Application of multiple-locus variable number tandem repeat analysis to identify outbreak-associated Neisseria meningitides serogroup C sequence type 4821 in China.

Neisseria meningitidis (N. meningitidis) serogroup C sequence type (ST)-4821 caused an outbreak in 2010 in Shandong province of China. Twenty-one non-outbreak-associated strains were isolated, along with twenty-eight N. meningitides serogroup C ST-4821 isolates. Therefore, it's essential to identify and clarify characterization of the real outbreak-associated strains with a rapid method during an outbreak investigation. In this study, multiple-locus variable number tandem repeat analysis (MLVA) was applied to analyze 84 N. meningitidis strains, among which 58 were recovered from two outbreaks and 26 were sporadic isolates. Three MLVA schemes with different combination of VNTR loci were tested, and two of them were suitable for isolates from China: scheme 2 with six loci was found to separate ST into finer resolution, and scheme 3 with five loci can be used to identify outbreak-associated isolates from the same outbreak that caused by N. meningitidis serogroup C ST-4821.

Fusion protein comprising factor H domains 6 and 7 and human IgG1 Fc as an antibacterial immunotherapeutic.

The emergence of antimicrobial resistance among several medically important pathogens represents a serious threat to human health globally and necessitates the development of novel therapeutics. Complement forms a key arm of innate immune defenses against invading pathogens. A mechanism of complement evasion employed by many pathogens is binding of complement inhibitors, including factor H (FH), a key downregulator of the alternative pathway. Most FH-binding bacteria engage FH through regions in FH spanned by domains 6 and 7 and/or 18 through 20. We created a chimeric protein that comprised human FH domains 6 and 7 fused to human IgG1 Fc (FH6,7/HuFc) and tested its activity as an immunotherapeutic against Neisseria meningitidis, which binds FH through domains 6 and 7. FH6,7/HuFc bound to meningococci and effectively blocked FH binding to bacteria. FH6,7/HuFc enhanced human C3 and C4 deposition and facilitated complement-mediated killing in a dose-responsive manner; complement activation and killing were classical pathway dependent. To investigate in vivo efficacy, infant Wistar rats were treated intraperitoneally (IP) with different doses of FH6,7/HuFc and challenged 2 h later with serogroup C strain 4243 given IP. At 8 to 9 h after the challenge, the FH6,7/HuFc-treated rats had >100-fold fewer CFU per ml of blood than control animals pretreated with phosphate-buffered saline (PBS) or FH18-20/HuFc, which does not bind to meningococci (P < 0.0001). These data provide proof of concept of the utility of FH/Fc fusion proteins as anti-infective immunotherapeutics. Because many microbes share a common binding region(s) in FH, FH/Fc chimeric proteins may be a promising candidate for adjunctive therapy against drug-resistant pathogens.

Cluster of invasive Neisseria meningitidis infections on a cruise ship, Italy, October 2012.

We describe a cluster of four cases of invasive meningococcal disease that occurred on a cruise ship sailing along the Italian coast in October 2012. All four cases were hospitalised with severe illness and one of them died. This report illustrates the importance of rapid implementation of emergency control measures such as administration of prophylaxis to all crew members and passengers to prevent the spread of the disease in such a close environment.

Phenotypic and molecular characterization of serogroup C Neisseria meningitidis associated with an outbreak in Bahia, Brazil.

OBJECTIVE: To characterize meningococcal strains isolated from five cases of meningococcal disease (MD) associated with an outbreak in Trancoso - BA, occurred in October 2009. All cases, with the exception of a 39-year-old male, attended a dance party with approximately 1000 youngsters in a rural site. MATERIALS AND METHODS: The epidemiological investigation was conducted by the Epidemiological Surveillance Service of Bahia State. Meningococcal strains were characterized at Adolfo Lutz Institute, the Brazilian National Reference Laboratory for Bacterial Meningitis by conventional techniques (serotype, serosubtype and antimicrobial susceptibility test) and by molecular methods (Pulsed-field gel electrophoresis - PFGE and Multilocus Sequence Typing - MLST). RESULTS: The PFGE showed 2 closely related restriction profiles, designated as PFGE types A and A1, having 92% relatedness to each other. MLST characterization showed both A and A1 clones were ST-3780, which belongs to the ST-103 complex. All isolates displayed the phenotype C:23:P1.5 and were susceptible to all antibiotics tested. CONCLUSIONS: This is the first reported MD outbreak associated with serogroup C ST-103 complex in Brazil, as well as the party and illicit drug-use associated outbreak.

Persistence of serum bactericidal antibody one year after a booster dose of either a glycoconjugate or a plain polysaccharide vaccine against serogroup C Neisseria meningitidis given to adolescents previously immunized with a glycoconjugate vaccine.

BACKGROUND: Bactericidal antibody induced by immunization of infants with serogroup C Neisseria meningitidis (MenC) vaccines wanes rapidly during childhood. Adolescents are at particular risk from meningococcal disease, therefore they might benefit from a booster dose of vaccine. The duration of serologic response to such a booster in adolescents is unknown. METHODS: In a previous study, English schoolchildren, aged 9 to 12 years, who had received a monovalent MenC glycoconjugate vaccine in 1999-2000, were given either a plain polysaccharide vaccine (MenC-PS group, n = 150) or a glycoconjugate vaccine (MenC-CRM group, n = 95) at 13 to 15 years of age. In this follow-up study, serum bactericidal antibody titers and specific immunoglobulin G concentrations were assessed 1 year later. Results were compared with unboosted controls of similar age (control group, n = 298). RESULTS: Compliance with study protocol was achieved for 146 of the MenC-PS group, 92 of the MenC-CRM group, and 293 of the control group. Compared with the control group, both the MenC-PS and MenC-CRM groups had a significantly higher (P < 0.0001) geometric mean serum bactericidal antibody titers 1 year after the booster dose (geometric mean titers for MenC-PS group 3388 [95% confidence interval {CI}: 2460-4665]; MenC-CRM group 4417 [95% CI: 2951-6609]; control group 316 [95% CI: 252-396]). Specific immunoglobulin G concentration also rose and remained elevated 1 year after the booster. CONCLUSIONS: A booster dose of MenC vaccine given to adolescents produced a marked rise in bactericidal antibody, which remained elevated 1 year later. Introduction of an adolescent booster of MenC vaccine might provide enhanced long-term population control of the disease.

[Testing of antibodies against serogroup C Neisseria meningitidis by serum bactericidal assay in healthy population, Liaoning province].

OBJECTIVE: To test the serum antibodies from healthy population by Serum Bactericidal Assay (SBA), in order to evaluate the level of protective antibodies against serogroup C Neisseria meningitidis in Liaoning province. METHODS: 240 serum samples were selected from eight age-group randomly. Serogroup C vaccine candidate strain (C11) and the prevail serogroup C strain (053442) were used for SBA. RESULTS: 48.33% of 240 serum samples were positive (titer > or = 1:2) to C11 vaccine strain. Protective rate of SBA was 35.83% (titer > or = 1:8), in which, > or = 6 years old were 13.33%, 7-19 years old was 61.67%, 20-39 years old were 46.67% and > or = 40 years old were 63.33%. Rate of SBA to 053442 was lower than that to C11 in the group over 15 years old by statistic analysis. CONCLUSION: Population under 6 years old showed lower SBA capacities. With the implemention of Expanded Program on Immunization, children under 3 years old should be considered how to give them meningococcal vaccine in order to improve the titer of antibodies against Neisseria meningitidis serogroup C.

Annual report of the Australian Meningococcal Surveillance Programme, 2007.

In 2007 there were 242 laboratory-confirmed cases of invasive meningococcal disease analysed by the National Neisseria Network, a nationwide network of reference laboratories. The phenotypes (serogroup, serotype and serosubtype) and antibiotic susceptibility of 127 isolates of Neisseria meningitidis from invasive cases of meningococcal disease were determined and an additional 115 cases were confirmed by non-culture based methods. Nationally, 192 (85%) confirmed cases where a serogroup was determined were infected with serogroup B and 14 (6.2%) with serogroup C meningococci. The total number of confirmed cases was 29 fewer than the 271 cases identified in 2006. The only jurisdiction to record a substantial increase in laboratory confirmed cases was New South Wales and this was in sporadic cases of serogroup B infection. Typical primary and secondary disease peaks were observed in those aged 4 years or less and in adolescents and young adults respectively. Serogroup B cases predominated in all age groups and jurisdictions. The common phenotypes circulating in Australia were B:15:P1.7, B:4:P1.4 and C:2a:P1.5. No evidence of meningococcal capsular 'switching' was detected. About three-quarters of all isolates showed decreased susceptibility to the penicillin group of antibiotics (minimum inhibitory concentration [MIC] 0.06-0.5 mg/L). All isolates remained susceptible to rifampicin. A single serogroup B isolate had decreased susceptibility to ciprofloxacin (MIC 0.06 mg/L). This was the first local isolate of this type since the original report of this phenomenon in Australia in 2000.

Characterisation of invasive meningococcal isolates from Italian children and adolescents.

Meningococcal invasive disease is a life-threatening infection that affects mostly children and adolescents. The present study was performed during 2003-2005 to compare the phenotypic characteristics of meningococcal isolates from these two main groups at risk with those of isolates from other age groups to assess whether strategies for treatment and prevention implemented elsewhere can also be applied in Italy. The results showed that serogroup C meningococci were predominant, and that a dramatic increase in the circulation of strains with decreased susceptibility to penicillin was associated mainly with a prevalent phenotype C:2b:P1.5,2, which belongs to the hyper-virulent ST8/A4 cluster.

The iron-regulated transcriptome and proteome of Neisseria meningitidis serogroup C.

Restricting bacterial growth by iron-chelating proteins that reduce iron availability in mucosal secretions and body fluids belongs to basic mechanisms of innate immunity. Most pathogens and commensals thus developed gene regulons responding to iron concentration and encoding iron acquisition systems and genes involved in host colonization and virulence. Here, we analyzed the steady-state composition of the iron-regulated proteome and transcriptome of an invasive serogroup C clinical isolate of Neisseria meningitidis. The proteome of meningococci grown under iron-depleted and iron-replete conditions was analyzed by 2-DE and proteins exhibiting significantly altered expression were identified by MALDI-TOF MS analysis. In parallel, total RNA was isolated from the same cultures and iron-regulated genes were identified using whole-genome DNA microarrays. The proteome and the transcriptome were found to overlap by only 19 iron-regulated genes/proteins, with 111 genes/proteins being significantly up-regulated in iron-replete cultures and 130 genes/proteins being up-regulated during iron starvation, respectively. Comparisons with published transcriptomic data for N. meningitidis serogroup B, moreover, indicate that expression of up to 20% of all meningococcal genes can be subject to regulation in function of iron availability.

Neisseria meningitidis C:2b:P1.2,5 with decreased susceptibility to penicillin isolated from a patient with meningitis and purpura fulminans.

This report describes the case of an 18-year-old woman with meningococcal meningitis and purpura fulminans. Cerebrospinal fluid culture revealed Neisseria meningitidis serogroup-serotype-serosubtype C:2b:P1.2,5 as the pathogenic organism. Following treatment with cefotaxime and management of multiple organ failure, the patient survived without sequelae. To the best of our knowledge this report represents the first case of a meningococcal strain with a minimum inhibitory concentration of 1.5 mug/ml for penicillin, without beta-lactamase production, to be documented in France. The prevalence of meningococci with reduced susceptibility to penicillin is increasing. The emergence of such strains might represent a serious problem affecting the empirical antibiotic treatment of meningococcal disease.

Identification of Neisseria meningitidis sequence type 66 in Poland.

Investigation of two cases of invasive meningococcal disease within a single family revealed the presence of isolates of Neisseria meningitidis phenotype C:2b:P1.2,P1.5 belonging to sequence type (ST) 66. The ST66 clone is a single-locus variant of the widely distributed ST8 complex, which has been observed previously in Spain, Belgium, Australia and New Zealand. This hypervariable meningococcal lineage has been responsible for local epidemics worldwide. This is the first report of ST66 meningococcal isolates of this phenotype from Poland.

Invasive culture-confirmed Neisseria meningitidis in Portugal: evaluation of serogroups in relation to different variables and antimicrobial susceptibility (2000-2001).

The first investigation of Neisseria meningitidis isolated from a large area covering an appreciable population in Portugal, before the voluntary vaccination period with the serogroup C conjugate vaccine, is reported. The serogroups and antimicrobial susceptibility of 116 isolates were studied. Serogroups C (50.0 %), B (47.4 %) and W135 (2.6 %) were found. Serogroup C was most common in the 1-15-years-old group and B in the less than 1-year-old and over 16-years-old groups (P = 0.042). Clinical diagnosis of meningococcal disease was primarily meningitis for patients with serogroup C and meningitis associated with sepsis for those with serogroup B. Penicillin resistance was significantly associated with serogroup C (P < 0.001). This work reinforces the importance for public health of monitoring the serogroup and antimicrobial susceptibility of isolates from patients with invasive meningococcal disease.

Neisseria meningitidis C:2b:P1.2,5 with intermediate resistance to penicillin, Portugal.

For 1 year, serogroup, serotype, serosubtype, and penicillin susceptibility of meningococci circulating in various regions in Portugal were evaluated. Most frequent phenotypes were B:4:P1.15 (13.4%) and C:2b:P1.2,5 (75.9%), which are also common in Spain. Overall, 27.5% of C:2b:P1.2,5 strains showed intermediate resistance to penicillin. Laboratory-based surveillance of meningococcal infection in Portugal provides important information to assess the adequacy of public health measures.