Pharyngeal carriage of Neisseria meningitidis in 2-19-year-old individuals in Uganda

In southern Uganda, only sporadic cases of serogroup A meningococcal disease have been reported since 2000. As part of an immunogenicity study of the tetravalent meningococcal polysaccharide vaccine, nasopharyngeal swab samples were collected twice, 4 weeks apart, from 2-19-year-old healthy individuals in Mbarara, Uganda. Only 15 (2.0%) of the 750 individuals carried meningococci asymptomatically. Most of the strains were non-serogroupable and none were serogroup A. However, two individuals carried a serogroup W135 strain, sequence type (ST)-11, similar to the clone that was responsible for the epidemic in Burkina Faso in 2002. Our study further demonstrates the geographical spread of serogroup W135 ST-11 strain and thus the potential epidemic risk.     

An evaluation of the immunogenicity and safety of a new trivalent meningococcal polysaccharide vaccine

The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination. The percentage of participants in the trivalent vaccine group who had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135 meningococci were 99, 98 and 91%, respectively. The corresponding figures in the tetravalent vaccine group were 99, 99 and 90%. The percentage of participants with various cut off levels of rSBA against serogroups A, W135 and C meningococci on day 28 and 11-month post-vaccination and the incidence of adverse events did not differ significantly between the two groups.     

Vaccine prevention of meningococcal disease, coming soon?

The past century has seen the use of a number of vaccines for prevention and control of meningococcal disease with varied success. The use of polysaccharide vaccines for the control of outbreaks of serogroup C infections in teenagers and young adults and epidemic serogroup A disease has been established for 30 years and an effective protein-polysaccharide conjugate vaccine against serogroup C was introduced into the UK infant immunisation schedule in 2000. The next generation of these glycoconjugate vaccines will be on the shelf soon, eventually offering the prospect of eradication of serogroups A, C, Y and W135 through routine infant immunisation. Despite these exciting prospects, serogroup B meningococci still account for a majority of infections in industrialised nations but development of safe, immunogenic and effective serogroup B meningococcal vaccines has been an elusive goal. Outer membrane vesicle vaccines for B disease are already used in some countries, and will likely be used more widely in the next few years, but efficacy for endemic disease in children has so far been disappointing. However, the innovations arising from the availability of the meningococcal genome sequence, public and scientific interest in the disease and recent pharmaceutical company investment in development of serogroup B vaccines may have started the countdown to the end of meningococcal infection in children.     

Emergence of serogroup X meningococcal disease in Africa: Need for a vaccine

Neisseria meningitidis is responsible for the seasonal burden and recurrent epidemics of meningitis in an area of sub-Saharan Africa known as the meningitis belt. Historically, the majority of the cases in the meningitis belt are caused by serogroup A meningococci. Serogroup C meningococci were responsible for outbreaks in the meningitis belt in the 1980s, while serogroup W (formerly W-135) has emerged as a cause of epidemic meningitis since 2000. Serogroup X meningococci have previously been considered a rare cause of sporadic meningitis, but during 2006–2010, outbreaks of serogroup X meningitis occurred in Niger, Uganda, Kenya,Togo and Burkina Faso, the latter with at least 1300 cases of serogroup X meningitis among the 6732 reported annual cases. While serogroup X has not yet caused an epidemic wave of the scale of serogroup A in 1996–1997 or serogroup W in Burkina Faso during 2002, the existing reports suggest a similar seasonal hyperendemicity and capacity for localised epidemics. Serogroup X incidence appears to follow a pattern of highly localised clonal waves, and in affected districts, other meningococcal serogroups are usually absent from disease. Currently, no licensed vaccine is available against serogroup X meningococci. Following the introduction of a monovalent serogroup A conjugate vaccine (MenAfriVac^®) in the meningitis belt and the upcoming introduction of pneumococcal conjugate vaccines, vaccine-based prevention of serogroup X may become a public health need. The serogroup X polysaccharide capsule is the most likely target for vaccine development, but recent data also indicate a potential role for protein-based vaccines. A multivalent vaccine, preferably formulated as a conjugate vaccine and covering at least serogroups A, W, and X is needed, and the efforts for vaccine development should be intensified.     

Carriage Rate and Effects of Vaccination after Outbreaks of Serogroup C Meningococcal Disease,Brazil, 2010

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.     

