Meningitis, Meningococcal

脑膜炎,脑膜炎球菌
  • 文章类型: Journal Article
    自1941年以来,智利记录了脑膜炎奈瑟菌的暴发,到目前为止,根据临床形式不同,发病率,杀伤力,和负责的血清群。
    目的:总结智利因脑膜炎奈瑟菌引起的急性细菌性脑膜炎流行病学的现有证据,分析1990年至2019年的发病率。
    方法:按照Cochrane协作标准对主要文章进行了系统综述。信息来源是PubMed,Scielo,和LILACS。包括关于脑膜炎奈瑟菌引起的急性细菌性脑膜炎的出版物,带有描述性的设计,英语和西班牙语。排除了有关疫苗和诊断技术有效性的研究。
    结果:在1990年至2019年之间,收集的证据仅集中在2012年。在当年报告的133例侵袭性脑膜炎球菌病(IMD)中,42例表现为脑膜炎。在由血清群W135菌株引起的IMD病例中,21.7%的病例表现为脑膜炎(13例),与“非W135”菌株相比,其中67.4%(29例)。由于IMD导致的死亡率在受血清群W135影响的患者中更高(26.7%),与受血清群“非W135”影响的患者相比(13.9%)。
    结论:2012年显示流行血清群从B到W的变化,脑膜炎病例减少,脑膜炎球菌血症和IMD致死率增加。
    Since 1941, outbreaks of Neisseria meningitidis have been recorded in Chile which, to date, have varied according to clinical form, incidence, lethality, and the responsible serogroup.
    OBJECTIVE: To summarize the available evidence on the epidemiological profile of acute bacterial meningitis due to Neisseria meningitidis in Chile, analyzing the incidence between 1990 and 2019.
    METHODS: A systematized review of primary articles was carried out following the Cochrane Collaboration standards. The information sources were PubMed, Scielo, and LILACS. Publications on acute bacterial meningitis due to Neisseria meningitidis were included, with a descriptive design, and in English and Spanish. Studies on the effectiveness of vaccines and diagnostic techniques were excluded.
    RESULTS: Between 1990 and 2019, the evidence collected focuses exclusively on the year 2012. Of the 133 cases of invasive meningococcal disease (IMD) reported that year, 42 cases presented with meningitis. Of the IMD cases caused by serogroup W135 strains, 21.7% of the cases presented with meningitis (13 cases), compared with the \"Non-W135\" strains, in which it was 67.4% (29 cases). Lethality due to IMD was higher in patients affected by serogroup W135 (26.7%), compared with patients affected by serogroup \"Non-W135\" (13.9%).
    CONCLUSIONS: The year 2012 shows a change in the prevalent serogroup from serogroup B to W, with a decrease in cases of meningitis and an increase in cases of meningo- coccemia and the lethality of IMD.
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  • 文章类型: Case Reports
    背景技术脑膜炎球菌性脑膜炎在日本很少见;然而,当爆发时,它们主要涉及国内感染病例,而不是海外感染病例。案例报告一名50多岁的日本糖尿病男子出现发烧和意识丧失,没有国际旅行的历史。在我们的医院里,通过革兰氏染色在患者的脑脊液(CSF)中检测到革兰氏阴性双球菌,尽管快速凝集试验以及血液和CSF培养均为阴性。多重聚合酶链反应(PCR)测试对脑膜炎球菌和parechovirus返回了阳性结果。脑部核磁共振显示有脑膜炎的发现,但没有脑炎的迹象.为了确定血清型和基因型,我们把样本送到国家传染病研究所,将血清群和序列类型(ST)分别鉴定为B型和2057型。尽管未知的抗菌药物敏感性,患者对头孢曲松每12小时2g的经验性治疗反应良好,出院后仍有头晕症状,头痛,左耳听力困难,左耳耳鸣.结论在日本,涵盖血清群A的疫苗,C,和W/Y是可用的,但不是常规给药。根据流行病学监测报告,血清群B是日本脑膜炎球菌性脑膜炎的第二大常见原因,然而,该国没有相应的疫苗。此病例促使人们对日本的脑膜炎球菌流行病学进行了回顾,包括疫苗接种和医院感染控制策略,以防止液滴传播,其中包括未采取事先措施的暴露后预防。
    BACKGROUND Meningococcal meningitis is rare in Japan; however, when outbreaks do occur, they predominantly involve domestically infected cases rather than those contracted overseas. CASE REPORT A Japanese man with diabetes in his 50s experienced fever and loss of consciousness, with no history of international travel. In our hospital, gram-negative diplococci were detected in the cerebrospinal fluid (CSF) of the patient by Gram staining, although the rapid agglutination test and cultures of blood and CSF were negative. Multiplex polymerase-chain reaction (PCR) testing returned positive results for meningococcus and parechovirus. Brain MRI revealed a finding of meningitis, but there were no indications of encephalitis. To determine the serotype and genotype, we sent the sample to the National Institute of Infectious Diseases, which identified the serogroup and sequence type (ST) as type B and 2057, respectively. Despite the unknown antimicrobial susceptibility, the patient responded well to empirical treatment with ceftriaxone at 2 g every 12 h, and was discharged with remaining symptoms of dizziness, headache, difficulty hearing in the left ear, and tinnitus in the left ear. CONCLUSIONS In Japan, vaccines covering serogroups A, C, and W/Y are available but not routinely administered. According to epidemiological surveillance reports, serogroup B is the second most common cause of meningococcal meningitis in Japan, yet there is no corresponding vaccine available in the country. This case has prompted a review of the epidemiology of meningococcus in Japan, encompassing strategies for vaccination and hospital infection control to prevent droplet transmission, which includes post-exposure prophylaxis when no prior measures have been implemented.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    奈瑟氏球菌属,定植在粘膜表面,包括人类独有的共生和致病物种。这两种致病性奈瑟菌密切相关,但引起的疾病却截然不同。脑膜炎球菌败血症和脑膜炎(脑膜炎奈瑟菌)和性传播淋病(淋病奈瑟菌)。尽管细菌生态位和传播机制存在明显差异,致病性奈瑟菌在核苷酸序列水平上具有高水平的保守性,基因含量和同质性。奈瑟球菌物种表达广谱O-连接的蛋白质糖基化,其中糖蛋白主要是位于细胞表面或周质中的跨膜蛋白或脂蛋白。在鉴定的糖蛋白中有不同的功能,例如IV型生物发生蛋白,涉及抗菌素耐药性的蛋白质,以及被建议作为疫苗候选物的表面蛋白。最丰富的糖蛋白,皮尔,是菌毛的主要亚基,是重要的定殖因子。由于蛋白质糖基化(pgl)基因的相位变化和多态性pgl基因含量,所连接的聚糖可以变化很大。糖基化在奈瑟菌中的确切作用还有待确定,但是越来越多的证据表明,聚糖的变异性可以成为逃避人体免疫系统的策略。此外,致病性和共生奈瑟菌似乎具有显着的糖基化差异。这里,蛋白质糖基化基因的最新知识和含义,聚糖多样性,对致病性奈瑟菌的糖蛋白和免疫原性进行了总结和讨论。
    The genus Neisseria, which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic Neisseria species are closely related but cause quite different diseases, meningococcal sepsis and meningitis (Neisseria meningitidis) and sexually transmitted gonorrhea (Neisseria gonorrhoeae). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic Neisseria have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of Neisseria express broad-spectrum O-linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation (pgl) genes and polymorphic pgl gene content. The exact roles of glycosylation in Neisseria remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal Neisseria appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic Neisseria are summarized and discussed.
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  • 文章类型: Journal Article
    受细菌荚膜多糖(CPS)中α-(2,9)-唾液酸表位特异性的启发,一种双重氟化的二糖已被验证为针对脑膜炎奈瑟菌血清群C和/或B的疫苗先导。模拟氟在药物发现中的重要性,这种分子编辑方法有多种用途,范围从控制α选择性化学唾液酸化到减轻竞争性消除。二唾液酸苷与两种载体蛋白(CRM197和PorA)的缀合可以产生半合成疫苗;然后在六组六只小鼠中进行了研究。比较所形成的抗体的个体水平并分类为高度聚糖特异性和保护性。所有糖缀合物均诱导稳定且长期的IgG应答并实现与天然CPS表位的结合。产生的抗体对MenC和/或MenB具有保护性;这在体外通过SBA和OPKA测定进行了验证。通过将MenC的氟化聚糖表位与MenB的外细胞膜蛋白合并,产生了针对两种血清群的二价疫苗.据设想,这种合成的验证,氟化二唾液酸苷生物等排体作为一种有效的抗原将开辟新的治疗途径。
    Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated in vitro by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.
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  • 文章类型: Case Reports
    一名13岁的男孩因严重的脑膜炎球菌性脑膜炎入院。免疫检查发现了备解素缺乏症,和CFP的基因测序确定了一个新的,外显子8中的私人和预测致病变异。患者接受广泛免疫和青霉素预防。患有侵袭性脑膜炎球菌病的儿童应进行补体缺乏检测。
    A 13-year-old boy was admitted with severe meningococcal meningitis. Immunologic workup revealed a properdin deficiency, and genetic sequencing of CFP identified a novel, private and predicted pathogenic variant in exon 8. The patient received broad immunizations and penicillin prophylaxis. Children with invasive meningococcal disease should be tested for complement deficiency.
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  • 文章类型: News
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  • 文章类型: Journal Article
    脑膜炎球菌性脑膜炎的实验室诊断依赖于常规技术。本研究旨在评估脑膜炎奈瑟菌(N.m)菌株和PBP2基因改变的表达。
    在2010年至2021年之间在卡萨布兰卡的伊本·罗赫德大学医院中心(IR-UHC)和马拉喀什的UHC穆罕默德六世的细菌学实验室中分离出的190株N.m菌株中,23个分离株是我们研究的一部分。我们首先通过E-Test试纸条确定了它们对青霉素G的敏感性状态,然后通过PCR搜索penA基因的表达,然后进行Sanger测序。
    在所有N.m.的确诊病例中,93.15%(n=177)是血清组B,75.2%(n=143)对青霉素G敏感,24.73%(n=47)对青霉素G敏感。未观察到对青霉素G的抗性。N.m中对青霉素G的敏感性降低的特征在于突变,即F504L,A510V,I515V,G541N和I566V位于编码青霉素结合蛋白2(PBP2)(镶嵌基因)的penA基因的C末端区域。
    我们的研究为N.m中青霉素G抗性的表型和基因型监测提供了有用的数据,并且可以有助于分析不同奈瑟菌物种之间的遗传交流。
    UNASSIGNED: the laboratory diagnosis of meningococcal meningitis relies on conventional techniques. This study aims to evaluate the correlation between the reduced sensitivity to penicillin G of Neisseria meningitidis (N.m) strains and the expression of the altered PBP 2 gene.
    UNASSIGNED: out of 190 strains of N.m isolated between 2010 and 2021 at the bacteriology laboratories of Ibn Rochd University Hospital Centre (IR-UHC) in Casablanca and the UHC Mohammed VI in Marrakech, 23 isolates were part of our study. We first determined their state of sensitivity to penicillin G by E-Test strips and searched for the expression of the penA gene by PCR followed by Sanger sequencing.
    UNASSIGNED: of all the confirmed cases of N.m, 93.15% (n=177) are of serogroup B, 75.2% (n = 143) are sensitive to penicillin G and 24.73% (n = 47) are of intermediate sensitivity. No resistance to penicillin G was observed. Reduced sensitivity to penicillin G in N.m is characterized by mutations namely F504 L, A510 V, I515 V, G541 N and I566 V located in the C-terminal region of the penA gene encoding the penicillin-binding protein 2 (PBP2) (mosaic gene).
    UNASSIGNED: our study presents useful data for the phenotypic and genotypic monitoring of resistance to penicillin G in N.m and can contribute to the analysis of genetic exchanges between different Neisseria species.
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  • 文章类型: Journal Article
    背景:脑膜炎奈瑟菌可引起危及生命的脑膜炎球菌性脑膜炎和脑膜炎球菌血症。来自CSF/血液培养物的旧的标准微生物结果是耗时的。本研究旨在将环介导等温核酸扩增(LAMP)的敏感性与CRISPR/Cas12a切割的特异性相结合,以证明快速检测脑膜炎奈瑟球菌的可靠诊断测定。
    方法:共收集n=139例疑似脑膜炎球菌病患者的样本,并用于评估。提取的DNA进行定性实时PCR,靶向脑膜炎奈瑟球菌的荚膜转运蛋白基因(ctrA)。LAMP特异性引物对,也针对CTRA,并对LAMP产物进行CRISPR/Cas12裂解反应。读数在横向流条上。灵敏度,特异性,比较了LAMP-CRISPR/Cas的阳性预测值(PPV)和阴性预测值(NPV)与实时PCR分析。用目标脑膜炎奈瑟球菌DNA的系列稀释物建立检测限(LOD),并通过Probit回归分析计算。
    结果:开发了针对脑膜炎奈瑟球菌ctrA基因的六种LAMP测定特异性引物,在所有脑膜炎球菌血清组中都是保守的。LAMP引物没有从其他测试的细菌DNA中扩增DNA,显示100%特异性。0.4M甜菜碱的使用增加了反应的灵敏度和稳定性。LAMP-CRISPR/Cas检测到脑膜炎球菌血清群(B,C,W).该测定没有显示交叉反应性,并且对脑膜炎奈瑟球菌具有特异性。LOD为74(95%CI:47-311)个脑膜炎奈瑟球菌拷贝。与黄金标准相比,LAMP-CRISPR/Cas表现良好。在139份疑似患者的样本中,检测的敏感性和特异性分别为91%和99%。
    结论:这种开发和优化的方法可以补充及时诊断脑膜炎球菌性脑膜炎和脑膜炎球菌血症的可用金标准。
    BACKGROUND: Neisseria meningitidis can cause life-threatening meningococcal meningitis and meningococcemia. Old standard microbiological results from CSF/blood cultures are time consuming. This study aimed to combine the sensitivity of loop-mediated isothermal nucleic acid amplification (LAMP) with the specificity of CRISPR/Cas12a cleavage to demonstrate a reliable diagnostic assay for rapid detection of N. meningitidis.
    METHODS: A total of n = 139 samples were collected from patients with suspected meningococcal disease and were used for evaluation. The extracted DNA was subjected to qualitative real-time PCR, targeting capsular transporter gene (ctrA) of N. meningitidis. LAMP-specific primer pairs, also targeting the ctrA, were designed and the LAMP products were subjected to CRISPR/Cas12 cleavage reaction. the readout was on a lateral flow strip. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LAMP-CRISPR/Cas was compared with real-time PCR assays. The limit of detection (LOD) was established with serial dilutions of the target N. meningitidis DNA and calculated by Probit regression analysis.
    RESULTS: Six LAMP assay-specific primers were developed targeting the ctrA gene of N. meningitidis, which is conserved in all meningococcal serogroups. The LAMP primers did not amplify DNA from other bacterial DNA tested, showing 100% specificity. The use of 0.4 M betaine increased the sensitivity and stability of the reaction. LAMP-CRISPR/Cas detected meningococcal serogroups (B, C, W). The assay showed no cross-reactivity and was specific for N. meningitidis. The LOD was 74 (95% CI: 47-311) N. meningitidis copies. The LAMP-CRISPR/Cas performed well compared to the gold standard. In the 139 samples from suspected patients, the sensitivity and specificity of the test were 91% and 99% respectively.
    CONCLUSIONS: This developed and optimized method can complement for the available gold standard for the timely diagnosis of meningococcal meningitis and meningococcemia.
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