Article(id=1320438060030997007, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, articleNumber=null, orderNo=null, doi=10.11847/zgggws1147830, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1746460800000, receivedDateStr=2025-05-06, revisedDate=1754236800000, revisedDateStr=2025-08-04, acceptedDate=1756828800000, acceptedDateStr=2025-09-03, onlineDate=1792746566063, onlineDateStr=2026-10-23, pubDate=1773072000000, pubDateStr=2026-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792746566063, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792746566063, creator=13701087609, updateTime=1792746566063, updator=13701087609, issue=Issue{id=1320438006813672182, tenantId=1146029695717560320, journalId=1319373219989389464, year='2026', volume='42', issue='3', pageStart='257', pageEnd='384', issueExtLink='null', onlineDate='null', pubDate='1773072000000', pubDateStr='2026-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792746553376, creator='13701087609', updateTime=1792748100383, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320444495519404406, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320444495519404407, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1320438006813672182, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=359, endPage=364, ext={EN=ArticleExt(id=1320438060236517904, articleId=1320438060030997007, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Epidemiological and genomic analyses of Neisseria meningitidis serogroup B infection in Hebei province: a case report, columnId=1320427692466492070, journalTitle=Chinese Journal of Public Health, columnName=Public Health Field Report, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the epidemiological and etiological characteristics of a case of epidemic cerebrospinal meningitis caused by Neisseria meningitidis (Nm) serogroup B infection in a maternity center in Zhangjiakou city, Hebei province in 2024.

Methods

An epidemiological investigation was carried out for the case, and samples of the case and close contacts were collected for isolation and culture. The isolates were subjected to strain identification, serogroup identification, and antimicrobial susceptibility testing. Molecular typing, average nucleotide consistency (ANI) analysis, and single nucleotide polymorphism (SNP) analysis were performed with 13 Nm serogroup B strains (including cases, close contacts, and healthy people) collected in Hebei province, 2024.

Results

Both the isolates from the case in Zhangjiakou and the isolates from close contacts were Nm strains of the B serogroup. The results of antimicrobial susceptibility testing showed that the isolate from the case (HE2024ZJK001) and one close contact (HE2024ZJK002) were sensitive to cefotaxime, ceftriaxone, meropenem, azithromycin, minocycline, chloramphenicol, and rifampin, while they were not sensitive to ciprofloxacin, levofloxacin, compound sulfamethoxazole, ampicillin, or penicillin. Both HE2024ZJK001 and HE2024ZJK002 belonged to a new sequence type (ST) ST-18512 and the same clonal complex (CC) CC4821. In addition, the two strains showed the ProA typing results of P1.20, 23, H factor-binding protein of variant 2 (v2), the sub-variant of v2.16, and the NHBA amino acid type of Peptide 669, and neither carried the NadA gene. The results of phylogenetic analyses based on ANI and SNP showed that the Zhangjiakou isolates (HE2024ZJK001 and HE2024ZJK002) had the same source and were most closely related to the Shijiazhuang isolate in Hebei province (HE12NME031) and the Guangdong isolate (Nm441107).

Conclusions

This case has been the first epidemic cerebrospinal meningitis case in Zhangjiakou since 2011, and it occurs in a place where mothers and infants are crowded. The results suggest that in the future, the health monitoring, especially epidemic cerebrospinal meningitis monitoring, should be strengthened for special groups of infants and young children to prevent local outbreaks.

, authors=Ruoxuan WANG1, Yuwen CAO2, Zhaoyi JIA2, Baohua HE2, Hui LIU3, Hongmin FAN1, Yinqi SUN2, Qi LI2, authorsList=Ruoxuan WANG, Yuwen CAO, Zhaoyi JIA, Baohua HE, Hui LIU, Hongmin FAN, Yinqi SUN, Qi LI, authorCompany=null, correspAuthors=Yinqi SUN, Qi LI, authorNote=null, correspAuthorsNote=
SUN Yinqi, E-mail:
LI Qi, E-mail:
, copyrightStatement=Copyright © 2026 Chinese Journal of Public Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320438061192819221, articleId=1320438060030997007, tenantId=1146029695717560320, journalId=1319373219989389464, language=CN, title=河北省1例B群脑膜炎奈瑟菌感染病例流行病学和基因组学分析, columnId=1320427692667818664, journalTitle=中国公共卫生, columnName=公共卫生案例, runingTitle=null, highlight=null, articleAbstract=
目的

分析2024年河北省张家口市某月子中心1例B群脑膜炎奈瑟菌(Neisseria meningitidis, Nm)感染致流行性脑脊髓膜炎(简称“流脑”)病例的流行病学及病原学特征。

方法

对病例进行流行病学调查,采集病例和密切接触者的样本进行分离培养,对获得的分离株进行菌株鉴定和血清群分析及药物敏感性实验;与2024年河北省收集到的其他地市的13株B群Nm菌株(包括病例、密切接触者和健康人群)进行分子分型、平均核苷酸一致性(ANI)检验分析和单核苷酸多态性(SNP)分析。

结果

张家口病例分离株和密切接触者分离株均为B血清群Nm菌株。12种药物敏感性结果表明,分离自病例(HE2024ZJK001)与1例密切接触者(HE2024ZJK002)的分离株均对头孢噻肟、头孢曲松、美罗培南、阿奇霉素、米诺环素、氯霉素和利福平共7种药物敏感;对环丙沙星、左氧氟沙星、复方新诺明、氨苄西林和青霉素不敏感。HE2024ZJK001和HE2024ZJK002均属于新的序列型(sequence type,ST)即ST-18512,并且属于同一克隆群(CC)CC4821克隆群,ProA分型均为P1.20,23,FHbp(H因子结合蛋白)均为变异2型(v2),亚变型均是v2.16,NHBA氨基酸型为Peptide 669,均不含有NadA基因。ANI及SNP系统进化分析结果一致,表明张家口分离株(HE2024ZJK001、HE2024ZJK002)属于同一菌株,且与河北石家庄分离株(HE12NME031)、广东省分离株(Nm441107)亲缘关系最密切。

结论

此病例为张家口自2011年来首次出现的流脑病例,并且发生在月子中心这种母婴人员密集的场所;应进一步加强接触婴幼儿特殊人群的健康监测,特别是流脑的监测,防止出现局部暴发。

, authors=王若璇1, 曹玉雯2, 贾肇一2, 何宝花2, 刘会3, 范红敏1, 孙印旗2, *, *, 李琦2, *, *, authorsList=王若璇, 曹玉雯, 贾肇一, 何宝花, 刘会, 范红敏, 孙印旗, 李琦, authorCompany=null, correspAuthors=孙印旗, 李琦, authorNote=

王若璇(1999—),硕士在读,研究方向:流行病与卫生统计学

, correspAuthorsNote=
孙印旗,E-mail:
李琦,E-mail:
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王若璇(1999—),硕士在读,研究方向:流行病与卫生统计学

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注:由外向内顺序为国家(由外向内的渐变颜色)、重点菌株年份、序列型(菌株数大于5和重点菌株序列型)、重点菌株地区(被标记为特殊符号)、来源。

, figureFileSmall=xCZjJqsF+lRfii6VuMimew==, figureFileBig=zczYcKLKJC8wuTHNGld+CQ==, tableContent=null), ArticleFig(id=1320438066901267030, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320438060030997007, language=EN, label=Tab.1, caption=

Results of antimicrobial susceptibility testing of Neisseria meningitidis isolates from the case and close contacts

, figureFileSmall=null, figureFileBig=null, tableContent=
药物名称HE2024ZJK001HE2024ZJK002
MIC值/(µL/mL)药敏判定MIC值/(µL/mL)药敏判定
青霉素0.380R0.250I
氨苄西林0.500I0.750I
头孢噻肟<0.016S<0.016S
头孢曲松<0.016S<0.016S
美罗培南0.064S0.064S
阿奇霉素1.000S1.500S
米诺环素0.250S0.250S
环丙沙星0.380R0.380R
左氧氟沙星0.250R0.250R
复方新诺明≥32.000R≥32.000R
氯霉素1.500S1.500S
利福平0.032S0.032S
), ArticleFig(id=1320438066985153111, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320438060030997007, language=CN, label=表1, caption=

