应(PCR) -杂交-荧光法检测CTX-M组的广谱β -内酰胺酶基因和mecA基因。结果和讨论。分析结果发现,与健康儿童相比,囊性纤维化儿童口咽分泌物微生物群中抗生素耐药性遗传决定因素的检测频率有统计学意义上的显著增加(p<0.001)。在患有囊性纤维化的儿童口咽分泌物中发现抗生素耐药位点的机会是健康儿童的38.5倍(95% CI: 5.1-289.5)。在28%的囊性纤维化儿童中,在口咽部分泌物的微生物组中检测到抗生素耐药性遗传决定因素的DNA。抗生素耐药性的遗传决定因素存在的高比例可能是抗生素治疗无效的原因。结论。由于囊性纤维化患者口咽分泌物微生物组中具有特殊临床和/或流行病学意义的遗传抗生素耐药位点发生率高,且耐药菌株在医疗机构外传播的风险高,有必要将该类患者纳入定期流行病学监测。
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引用次数: 0
Preservation of Antibodies to Vaccine-Controlled Infections in Children WITH Oncological Diseases 肿瘤疾病儿童疫苗控制感染抗体的保存
Q4 Medicine Pub Date : 2023-09-20 DOI: 10.31631/2073-3046-2023-22-4-35-43
S. M. Kharit, Yu. E. Konstantinova, O. V. Goleva, A. A. Ruleva, K. K. Tikhomirova, O. V. Iozefovich, I. V. Fridman
Relevance. Cancer therapy forms a temporary immunosuppressive state, which determines an increase in the frequency and severity of infectious diseases. Vaccination is a highly effective and safe way to protect against infection, but people with immunodeficiency have risks of inefficiency and complications. To substantiate the need for immunoprophylaxis in cancer patients after therapy, it is important to understand the preservation of their specific response after previous vaccinations.The aim of the study was to assess the safety of antibodies to vaccine–controlled infections in children with oncological diseases after therapyMaterials and methods. The safety of antibodies to vaccine-controlled infections was studied in 3 groups: 1 -in patients with oncological (n=62); 2-in the group (n=43) withoutoncological diseases, but who received immunosuppressive (IST) and/or polychemotherapy (PCT) and/or hematopoietic stem cell transplantation (HSCT), and 3– in healthy children (n=31 – comparison group). The concentration of antibodies was determined by the ELISA method. The minimum protective level was considered to be the amount for measles ³0.18 IU/ml, rubella - ³25 IU/ml; hepatitis B - ³10 IU/ml; diphtheria – 0.03 IU/ml and higher. The coefficient of positivity, estimated as protective against mumps, was ³1.0.Results. It was found that from 41.7% to 93.7% of children with cancer lose post-vaccination immunity to the studied vaccine antigens. The number of children who retained the protective level of antibodies in groups 1 and 2 was significantly less than in the comparison group. There were no significant differences in the level of those protected from diphtheria and rubella. The maximum effect on the loss of antibodies is provided by the performed HSCT. For diphtheria and rubella antibodies, the differences are not pronounced. The possible connection of genetic breakdowns in 35 examined children with oncological diseases and the safety of antibodies was analyzed. It turned out that in the presence of chromosomal deletions, antibodies to measles were lost in 100% of cases and to diphtheria in 75%, which was different from other chromosomal abnormalities.Conclusion. The safety of antibodies in patients with a history of cancer is influenced by the presence of HSCT in therapy, the type of genetic breakdown, as well as the peculiarity of the vaccine antigen. Children with oncological diseases, as well as with non-oncological ones, but who have received HSCT therapy, should be vaccinated again against vaccine-controlled infections, despite the indication of the presence of vaccinations before therapy.
