Phylodynamic analysis of a prolonged meningococcal epidemic reveals multiple introductions and pre-epidemic expansion

Abstract

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a form of bacterial meningitis and septicaemia, leading to isolated cases, outbreaks, and epidemics worldwide. Between 1991 and 2008, Aotearoa/New Zealand (NZ) experienced a prolonged hyperendemic group B IMD outbreak caused by the NZMenB epidemic strain, belonging to clonal-complex 41/44 (cc41/44) and identified by the PorA variant P1.7-2,4 (B:4:P1.7-2,4:cc41/44). NZMenB continues to account for approximately one-quarter of group B meningococcal disease cases in NZ. To understand NZMenB origin and initiation we used phylodynamic tools to analyse approximately 97 % of all NZMenB isolates submitted to the NZ Meningococcal Reference Laboratory from 1990 to 2019. We found NZMenB can be divided into three major clades: clade41, clade154, and clade42, each with distinct origins and expansion patterns. Our evidence from molecular dating and clonal expansion analysis suggests that NZMenB was circulating and had expanded before the epidemic. Comparison with international data showed multiple importations and re-introductions of NZMenB into NZ, while not suggesting close relationships with international variants. The recent COVID-19 health emergency and differing governmental responses have brought societal and environmental contributions to epidemics and pandemics into focus. We propose the NZMenB epidemic may have been triggered by increasing societal inequality and household crowding resulting from government policies at the time.

Keywords: NZMenB epidemic; Neisseria meningitidis; Phylodynamic analysis; Population genomics; Spatiotemporal evolution; Whole genome sequencing.