Abstract

Neisseria meningitidis, carried in the human nasopharynx asymptomatically by ~10% of the population, remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals. The epidemiology of invasive meningococcal disease (IMD) varies substantially by geography and over time and is now influenced by meningococcal vaccines and in 2020–2021 by COVID-19 pandemic containment measures. While 12 capsular groups, defined by capsular polysaccharide structures, can be expressed by N. meningitidis, groups A, B, and C historically caused most IMD. However, the use of mono-, bi-, and quadrivalent-polysaccharide-conjugate vaccines, the introduction of protein-based vaccines for group B, natural disease fluctuations, new drugs (e.g., eculizumab) that increase meningococcal susceptibility, changing transmission dynamics and meningococcal evolution are impacting the incidence of the capsular groups causing IMD. While the ability to spread and cause illness vary considerably, capsular groups W, X, and Y now cause significant IMD. In addition, group E and nongroupable meningococci have appeared as a cause of invasive disease, and a nongroupable N. meningitidis pathotype of the hypervirulent clonal complex 11 is causing sexually transmitted urethritis cases and outbreaks. Carriage and IMD of the previously “minor” N. meningitidis are reviewed and the need for polyvalent meningococcal vaccines emphasized.

Highlights

  • Neisseria meningitidis, a Gram-negative pathogen of humans, causes epidemic meningitis and rapidly fatal sepsis in many parts of the world

  • The acquisition of meningococci in the upper respiratory tract does not result in invasive disease, invasive meningococcal disease (IMD), even with antibiotic therapy and supportive care, has a mortality rate that remains at 10–15%

  • We provide an overview of carriage and invasive disease caused by “minor” N. meningitidis groups W, X, Y, and E

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Summary

Introduction

Neisseria meningitidis (the meningococcus), a Gram-negative pathogen of humans, causes epidemic meningitis and rapidly fatal sepsis in many parts of the world. Group A (MenA) N. meningitidis expressing a homopolymeric (α1 → 6) N-acetylmannosamine 1-phosphate capsule caused large pandemic outbreaks globally through much of the 20th century that persisted especially in the meningitis belt of sub-Saharan Africa until introduction of the. Meningococcal group E (MenE) expresses a capsule consisting of alternating D-galactosamine and 2-keto-3-deoxyoctulosonate (KDO) residues [5] and nongroupable (MenNG) strains, either with capsule null locus (cnl) or unencapsulated due to inactivation of capsule synthesis, rarely but are identified as a cause of invasive disease especially in immunocompromised individuals. We provide an overview of carriage and invasive disease caused by “minor” N. meningitidis groups W, X, Y, and E as well as nongroupable meningococci causing invasive disease and sexually transmitted infections.

Group W
Group X
Group Y
Group E
Nongroupable
Population
Meningococcal Vaccines
Findings
Conclusions
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