Influence of Two Vaccination Campaigns on Genetic Diversity of Invasive Neisseria meningitidis Isolates in Northern Spain (1997–2008)

BACKGROUND: Neisseria meningitidis diversifies rapidly, due to its high recombination rates. The aim of this study was to analyze the possible impact of two vaccination campaigns (a once-off A/C polysaccharide vaccination campaign in people aged 18 months to 20 years old in 1997, and a meningococcal C conjugate vaccination campaign in children aged < or = 6 years old from 2000 to 2008) on diversification of the population of invasive isolates obtained between 1997 and 2008. All of the 461 available isolates were included (2, 319, 123, 11 and 6 belonging to serogroups A, B, C, Y and W-135, respectively). METHODOLOGY/PRINCIPAL FINDINGS: The isolates were analyzed for diversity using multilocus sequence typing, eBURST and the S.T.A.R.T.2 program. One hundred and seven sequence types (ST) and 20 clonal complexes were obtained. Five different STs (ST11, ST8, ST33, ST1163 and ST3496) included 56.4% of the isolates. With the exception of ST11, all other STs were associated with a specific serogroup. Epidemic circulation of serogroup C ST8 isolates was detected in 1997-1998, as well as epidemic circulation of ST11 isolates (serogroups B and C) in 2002-2004. The epidemic behavior of serogroup B ST11 (ST11_B:2a:P1.5) was similar, although with lesser intensity, to that of ST11 of serogroup C. Although clonality increased during epidemic years, the overall diversity of the meningococcal population did not increase throughout the 12 years of the study. CONCLUSION: The overall diversity of the meningococcal population, measured by the frequency of STs and clonal complexes, numbers of alleles, polymorphic sites, and index of association, remained relatively constant throughout the study period, contradicting previous findings by other researchers

Experimental investigations of simulated meteoroid damage to various spacecraft structures progress report no. 1, period ending 30 sep. 1964

Space simulation experimental studies of penetration mechanics of meteoroids into typical spacecraft structure

Experimental investigations of simulated meteoroid damage to various spacecraft structures progress report no. 3, period ending 31 jan. 1965

Simulation of meteoroid interaction and impact damage to spacecraft structure

Experimental investigations of simulated meteoroid damage to various spacecraft structures Summary report

Optimum structural meteoroid protection requirements for Apollo and Mars mission spacecraf

Association of a Bacteriophage with Meningococcal Disease in Young Adults

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases

The elusive meningococcal meningitis serogroup: a systematic review of serogroup B epidemiology

<p>Abstract</p> <p>Background</p> <p>Invasive meningococcal disease (IMD), is a widely distributed, complex human disease affecting all age categories. The causative agent, <it>Neisseria meningitidis</it>, is spread through aerosol respiratory droplets. 13 different serogroups have been identified, each with varying epidemiological features including prevalence, virulence, immunogenicity, geographical and temporal distribution. Although preventative measures are available for several of the serogroups, meningococcal disease caused by serogroup B is of particular interest due to the challenge it presents concerning vaccine development.</p> <p>Methods</p> <p>A systematic review of peer reviewed studies and reports, the collection of data from national and international health resources, along with the analysis of the Multi Locus Sequence Typing database was carried out aimed at collecting information concerning serogroup B IMD and the epidemiology attached to it.</p> <p>Results</p> <p>A continuous output of related and novel STs occurring worldwide in terms of the hypervirulent clonal complexes was observed both in published studies and the MLST database in this case using the eburst software, which highlights the genetically diverse nature of serogroup B strains.</p> <p>Conclusions</p> <p>With the recent dominance of serogroup B IMD seen in many countries, along with the presence of antibiotic resistance, vaccine development needs to target areas of the bacterium which tackle this widespread and heterogeneous aspect of meningococcal meningitis disease.</p

Serogroup C meningococci in Italy in the era of conjugate menC vaccination

<p>Abstract</p> <p>Background</p> <p>To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005–2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies.</p> <p>Methods</p> <p>IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), <it>por</it>A VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures.</p> <p>Results</p> <p>In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome.</p> <p>Conclusion</p> <p>Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005–2007 National Vaccine Plan.</p

Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation.

Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8-30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates

Genetic Affinities within a Large Global Collection of Pathogenic Leptospira: Implications for Strain Identification and Molecular Epidemiology

Leptospirosis is an important zoonosis with widespread human health implications. The non-availability of accurate identification methods for the individualization of different Leptospira for outbreak investigations poses bountiful problems in the disease control arena. We harnessed fluorescent amplified fragment length polymorphism analysis (FAFLP) for Leptospira and investigated its utility in establishing genetic relationships among 271 isolates in the context of species level assignments of our global collection of isolates and strains obtained from a diverse array of hosts. In addition, this method was compared to an in-house multilocus sequence typing (MLST) method based on polymorphisms in three housekeeping genes, the rrs locus and two envelope proteins. Phylogenetic relationships were deduced based on bifurcating Neighbor-joining trees as well as median joining network analyses integrating both the FAFLP data and MLST based haplotypes. The phylogenetic relationships were also reproduced through Bayesian analysis of the multilocus sequence polymorphisms. We found FAFLP to be an important method for outbreak investigation and for clustering of isolates based on their geographical descent rather than by genome species types. The FAFLP method was, however, not able to convey much taxonomical utility sufficient to replace the highly tedious serotyping procedures in vogue. MLST, on the other hand, was found to be highly robust and efficient in identifying ancestral relationships and segregating the outbreak associated strains or otherwise according to their genome species status and, therefore, could unambiguously be applied for investigating phylogenetics of Leptospira in the context of taxonomy as well as gene flow. For instance, MLST was more efficient, as compared to FAFLP method, in clustering strains from the Andaman island of India, with their counterparts from mainland India and Sri Lanka, implying that such strains share genetic relationships and that leptospiral strains might be frequently circulating between the islands and the mainland

The Past and Future of Tuberculosis Research

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB's epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB