Three Outbreak-causing Neisseria meningitidis Serogroup C Clones,Brazil

During 2003–2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates.     

Meningococcal vaccination: a discussion with all adolescents,whether college-bound or not

ABSTRACT

Introduction: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.

Methods: IMD incidence by college attendance status and vaccination rates were analyzed using publicly available surveillance data.

Results: 64/158 IMD cases occurred in non-college 18–24-year-olds during 2015–2017. Among non-college cases, the MenACWY vaccination rates were 38%–57% vs 90%–100% among college cases when vaccination status was known; MenB vaccination was 0% vs 0%–7%, respectively. In 2018, 17.2% of all 17-year-olds received ≥1 dose of multidose MenB vaccines; ≤50% completed the series.

Conclusion: Meningococcal vaccination is emphasized for college-bound adolescents, but non-college adolescents bear much of the disease burden. Low vaccine receipt preserves their risk, underscoring the need to protect all adolescents through vaccination.     

Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles

Introduction: Meningococcal infection is a major cause of morbidity and mortality worldwide. Infection with Neisseria meningitidis is most common in young children, teenagers and people with certain medical conditions. Effective polysaccharide and glycoconjugate vaccines for serogroups A, C, W135 and Y have been developed. A similar capsular polysaccharide approach for serogroup B (MenB) has by most been judged as unsuitable, hence, no broad coverage vaccine has been licensed to date. The novel vaccine Bexsero (previously 4CMenB) has been developed and proven safe and immunogenic in clinical trials.

Areas covered: The authors outline the constituents of Bexsero and immunogenicity and safety data from preclinical and clinical trials published in peer-reviewed literature, meeting proceedings and publicly-available clinical trial websites from 2000 to 2010.

Expert opinion: Bexsero is well tolerated with a proven safety profile, and has demonstrated a robust immune response across different age groups against a range of diverse MenB strains. These data suggest that Bexsero has the ability to provide protection in infants, who are at the greatest risk of developing meningococcal disease.     

Sequence Type 4821 Clonal Complex Serogroup B Neisseria meningitidis in China, 1978–2013

Serogroup B Neisseria meningitidis strains belonging to sequence type 4821 clonal complex (CC4821), a hyperinvasive lineage first identified for serogroup C in 2003, have been increasingly isolated in China. We characterized the outer membrane protein genes of 48 serogroup B and 214 serogroup C strains belonging to CC4821 and analyzed the genomic sequences of 22 strains. Four serogroup B strains had porin A (i.e., PorA), PorB, and ferric enterobactin transport (i.e., FetA) genotypes identical to those for serogroup C. Phylogenetic analysis of the genomic sequences showed that the 22 CC4821 strains from patients and healthy carriers were unevenly clustered into 2 closely related groups; each group contained serogroup B and C strains. Serogroup B strains appeared variable at the capsule locus, and several recombination events had occurred at uncertain breakpoints. These findings suggest that CC4821 serogroup C N. meningitidis is the probable origin of highly pathogenic CC4821 serogroup B strains.     

2006～2010年湖北省流行性脑脊髓膜炎病原学和血清学监测分析

目的分析湖北省2006～2010年流行性脑脊髓膜炎(流脑)病原学和血清学监测结果,掌握湖北省流脑的变迁规律。方法对2006～2010年分离的脑膜炎奈瑟菌(Nm)菌株进行生化鉴定、血清学分型和药物敏感性检测,并采用多位点序列分型(MLST)和脉冲场凝胶电泳(PFGE)方法进行分子分型;对所有的脑脊液和血液标本进行Nm种属特异性荧光PCR检测;对健康人群血清,运用血清杀菌试验(SBA)进行C群杀菌力抗体水平测定。结果 2007年湖北省Nm以B群为主,2008～2010年以来C群为优势菌群;对青霉素等6种抗生素均敏感,但对环丙沙星、米诺环素、萘啶酸、复方新诺明4种抗生素出现多重耐药;分子分型结果显示,湖北省B群Nm菌株具有高度的遗传多样性,未发现明显优势的克隆群,C群优势病原株为ST-4821型。RT-PCR检测(988份脑脊液)确诊29例流脑病例,其中C群22例,A群2例、B群5例。C群杀菌力总保护率(抗体滴度≥1︰8)为38.10%。结论湖北省流脑菌株发生了从B群散发到C群流行的变迁,人群对C群Nm的免疫力不足。     

A randomized,phase 1/2 trial of the safety,tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants

Background

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed.

Methods

This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase.

Results

Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0 °C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0 °C; no fevers were >40.0 °C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose.

Conclusion

Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants.     

韶关市2009—2011年健康人群C群脑膜炎奈瑟菌血清杀菌力抗体检测结果分析

目的了解韶关市健康人群血清C群脑膜炎奈瑟菌杀菌力水平,以评价健康人群对C群脑膜炎奈瑟菌的保护水平。方法2009—2011年,每年随机抽取8个年龄组健康人群血清共计811份,采用血清杀菌力试验检测血清中杀菌力抗体水平。结果811份健康人群血清中C群脑膜炎奈瑟菌杀菌力抗体总阳性率为25．40％,总保护率为23．06％,GNT为l：5．13,95％置信区间1：4．57～1：5．89。结论韶关市健康人群对c群脑膜炎奈瑟菌的传染有易感性,年龄越低其对C群脑膜炎奈瑟菌的抵抗力越弱,应加大对A＋C群流脑疫苗宣传力度,普及适龄儿童A＋C群流脑疫苗的免疫接种。     

97例流行性脑脊髓膜炎患者的临床特征及流行病学分析

目的总结2008年以来四川省渠县流行性脑脊髓膜炎(流脑)的临床特征,为今后流脑防治工作积累经验。方法对97例流脑患者的临床资料进行回顾性分析,统计分析采用卡方检验。结果患者主要集中在青少年和成人,分别为43例(占44.6%)和34例(35.4%),婴幼儿最少,仅6例(6.2%)。临床分型以普通型为主,占72.3%,暴发型占27.7%。死亡7例(7.7%),共分离出49株脑膜炎奈瑟菌,培养阳性率为50.8%(49/97),其中,血培养阳性率为44.6%(43/97),脑脊液培养阳性者占31.4%(30/97)。药物敏感结果显示,无论是C群脑膜炎奈瑟菌还是其他群,对青霉素、头孢曲松、头孢噻肟等普遍敏感,而对复方磺胺甲噁唑、庆大霉素、环丙沙星等耐药率在80%以上。血清学分类显示,高达82.8%(80/97)的患者为C群菌株感染,与其他群流脑比较,C群感染者病重,病死率高。结论C群脑膜炎奈瑟菌已成为目前四川省渠县流脑流行的主要菌株,C群感染者多见于青少年和成人。治疗以青霉素、第三代头孢菌素类抗生素为佳。