河北省2012年-2013年流脑病例病原学监测及分子分型研究

目的对河北省2012年-2013年流行性脑脊髓膜炎(流脑)病例病原学监测结果进行分析,了解脑膜炎奈瑟菌(Neisseria meningitidis,Nm)的菌群种类及分子分型特征。方法对2012年-2013年从流脑病例中分离的脑膜炎奈瑟菌菌株进行培养、生化鉴定、血清学鉴定、种属及分群的荧光定量PCR检测以及多位点序列分型(MLST)和por A基因分型研究;并对2012年-2013年流脑病例的脑脊液和血清标本进行种属、分群的荧光定量PCR检测及MLST分析。结果2012年-2013年,从流脑病例中共检测出B群5例,C群14例,W135群2例;MLST结果显示除1例没有所属的克隆群外,其余16例标本均属于ST-4821克隆群;6株Nm菌株的por A基因分属于不同的型别。结论河北省2012年-2013年流脑病例以C群为主,B群流脑呈现增长趋势,本省首次出现了W135群流脑病例,病例大都为高致病性ST-4821克隆群,提示应加强本省Nm的监测。     

濮阳市流脑W135群基因型别及脑膜炎奈瑟菌检测分析

目的明确流脑菌群在濮阳市的分布及W135群在不同人群中的基因型别,为防控流脑提供依据。方法对健康人群、密切接触者的咽拭子,流脑患者的脑脊液、血液进行细菌培养、血清凝集、PCR鉴定、MLST基因分型、Por A基因亚型分型。结果 2009年-2013年健康人群检出Nm菌49株(B群27株,C群3株,W135群5株,未定群14株);流脑患者W135群1株;密切接触者W135群2株。流脑患者与密切接触者W135群菌株MLST基因分型均为ST-11,Por A VR基因亚型均为P1.5,2型。结论濮阳市流脑带菌以B群、W135群、C群为主,带菌谱与流脑发病有一定关联,有高致病性的W135群ST-11克隆系和致病性菌株P1.5,2型存在。应注意流脑菌群变化,加大监测和疫苗的应用,预防流脑流行。     

MLST分型技术应用于脑膜炎奈瑟菌的分子流行病学研究

目的 对广东省1967-2007年自流行性脑脊髓膜炎(流脑)病人中分离的脑膜炎奈瑟菌(neisseria meningitidis, N. Meningitidis)进行分子流行病学研究,了解菌株间的遗传进化关系.方法 采用多位点序列分型(Multilocus Sequence Tping, MLST)技术,分别对1967-2007年分离的16株N. Meningitidis菌株的7个看家基因的序列进行测定,并将序列与PubMLST数据库中储存的序列比对,确定其等位基因谱型及菌株序列型(sequence type, ST),并采用splits Tree在线软件分析菌株之间的进化关系.结果 16株N. Meningitidis菌株分为13株A群、2株C群和1株W135群,分属5大克隆系,分别为ST-5、ST-1、ST-4821、ST-11克隆系和未知克隆系的ST-254序列型,其中ST-5克隆系所占比例最多,占68.75% (11/16).1967-2006年的13株A群分离株中,11株属ST-5克隆系,占84.61% (11/13),另有1977年的1株分离株为ST-1克隆系和1株1984年的分离株为未知克隆系的ST-254序列型;2004和2006年的C群分离株属新出现的高致病性克隆系ST-4821;2007年首次分离的1株W135群菌株为ST-2960,属高致病性的ST-11/ET-37克隆系的子克隆.结论 分离于不同年代病人的广东N. Meningitidis分离株呈多克隆系并存,但近期以高致病性克隆系为主,特别是广东省首次出现高致病性ST-11/ET-37克隆系的W135群,提示应加强流脑的病原学监测.应用MLST分子分型技术,初步揭示了广东省脑膜炎奈瑟菌的遗传进化关系,基于等位基因图谱的MLST基因分型技术具有较高的分辨率,并通过互联网实现了序列数据库信息的全球共享.     

2006-2017年贵州省脑膜炎奈瑟菌多位点序列分型北大核心

目的了解2006-2017年贵州省脑膜炎奈瑟菌(Neisseria meningitidis,Nm)分离株的血清群和基因型特征。方法采用细菌分离培养和多位点序列分型(Multilocus sequence typing,MLST)技术,对2006-2017年贵州省Nm分离株进行血清群复核鉴定,对Nm的7个管家基因序列进行检测以确定克隆群(Clonal complex,CC)和序列型(Sequence type,ST),并构建遗传进化图谱以分析菌株间进化关系。结果共获得33株Nm,其中A群15株(45.5%)、C群4株(12.1%)、B群3株(9.1%)、W135群7株(21.2%)、不可分群4株(12.1%);得到6种CC和9种ST。A群、C群、W135群菌株的ST/CC基因型分别以ST-7/ST-5 Complex/subgroupⅢ(93.3%)、ST-4821/ST-4821 Complex(75.0%)、ST-6933/ST-174 Complex(85.7%)为主,B群基因型较分散。ST-5 Complex、ST-174 Complex基因型相对稳定,ST-4821 Complex具有遗传多样性;ST-5和ST-4821为高致病性克隆群。结论2006-2017年贵州省Nm存在多种基因型流行,A群、C群分别以ST-7/ST-5 Complex、ST-4821/ST-4821 Complex为优势基因型,B群基因型分散且活跃;需持续加强Nm分子流行病学监测。     

合肥市2012～2013年W135群流脑病原学检测结果分析

目的了解2012~2013年合肥市W135群流脑死亡病例及密接接触者病原学特征。方法对送检的2份死亡病例和9份密切接触者标本进行生化鉴定、血清分群、PCR检测和药物敏感性试验。对阳性菌株中的管家基因采用多位点测序分型(MLST)进行DNA测序。结果实验室证实11份标本均为W135群脑膜炎奈瑟氏球菌;测序结果显示这11株阳性菌株均属于ST-11 complex/ET-37 complex克隆群,为ST-11型;5株菌株对萘啶酸、环丙沙星、磺胺甲基异恶唑耐药。结论合肥市流脑死亡病例和密切接触者分离到W135群脑膜炎奈瑟氏球菌,出现流脑菌群变迁。     

多位点分型技术应用于浙江省脑膜炎奈瑟菌基因分型研究

目的对浙江省2004~2013年分离的54株脑膜炎奈瑟菌(Neisseria meningitidis,Nm)进行基因分型研究,了解菌株间的遗传进化关系。方法参照细菌分子分型和基因组差异公共数据库(Pubmlst)提供的引物与方法,获得多位点序列分型(Multilocus Sequence Typing,MLST)序列型(Sequence Type,ST)。采用进化分析软件(Splitstree)4、聚类分析软件(e BURST)V3等处理所得序列数据,并构建遗传进化图谱。结果 54株Nm得到21个STs,其中11个STs为新发现,主要序列型ST-7和ST-4821分别占29.63%和27.78%。不同血清群其STs/ST-克隆群(Complex)有明显不同,A群菌株78.95%(15/19)为ST-7/ST-5Complex(15/19);B群菌株STs分散,57.14%(8/14)呈单体存在;C群菌株82.35%(14/17)为ST-4821/ST-4821Complex。不同来源分离株其ST-Complex不同,来自病人及密切接触者分离株ST-5Complex分别占48.15%(13/27)及33.33%(4/12)、ST-4821Complex分别占40.74%(11/27)及25.00%(3/12),而来自健康带菌者分离株ST-4821Complex克隆群占40.00%(6/15)。7个管家基因的核苷酸多态性(Pi)范围为0.01298(adk)~0.11100(aro E)。Splitstree 4构建径向系统进化树显示,浙江省Nm菌株分属5个分枝,主要序列型ST-7及ST-4821分别分布于3分枝及2分枝中,4分枝中均为浙江省STs。e BURST V3聚类分析发现,浙江省STs/ST-5Complex基因型相对稳定,但浙江省STs/ST-4821Complex基因型已具遗传多样性变化。结论浙江省Nm以A群78.95%(15/19)ST-7/ST-5Complex和C群82.35%(14/17)ST-4821/ST-4821Complex两大克隆群占绝对优势,B群57.14%(8/14)呈单体分散。浙江省A、B、C群均存在ST-4821Complex相同基因型菌株,可能不同血清群之间已产生荚膜转换,其种群间已显示基因重组进化特征,这是中国首次从A群Nm中检出ST-4821/ST-4821Complex及ST-5798/ST-4821Complex菌株。     

纹带棒状杆菌多位点序列分型及应用

目的 建立纹带棒状杆菌的多位点序列分型（MLST）方法,探讨临床分离纹带棒状杆菌的种群结构和遗传进化关系。方法 筛选出7个管家基因（gyrA、gyrB、hsp65、sodA、secA1、rpoB、16S rRNA）,设计引物并进行PCR扩增和测序,测序所得序列通过SeqMan软件进行拼接。采用DnaSP 5.10.01软件、Splits tree 4.14.2软件对管家基因的多样性及基因重组特征进行评价;采用MEGA 7.0.14软件基于序列型别（ST）采用M-L法构建系统发育树,采用BioNumerics软件基于ST特征值构建最小生成树,并用eBURST软件分析ST间遗传进化关系。结果 所选的7个位点在所有试验菌株中均获得了预期的扩增产物;Splits tree表明所有纹带棒状杆菌的聚类一致,提示基因重组是推动纹带棒状杆菌进化的潜在动力;MLST将344株纹带棒状杆菌分成72个STs,85.7%的菌株形成克隆复合体（CC）结构,CC19形成了优势克隆复合体,但包含菌株数最多的ST为该克隆复合体中的ST16。ST具有一定的地域聚集性且与分离年份具有一定的相关性。结论 我国纹带棒状杆菌呈现高度的遗传多样性,CC19为优势克隆复合体。本研究建立的MLST分型方案可用于纹带棒状杆菌的分型,但尚需优化改进。     

贵州省一起学校流行性脑脊髓膜炎爆发疫情的病原学鉴定和多位点序列分型研究

目的报告一起学校流行性脑脊髓膜炎(流脑)爆发疫情的病原学特征。方法对疑似流脑病例进行流行病学调查,采集患者脑脊液和血标本及首例病例密切接触者咽拭子标本,进行病原学分离鉴定、实时荧光定量聚合酶链反应(Polymerase Chain Reaction,PCR)检测和多位点序列分型(Multi-locus Sequence Typing,MLST)分析。结果该起流脑爆发疫情由C群脑膜炎奈瑟菌引起,MLST分型为ST-4821高致病克隆群。结论该起疫情由C群脑膜炎奈瑟菌ST-4281引起,该克隆群为中国独有的高致病基因群,本结果有利于制定全省流脑防控策略。     

健康人群脑膜炎奈瑟菌带菌率以及血清群分布特征研究

目的了解来宾市健康人群脑膜炎奈瑟菌（Neisseria meningitidis,Nm）的带菌状况,揭示优势菌群,评估流行性脑脊髓膜炎（流脑）流行风险,为制定流脑预防控制策略提供参考。方法将调查对象分为5个年龄组,每个年龄组至少调查200人。每个调查对象采集1份咽拭子,共采集1311份咽拭子进行Nm分离培养和血清群鉴定。结果2011年,来宾市健康人群Nm带菌率为8.54%,其中B群占31.25%,W135群占15.18%,C群占1.79%,A群、X群、Y群各占0.89%,不可分群占49.11%;青年人带菌率高于少年儿童,男性带菌率高于女性。同年来宾市发生的3例流脑均为W135群。结论来宾市健康人群Nm带菌以不可分群菌株为主,可分群菌株中以B群和W135群为优势菌群;W135群为来宾市流脑的主要流行菌群,应在继续推行A＋C群脑膜炎球菌疫苗（Meningococcal Vacune,MenV）接种的同时,加强W135群MenV的接种,以期有效预防控制流脑疫情。     

广东省2014年食源性副溶血弧菌病原学特征分析

目的 了解2014年广东省食源性副溶血弧菌分离株的血清型别、抗生素敏感性、毒力基因携带情况以及分子分型特征。方法 对60株副溶血弧菌分离株进行血清分型、抗生素敏感性试验及检测耐热直接溶血素基因(tdh)和耐热相关溶血素基因(trh),并进行脉冲场凝胶电泳(PFGE)和多位点序列(MLST)分型。结果 60株分离株可分为13个血清型,主要型别为O3:K6、O4:K8、O1:K36和O4:KUT;对氨苄西林、磺胺复合物和头孢噻吩的耐药率分别为100.0%、43.3%和28.3%,有56.7%(34/60)的菌株对2类及以上抗生素同时耐药,2株菌对3类抗生素同时耐受。毒力基因PCR检测发现,有63.3%(38/60)的分离株为tdh⁺trh^-菌株,仅1株为tdh⁺trh+菌株。分子分型显示,经NotⅠ酶消化后,60株副溶血弧菌可产生48个PFGE谱型,可分为3个聚类(Cluster A、B和C)。其中Cluster B的菌株主要分离自食源性疾病监测中心散发病例,血清型以O3:K6为主,PFGE谱型的相似度在62.6%～100.0%;Cluster C主要是由4株O4:K8型菌株组成,谱型相似度为56.7%～62.5%。60株菌MLST分型可分为26个ST型,其中33株菌为ST-3型,主要是O3:K6和O1:K36菌株;4株O4:K8菌株聚集成另一个不同于ST-3型的相对优势的菌群。结论 2014年广东省副溶血弧菌菌型多样性可能是疾病高发的原因之一,O4:K8型菌株的分子特征与其他优势血清型别明显不同,应高度警惕该型菌株引起暴发的可能。     

Multicomponent meningococcal serogroup B vaccination elicits cross-reactive immunity in infants against genetically diverse serogroup C,W and Y invasive disease isolates

BackgroundThe multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains.MethodsA total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB.ResultsSerogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%.ConclusionThis is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination.     

Molecular characteristics and epidemiology of meningococcal carriage, Burkina Faso, 2003

To describe Neisseria meningitidis strains in the African meningitis belt in 2003, we obtained 2,389 oropharyngeal swabs at 5 monthly visits a representative population sample (age range 4-29 years) in Bobo-Dioulasso, Burkina Faso. A total of 152 carriage isolates were grouped, serotyped, and genotyped. Most isolates were NG:NT:NST sequence type (ST) 192 (63% of all N. meningitidis), followed by W135:2a:P1.5,2 of ST-11 (16%) and NG:15:P1.6 of ST-198 (12%). We also found ST-2881 (W135:NT:P1.5,2), ST-751 (X:NT:P1.5), and ST-4375 (Y:14:P1.5,2) but not serogroups A or C. Estimated average duration of carriage was 30 days (95% confidence interval 24-36 days). In the context of endemic group W135 and meningococcal A disease, we found substantial diversity in strains carried, including all strains currently involved in meningitis in this population, except for serogroup A. These findings show the need for large samples and a longitudinal design for N. meningitidis serogroup A carriage studies.     

Asymtomatic carriage of Neisseria meningitidis and Neisseria lactamica in relation to Streptococcus pneumoniae and Haemophilus influenzae colonization in healthy children: apropos of 1400 children sampled

Meningococcal disease is one of the most important causes of morbidity and mortality among children in many parts of the world. Main reservoir of carriage and site of meningococcal dissemination appears to be the upper respiratory tract. Colonization of Neisseria meningitidis and lactamica and factors affecting this carriage were determined in a group of healthy children aged 0–10 years. Meningococcus and N. lactamica carriage were detected in 17 (1.23%) and 245 (17.7%) of 1382 subjects, respectively. Number (%) of serogroups for meningococci was 1 (6), 5 (29), 0 (0), 1 (6), 1 (6), and 9 (53) for A, B, C, D, W135, and Y, respectively. Having more than three household members, elementary school attendance, pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae were associated with carriage of meningococci, whereas age less than 24-month was associated with carriage of N. lactamica. There was a reverse carriage rate between N. meningitidis and N. lactamica by age which may suggest a possible protective role of N. lactamica against meningococcal colonization among pre-school children.     