病例与密切接触者Nm分离株药敏实验结果

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药物名称HE2024ZJK001HE2024ZJK002
MIC值/(µL/mL)药敏判定MIC值/(µL/mL)药敏判定
青霉素0.380R0.250I
氨苄西林0.500I0.750I
头孢噻肟<0.016S<0.016S
头孢曲松<0.016S<0.016S
美罗培南0.064S0.064S
阿奇霉素1.000S1.500S
米诺环素0.250S0.250S
环丙沙星0.380R0.380R
左氧氟沙星0.250R0.250R
复方新诺明≥32.000R≥32.000R
氯霉素1.500S1.500S
利福平0.032S0.032S
), ArticleFig(id=1320438067056456280, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320438060030997007, language=EN, label=Tab.2, caption=

Basic information and molecular typing results of Neisseria meningitidis isolates in Hebei province

, figureFileSmall=null, figureFileBig=null, tableContent=
ID号样本编号地区来源多位点序列分析抗原基因
序列型(ST)克隆群(CC)PorA-VR1PorA-VR2FHbpNHBANadA
165016HE2024ZJK001张家口病例1851248212023v2.16669None
165017HE2024ZJK002张家口密接1851248212023v2.16669None
166643HE2024HS001衡水健康人群5819UA18-259-18v1.5711059None
166644HE2024DZ001定州健康人群14387UA5-32v2.2524None
166645HE2024DZ002定州健康人群14387UA5-32v2.2524None
166646HE2024DZ003定州健康人群14387UA5-32v2.2524None
166653HE2024CZ001沧州健康人群7962UA21-10newv2.16688None
165376HE2024CZ002沧州健康人群18590UA21-228v2.211060None
165377HE2024HD001邯郸健康人群18594UA5-1newv2.16newNone
166647HE2024BD002保定健康人群867441/4412-1513-78v2.5729None
166648HE2024BD003保定病例7962UA12-113-2v2.16688None
166649HE2024BD004保定密接7962UA12-113-2v2.16688None
166650HE2024BD005保定密接7962UA12-113-2v2.16688None
166651HE2024BD006保定病例566448212023-7v2.16910None
166652HE2024TS001唐山病例32327-223-6v2.101528None
), ArticleFig(id=1320438067144536665, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1320438060030997007, language=CN, label=表2, caption=

河北省Nm分离株基本信息及分子分型结果

, figureFileSmall=null, figureFileBig=null, tableContent=
ID号样本编号地区来源多位点序列分析抗原基因
序列型(ST)克隆群(CC)PorA-VR1PorA-VR2FHbpNHBANadA
165016HE2024ZJK001张家口病例1851248212023v2.16669None
165017HE2024ZJK002张家口密接1851248212023v2.16669None
166643HE2024HS001衡水健康人群5819UA18-259-18v1.5711059None
166644HE2024DZ001定州健康人群14387UA5-32v2.2524None
166645HE2024DZ002定州健康人群14387UA5-32v2.2524None
166646HE2024DZ003定州健康人群14387UA5-32v2.2524None
166653HE2024CZ001沧州健康人群7962UA21-10newv2.16688None
165376HE2024CZ002沧州健康人群18590UA21-228v2.211060None
165377HE2024HD001邯郸健康人群18594UA5-1newv2.16newNone
166647HE2024BD002保定健康人群867441/4412-1513-78v2.5729None
166648HE2024BD003保定病例7962UA12-113-2v2.16688None
166649HE2024BD004保定密接7962UA12-113-2v2.16688None
166650HE2024BD005保定密接7962UA12-113-2v2.16688None
166651HE2024BD006保定病例566448212023-7v2.16910None
166652HE2024TS001唐山病例32327-223-6v2.101528None
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河北省1例B群脑膜炎奈瑟菌感染病例流行病学和基因组学分析
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王若璇 1 , 曹玉雯 2 , 贾肇一 2 , 何宝花 2 , 刘会 3 , 范红敏 1 , 孙印旗 2, *, * , 李琦 2, *, *
中国公共卫生 | 公共卫生案例 2026,42(3): 359-364
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中国公共卫生 |公共卫生案例 2026 , 42 (3) : 359 -364
河北省1例B群脑膜炎奈瑟菌感染病例流行病学和基因组学分析
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王若璇1, 曹玉雯2, 贾肇一2, 何宝花2, 刘会3, 范红敏1, 孙印旗2, *, * , 李琦2, *, *
作者信息
  • 1华北理工大学公共卫生学院,唐山 063210
  • 2河北省疾病预防控制中心 河北省传染病病原鉴定分析与流行病学重点实验室,石家庄 050021
  • 3张家口市疾病预防控制中心,张家口 075000
通讯作者:
孙印旗,E-mail:
李琦,E-mail:
作者简介:

王若璇(1999—),硕士在读,研究方向:流行病与卫生统计学

Epidemiological and genomic analyses of Neisseria meningitidis serogroup B infection in Hebei province: a case report
Ruoxuan WANG1, Yuwen CAO2, Zhaoyi JIA2, Baohua HE2, Hui LIU3, Hongmin FAN1, Yinqi SUN2 , Qi LI2
Affiliations
  • 1School of Public Health, North China University of Science and Technology, Tangshan 063210, China
  • 2Hebei Key Laboratory of Pathogens and Epidemiology of Infectious Diseases, Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, China
  • 3Zhangjiakou Center for Disease Control and Prevention, Zhangjiakou 075000, China
  • Corresponding Author:
    SUN Yinqi, E-mail:
    LI Qi, E-mail:
出版时间: 2026-03-10 doi: 10.11847/zgggws1147830
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目的

分析2024年河北省张家口市某月子中心1例B群脑膜炎奈瑟菌(Neisseria meningitidis, Nm)感染致流行性脑脊髓膜炎(简称“流脑”)病例的流行病学及病原学特征。

方法

对病例进行流行病学调查,采集病例和密切接触者的样本进行分离培养,对获得的分离株进行菌株鉴定和血清群分析及药物敏感性实验;与2024年河北省收集到的其他地市的13株B群Nm菌株(包括病例、密切接触者和健康人群)进行分子分型、平均核苷酸一致性(ANI)检验分析和单核苷酸多态性(SNP)分析。

结果

张家口病例分离株和密切接触者分离株均为B血清群Nm菌株。12种药物敏感性结果表明,分离自病例(HE2024ZJK001)与1例密切接触者(HE2024ZJK002)的分离株均对头孢噻肟、头孢曲松、美罗培南、阿奇霉素、米诺环素、氯霉素和利福平共7种药物敏感;对环丙沙星、左氧氟沙星、复方新诺明、氨苄西林和青霉素不敏感。HE2024ZJK001和HE2024ZJK002均属于新的序列型(sequence type,ST)即ST-18512,并且属于同一克隆群(CC)CC4821克隆群,ProA分型均为P1.20,23,FHbp(H因子结合蛋白)均为变异2型(v2),亚变型均是v2.16,NHBA氨基酸型为Peptide 669,均不含有NadA基因。ANI及SNP系统进化分析结果一致,表明张家口分离株(HE2024ZJK001、HE2024ZJK002)属于同一菌株,且与河北石家庄分离株(HE12NME031)、广东省分离株(Nm441107)亲缘关系最密切。

结论

此病例为张家口自2011年来首次出现的流脑病例,并且发生在月子中心这种母婴人员密集的场所;应进一步加强接触婴幼儿特殊人群的健康监测,特别是流脑的监测,防止出现局部暴发。

流行性脑脊髓膜炎  /  脑膜炎奈瑟菌  /  B血清群  /  CC4821  /  多位点序列分型
Objective

To analyze the epidemiological and etiological characteristics of a case of epidemic cerebrospinal meningitis caused by Neisseria meningitidis (Nm) serogroup B infection in a maternity center in Zhangjiakou city, Hebei province in 2024.

Methods

An epidemiological investigation was carried out for the case, and samples of the case and close contacts were collected for isolation and culture. The isolates were subjected to strain identification, serogroup identification, and antimicrobial susceptibility testing. Molecular typing, average nucleotide consistency (ANI) analysis, and single nucleotide polymorphism (SNP) analysis were performed with 13 Nm serogroup B strains (including cases, close contacts, and healthy people) collected in Hebei province, 2024.

