流行性脑脊髓膜炎疫苗的研究进展

脑膜炎奈瑟菌(Neisseria meningitidis,Nm)从发现至今已超过100年,它所引起的流行性脑脊髓膜炎(流脑)曾数度引发严重的公共卫生问题。流脑疫苗的研究经历了漫长而曲折的历程,疫苗制备技术不断更新。近年来,随着反向疫苗学技术的问世,流脑疫苗尤其是B群流脑疫苗的研究取得了突破性进展。本文将以流脑死菌苗、荚膜多糖疫苗、结合疫苗、基因工程疫苗等的研究历程,从技术发展的角度阐述流脑疫苗的研究进展。     

流行性脑脊髓膜炎的免疫预防研究进展

流行性脑脊髓膜炎(简称流脑)是由脑膜炎奈瑟菌(Neisseria meningitidis,Nm)感染脑膜或脑脊髓膜引起的急性呼吸道传染病。该病传染性强、起病急、病情重,在中国曾引起数次大流行。流脑从发现到现在已经有100多年的历史,但至今仍然未得到有效控制。本文对中国流脑近几年的流行趋势、各省的研究进展和流脑疫苗免疫状况作一综述,为流脑的预防控制起到指导作用。     

高密市2013—2014年健康人群流行性脑脊髓膜炎带菌率调查与分析

目的了解2013-2014年高密市健康人群流行性脑脊髓膜炎带菌状况,为预防控制流脑提供科学依据。方法按分层整群抽样方法,在全市范围于流脑流行前期、流行期和流行末期采集7个年龄组健康人群咽拭子996份,现场接种巧克力双抗平板分离培养后,进行染色镜检、生化鉴定及血清凝集分型。结果咽拭子脑膜炎奈瑟菌阳性检出8份,带菌率0.80%;菌株分别为A、B、C、W135群,其中A群4株,占50%。2014年1~3岁、7~15岁儿童流脑带菌率最高,分别为3.42%、2.07%,各年龄组带菌率差异有统计学意义(P=0.002)。各镇街人群带菌率以拒城河镇和密水街办为最高,分别为1.81%和1.22%,各镇街差异均无统计学意义。结论高密市健康人群流脑带菌率为0.80%,1~3岁和7~15岁人群流脑带菌率较高,A群流脑菌群是主要流行株。     

2019年河南省健康人群流行性脑脊髓膜炎A群、C群抗体水平监测

目的了解2019年河南省健康人群流行性脑脊髓膜炎(epidemic cerebrospinal meningitis,简称流脑)A群、C群抗体水平状况,为科学制定防控策略提供依据。方法采用分层随机抽样的方法采集健康人群血清,用间接ELISA检测流脑A群、C群抗体浓度。结果共检测1 689份健康人群血清标本,其中流脑A群抗体阳性率为54.23%,抗体质量浓度中位数为2.18μg/mL;流脑C群抗体阳性率为51.51%,抗体质量浓度中位数为2.07μg/mL。不同地区之间流脑A群、C群抗体水平的差异、阳性率的差异均有统计学意义(P<0.05)。不同年龄组之间流脑A群、C群抗体水平的差异、阳性率的差异均有统计学意义(P<0.05)。结论河南省健康人群流脑A群、C群抗体水平和阳性率都比较低,有发生流脑暴发和流行的血清学基础,应加强流脑监测和预防接种的管理工作。     

流行性乙型脑炎减毒株的研究进展

本文介绍了流行性乙型脑炎病毒株的研究简史,并着重阐述了现用减毒活疫苗株ＳＡ_（１４）－１４－２的生物学特点、分子生物学、免疫效果及其机理。     

脑膜炎奈瑟菌疫苗研制进展

由脑膜炎奈瑟菌引起的流行性脑脊髓膜炎是一种对人类危害严重的传染性疾病,曾在全球引起多次大流行,所以关于其预防引起了全世界的高度重视。目前应用和研究的脑膜炎奈瑟菌疫苗主要有荚膜多糖疫苗、多糖与蛋白结合疫苗、B群改良疫苗、去毒脂多糖结合疫苗等,本文就以上疫苗的研制情况进行综述。     