的相关性。癌症治疗形成暂时的免疫抑制状态,这决定了传染病发生频率和严重程度的增加。疫苗接种是一种非常有效和安全的预防感染的方法,但免疫缺陷患者存在效率低下和并发症的风险。为了证实癌症患者在治疗后需要免疫预防,重要的是要了解他们在先前接种疫苗后的特异性反应的保存。本研究的目的是评估儿童肿瘤疾病治疗后抗疫苗控制感染抗体的安全性。在三组中研究了抗体对疫苗控制感染的安全性:1 -in肿瘤患者(n=62);2例为无肿瘤疾病,但接受免疫抑制(IST)和/或多化疗(PCT)和/或造血干细胞移植(HSCT)的组(n=43), 3例为健康儿童(n=31 -对照组)。ELISA法测定抗体浓度。麻疹的最低保护水平为0.18 IU/ml,风疹为25 IU/ml;乙型肝炎- 10 IU/ml;白喉- 0.03 IU/ml及以上。阳性系数,估计对腮腺炎有保护作用,为³1.0。结果。结果发现,41.7% ~ 93.7%的癌症儿童在接种疫苗后对所研究的疫苗抗原失去免疫力。第1组和第2组保持抗体保护水平的儿童人数明显少于对照组。在预防白喉和风疹的人群中,免疫球蛋白水平没有显著差异。对抗体损失的最大影响是通过进行造血干细胞移植。对于白喉和风疹抗体,差异并不明显。分析了35例肿瘤疾病患儿的遗传缺陷与抗体安全性的可能联系。结果发现,在存在染色体缺失的情况下,麻疹抗体100%丢失,白喉抗体75%丢失,这与其他染色体异常不同。结论。在有癌症病史的患者中,抗体的安全性受到治疗中HSCT的存在、遗传破坏的类型以及疫苗抗原的特性的影响。患有肿瘤疾病的儿童,以及患有非肿瘤疾病的儿童,但接受了造血干细胞移植治疗,应再次接种疫苗,以防止疫苗控制的感染,尽管有迹象表明在治疗前接种疫苗。
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引用次数: 0
Assay of Diphtheria Vaccine Potency by Intradermal Challenge Test 皮内激射法测定白喉疫苗效力
Q4 Medicine Pub Date : 2023-09-20 DOI: 10.31631/2073-3046-2023-22-4-12-23
E. I. Komarovskaya, О. V. Perelygyna
Relevance. Modern identifying potency (immunogenicity) of diphtheria toxoid tests are based on determining immunized animals resistance for administration challenge toxin or evaluation of protective antibodies level in serum. In Russia to assess the potency of diphtheria toxoid (DT) the challenge lethal method has been used for more than 60 years, challenge is based on determination of potency via its possibility to defend immunized animals from lethal doses of diphtheria toxin. This method is used as «golden standard». Last decade European Union Regulatory politic is headed to reduce of using animals in pharmaceutical practice, "The Three Rs" approach. In frameworks of this approach alternative methods of evaluating immunogenicity DT were purposed, particularly, intradermal challenge method. Within this test the potency of diphtheria toxoid is evaluated by its possibility to protect immunized animals from intradermal administration of diphtheria toxin. In the production of a number of foreign vaccines intradermal challenge test is used for assessing potency. Aim. Comparative characteristics of methods of lethal challenge test and intradermal challenge tests to determine the potency of diphtheria toxoid in combined vaccines and toxoids made in Russia. Materials and methods. Materials of domestic and foreign manufacturers were used in the work: combined vaccines for diphtheria prevention, diphtheria toxins, reference-vaccine. The determination of the potency of diphtheria toxoid was carried out on guinea pigs by pharmacopoeias methods: lethal challenge test and intradermal challenge tests. Results. To assess the potency of diphtheria toxoid using, a technique was used in accordance with WHO recommendations; for this, guinea pigs similar in sensitivity to diphtheria toxin to Dunkin Hartley pigs were selected. The suitability of the diphtheria toxin used in Russia for determining the potency of diphtheria toxoid by the method of intradermal challenge test was assessed when evaluating the effectiveness of vaccines for the prevention of diphtheria. Comparative tests of the intradermal challenge tests and lethal challenge tests were carried out to determine the potency of diphtheria toxoid. Conclusions. The conducted studies have demonstrated the fundamental possibility of using the intradermal challenge tests to assess the potency of diphtheria toxoid. However, for a number of factors, such as the variability of results, the number of animals, etc., the intradermal challenge tests is inferior to the method of lethal challenge tests in assessing the potency of diphtheria vaccines in routine practice.
的相关性。现代鉴定白喉类毒素试验的效力(免疫原性)是基于确定免疫动物对给药挑战毒素的抗性或血清中保护性抗体水平的评估。在俄罗斯,评估白喉类毒素(DT)效力的攻毒致死法已经使用了60多年,攻毒是基于通过其保护已免疫动物免受致命剂量白喉毒素侵害的可能性来确定效力。这种方法被用作“黄金标准”。过去十年,欧盟的监管政策旨在减少在制药实践中使用动物,即“三个r”方法。在这种方法的框架下,评估免疫原性DT的替代方法是有目的的,特别是皮内激发法。在这项试验中,白喉类毒素的效力是通过其保护免疫动物免受白喉毒素皮内注射的可能性来评估的。在许多国外疫苗的生产中,采用皮内激射试验来评估效力。的目标。在俄罗斯制造的联合疫苗和类毒素中确定白喉类毒素效力的致死攻击试验和皮内攻击试验方法的比较特点。材料和方法。工作中使用了国内外生产厂家的材料:预防白喉联合疫苗、白喉毒素、参比疫苗。采用药典方法:致死性攻毒试验和皮内攻毒试验对豚鼠进行了白喉类毒素效价的测定。结果。为了评估使用白喉类毒素的效力,按照世卫组织的建议使用了一种技术;为此,选择了对白喉毒素敏感性与唐金-哈特利猪相似的豚鼠。在评估预防白喉疫苗的有效性时,评估了俄罗斯使用白喉毒素以皮内激射试验方法确定白喉类毒素效力的适宜性。为确定白喉类毒素的效力,进行了皮内攻击试验和致死攻击试验的比较试验。结论。所进行的研究表明,利用皮内激发试验评估白喉类毒素效力的基本可能性。然而,由于一些因素,例如结果的可变性、动物的数量等,皮内激射试验在常规实践中评估白喉疫苗效力方面不如致命激射试验。
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引用次数: 0
Mucosal Vaccines against Bacterial and Viral Pathogens 抗细菌和病毒病原体的粘膜疫苗
Q4 Medicine Pub Date : 2023-09-20 DOI: 10.31631/2073-3046-2023-22-4-4-11
A. N. Suvorov, Т. A. Kramskaya, T. V. Gupalova, Yu. A. Desheva, G. F. Leontieva
The mucosal membranes of the human body play a crucial role in the development, maintenance, and regulation of barrier functions and immune homeostasis, representing an integral component of the overall immune system. Mucosal vaccines elicit immune processes in the lymphoid tissue associated with the mucosal membranes. A critical objective of mucosal immunization is the identification of an antigen delivery vector capable of ensuring optimal vaccine efficacy. The authors of this article have conducted extensive research on the probiotic properties of enterococci over an extended period. They employ a safe and beneficial probiotic strain, Enterococcus faecium L3, as a delivery vector for vaccine antigens. Initially, the gene encoding the pathogenicity factor Bac, derived from group B streptococci (Streptococcus agalactiae), was successfully integrated into the genome of the probiotic strain E. faecium L3. Intravaginal, oral, and intranasal mucosal immunization methods utilizing the L3-Bac+ probiotic, which expresses antigenic determinants of pathogenic streptococci, were found to confer protection against bacterial infection in laboratory animals. Subsequently, recombinant technologies were refined, leading to the development of a universal method for incorporating a region of interest from the gene into the structure of the major pili protein gene of E. faecium L3. Using this technology, candidate vaccines against various infections, including Streptococcus pneumoniae, influenza A virus, and SARS-CoV-2 following the onset of the Covid-19 pandemic, have been obtained and tested. In this study, alongside the presentation of our own data, the challenges associated with utilizing recombinant probiotic bacteria as vectors for vaccine antigen delivery are discussed.
人体粘膜在屏障功能和免疫稳态的发育、维持和调节中起着至关重要的作用,是整个免疫系统不可分割的组成部分。粘膜疫苗引起与粘膜相关的淋巴组织的免疫过程。黏膜免疫的一个关键目标是确定能够确保最佳疫苗效力的抗原递送载体。本文作者对肠球菌的益生菌特性进行了长时间的广泛研究。他们使用一种安全有益的益生菌菌株,粪肠球菌L3,作为疫苗抗原的传递载体。最初,编码来自B群链球菌(无乳链球菌)的致病性因子Bac的基因被成功整合到益生菌E. faecium L3的基因组中。使用表达致病性链球菌抗原决定因子的L3-Bac+益生菌的阴道内、口服和鼻内粘膜免疫方法被发现对实验动物的细菌感染具有保护作用。随后,重组技术得到了改进,从而开发了一种通用方法,将该基因的感兴趣区域整合到粪肠杆菌L3的主要毛蛋白基因的结构中。利用这项技术,已获得并测试了针对各种感染的候选疫苗,包括肺炎链球菌、甲型流感病毒和Covid-19大流行后的SARS-CoV-2。在本研究中,除了介绍我们自己的数据外,还讨论了利用重组益生菌作为疫苗抗原递送载体的挑战。
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引用次数: 0
Epidemic Process Manifestations and Leading Factors of Transmission of The Pathogenes of the Enterovirus Infection Basic Clinical Forms 肠道病毒感染病原菌的流行过程表现及传播主导因素基本临床表现
Q4 Medicine Pub Date : 2019-01-03 DOI: 10.31631/2073-3046-2018-17-6-70-75
В. И. Сергевнин, М. А. Трясолобова
