Genetic Features of a Representative Panel of 110 Meningococcal B Isolates to Assess the Efficacy of Meningococcal B Vaccines.

Predictions of vaccine efficacy against Neisseria meningitidis serogroup B (NmB) disease are hindered by antigenic variability, limiting the representativeness of individual NmB isolates. A qualitative human serum bactericidal assay using endogenous complements of individual subjects (enc-hSBA) enables large panels of NmB isolates to be tested. A 110-isolate panel was randomly selected from 442 invasive NmB isolates from United States cases reported to the Centers for Disease Control (CDC) from 2000 to 2008.

Phylogenetic Structure and Comparative Genomics of Multi-National Invasive Serotype a Isolates.

Recent reports have indicated a rise of invasive disease caused by serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis.

Enhancing Meningococcal Genomic Surveillance in the Meningitis Belt Using High-Resolution Culture-Free Whole-Genome Sequencing.

Rollout of meningococcal serogroup A conjugate vaccine in Africa started in 2010, aiming to eliminate meningitis outbreaks, in meningitis belt countries. Since then, studies have been conducted, primarily using isolates, to assess the vaccine impact on the distribution of meningococcal strains in the region. Here, we implemented an innovative, culture-free whole-genome sequencing approach on almost 400 clinical specimens collected between 2017 and 2019 from meningococcal meningitis cases in 6 African countries.

Direct Real-Time PCR for the Detection and Serotyping of Haemophilus influenzae without DNA Extraction.

To monitor the burden and changes in Haemophilus influenzae (Hi) disease, direct real-time PCR (drt-PCR) assays have been developed for Hi detection in monoplex form and its six serotypes in triplex form, directly from cerebrospinal fluid (CSF) specimens. These assays target the gene for the species detection (Hi-) and serotype-specific genes in region II of the capsule biosynthesis locus (Hi-abf and Hi-cde), identified through comparative analysis of Hi and non-Hi whole-genome sequences. The lower limit of detection (LLD) is 293 CFU/mL for the Hi- assay and ranged from 11 to 130 CFU/mL for the triplex serotyping assays.

Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015-2016.

In January and February 2015, serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates ( = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS).

Neisseria meningitidis Serogroup C Clonal Complex 10217 Outbreak in West Kpendjal Prefecture, Togo 2019.

Togo has reported seasonal meningitis outbreaks caused by non-Neisseria meningitidis serogroup A (NmA) pathogens since the introduction of meningococcal serogroup A conjugate vaccine (MACV, MenAfriVac) in 2014. From 2016 to 2017, NmW caused several outbreaks. In early 2019, a NmC outbreak was detected in the Savanes region of Togo and its investigation is described here.

Evaluating a Cluster and the Overall Trend of Invasive Haemophilus influenzae Serotype b in Alaska 2005-2019.

Background: In 2019, 5 cases of invasive Haemophilus influenzae serotype b (Hib) occurred in the Anchorage region of Alaska over a period of 16 days. No cases had occurred in Alaska in the preceding 26 months.

Methods: Alaska Hib isolates from 2005 through 2019 were analyzed using whole-genome sequencing (WGS).

Serogroup A, C, W, and Y meningococcal disease in persons previously vaccinated with a serogroup ACWY meningococcal vaccine - United States, 2014-2018.

Background: The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with a quadrivalent meningococcal conjugate serogroup A,C,W,Y (MenACWY) vaccine at 11-12 years of age, with a booster dose at 16 years. ACIP also recommends meningococcal vaccination for persons at increased risk of meningococcal disease, including a 2-dose primary series and regular booster doses for persons at increased risk because of underlying medical conditions. U.

Genomic Diversity of Haemophilus influenzae Serotype a in an Outbreak Community-Alaska, 2018.

Background: Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, 4 invasive Hia cases occurred in an Alaska community. We used whole-genome sequencing (WGS) to evaluate the relationship of the bacteria from this community and other Alaska patients with invasive Hia.

Genetic Diversity of Meningococcal Serogroup B Vaccine Antigens among Carriage Isolates Collected from Students at Three Universities in the United States, 2015-2016.

Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by serogroup B and at a university where outbreak and response activities had not occurred.

Web-Based Genome Analysis of Bacterial Meningitis Pathogens for Public Health Applications Using the Bacterial Meningitis Genomic Analysis Platform (BMGAP).

Effective laboratory-based surveillance and public health response to bacterial meningitis depends on timely characterization of bacterial meningitis pathogens. Traditionally, characterizing bacterial meningitis pathogens such as (Nm) and (Hi) required several biochemical and molecular tests. Whole genome sequencing (WGS) has enabled the development of pipelines capable of characterizing the given pathogen with equivalent results to many of the traditional tests.

Meningococcal carriage in young adults six years after meningococcal C conjugate (MCC) vaccine catch-up campaign in Salvador, Brazil.

Meningococcal carriage studies are important to improve the knowledge of disease epidemiology as well as to support appropriate vaccination strategies. We conducted a cross-sectional study to determine the prevalence and genotypic characteristics of meningococci collected from young adults in Salvador, Brazil six years after a meningococcal C conjugate vaccine catch-up campaign. From August through November 2016, oropharyngeal swabs were collected from 407 students aged 1824 years attending a private college in Salvador, Brazil.

Genomic characterization of Haemophilus influenzae: a focus on the capsule locus.

Background: Haemophilus influenzae (Hi) can cause invasive diseases such as meningitis, pneumonia, or sepsis. Typeable Hi includes six serotypes (a through f), each expressing a unique capsular polysaccharide. The capsule, encoded by the genes within the capsule locus, is a major virulence factor of typeable Hi.

Genetic Similarity of Gonococcal Homologs to Meningococcal Outer Membrane Proteins of Serogroup B Vaccine.

The human pathogens and share high genome identity. Retrospective analysis of surveillance data from New Zealand indicates the potential cross-protective effect of outer membrane vesicle (OMV) meningococcal serogroup B vaccine (MeNZB) against A licensed OMV-based MenB vaccine, MenB-4C, consists of a recombinant FHbp, NhbA, NadA, and the MeNZB OMV. Previous work has identified several abundantly expressed outer membrane proteins (OMPs) as major components of the MenB-4C OMV with high sequence similarity between and , suggesting a mechanism for cross-protection.

Invasive Meningococcal Disease due to Nongroupable -Active Bacterial Core Surveillance Sites, 2011-2016.

We characterized 22 meningococcal disease cases due to nongroupable , a rare cause of invasive disease. Disease presentation and severity were similar to those for serogroupable meningococcal disease. However, 7 (32%) patients had complement deficiency or abnormal complement testing results, highlighting the importance of complement testing for nongroupable cases.

Phylogenetic relationships and regional spread of meningococcal strains in the meningitis belt, 2011-2016.

Background: Historically, the major cause of meningococcal epidemics in the meningitis belt of sub-Saharan Africa has been Neisseria meningitidis serogroup A (NmA), but the incidence has been substantially reduced since the introduction of a serogroup A conjugate vaccine starting in 2010. We performed whole-genome sequencing on isolates collected post-2010 to assess their phylogenetic relationships and inter-country transmission.

Methods: A total of 716 invasive meningococcal isolates collected between 2011 and 2016 from 11 meningitis belt countries were whole-genome sequenced for molecular characterization by the three WHO Collaborating Centers for Meningitis.

Draft Genome Sequences for a Diverse Set of Seven and Species.

is a complex genus that includes commensal and pathogenic species that pose a public health threat to humans. While the pathogenic species have been studied extensively, many commensals have limited genomic information available. Here, we present 24 draft genomes for a diverse set of 7 and species.

BMScan: using whole genome similarity to rapidly and accurately identify bacterial meningitis causing species.

Background: Bacterial meningitis is a life-threatening infection that remains a public health concern. Bacterial meningitis is commonly caused by the following species: Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Escherichia coli. Here, we describe BMScan (Bacterial Meningitis Scan), a whole-genome analysis tool for the species identification of bacterial meningitis-causing and closely-related pathogens, an essential step for case management and disease surveillance.