1例流行性脑脊髓膜炎病例的菌群鉴定及分析

目的对2015年河南省1例流行性脑脊髓膜炎(流脑)病例的菌群进行分子分型鉴定及分析,为河南省流脑预防和控制工作提供科学依据。方法对患者脑脊液和血液标本以及37例密切接触者咽拭子标本进行细菌培养,提取DNA进行PCR及多位点序列分型(multilocus sequence typing,MLST)分析。用ELISA检测密切接触者血清标本的脑膜炎奈瑟菌A群和C群抗体水平。结果患者和1例密切接触者分离的菌株经细菌培养及PCR鉴定,分别为C群和B群脑膜炎奈瑟菌。MLST分型显示,患者和密切接触者标本分别为ST4821型和ST5664型,两者均为ST4821克隆群。37例密切接触者脑膜炎奈瑟菌A群和C群抗体阳性率分别为91.89%和21.62%,平均抗体质量浓度分别为6.50μg/m L和1.73μg/m L。结论引起流脑疫情的致病菌为C群ST4821型脑膜炎奈瑟菌,当地C群平均抗体含量偏低,需加强流脑A+C疫苗的接种,有效预防流脑的暴发。     

层析法去除A群流脑多糖疫苗粗糖中杂蛋白

目的:建立用层析法去除脑脊髓膜炎球菌A群荚膜多糖样品中的杂蛋白的方法,以替代传统的苯酚抽提。方法:A群流脑多糖粗糖经过新型多模式离子交换填料Capto adhere,使用低盐上样高盐洗脱,洗脱的目的峰再经过Sephardex G-25凝胶过滤脱盐换成水,即为流脑多糖精糖原液。结果:采用上述方法制备的精制多糖样品中杂蛋白占固总的比例低于0.2%,符合WHO现行规程中的杂蛋白比例低于1%的要求,核酸、内毒素等生化指标均符合现行规程,整个层析过程的回收率大于65%。结论:层析法去除A群流脑多糖粗糖中的杂蛋白是有效的,比传统的苯酚抽提的方法更有利于环保,易于操作,易于放大。     

2007年重庆市流脑流行季节前健康人群抗体水平和带菌率调查

为了解重庆市流脑流行季节前健康人群免疫水平和带菌状况,预测发病趋势,提出新的免疫策略,提供有效的预防措施。按照全国流脑监测方案并结合重庆市2006年流脑疫情情况,选择重庆市北碚区、长寿区和万盛区为2007年流脑监测点,采集0~、5~、10~、15~、25~、35~及45岁以上共7个年龄组人群的静脉血和咽拭子,分别进行抗体水平和带菌率检测。结果显示,重庆市健康人群A群流脑IgG抗体的阳性率为76.02%(485/638),C群流脑IgG抗体的阳性率为47.65%(304/638),健康人群脑膜炎奈瑟菌(简称Nm)带菌率为0.47%(3/638)。重庆市健康人群A群流脑IgG抗体阳性率维持在较高水平,而C群流脑IgG抗体的阳性率较低,提示该市大部分人群对A群流脑有免疫作用,但C群抗体水平较低,有引起局部流脑爆发的风险。     

Increased activin levels in cerebrospinal fluid of rabbits with bacterial meningitis are associated with activation of microglia

Activin, a member of the transforming growth factor superfamily, is upregulated in a number of inflammatory episodes such as septicemia and rheumatoid arthritis. In the CNS, activin has been predominantly assessed in terms of a neuroprotective role. In this report we characterized the activin response in the CNS in a rabbit model of meningitis. In normal animals, cerebrospinal fluid (CSF) activin levels were higher than those in serum, indicating an intracranial secretion of this cytokine. Following intracisternal inoculation with Streptococcus pneumoniae, activin in CSF was unchanged for the first 12 h and then rose progressively; levels were increased approximately 15-fold within 24 h. Activin levels were correlated positively with CSF protein content and with the number of apoptotic neurons in the dentate gyrus. No apparent correlation was observed between CSF activin concentrations and bacterial titer, lactate concentrations or leukocyte density. Using immunohistochemistry, activin staining was localized to epithelial cells of the choroid plexus, cortical neurons and the CA3 region of the hippocampus, with similar staining intensities in both normal and meningitic brains. However, in meningitic brains there was also strong staining in activated microglia and infiltrating macrophages. Taken together, these results demonstrate that activin forms part of the CNS response to immune challenge and may be an important mediator to modulate inflammatory processes in the brain.     

Raman spectroscopy provides a powerful,rapid diagnostic tool for the detection of tuberculous meningitis in ex vivo cerebrospinal fluid samples

In this letter, we propose a novel method for diagnosis of tuberculous meningitis using Raman spectroscopy. The silicate Raman signature obtained from Mycobacterium tuberculosis positive cases enables specific and sensitive detection of tuberculous meningitis from acquired cerebrospinal fluid samples. The association of silicates with the tuberculosis mycobacterium is discussed. We envision that this new method will facilitate rapid diagnosis of tuberculous meningitis without application of exogenous reagents or dyes and can be aptly used as a complementary screening tool to the existing gold standard methods. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

成人化脓性脑膜炎患者脑脊液变化

分析成人化脓性脑膜炎患者脑脊液细胞、病原菌等的变化及其关系, 为该病的有效诊断、病情监测和针对性治疗提供参考。

对我院32例成人化脓性脑膜炎患者用药前后不同时期的脑脊液分别进行常规、生化与细胞学检测, 对检测结果进行统计分析。

与恢复期比较, 患者急性期时脑压、脑脊液白细胞总数与乳酸脱氢酶水平显著升高(均P < 0.05)。32例患者中, 15例脑脊液细菌培养呈阳性。典型菌与非典型菌感染者急性期脑脊液白细胞总数、小淋巴细胞、单核吞噬细胞和嗜中性粒细胞比例差异均有统计学意义(均P < 0.05)。

成人化脓性脑膜炎患者脑脊液变化显著, 脑脊液细胞学变化与感染类型相关, 可为个性化诊疗提供参考。

     

Molecular diagnosis of eosinophilic meningitis due to Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) by polymerase chain reaction-DNA sequencing of cerebrospinal fluids of patients

Cerebrospinal fluid (CSF) samples from clinically diagnosed patients with detectable Angiostrongylus canto-nensis-specific antibodies (n = 10), patients with clinically suspected cases that tested negative for A. cantonensis-an-tibodies (n = 5) and patients with cerebral gnathostomiasis (n = 2) and neurocysticercosis (n = 2) were examined by a single-step polymerase chain reaction (PCR) method using the AC primers for the 66-kDa native protein gene. The PCR method detected A. cantonensis DNA in CSF samples from four of 10 serologically confirmed angiostrongyliasis cases. The PCR results were negative for the remaining CSF samples. The nucleotide sequences of three positive CSF-PCR samples shared 98.8-99.2% similarity with the reference sequence of A. cantonensis. These results indicate the potential application of this PCR assay with clinical CSF samples for additional support in the confirmation of eosinophilic meningitis due to A. cantonensis.     

The effect of superspreading on epidemic outbreak size distributions

Recently, evidence has been presented to suggest that there are significant heterogeneities in the transmission of communicable diseases. Here, a stochastic simulation model of an epidemic process that allows for these heterogeneities is used to demonstrate the potentially considerable effect that heterogeneity of transmission will have on epidemic outbreak size distributions. Our simulation results agree well with approximations gained from the theory of branching processes. Outbreak size distributions have previously been used to infer basic epidemiological parameters. We show that if superspreading does occur then such distributions must be interpreted with care. The simulation results are discussed in relation to measles epidemics in isolated populations and in predominantly urban scenarios. The effect of three different disease control policies on outbreak size distributions are shown for varying levels of heterogeneity and disease control effort.