Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage

Abstract

SummaryObjectivesNeisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000–2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution.MethodsRepresentatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks.ResultsMenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the ‘Hajj outbreak’ strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct.ConclusionsHigh resolution ‘genomic’ multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally.

The Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection

“…Epidemiology has been dynamic in the last 5 years, with increased MenW circulation (W:2a:P1.5,2:ST-11 and W:2a: P1.2:ST-11 accounted for 78% of all isolates). In Argentina, the MenW strains are distinct from the MenW strain that was first identified in Europe following the Hajj pilgrimage in 2000 (the so-called Hajj outbreak strain) [35], as is also the case with the strains in Chile. Argentina recently announced the plan to introduce the quadrivalent conjugate vaccine for infants at 3, 5, and 15 months old, with an adolescent dose at 11 years.…”

“…In Brazil, MenC remains the most common cause of disease; disease due to MenW has not increased as much as in Argentina or Chile, although the same MenW strain is involved [35]. Infant immunization with MenC conjugate vaccine follows schedule of immunization at 3 and 5 months, with a booster dose at 12 months, and a single dose for toddlers ages 12-23 months, but without a 'catch-up' campaign in older age groups [36].…”

Meningococcal disease in the Middle East and Africa: Findings and updates from the Global Meningococcal Initiative

“…38 Modeling showed that follow-up vaccine strategies were needed to maintain protection and helped to inform current WHO MenA vaccine recommendations for sub-Saharan Africa. 41 The reasons for this rapid expansion are unclear and further investigation is required. In addition, a number of groups in the United Kingdom and France have recently noted that MenW ST-11 is associated with some unusual symptoms, such as septic arthritis.…”

Whole genome sequencing as a novel approach for characterising Neisseria meningitidis in Australia

“…For instance, meningococci belonging to cc11 have been isolated as expressing either a serogroup B, serogroup C or serogroup W capsule 14 .…”

“…The core genome of the meningococcus has been characterised and is defined by 1605 core loci 16 . Comparison of meningococcal core genomes has previously been used to characterise N. meningitidis isolates causing outbreaks and epidemics 14,17 . With the collaboration of PathWest and under the supervision of A/Prof Charlene Kahler (UWA), I was able to implement one such analysis in Australia, as described below.…”