Results

Both the isolates from the case in Zhangjiakou and the isolates from close contacts were Nm strains of the B serogroup. The results of antimicrobial susceptibility testing showed that the isolate from the case (HE2024ZJK001) and one close contact (HE2024ZJK002) were sensitive to cefotaxime, ceftriaxone, meropenem, azithromycin, minocycline, chloramphenicol, and rifampin, while they were not sensitive to ciprofloxacin, levofloxacin, compound sulfamethoxazole, ampicillin, or penicillin. Both HE2024ZJK001 and HE2024ZJK002 belonged to a new sequence type (ST) ST-18512 and the same clonal complex (CC) CC4821. In addition, the two strains showed the ProA typing results of P1.20, 23, H factor-binding protein of variant 2 (v2), the sub-variant of v2.16, and the NHBA amino acid type of Peptide 669, and neither carried the NadA gene. The results of phylogenetic analyses based on ANI and SNP showed that the Zhangjiakou isolates (HE2024ZJK001 and HE2024ZJK002) had the same source and were most closely related to the Shijiazhuang isolate in Hebei province (HE12NME031) and the Guangdong isolate (Nm441107).

Conclusions

This case has been the first epidemic cerebrospinal meningitis case in Zhangjiakou since 2011, and it occurs in a place where mothers and infants are crowded. The results suggest that in the future, the health monitoring, especially epidemic cerebrospinal meningitis monitoring, should be strengthened for special groups of infants and young children to prevent local outbreaks.