A phase III observer-blind randomized,controlled study to evaluate the immune response and the correlation with nasopharyngeal carriage after immunization of university students with a quadrivalent meningococcal ACWY glycoconjugate or serogroup B meningococcal vaccine

BackgroundUniversity students have high rates of pharyngeal carriage of Neisseria meningitidis. Interruption of carriage acquisition is an important mechanism of vaccines for inducing herd protection. 4CMenB and MenACWY-CRM vaccines have been shown to be immunogenic against meningococcal serogroups B and ACWY respectively in younger age groups, and also to elicit a modest impact on meningococcal carriage in vaccinated students. However, vaccine responses in university students and the impact of serum bactericidal antibody (SBA) titers on meningococcal carriage are undetermined.MethodsImmunogenicity of two 4CMenB doses or one MenACWY-CRM dose was measured in university students at Months 2, 4, 6 and 12 post-first vaccination. Immunogenicity of one MenACWY-CRM dose in students with previous meningococcal serogroup C conjugate vaccination was also assessed. Immune responses were measured with an SBA assay using human complement (hSBA) against three reference strains for serogroup B and against one strain for each for serogroups C and Y. Correlations between hSBA titers and meningococcal carriage were analyzed.ResultsAll subjects demonstrated robust functional antibody responses to both vaccines at Month 2 and a high proportion maintained protective hSBA titers up to Month 12. At baseline, carriage of disease-associated serogroup B strains and serogroups C and Y were higher in subjects with already-protective hSBA titers. Post-vaccination, while both 4CMenB and MenACWY-CRM elicited robust immunogenicity in students, significant correlations between post-vaccination hSBA titers and carriage of disease-associated serogroups were not observed.Conclusions4CMenB and MenACWY-CRM were both highly immunogenic. There was no correlation between carriage and post-vaccination hSBA titers.     

Evaluation of serogroup C and ACWY meningococcal vaccine programs: Projected impact on disease burden according to a stochastic two-strain dynamic model

ObjectiveAdvisory committees in Canada and the United States have updated recommendations for quadrivalent meningococcal conjugate vaccines against serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective meningococcal vaccination policies using a stochastic dynamic model. Canada was used as an example.MethodsOur stochastic dynamic model of Neisseria meningitidis (Nm) transmission in an age-structured population assumed partial cross-immunity among two aggregated serogroup categories: ‘AWY’ containing A, W135, and Y; and ‘Other’ containing B, C, and ungroupable types. We compared the impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and invasive meningococcal disease (IMD). Our model was parameterized with Canadian epidemiological and demographic data and employed probabilistic sensitivity analysis.ResultsRoutine infant immunization at 12 months and boosting at 15 years with a quadrivalent vaccine is projected to have the largest impact on total IMD incidence: a 74% reduction over 40 years. Routine infant immunization with a monovalent vaccine at 12 months only has much less impact and also generates strain replacement appearing after approximately ten years of continuous use.ConclusionsImmunizing infants at 12 months and boosting adolescents at 15 years with an ACWY vaccine is predicted to be most effective at reducing IMD incidence.     

Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci

Expansion of quinolone-resistant Neisseria meningitidis clone China^{CC4821-R1-C/B} from sequence type (ST) 4821 clonal complex (CC4821) caused a serogroup shift from serogroup A to serogroup C invasive meningococcal disease (IMD) in China. To determine the relationship among globally distributed CC4821 meningococci, we analyzed whole-genome sequence data from 173 CC4821 meningococci isolated from 4 continents during 1972–2019. These meningococci clustered into 4 sublineages (1–4); sublineage 1 primarily comprised of IMD isolates (41/50, 82%). Most isolates from outside China (40/49, 81.6%) formed a distinct sublineage, the Europe–USA cluster, with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(CC4821), harboring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone China^{CC4821-R1-C/B} has expanded to other countries. The increasing distribution worldwide of serogroup B CC4821 raises the concern that CC4821 has the potential to cause a pandemic that would be challenging to control, despite indirect evidence that the Trumenba vaccine might afford some protection.     

