ABSTRACT
Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n = 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (n = 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.
Subject(s)
Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/microbiology , Genetic Variation , Meningococcal Infections/epidemiology , Meningococcal Infections/microbiology , Neisseria meningitidis, Serogroup Y/classification , Neisseria meningitidis, Serogroup Y/genetics , Genome, Bacterial , Humans , Molecular Epidemiology , Molecular Sequence Data , Neisseria meningitidis, Serogroup Y/isolation & purification , Phylogeography , Sequence Analysis, DNA , Sweden/epidemiologyABSTRACT
It is essential in an outbreak investigation that strain characterization of Neisseria meningitidis is performed in a rapid and accurate manner. This study evaluated two new molecular typing methods, multiple-locus variable number tandem repeat analysis (MLVA) and repetitive sequence-based PCR (rep-PCR) (DiversiLab; bioMérieux) and compared them with current recommended methodologies. This retrospective study included 36 invasive N. meningitidis serogroup C isolates collected in Sweden 2001 through 2009 and previously subjected to outbreak investigation. All strains were typed with highly variable-MLVA (HV-MLVA) and rep-PCR. The isolates were further characterized by multilocus sequence typing (MLST) and sequencing of the fetA, fHbp, penA, porA and porB genes. The results showed that HV-MLVA had the highest index of diversity (0.99) and rep-PCR had the highest congruence (40%) with the currently recommended typing methods. The HV-MLVA correlated best to the spatiotemporal connections and had the overall highest Adjusted Wallace coefficients, suggesting that HV-MLVA can predict the results of the other typing methods in the study. We therefore suggest that after initial confirmation of species, serogroup and genosubtype, HV-MLVA should be used as the most discriminatory method for first hand investigation of N. meningitidis serogroup C isolates.
