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Assessment of changes in the phenotype, intensity of degranulation, death and lysis of neutrophils in <i>ex vivo</i> modeling of <i>Staphylococcal</i> bacteremia 评估离体细胞中中性粒细胞表型、脱颗粒强度、死亡和溶解的变化;葡萄球菌&lt;/i&gt;菌血症
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-384
Aleksandr L. Kravtsov, Svetlana A. Bugorkova, Svetlana N. Klyueva, Tatyana P. Shmelkova, Vitaly A. Kozhevnikov
Introduction. At present, it is important to study the interaction of Staphylococcus aureus with human innate immunity cells under conditions of ex vivo bacteremia modeling, but not only in experiments with phagocytes previously isolated from the blood. Purpose: comparative assessment of changes in the phenotype, intensity of aurophilic degranulation, death and lysis of neutrophils in whole blood samples from apparently healthy donors following the addition of live and killed microbial cells of S. aureus ATCC 6538 (209-P). Materials and methods. Bacteremia was modeled by adding microbes to whole blood (with heparin) at doses ranging from 108 to 101 mc/ml. The bactericidal effect was determined at different time points of blood incubation at 37C (for 6 hours) by the microbiological method. The blood leukocyte immunophenotyping was performed using flow cytometry according to the Lyse/No-Wash protocol to determine the expression of markers of azurophilic degranulation (CD63), early apoptosis (CD95) on the surface of neutrophilic granulocytes (NG) and cell adhesion (CD62L), as well as to assess the surface expression density of the molecular trigger of netosis FcᵧRIIIb (CD16) and tyrosine protein phosphatase (CD45), which is a regulator of FcR-mediated cell signaling during phagocytosis and netosis. The presence of degenerative changes in NG was confirmed by microscopy in the analysis of blood smears stained according to RomanovskyGiemsa. Results. Significant differences were revealed in the response of human blood NG to live and killed S. aureus cells according to the studied phenotypic parameters. Only live microbes triggered azurophilic degranulation in NCs and stimulated, starting from 2 h incubation, the appearance of a large number of NG with the CD95+ phenotype in the blood. In addition, live bacteria induced in phagocytes twice as much functional rearrangement in terms of CD45 expression. They induced a rapid decrease in the density of CD16 expression on NG and activated NG lysis in the blood with an intensity depending on the initial microbial concentration. Following 6 h incubation at concentrations of more than 105 mc/ml, flow cytometry detected the presence in the blood of a population of low density neutrophils characteristic of sepsis (Low Density Neutrophils with the CD63+CD16low phenotype), whose cells are prone to spontaneous autolysis (netosis). Conclusion. Under the conditions of ex vivo modeling of bacteremia, various strategies of human blood neutrophils in the implementation of the mechanisms of protection of the macroorganism from infection were evaluated, and the prospects of using the obtained information to identify individuals at high risk of developing staphylococcal sepsis were determined.
介绍。目前,在体外菌血症模型的条件下研究金黄色葡萄球菌与人先天免疫细胞的相互作用是很重要的,但不仅仅是用先前从血液中分离的吞噬细胞进行实验。 目的:比较评估在添加金黄色葡萄球菌ATCC 6538 (209-P)活菌和灭菌后,明显健康的献血者全血标本中嗜金粒细胞表型、亲金脱颗粒强度、死亡和溶解中性粒细胞的变化。材料和方法。通过向全血(含肝素)中添加108至101 mc/ml剂量的微生物来模拟菌血症。采用微生物学方法测定血液在37℃(6小时)孵育不同时间点的杀菌效果。根据Lyse/No-Wash方案,采用流式细胞术进行血液白细胞免疫分型,测定中性粒细胞(NG)表面的嗜氮脱粒(CD63)、早期凋亡(CD95)和细胞粘附(CD62L)标志物的表达,并评估netosis分子触发因子FcᵧRIIIb (CD16)和酪氨酸蛋白磷酸酶(CD45)的表面表达密度。它是吞噬和吞噬过程中fcr介导的细胞信号的调节剂。根据romanovsky - giemsa . 结果。根据研究的表型参数,人血NG对活的和死的金黄色葡萄球菌的反应有显著差异。只有活的微生物才能触发nc的亲氮脱粒,并从培养2小时开始刺激大量具有CD95+表型的NG在血液中出现。此外,就CD45表达而言,活菌诱导吞噬细胞的功能重排是其两倍。它们诱导了NG上CD16表达密度的快速下降,并激活了血液中NG的裂解,其强度取决于初始微生物浓度。在超过105 mc/ml的浓度下孵育6小时后,流式细胞术检测到血液中存在脓毒症特征的低密度中性粒细胞(CD63+CD16low表型的低密度中性粒细胞),其细胞易于自发自溶(netosis)。结论。在离体模拟菌血症的条件下,评估了人类血液中性粒细胞在实施大型生物感染保护机制中的各种策略,并确定了利用所获得的信息识别葡萄球菌脓毒症高危个体的前景。
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引用次数: 0
Antimicrobial resistance and virulence of carbapenem-resistant <i>Klebsiella pneumoniae</i> strains isolated from children in intensive care and surgical units 耐碳青霉烯肺炎克雷伯菌的耐药性和毒力;从重症监护室和外科病房的儿童中分离出的菌株
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-373
Irina E. Novikova, Zulfirya Z. Sadeeva, Natalya M. Alyabyeva, Ekaterina A. Samoylova, Olga V. Karaseva, Olga G. Yanyushkina, Anna V. Lazareva
Introduction. Infections associated with carbapenem-resistant (Carba-R) Klebsiella pneumoniae (KP) are a serious public health problem because they lead to an increase in hospital stays, treatment costs, and an increase in patient morbidity and mortality. Aim to characterize antimicrobial resistance, virulence factors and genotypes of Carba-R KP strains isolated from patients in intensive care and surgical units. Materials and methods. In total, 455 KP strains that were resistant to meropenem and/or imipenem, or susceptible to meropenem and/or imipenem at increased exposure were collected in 20182020. For further analysis, total 90 KP strains isolated from clinically significant sites blood/сerebrospinal fluid/urine/lower respiratory tract/wounds/abdominal cavity of patients in intensive care and surgical units were selected. Antibiotic susceptibility was determined using the broth microdilution method. Carbapenemase genes were detected by real-time PCR. The virulence genes and K1/K2 capsular serotypes were determined by multiplex PCR. Sequence types (ST) were determined using multilocus sequence typing. Results. Most of the selected isolates (97%) were recognized as extensively drug-resistant pathogens, three isolates were classified as multidrug-resistant pathogens. The major determinant of carbapenem resistance was blaOXA-48-like (53%), blaNDM-group was detected in 13% strains, a combination of blaNDM-group and blaOXA-48-like genes was found in 31% isolates. Two isolates harbored blaKPC-group. Most of the isolates had the virulence genes entB (100%), mrkD (99%), and ybtS (78%). The iutA gene was found in 16% strains. Four isolates had kfu gene and four strains carried rmpA gene. The K2 capsule type was determined in 13% isolates. Four ST dominated in the studied population: ST395 (26%), ST2975 (19%), ST198 (12%) and ST307 (11%). Conclusion. Carba-R KP isolates had a high level of resistance not only to carbapenems, but also to antibiotics of other classes. Carbapenem resistance was mainly associated with OXA-48 carbapenemase. The entB, mrkD and ybtS genes were the main determinants of virulence. The epidemically successful clones CG395 and CG307 were the predominant genetic lines. Resistance to antimicrobials was combined with the presence of various virulence factors. The data obtained are important for the epidemiological surveillance of the spread of KP and have important clinical implications.
介绍。与碳青霉烯耐药肺炎克雷伯菌(KP)相关的感染是一个严重的公共卫生问题,因为它们会导致住院时间增加、治疗费用增加以及患者发病率和死亡率增加。目的了解重症监护病房和外科病房患者分离的Carba-R KP菌株的耐药性、毒力因子和基因型。 材料和方法。2018 - 2020年共收集到455株对美罗培南和/或亚胺培南耐药,或对暴露量增加的美罗培南和/或亚胺培南敏感的KP菌株。为进一步分析,共从重症监护病房和外科病房患者的临床重要部位血液/ 脑脊液/尿液/下呼吸道/伤口/腹腔分离出90株KP菌株。采用微量肉汤稀释法测定药敏。实时荧光定量PCR检测碳青霉烯酶基因。采用多重PCR检测毒力基因和荚膜K1/K2血清型。序列类型(ST)采用多位点序列分型确定。 结果。大多数(97%)被认为是广泛耐药病原体,3株被归类为多重耐药病原体。耐药的主要决定因素是blaoxa -48样基因(53%),blandm基因组占13%,blandm基因组与blaoxa -48样基因组合占31%。两个分离株含有blaKPC-group。大多数分离株具有entB(100%)、mrkD(99%)和ybtS(78%)毒力基因。在16%的菌株中发现了iutA基因。4株菌株携带kfu基因,4株菌株携带rmpA基因。13%的菌株被确定为K2胶囊型。4个基因型在研究人群中占主导地位:ST395(26%)、ST2975(19%)、ST198(12%)和ST307(11%)。结论。Carba-R KP分离株不仅对碳青霉烯类抗生素具有较高的耐药性,而且对其他种类的抗生素也具有较高的耐药性。碳青霉烯耐药主要与OXA-48碳青霉烯酶有关。entB、mrkD和ybtS基因是毒力的主要决定因素。流行成功的无性系CG395和CG307为优势遗传系。对抗菌素的耐药性与各种毒力因子的存在相结合。获得的数据对KP传播的流行病学监测具有重要意义,并具有重要的临床意义。
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引用次数: 0
A modern view of diarrheagenic <i>Escherichia coli</i> — a causative agent of acute intestinal infections 致泻性大肠杆菌&lt;/i&gt;-急性肠道感染的病原体
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-410
Mariia A. Makarova
