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.

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%–100%) for N. meningitidis, 97.8% (85.5%–99.9%) for S. pneumoniae, and 66.7% (9.4%–99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.

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The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil.

Meningococcal disease is characterized by cyclic fluctuations in incidence, serogroup distribution, and antigenic profiles. In greater São Paulo, Brazil, there has been a constant increase in the incidence of serogroup C meningococcal disease since the late 1980s. To gain an understanding of changes in serogroup C meningococcal disease over three decades in greater São Paulo, Brazil, 1,059 invasive Neisseria meningitidis serogroup C isolates from 1976 and 2005 were analyzed. Three major clone complexes, sequence type (ST)-11, ST-8, and ST-103, were identified by multilocus sequence typing, and the isolates were characterized by serotyping and 16S rRNA typing. During the 30-year period, there were two major antigenic replacements: from 2a:P1.(5,2) to 2b:P1.3 and subsequently to 23:P1.14-6. All strains of clone ST-103 were characterized as serotype 23 and serosubtype P1.14-6. The origin of 23:P1.14-6 ST-103 complex strains is unknown, but efforts are needed to monitor its spread and define its virulence. The antigenic replacements we observed likely represent a mechanism to sustain meningococcal disease in the population as immunity to circulating strains accumulated.

Polysaccharide vaccine did not affect carriage nor interrupt transmission of an epidemic strain.

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