Dataset Information

Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) Neisseria meningitidis clone in the African meningitis belt.

ABSTRACT: Countries of the African 'meningitis belt' are susceptible to meningococcal meningitis outbreaks. While in the past major epidemics have been primarily caused by serogroup A meningococci, W strains are currently responsible for most of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the first time in 2002, with the first meningitis cases caused by these bacteria reported in 2003. Here we describe results of a comparative whole-genome analysis of 74 W:ST-2881 strains isolated within the framework of two longitudinal colonization and disease studies conducted in Ghana and Burkina Faso. Genomic data indicate that the W:ST-2881 clone has emerged from Y:ST-175(CC175) bacteria by capsule switching. The circulating W:ST-2881 populations were composed of a variety of closely related but distinct genomic variants with no systematic differences between colonization and disease isolates. Two distinct and geographically clustered phylogenetic clonal variants were identified in Burkina Faso and a third in Ghana. On the basis of the presence or absence of 17 recombination fragments, the Ghanaian variant could be differentiated into five clusters. All 25 Ghanaian disease isolates clustered together with 23 out of 40 Ghanaian isolates associated with carriage within one cluster, indicating that W:ST-2881 clusters differ in virulence. More than half of the genes affected by horizontal gene transfer encoded proteins of the 'cell envelope' and the 'transport/binding protein' categories, which indicates that exchange of non-capsular antigens plays an important role in immune evasion.

SUBMITTER: Lamelas A

PROVIDER: S-EPMC5610715 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) <i>Neisseria meningitidis</i> clone in the African meningitis belt.

Lamelas Araceli A Hauser Julia J Dangy Jean-Pierre JP Hamid Abdul-Wahab M AM Röltgen Katharina K Abdul Sater Mohamad R MR Hodgson Abraham A Sie Ali A Junghanss Thomas T Harris Simon R SR Parkhill Julian J Bentley Stephen D SD Pluschke Gerd G

Microbial genomics 20170621 8

Countries of the African 'meningitis belt' are susceptible to meningococcal meningitis outbreaks. While in the past major epidemics have been primarily caused by serogroup A meningococci, W strains are currently responsible for most of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the first time in 2002, with the first meningitis cases caused by these bacteria reported in 2003. Here we describe ...[more]

PMID: 29026659

Similar Datasets

Project description:In the African "meningitis belt," outbreaks of meningococcal meningitis occur in cycles, representing a model for the role of host-pathogen interactions in epidemic processes. The periodicity of the epidemics is not well understood, nor is it currently possible to predict them. In our longitudinal colonization and disease surveys, we have observed waves of clonal replacement with the same serogroup, suggesting that immunity to noncapsular antigens plays a significant role in natural herd immunity. Here, through comparative genomic analysis of 100 meningococcal isolates, we provide a high-resolution view of the evolutionary changes that occurred during clonal replacement of a hypervirulent meningococcal clone (ST-7) by a descendant clone (ST-2859). We show that the majority of genetic changes are due to homologous recombination of laterally acquired DNA, with more than 20% of these events involving acquisition of DNA from other species. Signals of adaptation to evade herd immunity were indicated by genomic hot spots of recombination. Most striking is the high frequency of changes involving the pgl locus, which determines the glycosylation patterns of major protein antigens. High-frequency changes were also observed for genes involved in the regulation of pilus expression and the synthesis of Maf3 adhesins, highlighting the importance of these surface features in host-pathogen interaction and immune evasion. Importance: While established meningococcal capsule polysaccharide vaccines are protective through the induction of anticapsular antibodies, findings of our longitudinal studies in the African meningitis belt have indicated that immunity to noncapsular antigens plays a significant role in natural herd immunity. Our results show that meningococci evade herd immunity through the rapid homologous replacement of just a few key genomic loci that affect noncapsular cell surface components. Identification of recombination hot spots thus represents an eminent approach to gain insight into targets of protective natural immune responses. Moreover, our results highlight the role of the dynamics of the protein glycosylation repertoire in immune evasion by Neisseria meningitidis. These results have major implications for the design of next-generation protein-based subunit vaccines.

Project description:ObjectiveThe optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA) are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.MethodsThe model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection) using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.ResultsThe model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84) and incidence of invasive disease (mean R2 0.89). The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.DiscussionWe have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the feasibility and benefits of MenA vaccination strategies.

Dataset Information

Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) Neisseria meningitidis clone in the African meningitis belt.

Publications

Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175) <i>Neisseria meningitidis</i> clone in the African meningitis belt.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets