Invasive meningococcal disease in Shanghai, China from 1950 to 2016: implications for serogroup B vaccine implementation

Abstract

Serogroup B invasive meningococcal disease (IMD) is increasing in China, but little is known about the causative meningococci. Here, IMD and carriage isolates in Shanghai characterised and the applicability of different vaccines assessed. Seven IMD epidemic periods have been observed in Shanghai since 1950, with 460 isolates collected including 169 from IMD and 291 from carriage. Analyses were divided according to the period of meningococcal polysaccharide vaccine (MPV) introduction: (i) pre-MPV-A, 1965-1980; (ii) post-MPV-A, 1981-2008; and (iii) post-MPV-A + C, 2009-2016. Over this period, IMD incidence decreased from 55.4/100,000 to 0.71 then to 0.02, corresponding to successive changes in meningococcal type from serogroup A ST-5 complex (MenA:cc5) to MenC:cc4821, and finally MenB:cc4821. MenB IMD became predominant (63.2%) in the post-MPV-A + C period, and 50% of cases were caused by cc4821, with the highest incidence in infants (0.45/100,000) and a case-fatality rate of 9.5%. IMD was positively correlated with population carriage rates. Using the Bexsero Antigen Sequence Type (BAST) system, fewer than 25% of MenB isolates in the post-MPV-A + C period contained exact or predicted cross reactive matches to the vaccines Bexsero, Trumenba, or an outer membrane vesicle (OMV)-based vaccine, NonaMen. A unique IMD epidemiology was seen in China, changing periodically from epidemic to hyperepidemic and low-level endemic disease. At the time of writing, MenB IMD dominated IMD in Shanghai, with isolates potentially beyond coverage with licenced OMV- and protein-based MenB vaccines.

Figure 1

Invasive meningococcal disease incidence in Shanghai, China during 1950–2016, as reported in National Notifiable Diseases Registry System. The times of introduction of serogroup A (1980) and serogroups A and C polysaccharide vaccines (2008) in Shanghai, China were indicated with red arrow. Inset figure shows the incidence after 1970. The highest incidences in different epidemic period were labelled. MenA, serogroup A meningococcus; MPV, meningococcal polysaccharide vaccine.

Figure 2

Analysis of invasive meningococcal disease incidence in Shanghai, China by age group.

Figure 3

Seasonality of invasive meningococcal disease in Shanghai, China.

Figure 4

Relationship between invasive meningococcal disease incidence and meningococcal carriage rate observed in Shanghai, China.

Figure 5

Minimum-spanning tree analysis of multilocus sequence types of invasive and carriage N. meningitidis before and after introduction of meningococcal vaccines in China. Isolates were obtained during the pre-MPV-A (1965–1980), post-MPV-A (1981–2008), and post-MPV-A + C (2009–2016) periods. Sequence types (STs) are displayed as circles. The size of each circle indicates the number of isolates with this particular type. Serogroup is distinguished by different colours. The shaded halo surrounding the STs encompasses related sequence types that belong to the same clonal complex. Heavy solid lines represent single-locus variants, and light solid lines represent double-locus variants. Sequences types sharing no less than 4 loci, but not assigned to any clonal complexes in the PubMLST database were assigned to ST-clusters. NG, nongroupable.

Figure 6

Prevalence of peptide variants, and potentially immunologically cross-reactive variants, for three serogroup B-substitute vaccines (Bexsero, Trumenba, and NonaMen) among 460 invasive and carriage meningococci from Shanghai, China in the pre-MPV-A, post-MPV-A, and post-MPV-A + C periods. Bexsero and Trumenba are two protein-based serogroup B substitute meningococcal vaccines, which have been licensed in Europe and the USA, while NonaMen is a 9-valent investigational outer membrane vesicle (OMV) vaccine, which has undergone pre-clinical testing. Three periods were defined, pre-MPV-A (1965–1980), post-MPV-A (1981–2008), and post-MPV-A + C (2009–2016), according to the time of two meningococcal polysaccharide vaccines introduced in China (1980 serogroup A, 2008 A and C).