Acute intestinal infections caused by Escherichia coli affect the gastrointestinal tract, leading to development of diarrheal syndrome, intoxication, and, in some cases, generalization of the pathological process. Diarrheagenic E. coli (DEC) strains differ from non-pathogenic (commensal) strains by the presence of specific virulence genes, pathogenesis characteristics, clinical and epidemiological manifestations of the diseases they cause. Based on the virulence determinants, 6 pathogenic DEC groups are distinguished: enteropathogenic, enterotoxigenic, enteroinvasive, shiga toxin-producing, enteroaggregative, diffusely adherent E. coli strains. The strains of each pathogenic group have distinct pathogenic mechanisms responsible for inflammatory processes in different compartments of the human intestine, which are clinically manifested as diarrheal syndrome. This paper presents a review of current scientific publications on epidemiology, pathogenesis, genetic properties, and antigenic characteristics of pathogenic E. coli. Although DEC biological properties have been extensively studied, many aspects require deeper insights to develop effective laboratory-based diagnostic techniques, treatment methods, epidemic control measures, and prevention strategies against E. coli infections.
大肠杆菌引起的急性肠道感染影响胃肠道,导致腹泻综合征、中毒,在某些情况下,病理过程普遍化。致泻性大肠杆菌(DEC)菌株与非致病性(共生)菌株的区别在于它们所引起的疾病存在特定的毒力基因、发病特点、临床和流行病学表现。根据毒力决定因素,区分出6种致病性DEC:肠致病性、肠产毒性、肠侵袭性、志贺毒素产生型、肠聚集型、弥漫性粘附型大肠杆菌菌株。每个致病组的菌株具有不同的致病机制,负责人体肠道不同区室的炎症过程,临床表现为腹泻综合征。本文综述了致病性大肠杆菌的流行病学、发病机制、遗传特性和抗原特征等方面的最新研究成果。尽管DEC的生物学特性已经得到了广泛的研究,但为了开发有效的基于实验室的诊断技术、治疗方法、流行病控制措施和预防大肠杆菌感染的策略,许多方面还需要更深入的了解。
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引用次数: 0
Spectrum and functional properties of <i>ERG11</i> gene mutations in fluconazole-resistant <i>Candida albicans</i> strains isolated from HIV-infected patients &lt;i&gt;ERG11&lt;/i&gt;耐氟康唑基因突变&lt;i&gt;白色念珠菌&lt;/i&gt;从hiv感染患者中分离的菌株
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-407
Yuri V. Nesvizhsky, Stanislav S. Afanasiev, Alexander D. Voropaev, Yulia N. Urban, Mariam E. Suleimanova, Maxim S. Afanasiev, Elena V. Budanova, Elena A. Voropaeva
Rationale. The low efficacy of azole antimycotics in treatment of Candida infections, especially in HIV-infected patients, is often associated with overexpression of the ERG11 gene in Candida spp., which results in increased production of ergosterol the target of the above antimycotic drugs. Researchers have found ERG11 gene mutations that can modify its overexpression effects by increasing or decreasing it. However, the findings reported by different laboratories and countries are highly contradictory. The purpose of the study is to explore the spectrum and functional properties of ERG11 gene mutations in fluconazole-resistant Candida albicans strains isolated from HIV-infected patients. Materials and methods. The study was performed using 10 C. albicans strains inherently resistant to fluconazole and voriconazole and isolated from the oropharynx of HIV-infected patients; the strains were provided from the collection of the Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology. The strains were assessed by their sensitivity to antimycotic agents: anidulafungin, micafungin, caspofungin, posaconazole, voriconazole, itraconazole, fluconazole, amphotericin B, 5-flucytosine. Expression levels of the ERG11 gene were measured by quantitative PCR. ERG11 gene mutations were identified by Sanger sequencing. Results. Five mutations (E266D, G464S, I471L, D116E, and V488I) were detected in the ERG11 gene in seven C. albicans strains; six strains carried non-associated co-occurring mutations. Increased expression of the ERG11 gene was found in six C. albicans strains. The V488I mutation demonstrated a strong negative association with the increased expression of the ERG11 gene (r = 0.845; p 0.05). The minimum inhibitory concentration (MIC) in strains carrying mutations was a hundred times as low (p 0.05) as MIC in strains without mutations. In mutation carriers, posaconazole and itraconazole MICs were on average 16.5 times as low as MICs of voriconazole and fluconazole (p 0.001). The presence of mutations in the ERG11 gene had almost no effect on MICs of the tested antimycotics of the echinocandin, polyene, and pyrimidine groups. Conclusion. Multiple mutations were detected in the ERG11 gene in most of the C. albicans strains isolated from HIV-infected patients and resistant to fluconazole and voriconazole. Except for the V488I mutation, the detected mutations were not associated with the overexpression of the ERG11 gene and decreased the effects of overexpression of the ERG11 gene by up to 100 times, though they did not eliminate the inherent resistance to triazole antimycotics.
基本原理。唑类抗真菌药物治疗念珠菌感染的低疗效,特别是在hiv感染患者中,通常与念珠菌中ERG11基因的过度表达有关,这导致麦角甾醇的产生增加,而麦角甾醇是上述抗真菌药物的靶点。研究人员发现ERG11基因突变可以通过增加或减少其过度表达来改变其影响。然而,不同实验室和国家报告的结果是高度矛盾的。 本研究的目的是探讨从hiv感染患者中分离的耐氟康唑白色念珠菌菌株中ERG11基因突变的谱和功能特性。材料和方法。该研究使用从hiv感染者口咽分离的10株对氟康唑和伏立康唑固有耐药的白色念珠菌菌株进行;菌株来自盖布里切夫斯基莫斯科流行病学和微生物学研究所。测定各菌株对抗真菌药物的敏感性:阿尼杜冯宁、米卡冯宁、卡波冯宁、泊沙康唑、伏立康唑、伊曲康唑、氟康唑、两性霉素B、5-氟胞嘧啶。采用定量PCR法检测ERG11基因的表达水平。Sanger测序鉴定ERG11基因突变。 结果。在7株白色念珠菌中检测到ERG11基因的5个突变(E266D、G464S、I471L、D116E和V488I);6个菌株携带不相关的共发生突变。在6株白色念珠菌中发现ERG11基因表达增加。V488I突变与ERG11基因表达增加呈显著负相关(r = 0.845;p 0.05)。携带突变菌株的最低抑菌浓度(MIC)是未携带突变菌株的100倍(p 0.05)。突变携带者中泊沙康唑和伊曲康唑的mic平均是伏立康唑和氟康唑的16.5倍(p < 0.001)。ERG11基因突变的存在对棘白菌素、多烯和嘧啶基团抗真菌药物的mic几乎没有影响。 结论。对氟康唑和伏立康唑耐药的大多数白色念珠菌株中检测到ERG11基因的多重突变。除V488I突变外,检测到的突变与ERG11基因过表达无关,并将ERG11基因过表达的影响降低了100倍,尽管它们并没有消除对三唑类抗真菌药物的固有抗性。
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引用次数: 0
Analysis of entomological indicators and distribution of <i>Aedes aegypti</i> larvae in dengue endemic areas 埃及伊蚊&lt;i&gt;昆虫学指标及分布分析登革热流行地区的幼虫
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-406
Agung Sutriyawan, Abdul Manap, Neti Sulami, Agung Setiyadi, Dian Mariza Riskiah, Ratna Dian Kurniawati, Khariri Khariri
Background. The cause of dengue fevers endemicity is vector larvae density, with Aedes aegypti as the prime vector. Bandung municipality is a high dengue fever endemic area. Hence, studying the habitat characteristics of the Aedes mosquito is essential to controlling the populations of mosquitos. Purpose. This study aimed to identify the aedes larvae breeding sites and the relationship between the breeding risk index, hygiene risk index, maya index, and the existence of larvae with the incidence of dengue fever. Method. The design used in this research was a cross-sectional survey. The sampling technique used simple random sampling. The quantity of the sample was 544 directly observed houses. Results. The entomological parameters obtained were house index (23.89%), container index (7.81%), Breteau index (50.73%), and larva free number (76.10%). The breeding risk index, hygiene risk index, and maya index are in the low category. The chi-square test conveyed that the breeding risk index, maya index, and the existence of larvae were significantly associated with the incidence of dengue fever. Conclusion. The entomological index may influence the high incidence of dengue fever. These findings and results may help the authorities to improve mosquito nest eradication in attempts to prevent dengue transmission.
背景。登革热流行的原因是病媒幼虫密度,埃及伊蚊是主要病媒。万隆市是登革热高发地区。因此,研究伊蚊的生境特征对控制蚊群具有重要意义。目的。本研究旨在查明伊蚊幼虫孳生地点及其孳生风险指数、卫生风险指数、玛雅指数和幼虫存在与登革热发病的关系。 方法。本研究采用的设计是横断面调查。抽样技术采用简单随机抽样。样本量为544间直接观察房屋。 结果。昆虫学参数分别为屋指数(23.89%)、容器指数(7.81%)、布雷图指数(50.73%)和游离幼虫数(76.10%)。养殖风险指数、卫生风险指数和玛雅指数均处于低水平。卡方检验结果显示,繁殖风险指数、maya指数和幼虫的存在与登革热的发病率显著相关。 结论。昆虫学指数可能影响登革热的高发。这些发现和结果可能有助于当局加强消灭蚊虫巢穴,以防止登革热传播。
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引用次数: 0
Genetic characterization and phylogenetic analysis of human norovirus infection in individual municipalities of the Sverdlovsk region in 2022 2022年斯维尔德洛夫斯克州各市人类诺如病毒感染的遗传特征和系统发育分析
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-402
Roman O. Bykov, Svetlana V. Scriabina, Anastasia S. Kilyachina, Tarek M. Itani, Vladislav I. Chalapa, Polina K. Starikova, Stanislav S. Koltunov, Angelika V. Ponomareva, Alexander V. Semenov
Introduction. Human Noroviruses (HuNoV) are highly contagious pathogens responsible of acute human norovirus infection (HuNoVI). GII.4 is the prevailing norovirus genotype in the incidence of gastroenteritis worldwide. Currently there are no studies on the molecular monitoring and phylogenetic analysis of HuNoV in the territory of the Sverdlovsk region, therefore it is not possible to objectively assess their genetic diversity. The aim of the study is to carry out genotyping and phylogenetic analysis of HNoVI in municipalities of the Sverdlovsk region: Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky in 2022. Materials and methods. Fecal samples were collected from children suffering from HuNoVI in the municipalities of the Sverdlovsk region. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction with degenerate primers flanking the ORF1/ORF2 junction. The amplified samples were genotyped by Sanger sequencing. Multiple sequence alignments were carried out and phylogenetic trees were constructed. Results. The total number of studied samples was 220. According to sequencing results, 73 positive sequences of HuNoV were typed, which represents 33% of the total volume of the studied samples. The largest share of genotypes is occupied by noroviruses GII (58%), noroviruses GI (42%). Noroviruses GII.17, GI.3 were the dominant genotypes. Phylogenetic analysis demonstrates that the identified sequences on the territory of the Sverdlovsk region have the smallest genetic distance, which gives grounds for their unification into a common cluster. Conclusion. For the first time, a genetic analysis of HuNoV was carried out in the territory of the Sverdlovsk region. The norovirus genotyping system based on the amplification of the ORF1/ORF2 region makes it possible to successfully identify various genotypes of noroviruses from the Sverdlovsk region. It has been confirmed that GII noroviruses remain the dominant genetic group. The results of phylogenetic analysis demonstrate the greatest homology in the formed clusters between isolates from Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky.
介绍。人诺如病毒是引起急性人诺如病毒感染的高传染性病原体。GII.4是全世界胃肠炎发病率中流行的诺如病毒基因型。目前在斯维尔德洛夫斯克地区还没有对HuNoV进行分子监测和系统发育分析的研究,因此无法客观地评价其遗传多样性。 该研究的目的是在2022年在斯维尔德洛夫斯克地区:叶卡捷琳堡、下塔吉尔、卡明斯克-乌拉尔斯基市开展HNoVI基因分型和系统发育分析。材料和方法。从斯维尔德洛夫斯克州各市感染HuNoVI的儿童身上收集了粪便样本。从粪便样本中提取病毒RNA,然后用ORF1/ORF2连接处的简并引物进行逆转录聚合酶链反应。扩增样品经Sanger测序分型。进行了多次序列比对,构建了系统发育树。 结果。研究样本总数为220个。根据测序结果,共分型HuNoV阳性序列73条,占研究样本总量的33%。诺如病毒GII(58%)和GI(42%)占据了基因型的最大份额。诺如病毒GII.17、gii .3为优势基因型。系统发育分析表明,在斯维尔德洛夫斯克地区鉴定的序列具有最小的遗传距离,这为它们统一为一个共同的集群提供了依据。 结论。首次在斯维尔德洛夫斯克地区对HuNoV进行了遗传分析。基于ORF1/ORF2区扩增的诺如病毒基因分型系统可以成功鉴定来自斯维尔德洛夫斯克地区的诺如病毒的各种基因型。已证实,GII诺如病毒仍然是主要的遗传群体。系统发育分析结果表明,叶卡捷琳堡、下塔吉尔、卡门斯克-乌拉尔斯基分离株形成的聚类具有最大的同源性。
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引用次数: 0
Promising pharmaceutical development of vaccines for the prevention of meningococcal infection 用于预防脑膜炎球菌感染的疫苗的有前途的药物开发
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-383
Maria V. Savkina, Lidiya V. Sayapina, Maxim A. Krivykh, Yury I. Obukhov
Meningococcal infection (MI) refers to anthroponoses; is an acute infectious disease with an aerosol transmission mechanism, characterized by various forms of the infectious process: from local (nasopharyngitis) and asymptomatic infections to generalized forms of invasive infection with the development of meningococcemia and meningitis. The causative agent of MI is meningococcus (Neisseria meningitidis) that belongs to the pathogen risk group 2. Preventive vaccination against MI is included in the calendar of preventive vaccinations according to epidemic indications. The problem of MI retains a great medical and social significance for Russian health care due to the continuing high rates of associated mortality, disability, high costs of treatment and rehabilitation. Vaccines against five of the six main N. meningitidis serogroups have been registered worldwide. Serogroup X vaccine is under development. Recently, there has been an increase in the heterogeneity of the meningococcal population due to serogroups W, Y, and X. The polysaccharide vaccines developed in Russia have restrictions on their use, and there is no full-cycle production of meningococcal conjugate vaccines in the Russian Federation. Given the above, the development and registration of new vaccines against MI is an urgent task. The purpose of this work is to analyze the current state of development of vaccines for MI prevention. Currently, depending on the production technology, the following types of meningococcal vaccines are available: polysaccharide, conjugated, based on outer membrane vesicles (OMV), protein and based on synthetic polysaccharides. Serogroup-targeted meningococcal vaccines are effective in reducing the public health burden of invasive MI. Polysaccharide conjugate and protein/OMV vaccines are among the most promising vaccines for most invasive meningococcal serogroups. In modern conditions, with the progress in technologies for future polysaccharide conjugate vaccines, new opportunities are opening up for the use of such approaches as chemical/enzymatic synthesis, improved characteristics of the carrier protein, and site-specific conjugation. The development of a single vaccine against the main invasive meningococcal serogroups, rather than its individual antigenic variants, does not lose its relevance. It is timely to develop in the near future a vaccine against N. meningitidis serogroup X, which was previously a rare cause of sporadic meningitis, but has caused outbreaks in various African countries in 20062010 and in recent years.
脑膜炎球菌感染(MI)是指人痘病;是一种具有气溶胶传播机制的急性传染病,其特征是多种形式的感染过程:从局部(鼻咽炎)和无症状感染到随着脑膜炎球菌病和脑膜炎的发展而发生的广泛性侵袭性感染。MI的病原体是脑膜炎球菌(脑膜炎奈瑟菌),属于病原体危险组2。根据流行病的适应症,预防MI疫苗接种已列入预防性疫苗接种日程表。由于相关的死亡率、残疾率、治疗和康复费用居高不下,心梗问题对俄罗斯卫生保健仍然具有重大的医疗和社会意义。针对六种主要脑膜炎奈瑟菌血清群中的五种的疫苗已在世界范围内登记。血清X组疫苗正在研制中。最近,由于W、Y和x血清群的存在,脑膜炎球菌种群的异质性有所增加。俄罗斯开发的多糖疫苗的使用受到限制,俄罗斯联邦没有完整周期的脑膜炎球菌结合疫苗生产。鉴于上述情况,开发和注册针对MI的新疫苗是一项紧迫的任务。本工作的目的是分析目前预防心肌梗死疫苗的发展状况。目前,根据生产技术的不同,可获得以下类型的脑膜炎球菌疫苗:多糖,结合,基于外膜囊泡(OMV),蛋白质和基于合成多糖。针对血清群的脑膜炎球菌疫苗可有效减轻侵袭性脑梗死的公共卫生负担。多糖结合疫苗和蛋白/OMV疫苗是针对大多数侵袭性脑膜炎球菌血清群最有希望的疫苗。在现代条件下,随着未来多糖结合疫苗技术的进步,化学/酶合成、改进载体蛋白的特性和位点特异性结合等方法的使用正在开辟新的机会。开发针对主要侵袭性脑膜炎球菌血清群的单一疫苗,而不是针对其单个抗原变体,并没有失去其相关性。在不久的将来开发一种针对脑膜炎奈瑟菌X血清群的疫苗是及时的,它以前是散发脑膜炎的罕见病因,但在2006 - 2010年和近年来在非洲各国引起了疫情。
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引用次数: 0
Type 4 secretion system in Clostridioides difficile: Structural features and its role as a pathogenicity factor 艰难梭菌的4型分泌系统:结构特征及其作为致病因子的作用
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-386
Julya V. Sorokina, Yuriy F. Belyi
Clostridioides difficile is a gram-positive microorganism causing damage to the human intestinal wall, clinically manifesting as antibiotic-associated diarrhea and pseudomembranous colitis. C. difficile infection remains a serious problem; the increasing frequency of nosocomial outbreaks and the emergence of community-acquired forms heighten the need for new prevention and treatment methods. The pathogenesis of C. difficile infection is associated with the toxins produced by bacteria and a large group of proteins promoting the replication of the pathogen in host tissues and its spread in the human population. Recent studies show that mobile genetic elements play a key role in the high virulence of C. difficile. Type 4 secretion systems (T4SS) are significant components of these elements; their impressive diversity among gram-positive microorganisms in general and in C. difficile, in particular, implies their high evolutionary and, consequently, medical significance. Further studies of the T4SS composition and structure will provide a deeper insight into mechanisms underlying the development of respective infections and will help outline pathogenically grounded approaches to prevention and treatment of diseases caused by C. difficile. On the other hand, the key components of the secretion machinery of the pathogen can be used in bioinformatic analysis and for searching new adaptive clusters in the genome of highly virulent strains.
艰难梭菌是一种革兰氏阳性微生物,对人体肠壁造成损害,临床表现为抗生素相关性腹泻和假膜性结肠炎。艰难梭菌感染仍然是一个严重的问题;医院内疫情的日益频繁和社区获得性形式的出现增加了对新的预防和治疗方法的需求。艰难梭菌感染的发病机制与细菌产生的毒素和一大群促进病原体在宿主组织中的复制及其在人群中的传播的蛋白质有关。最近的研究表明,移动遗传因子在艰难梭菌的高毒力中起关键作用。4型分泌系统(T4SS)是这些元素的重要组成部分;它们在一般革兰氏阳性微生物中,特别是在艰难梭菌中令人印象深刻的多样性,意味着它们具有高度的进化意义,因此具有医学意义。对T4SS组成和结构的进一步研究将提供对各自感染发展机制的更深入了解,并将有助于概述由艰难梭菌引起的疾病的预防和治疗的病原学基础方法。另一方面,病原体分泌机制的关键成分可用于生物信息学分析和在高毒菌株基因组中寻找新的适应性簇。
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引用次数: 0
Species characteristics of bacteria of the genus <i>Lactobacillus</i> identified in different loci of the human body (literature review) 乳酸菌属细菌的种类特征&lt;/i&gt;在人体不同位点发现(文献回顾)
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-332
Victoriya V. Tashlanova, Lyubov V. Kataeva, Tatyana F. Stepanova
Bacteria of the genus Lactobacillus are inhabitants of the surfaces of human mucous membranes, such as the oral cavity, digestive and urogenital tracts. Moreover, there is evidence that they are found in breast milk and sputum. In view of the many genetic differences, metabolic abilities and other functions of the species included in this genus, a revision of the classification of the genus Lactobacillus is proposed in 2020. Recently, in the scientific medical literature, the issues related to the influence of lactobacilli on the human microbiome, maintaining health and preventing pathological conditions of the body have been actively discussed. This review is devoted to the functional characteristics and analysis of the species diversity of Lactobacillus spp. circulating in various body systems, their participation in the formation and regulation of defense mechanisms. However, negative impacts are also noted, most often associated with the transfer of genetic determinants of resistance to antimicrobial drugs from lactobacilli to gram-negative microbiota.
乳酸菌属的细菌是人类粘膜表面的居民,如口腔、消化道和泌尿生殖道。此外,有证据表明它们存在于母乳和痰中。鉴于该属所包括的物种的许多遗传差异,代谢能力和其他功能,在2020年提出了乳杆菌属分类的修订。近年来,在科学医学文献中,乳酸菌对人体微生物群的影响、维持健康和预防身体病理状况等问题得到了积极的讨论。本文综述了乳杆菌在人体各系统中的功能特点、种类多样性及其参与防御机制形成和调控的研究进展。然而,负面影响也被注意到,最常见的是与抗微生物药物耐药性的遗传决定因素从乳酸菌转移到革兰氏阴性菌群有关。
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引用次数: 0
Characterisation of the COVID-19 epidemic process in Moscow and search for possible determinants of the trends of the observed changes 描述莫斯科COVID-19流行过程并寻找观察到的变化趋势的可能决定因素
Q3 Medicine Pub Date : 2023-09-21 DOI: 10.36233/0372-9311-375
Vladimir A. Gushchin, Andrei A. Pochtovyi, Daria D. Kustova, Darya A. Ogarkova, Denis A. Kleymenov, Tatyana A. Semenenko, Denis Yu. Logunov, Vladimir I. Zlobin, Alexander L. Gintsburg
Background. Constant assessment of the dynamics of the main characteristics of the epidemic process is the basic function of epidemiological surveillance of infectious diseases. The search for factors that determine changes in the characteristics of the epidemic process makes it possible to develop timely management decisions and reduce the risk of an increase in the scale of the pandemic. Moscow is the main centre of attraction for the population of other Russian regions with the most complex structure of social links and the highest population density. The purpose of the study is to identify factors that potentially determine the trends of observed changes using a molecular epidemiological analysis of the main characteristics of the epidemic process of a new coronavirus infection (COVID-19). Materials and methods. For the analysis, the data of Russian national genome sequence database of SARS-CoV-2 virus (VGARus) were combined with information on morbidity and mortality presented at the official internet resources стопкоронавирус.рф and Yandex DataLens, the dynamics of vaccination, COVID-19 disease incidence and hospitalization from the portal Gogov.ru. A multicentre retrospective observational epidemiological study was conducted to examine the sex and age structure of hospitalised patients. Anonymized case histories of patients with COVID-19 collected at different follow-up periods in the institutions of Moscow (41,561 cases) served as a source of data for the sex and age structure analysis. Results. We identified 11 periods with significantly different complex epidemiological characteristics. A decrease in the incidence among young people of working age during the period of restrictive measures was revealed. In 3 out of 11 worsening of the epidemic situation coincided with the beginning of the circulation of a new genetic variant of the pathogen COVID-19 (variants Wuhan, Delta, Omicron). A decrease in the incidence in the summer period was noted, regardless of the circulating genetic variants. Conclusion. A significant part of the observed dynamics of the characteristics of the epidemic process in Moscow can be explained by the properties of the pathogen, seasonality and dynamics of magnitude of the herd immunity. The influence of the dynamics of the herd immunity indicators on the course of the epidemic process is to be studied further.
背景。不断评估流行过程主要特征的动态是传染病流行病学监测的基本功能。寻找决定流行病进程特征变化的因素,就有可能制定及时的管理决策,并减少流行病规模扩大的风险。莫斯科是吸引俄罗斯其他地区人口的主要中心,拥有最复杂的社会联系结构和最高的人口密度。本研究的目的是通过对新型冠状病毒感染(COVID-19)流行过程的主要特征进行分子流行病学分析,确定可能决定观察到的变化趋势的因素。材料和方法。为了进行分析,将俄罗斯国家SARS-CoV-2病毒基因组序列数据库(VGARus)数据与官方互联网资源стопкоронавирус提供的发病率和死亡率信息相结合。来自门户网站Gogov.ru的疫苗接种动态、COVID-19疾病发病率和住院率。对住院患者的性别和年龄结构进行了多中心回顾性观察性流行病学研究。在莫斯科各机构收集的不同随访时期的COVID-19患者的匿名病史(41,561例)作为性别和年龄结构分析的数据来源。 结果。我们确定了11个具有显著不同复杂流行病学特征的时期。在采取限制措施期间,工作年龄青年的发病率有所下降。在疫情恶化的11个国家中,有3个国家恰逢病原体COVID-19新的遗传变异(武汉、德尔塔、欧米克隆变异)开始传播。注意到,与流行的遗传变异无关,夏季发病率有所下降。 结论。观察到的莫斯科流行过程特征的很大一部分动态可以用病原体的特性、季节性和群体免疫幅度的动态来解释。群体免疫指标动态对疫情进程的影响有待进一步研究。
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