Relevance .The urgency of the problem of non-polio enterovirus infection is determined by the wide spread of pathogens, the occurrence of outbreak of morbidity, polymorphism of clinical manifestations and the lack of specific prophylaxis. Most often non-polio enterovirus infection is asymptomatic. Clinically expressed  forms can be serous meningitis, herpetic sore throat, eczematous fever, vesicular pharyngitis, gastroenteritis,  epidemic myalgia (pleurodynia), tonsillitis, myocarditis, pericarditis, hemorrhagic conjunctivitis, uveitis, etc. The aim of the work is a comparative evaluation of the epidemic process  manifestations and the leading factors of serous meningitis (SM)  pathogens,  enterovirus  etiology herpetic angina  (HA) transmission  and enterovirus  etiology gastroenteritis  (GE). Materials  and  methods . Manifestations of the epidemic process of SM and HA were studied according to the official registration of the incidence of the population of Perm for the 2010–2017.  In conditions of analytical «case-control»  method the epidemiological survey of 350 epidemiological focuses of SM and 142 focuses of HA and 61 focuses of GE were conducted.  Results . According to official registration data, the incidence rates of NEVI in the population of Perm during the last 7 years (2010–2017) ranged from 0.3 to 21.5, averaging 5.4 per 100 thousand population. There were mainly three clinical forms registered - serous meningitis, herpetic sore throat, gastroenteritis, the proportion of which was 45.3; 36.6 and 12.4%, respectively. The findings clearly demonstrate that it is similarity between epidemic process manifestations of SM, HA and enterovirus etiology gastroenteritis. Conclusion . In both clinical variants of enterovirus infection the priority role is the water way of transmission of the pathogen by drinking water from centralized and decentralized sources of water system, as well as swimming in surface water.
相关性。非脊髓灰质炎肠道病毒感染问题的紧迫性取决于病原体的广泛传播、发病率的爆发、临床表现的多态性以及缺乏特定的预防措施。大多数非脊髓灰质炎肠道病毒感染是无症状的。临床表现形式可为浆液性脑膜炎、疱疹性咽喉痛、湿疹热、水泡性咽炎、肠胃炎、流行性肌痛(胸膜炎)、扁桃体炎、心肌炎、心包炎、出血性结膜炎、葡萄膜炎等。本工作的目的是比较评估浆液性脑膜炎(SM)病原体、肠道病毒病因疱疹性咽峡炎(HA)传播和肠道病毒病因肠胃炎(GE)的流行过程表现和主导因素。材料和方法。根据2010-2017年彼尔姆人口发病率的官方登记,研究了SM和HA的流行过程表现。在病例对照分析法的条件下,对350个SM流行病学重点、142个HA流行病学重点和61个GE流行病学重点进行了流行病学调查。结果。根据官方登记数据,过去7年(2010-2017年),彼尔姆人口中的新冠肺炎发病率在0.3至21.5之间,平均每10万人口5.4例。临床表现主要有浆液性脑膜炎、疱疹性咽痛、肠胃炎三种,占45.3;分别为36.6%和12.4%。研究结果清楚地表明SM、HA的流行过程表现与肠道病毒病因肠胃炎相似。结论在肠道病毒感染的两种临床变体中,首要作用是通过饮用集中式和分散式水源系统的水以及在地表水中游泳来传播病原体。
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引用次数: 16
Pre-Epidemic Diagnosis in the System Risk-Oriented Epidemiological Surveillance of Infectious Diseases 面向风险的传染病流行病学监测系统中的流行前诊断
Q4 Medicine Pub Date : 2018-10-23 DOI: 10.31631/2073-3046-2018-17-5-31-37
E. G. Simonova, V. I. Sergevnin
This article is devoted to both theoretical and practical aspects of modern epidemiology of infectious diseases associated with the improvement of pre-epidemic diagnostics and the need for its implementation in the system of risk-based surveillance. The authors summarized and systematized the current data on the factors of epidemiological risk as well as suggested methodological approaches to identify and assess the prerequisites and precursors of complication of the epidemiological situation. In addition, they took into consideration the existing problems of pre-epidemic diagnosis and ways to solve them.
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引用次数: 9
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