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突尼斯突尼斯脑膜炎奈瑟菌分离株的表型和基因型特征:高度多样性及其对疫苗接种策略的影响。

Phenotypic and genotypic characterization of meningococcal isolates in Tunis, Tunisia: High diversity and impact on vaccination strategies.

机构信息

University of Tunis El Manar, Children's Hospital of Tunis, Laboratory of Microbiology, LR18ES39, Beb Saadoun, 1007 Tunis, Tunisia; Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France.

Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France.

出版信息

Int J Infect Dis. 2020 Feb;91:73-78. doi: 10.1016/j.ijid.2019.11.013. Epub 2019 Nov 20.

Abstract

OBJECTIVES

The aim of this study was to characterize Neisseria meningitidis (Men) isolates in Tunisian paediatric patients with invasive meningococcal disease (IMD) in order to target therapeutic and preventive strategies.

METHODS

Fifty-nine isolates of Men and four cerebrospinal fluid samples that were culture-negative but Men-positive by PCR (NC-MenPPCR) (2009-2016) were collected from IMD patients. Isolates were analysed for their antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to characterize isolates and multilocus sequence typing for NC-MenPPCR. Coverage of Men serogroup B (MenB) was determined by Genetic Meningococcal Antigen Typing System (gMATS) and fHbp expression by ELISA.

RESULTS

MenB was the predominant type (88.9%). The majority of isolates (81%) had reduced susceptibility to penicillin G with altered penA alleles. The clonal complex CC461 (27.1%) was the most frequent. Among the MenB vaccine targets neisserial heparin binding antigen (NHBA) and fHbp, the predominant variants were NHBA118 (30.8%) and fHbp peptide 47 (25%), respectively. The nadA gene was present in 17.3% of isolates. Using gMATS, 36.5% of MenB were predicted to be covered by the 4CMenB vaccine. ELISA showed that 92.4% of the MenB were expected to be killed by anti-fHbp antibodies.

CONCLUSIONS

MenB was the leading serogroup in IMD, and more than 90% had a sufficient level of fHbp expression for vaccine coverage. The study results will be useful for the Tunisian vaccination programme.

摘要

目的

本研究旨在对突尼斯小儿侵袭性脑膜炎奈瑟菌病(IMD)患者的脑膜炎奈瑟菌(Men)分离株进行特征分析,以确定治疗和预防策略。

方法

收集了 2009 年至 2016 年间 59 株 Men 分离株和 4 份脑脊液样本(NC-MenPPCR)(PCR 检测为 Men 阳性但培养为阴性),这些样本来自 IMD 患者。对分离株进行了药敏分析。采用全基因组测序(WGS)对分离株进行特征分析,采用多位点序列分型(MLST)对 NC-MenPPCR 进行分析。采用基因脑膜炎奈瑟菌抗原分型系统(gMATS)测定 MenB 群的覆盖率,采用 ELISA 测定 fHbp 的表达。

结果

MenB 是主要的血清型(88.9%)。大多数分离株(81%)对青霉素 G 的敏感性降低,其 penA 等位基因发生了改变。最常见的克隆复合体是 CC461(27.1%)。在脑膜炎奈瑟菌肝素结合抗原(NHBA)和 fHbp 的 MenB 疫苗靶点中,主要的变体分别是 NHBA118(30.8%)和 fHbp 肽 47(25%)。nadA 基因存在于 17.3%的分离株中。使用 gMATS,4CMenB 疫苗预计能覆盖 36.5%的 MenB。ELISA 显示,92.4%的 MenB 预计能被抗 fHbp 抗体杀死。

结论

MenB 是 IMD 的主要血清型,超过 90%的 MenB 具有足够水平的 fHbp 表达,可用于疫苗覆盖。研究结果将对突尼斯的疫苗接种计划具有重要意义。

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