中国W群脑膜炎奈瑟菌分子流行病学特征

Molecular epidemiological characteristics of serogroup W Neisseria meningitidis in China

目的分析中国W群脑膜炎奈瑟菌(Neisseria meningitidis,Nm)的分子流行病学特征。方法选择1979-2018年分离于中国19个省份的流行性脑脊髓膜炎(流脑)病例和健康携带者W群Nm菌株,进行多位点序列分型(MLST),分析序列型(ST型)并构建最小生成树,以及分析部分菌株疫苗相关蛋白PorA(114株)、FHbp(93株)、NadA(52株)和NHBA(51株)的分子型别和序列特征。结果共获得246株W群Nm,其中流脑病例19株、健康携带者227株。所有菌株分为24种ST型,其中20种(240株)可归入5个已知克隆群—CC11、CC4821、CC174、CC175和CC5,4种(6株)不能归入任何克隆群。健康携带者Nm菌株的克隆群2004年前主要为CC174(7株),2005年后主要为CC11(121株)和CC4821(73株)。流脑病例Nm菌株的PorA型主要为P1.5,2(16株)、P1.5-3,10-2(1株)。93条完整的FHbp蛋白氨基酸序列分为变异2型(91株)、变异1型(1株)和变异3型(1株)。52株检测菌株中32株含有nadA基因,其中30株属于CC11,均为NadA-2/3型。51条NHBA氨基酸序列包括6种型别,主要为29型(28株)和697型(18株)。结论2005年后中国W群Nm主要流行克隆群发生变化,以CC11和CC4821为主且其疫苗相关蛋白多态性较强;应更有针对性地研发疫苗或开展通用疫苗研究。

Objective To analyze molecular epidemiological characteristics of serogroup W Neisseria meningitides(Nm)in China.Methods We obtained serogroup W Nm strains isolated from meningococcal meningitis(MM)cases and healthy carriers during 1979-2018 from 19 provinces of China for multilocus sequence typing(MLST)to determine sequence types(ST)and construct a minimum spanning tree.We analyzed genetic diversity of vaccine-related proteins including PorA(114 strains),FHbp(93 strains),NadA(52 strains),and NHBA(51 strains).Results A total of 246 serogroup W Nm strains were obtained,19 from MM cases and 227 from healthy carriers.All strains were identified as one of 24 STs,among which 20 STs(240 strains)were categorized into 5 known clonal complexes(CCs)—CC11,CC4821,CC174,CC175,and CC5;4 STs(6 strains)could not be categorized into any CC.Before 2004,the most common CCs from healthy carriers were CC174(7 strains),and from 2005 onward,the most common were CC11(121 strains)and CC4821(73 strains).The common PorA types of serogroup W Nm strains from MM cases were P1.5,2(16 strains)and P1.5-3,10-2(1 strain).Ninety-three complete FHbp amino acid sequences were divided into variant type 2(91 strains),variant type 1(1 strain),and variant type 3(1 strain).Among 52 strains detected,32 comprised nadA genes of which 30 strains belonged to CC11 and NadA-2/3.The 51 amino acid sequences of NHBA comprised 6 peptide types with common types being type 29(28 strains)and type 697(18 strains).Conclusions The predominant clonal complexes of serogroup W Nm in China have changed to CC11 and CC4821 since 2005;their vaccine-related proteins have diverse polymorphisms.We suggest to conduct research and development of a more targeted or universal vaccine against meningococcal disease.