The first large epidemic of meningococcal disease caused by serogroup W135, Burkina Faso, 2002

In 2001 a significant proportion of cases of meningococcal meningitis toward the end of a serogroup A epidemic in Niger and Burkina Faso was found to be caused by serogroup W135 meningococci. The World Health Organization put in place in several African countries an extended surveillance scheme in preparation for a possible epidemic situation. In January 2002, the first large epidemic of meningococcal disease caused by serogroup W135 started in Burkina Faso, resulting in more than 12,000 cases and 1400 deaths. We report here the results of the laboratory-based surveillance and the characteristics of the epidemic clone.     

Meningococcal disease in South Africa, 1999-2002

We describe the epidemiology of invasive meningococcal disease in South Africa from August 1999 through July 2002, as reported to a laboratory-based surveillance system. Neisseria meningitidis isolates were further characterized. In total, 854 cases of laboratory-confirmed disease were reported, with an annual incidence rate of 0.64/100,000 population. Incidence was highest in infants < 1 year of age. Serogroup B caused 41% of cases; serogroup A, 23%; serogroup Y, 21%; serogroup C, 8%; and serogroup W135, 5%. Serogroup B was the predominant serogroup in Western Cape Province, and disease rates remained stable. Serogroup A was most prevalent in Gauteng Province and increased over the 3 years. On pulsed-field gel electrophoresis analysis, serogroup A strains showed clonality, and serogroup B demonstrated considerable diversity. Selected isolates of serogroup A belonged to sequence type (ST)-1 (subgroup I/II) complex, serogroup B to ST-32/electrophoretic type (ET)-5 complex, and serogroup W135 to ST-11/ET-37 complex.     

The concept of "tailor-made", protein-based, outer membrane vesicle vaccines against meningococcal disease

Protein-based, outer membrane vesicle (OMV) vaccines have previously proven to be efficacious against serogroup B meningococcal disease in Norway and Cuba. Currently, a public health intervention is going on in order to control a serogroup B epidemic in New Zealand. The scale-up and standardization of vaccine production required for controlling the New Zealand epidemic has allowed the establishment of large-scale GMP manufacturing for OMV vaccines. The outcome of this will be licensing of the vaccine in New Zealand and possibly other countries. The availability of licensed OMV vaccines raises the question of whether such vaccines may provide the opportunity to control other outbreaks and epidemics. For instance, such a vaccine could control a localised outbreak of group B meningococci in Normandy, France. "Tailor-made" vaccines, focusing on the sub-capsular antigens may also be considered for use in sub-Saharan Africa for the prevention of the recurrent outbreaks by serogroups A and W135 meningococci. This assumption is based on the epidemiological observation that meningococcal outbreaks in Africa are clonal and are strikingly stable regarding their phenotypic characteristics.     

Priorities for research on meningococcal disease and the impact of serogroup A vaccination in the African meningitis belt

For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in areas of the African Sahel and sub-Sahel known as the African meningitis belt. Until recently, the main approach to the control of these epidemics has been reactive vaccination with a polysaccharide vaccine after an outbreak has reached a defined threshold and provision of easy access to effective treatment but this approach has not prevented the occurrence of new epidemics. Meningococcal conjugate vaccines, which can prevent meningococcal carriage and thus interrupt transmission, may be more effective than polysaccharide vaccines at preventing epidemics. Because the majority of African epidemics have been caused by serogroup A meningococci, a serogroup A polysaccharide/tetanus toxoid protein conjugate vaccine (PsA–TT) has recently been developed. Results from an initial evaluation of the impact of this vaccine on meningococcal disease and meningococcal carriage in Burkina Faso have been encouraging.     

Age-specific seroprevalence of serogroup C meningococcal serum bactericidal antibody activity and serogroup A, C, W135 and Y-specific IgG concentrations in the Turkish population during 2005

Like many other developing countries; there is no accurate information about the antibody levels against Neisseria meningitidis in Turkey. We collected serum samples from four health centers located in different geographic regions and stratified according to age in order to obtain a baseline seroprevalence of protective antibodies to meningococcal serogroup C and provide data on seroprevalence of IgG antibodies to serogroups A, C, W135 and Y. Sera were tested for serum bactericidal antibodies (SBA) to serogroup C meningococci using rabbit serum as the complement source and by a bead based assay for serogroup A, C, W135 and Y-specific IgG. It was observed that 30% and 12% of individuals within the study population had SBA titers of > or =8 and > or =128, respectively. Overall; at least 70% of the population are susceptible (SBA titer <8) to meningococcal serogroup C disease. The rate of susceptibility was highest in infants aged 7-12 months and young children (1-4 years). Regardless of age, for serogroup A, C, W135 and Y, 60.5%, 27.2%, 12.3% and 19.2% of subjects, respectively, had serogroup-specific IgG concentrations > or =2 microg/mL. These data highlight that a large proportion of the Turkish population are susceptible to serogroups C, W135 and Y and should be considered, along with serogroup-specific disease incidence data, in future decisions on possible meningococcal vaccination programmes.     

A second controlled field trial of a serogroup A meningococcal polysaccharide vaccine in Alexandria.

The encouraging results of an earlier controlled field trial of the serogroup A meningococcal polysaccharide vaccine in the prevention of clinical disease prompted this study, the aim of which was to evaluate further the effectiveness of another lot of this type of vaccine, the duration of immunity, and the effectiveness against meningococcal carriage. A controlled field trial was carried out in early 1973 on 176 646 schoolchildren 6-15 years of age, of whom half received the serogroup A polysaccharide vaccine and the other half tetanus toxoid as a control. The incidence of cerebrospinal meningitis caused by serogroup A meningococci was 89% lower in the immunized group than in the controls for one year only. With regard to its effect on carriage, the vaccine was found to reduce to less than half the rate of new acquisition of serogroup A meningococci during the period immediately following immunization. The duration of the carrier state was also shortened in the immunized group.     

B群脑膜炎球菌疫苗研究进展

脑膜炎奈瑟菌（Neisseria Meningitidis,Nm）感染仍然严重威胁人群健康,接种疫苗是预防该类疾病的有效手段。根据荚膜多糖的特征,Nm分为A、B、C、W135、Y等不同的血清群。A、C、W135、Y群Nm多糖疫苗以及多糖-蛋白结合疫苗,已经得到广泛应用并证明了其有效性。由于B群Nm菌株的荚膜多糖免疫原性较低,并且与人体神经组织具有同源性,因此B群Nm多糖不能用于疫苗抗原成分。近年来,国际上开展了大量B群Nm蛋白疫苗研究工作,以疫苗外膜蛋白为基础的疫苗研究,以及反向疫苗学技术在B群疫苗研究中的应用,使B群Nm疫苗的研究取得了长足进展。某些B群疫苗显示出良好的免疫原性和有效性,并且已经有B群蛋白疫苗获得许可并规模化应用。     

ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗免疫学效果的Meta分析

目的 评价ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗(MPCV-ACYW135-TT)的免疫学效果.方法 检索National Center for Biotechnology Information (NCBI)、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关评价MPCV-ACYW135免疫学效果的随机对照试验(RCT)的研究纳入分析.以接种疫苗1个月后产生的血清杀菌活性(SBA)抗体阳转率(PRR)和几何平均滴度(GMT)作为结局指标,合并不同研究中试验组与对照组间的PRR和GMT的率差(RD)或标准化均数差(SMD).使用RevMan5.1软件进行Meta分析.结果 共纳入13篇文献:有9篇比较了MPCV-ACYW135-TT和ACYW135群脑膜炎球菌多糖疫苗(MPV-ACYW135)之间免疫学效果差异,4篇比较了MPCV-ACYW135-TT和C群脑膜炎球菌多糖结合白喉毒素变异体197疫苗(MPCV-C-CMR197)之间免疫学效果差异.相比于MPV-A-CYW135;受试者在接种MPCV-ACYW135-TT后产生的针对A、C、Y和W135这4个血清型抗体PRR的RD在0.03～0.15之间;产生的针对A、Y和W135这3个血清型抗体GMT的SMD在0.33～1.22之间.1～2岁组幼儿在接种MPCV-ACYW135-TT后产生的针对C群抗体GMT与接种MPCV-C-CMR197差异无统计学意义(H＞0.05).结论 MPCV-ACYW135-TT与其他已上市应用的脑膜炎球菌疫苗有相似的免疫效果.     

Development and characterisation of outer membrane vesicle vaccines against serogroup A Neisseria meningitidis

Neisseria meningitidis bacteria of serogroup A are causing recurring meningitis epidemics on the African continent. An outer membrane vesicle (OMV) vaccine against serogroup A meningococci made from a subgroup III serogroup A meningococcal strain was previously shown to induce antibodies with serum bactericidal activity (SBA) in mice. We have here further investigated the properties of OMV vaccines made from five different subgroup III serogroup A meningococcal strains grown in a synthetic medium with low iron content. In addition to the major outer membrane proteins (PorA, PorB, RmpM, Opa and OpcA), small amounts of the NadA, TdfH, Omp85, FetA, FbpA and NspA outer membrane proteins, as well as lipooligosaccharides, were detected in the vaccines. The OMV vaccines were used to immunise mice. Anti-meningococcal IgG antibodies in the mouse sera were analysed by immunoblotting and by enzyme-linked immunosorbent assay against OMVs, and against live meningococcal cells in SBA and a flow-cytometric assay. The vaccines induced antibodies with high SBA and opsonophagocytic activity. The strongest IgG responses were directed against PorA. Significant SBA responses were also observed against a subgroup III strain, which did not express PorA, whereas no SBA was observed against a clone IV-1 serogroup A strain. An OMV vaccine from serogroup A meningococci may be an alternative to polysaccharide and conjugate polysaccharide vaccines for Africa.     

Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994-9

We examined the serological characteristics of 774 invasive meningococcal isolates collected through an active laboratory-based surveillance system in Scotland from 1994 to 1999. Of these, 72-73% of isolates were tested for susceptibility to several antimicrobial agents. Meningococci with high-level resistance to sulphadiazine had a prevalence of 10% and incidence of 0.22 per 100,000 population. High-level resistance to penicillin and other antibiotics was not detected. The prevalence of moderate penicillin resistant meningococci was 8.3%. There was no increase in moderate penicillin resistant meningococcal isolates during the study period, but there were temporal and geographic variations. The estimated incidence of moderate penicillin resistant meningococci was 0.15 per 100,000 population. High and low incidence of moderate penicillin resistant meningococci appeared to correlate with the number of doses of penicillin prescribed in some geographic locations. The majority of moderate penicillin resistant isolates belonged to serogroups B (52.2%) and C (39.2%). However, the prevalence of moderate penicillin resistance in serogroup W135 was substantially higher (51.7%) than serogroups B (7.8%) and C (7.6%). Serogroup W135 accounted for a higher proportion of moderate penicillin resistance (8.7%) than disease (1%). There was no predominant penicillin resistant serotype/subtype within any serogroup. Constant surveillance is necessary to monitor the emergence and spread of resistance and to guide appropriate public health interventions in preventing drug resistant meningococci.     

流行性脑脊髓膜炎的流行病学监测与预防

流行性脑脊髓膜炎(流脑)仍然是一种常见的急性传染病,它严重地威胁着儿童的健康.文章介绍了最近在非洲、欧洲、大洋洲、美国和我国出现的流脑流行情况,在上述地区和国家中脑膜炎球菌血清群、血清型与血清亚型的分布,脑膜炎球菌对抗菌药物的耐药性.为了有效地控制流脑的流行,必须加强对流脑的监测与预防.为此,提出了在流脑流行病学监测中,不仅监测流脑一般的发病率与病死率,还应监测它的年龄组发病率.还必须检查脑膜炎球菌血清群的变迁与该菌对抗菌药物的耐药性,以及该菌在健康人群中的带菌率与人群的抗体水平.给儿童注射脑膜炎球菌多糖疫苗是预防流脑的主要措施.为了增强脑膜炎球菌多糖疫苗对幼儿的预防效果,有的国家正在使用C群脑膜炎球菌多糖与载体蛋白结合所制成的结合疫苗.关于B群脑膜炎球菌疫苗的研究近况在此文中亦做了介绍.当缺乏疫苗时,给病人密切接触者口服抗菌药物作为辅助的预防措施,对于减少流脑第2代病人也将会产生一些效果.     

Anticapsular polysaccharide meningococcal antibodies in Israeli military recruits: immune status and the effect of simultaneous administration of immune globulin on the response to polysaccharide vaccine

The effect of the administration of immune globulin (Ig), given during summer months to prevent hepatitis A, on the immune response to a simultaneously administered quadrivalent meningococcal polysaccharide vaccine (QMPV) was studied in Israeli military recruits. Data were obtained for the first time regarding the immune status of an Israeli population. Anticapsular polysaccharide antibodies were determined using a standardized ELISA assay before, 2 weeks and 3 months after QMPV immunization with or without Ig in two groups of recruits chosen to span the date determining seasonal administration or non-administration of Ig. Pre-vaccination antibody concentrations were > or = 2 microg/ml in 98.4 and 38.9% of subjects against serogroups A and C meningococci, respectively. These levels are consistent with the extremely low incidence of disease due to serogroup A in Israel, and with the previously documented occurrence of serogroup C disease in servicemen and women. Co-administration of Ig was associated with some reduction in antibody concentrations 3 months after vaccination, especially against serogroup A meningococci (P<0.05), but not to an extent likely to be of clinical significance.     

