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

Mingliang Chen,Martin C J Maiden,Jian Chen,Min Chen,Chi Zhang,Tian Tan,Charlene M C Rodrigues,Odile B Harrison,Xi Zhang

doi:10.1038/s41598-018-30048-x

Mingliang Chen, Martin C J Maiden + Show 7 more

Open Access

https://doi.org/10.1038/s41598-018-30048-x

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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.

Highlights

Serogroup B invasive meningococcal disease (IMD) is increasing in China, but little is known about the causative meningococci
Epidemiology and characterisation of N. meningitidis isolates associated with IMD and carriage in Shanghai
This study provides a comparative analysis of IMD and meningococcal carriage isolates obtained in Shanghai, China, and the likely impact of novel vaccines on disease and carriage

Summary

Introduction

Serogroup B invasive meningococcal disease (IMD) is increasing in China, but little is known about the causative meningococci. In China, during the 1950s to 1980s, serogroup A (MenA) isolates were responsible for over 95% of cases[5], with incidence peaking in 1967 (403/100,000)[6] These were predominantly due to ST-5 clonal complex (cc5) and cc[17], and in response, a non-conjugate MenA meningococcal polysaccharide vaccine (MPV) was routinely administered from 1980 onwards[6,7]. Prevention of MenB IMD is challenging due to the poorly immunogenic serogroup B capsular polysaccharide and concerns about autoimmunity, due to its structural similarity to structures occurring on human tissue To address this deficit, two protein-based vaccines, Bexsero (4CMenB) and Trumenba (bivalent rLP2086), have been developed and licensed in Europe and the USA11,12. In response to increasing MenB IMD7, we assessed the potential impact of protein-based vaccines to local prevalent serogroups and clonal complexes

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