Prevalence of factor H Binding Protein sub-variants among Neisseria meningitidis in China

ObjectiveTo study the prevalence of the fHbp genes in Neisseria meningitidis (N. meningitidis) isolates for further evaluation and development of serogroup B meningococcal vaccines in China.MethodsA panel of 1012 N. meningitidis strains was selected from the national culture collection from 1956 to 2016, according to the years of isolation, locations, and strain sources. These were tested by FHbp variant typing. Multi-locus sequence typing (MLST) was performed on 822 of these samples, including 242 strains from clinical strains and 580 carrier-derived strains. Analysis based on sequence types, serogroups, and FHbp variations were used to summarize the prevalence and characteristics of N. meningitidis.ResultsThere were 8 serogroups of N. meningitidis as well as a collection of nongroupable strains in this study. 1008 of 1012 N. meningitidis strains tested were positive for the fHbp gene. Serogroup A N. meningitidis (MenA) strains belonging to ST-1 and ST-5 clonal complexes harbored genes only encoding variant 1 (v1) FHbp. All MenW strains encoded v2 FHbp. 61.9% of clinical MenB strains were positive for v2 FHbp vs. 32.1% that were positive for v1. Among fHbp-positive carrier-derived MenB strains, v2 FHbp accounted for 90.8%. 79.7% of clinical MenC strains were positive for v1 FHbp and 20.3% were positive for v2 FHbp. Among carrier-derived MenC strains, v2 FHbp predominated. The number of major serogroups of N. meningitidis analyzed by MLST was 822, and the encoded FHbp showed CC- or ST-specific characteristics.ConclusionfHbp genes were detected in almost all N. meningitidis strains in this study. Therefore, it is possible that a vaccine against MenB or meningococci irrespective of serogroups, which includes FHbp, could be developed. Meningococcal vaccine development for China is a complex issue and these findings warrant further attention with respect to vaccine development.     

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)₃. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.     

High case-fatality rates of meningococcal disease in Western Norway caused by serogroup C strains belonging to both sequence type (ST)-32 and ST-11 complexes, 1985-2002

A total of 293 meningococcal disease (McD) patients from Western Norway hospitalized during 1985-2002 were examined for risk factors related to death. The case-fatality rate (CFR) increased from 4% during 1985-1993 to 17% during 1994-2002. We analysed the phenotypic and genotypic characteristics of the meningococcal patient isolates, with the aim of identifying whether highly virulent meningococcal strains contributed to the increased CFR. The Norwegian epidemic strain B:15:P1.7,16/ST-32 complex was overall the most common phenotype/genotype (n=75) and caused most deaths (n=9; CFR 12.0%). However, fatality was significantly associated with disease caused by serogroup C meningococcal strains; C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains, which had the highest CFRs of 21.1% and 18.2% respectively. Serogroup B strains of the ST-32 complex differing by serotype and/or serosubtype from the epidemic strain had a CFR of 5.1%, while the CFR of disease caused by other strains (all phenotypes and genotypes pooled) was 2.2%. The distribution of phenotypes/clonal complexes varied significantly between 1985-1993 and 1994-2002 (P<0.001); B:15/ST-32 complex strains decreased whereas both C:15:P1.7,16/ST-32 complex strains and strains with other phenotypes/clonal complexes increased. Our results indicate that C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains were highly virulent strains and contributed to the high CFR of McD in patients from Western Norway. To reduce fatality, rapid identification of such virulent strains is necessary. In addition, early and specific measures should include public information, vaccination of populations at risk of disease and carriage eradication, when clustering of patients occurs.     

Populations of pharyngeal meningococci in Niger

This study investigated the carriage of Neisseria meningitidis group W135 (NmW135) belonging to sequence type (ST)-2881, ST-11 and NmA ST-7, as these three lineages have been responsible for sporadic cases in 2003 in Niamey (Niger). ST-7 and ST-11 were also the two genotypes involved in recent outbreaks in the African meningitis belt. Among the 97 Nm isolates obtained from 287 schoolchildren swabbed three times, 1 was identified as NmA, 34 as NmW135, 8 as NmY and 54 were non-groupable (NG). Among the 86 isolates genotyped, 59.3% belonged to ST-192, 24.4% to ST-2881, 5.8% to ST-2880, 4.6% to ST-175, 3.5% to ST-4899, 1.2% to ST-11 and 1.2% to ST-7. Most of the isolates recovered were weakly pathogenic Nm NG ST-192 and NmW135 ST-2881. These results, although preliminary, are important to consider before introduction of a NmA conjugate meningococcal vaccine in Africa.