Evaluation of serogroup A meningococcal vaccines in Africa: a demonstration project

Endemic and epidemic meningococcal disease constitutes a major public-health problem in African countries of the 'meningitis belt' where incidence rates of the disease are many-fold higher (up to 25 cases per 100,000 population) than those in industrialized countries, and epidemics of meningococcal disease occur with rates as high as 1,000 cases per 100,000 people. Using the precedent established during the licensing of conjugate vaccines against Haemophilus influenzae type b and serogroup C meningococci and components of currently-licensed meningococcal polysaccharide vaccines, new meningococcal conjugate vaccines will likely be licensed using immunological endpoints as surrogates for clinical protection. Post-licensure evaluation of vaccine effectiveness will, therefore, be of increased importance. One vaccine being developed is the serogroup A meningococcal (Men A) conjugate vaccine produced by the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization and the Program for Applied Technology in Health. This vaccine will likely be the first meningococcal conjugate vaccine introduced on a large scale in Africa. This paper summarizes the general steps required for vaccine development, reviews the use of immunogenicity criteria as a licensing strategy for new meningococcal vaccines, and discusses plans for evaluating the impact of a meningococcal A conjugate vaccine in Africa. Impact of this vaccine will be measured during a vaccine-demonstration project that will primarily measure the effectiveness of vaccine. Other studies will include evaluations of safety, vaccine coverage, impact on carriage and herd immunity, and prevention-effectiveness studies.     

Microbiological and epidemiological investigation of the Neisseria meningitidis serogroup A epidemic in Niger in 2009: last wave before the introduction of the serogroup A meningococcal conjugate vaccine?

The 2009 meningitis season in Niger was characterized by an early onset, beginning in the very first weeks of the year and peaking from the 12th to the 15th week with 5655 clinical cases over the 4 weeks. From 1 January 2009 to 28 June 2009 (week 26), a total of 13,733 clinical cases of meningitis were reported to the national epidemiological surveillance system with a case-fatality rate of 4·2%. During the season 25 of the 42 health districts reached the epidemic threshold and 11 the alert threshold. Reactive mass vaccination campaigns involving a total of 5 166,741 doses of the polysaccharide meningococcal bivalent (A+C) vaccine progressively controlled the outbreak in most parts of the country. A total of 3755 cerebrospinal fluid samples representing 28·1% of the suspected meningitis cases were analysed. Serogroup A meningococci were the causative agent in 97·5% of the meningococcal cases. Multi-locus sequence typing of 26 meningococal serogroup A strains showed 25 sequence type (ST)7 and one ST2859, both sequence types belonging to the ST5 clonal complex (CC5) of subgroup III. This is the largest epidemic observed in Niger since those of 1995-1996 (59,948 notified cases) and 2000 (14,633 notified cases).     

Immunogenicity, reactogenicity and persistence of meningococcal A, C, W-135 and Y-tetanus toxoid candidate conjugate (MenACWY-TT) vaccine formulations in adolescents aged 15-25 years

Development of meningococcal serogroups A, C, W-135 and Y conjugate vaccines could expand coverage against devastating meningococcal diseases. The immunogenicity of one dose of each one of five MenACWY-TT formulations versus a licensed ACWY polysaccharide vaccine was evaluated in 175 healthy subjects of 15-25 years. Serum bactericidal titers (rSBA) were evaluated before and after vaccination. The percentage of rSBA responders to each serogroup A, C, W-135 and Y did not statistically differ from the control for each of the five formulations except for serogroup A that was lower after administration of one formulation. In the 3-year follow-up of the first study where the latter formulation was assessed, bactericidal antibody persistence was similar to the licensed ACWY polysaccharide vaccine for MenA and MenC and higher for MenW-135 and MenY. Our results present five investigational MenACWY-TT conjugate vaccine formulations which are well tolerated and highly immunogenic in adolescents.