epidemic cerebrospinal meningitis  /  Neisseria meningitidis  /  serogroup B  /  CC4821  /  multilocus sequence typing
王若璇, 曹玉雯, 贾肇一, 何宝花, 刘会, 范红敏, 孙印旗, 李琦. 河北省1例B群脑膜炎奈瑟菌感染病例流行病学和基因组学分析. 中国公共卫生, 2026 , 42 (3) : 359 -364 . DOI: 10.11847/zgggws1147830
Ruoxuan WANG, Yuwen CAO, Zhaoyi JIA, Baohua HE, Hui LIU, Hongmin FAN, Yinqi SUN, Qi LI. Epidemiological and genomic analyses of Neisseria meningitidis serogroup B infection in Hebei province: a case report[J]. Chinese Journal of Public Health, 2026 , 42 (3) : 359 -364 . DOI: 10.11847/zgggws1147830
流行性脑脊髓膜炎(简称“流脑”)是由脑膜炎奈瑟菌(Neisseria meningitidis, Nm)简称脑膜炎球菌引起的急性化脓性中枢神经系统感染,发病具有病程进展快、传染性强、隐性感染率高和病死率高等特点[1]。流脑病死率在全球范围内超过10%,致残率约为10%~20%,造成了严重的疾病负担[2]。人群普遍易感,尤其儿童感染后易发病,成人与儿童相比有较强的免疫力,感染病菌后仅有1%~2%会发生脑膜炎,并且健康人群有一定的Nm携带率[3]。根据细菌表面荚膜多糖的结构和特性,Nm分为12个血清群,还有许多菌株不可进行血清群分群,因而被称为不可分群,通常引起流脑的为A、B、C、X、W、Y群[4]。流脑血清群不断变迁,我国A群和C群随着针对的疫苗接种病例数逐渐下降,而B群发病率呈上升趋势[5],河北省的血清群变化趋势亦如此,B群Nm已逐渐成为河北省的流行菌株[6]。本研究对河北省张家口市1例流脑病例进行流行病学调查,结合其流行病学特征、临床表现与实验室检测结果,证实为B群Nm感染引起的流脑病例。对病例和密切接触者的分离株进行菌株的种属鉴定、血清学分型、药物敏感性实验和基因测序和基因组特征分析,并与选取的同克隆群菌株进行遗传进化关系比对,为监测和防控流脑疫情提供科学依据。
2024年8月河北省张家口市确诊的1例B群流脑感染患儿。病例男婴,于2024年7月21日在张家口出生,出生后健康情况良好。7月25日出院,由月子会所专车接入会所,直至出现症状前一直由月嫂一对一照料。患儿于8月17日突发高热(体温38.9 ℃)、恶心呕吐、颈项强直,皮肤出现少量瘀点瘀斑,于发病2 h内送往某医院就诊,8月20日患儿被确诊为流脑。医院给予患儿美罗培南和万古霉素治疗,预后良好。
8月21日张家口市疾控中心收集患儿血清、脑脊液样本及阳性培养物,当日送河北省疾病预防控制中心检测,22日反馈结果为B群Nm菌株。对此病例分离菌株和从病例密切接触者(以下简称“密接”)样本中分离出的1株B群菌株进行病原学及基因组学分析,同时将2024年河北省收集到的来自其他地区的流脑病例的3株B群Nm菌株(保定2株、唐山1株),分离自病例密接的2株B群Nm(保定2株)以及健康带菌者的8株B群Nm(保定1株、邯郸1株、衡水1株、定州3株、沧州2株),共13株B群Nm菌株与本次分离的2株B群Nm菌株进行对比分析。本研究经河北省疾病预防控制中心伦理委员会审查通过[编号:IRB(S)2020-007]。
2024年8月20日12时河北省张家口市疾病预防控制中心接到桥西区疾控中心报告后,疾病预防控制中心人员立即按照《全国流行性脑脊髓膜炎监测方案》,对病例进行流行病学调查,了解病例的基本情况、临床表现和就(确)诊经过等,收集病例临床样本(血液/脑脊液等)进行Nm;调查病例密切接触者,共采集密接人员(家人朋友6人、月子中心工作人员4人、摄影师2人、月嫂1人)13份咽拭子样本培养Nm。用含氯消毒剂物表擦拭病例接触过的物品,场所每日开窗通风;实施涉疫场所(月子中心)关停措施;指导患儿密接人员做好自我健康监测,阳性分离株者予以预防性服药。
MH血平板、巧克力平板和巧克力双抗平板(广州市迪景微生物科技有限公司);Nm分群诊断血清(美国REMEL公司);Nm种属鉴定和血清分群核酸检测试剂盒(江苏硕世生物科技股份有限公司);E-test药敏试纸条(意大利Liofilchem公司);核酸提取试剂(江苏硕世生物科技股份有限公司)。
CO2培养箱(日本三洋公司);QuantStudio 5荧光定量PCR扩增仪(新加坡Life Technologies公司);MALDI-TOF-MS微生物质谱仪(重庆市中元汇吉生物技术股份有限公司);超微量紫外线分光光度计(杭州米欧仪器有限公司);荧光定量仪Qubit 4.0(美国赛默飞世尔科技公司)。
在无菌操作下,将阳性血培养瓶中液体转种至血平板;密切接触者咽拭子样本接种于巧克力双抗平板,保温运送至实验室,放入37 ℃、5% CO2培养箱中培养20 h,从平板上挑出特征性菌落继续传代培养,挑选可疑菌落,均匀涂布于质谱仪的靶点上,经质谱仪鉴定后,将Nm转种至血平板,之后采用玻片凝集法鉴定血清群。根据Nm种属鉴定和血清分群核酸检测试剂盒说明书,鉴定real-time PCR种属和血清群。
采用E-test试纸条法对此次分离株进行药物敏感性试验。将血平板上菌株转种至巧克力平板,之后用生理盐水配制0.5麦氏单位的菌悬液,将E-test试纸条平整贴于已均匀涂布菌液的MH血平板,置于5% CO2培养箱中,37 ℃培养20 h,观察结果读取最小抑菌浓度(minimal inhibitory concentration, MIC)。按照最新美国临床实验室标准化协会(Clinical and Laboratory Standards Institute, CLSI)标准判定为敏感、中介和耐药。质控菌株为肺炎链球菌ATCC 49619和大肠埃希菌ATCC 25922。
将提取浓度和纯度合格的Nm菌株DNA样品随机打断成长度为350 bp左右的片段,运用Illumina Nextseq 2000平台测序,将测序得到的低质量原始数据(raw data)过滤掉,从而获得结果更加可靠的数据(clean data),随后使用SPAdes 3.15.2组装软件[7],组装预处理后的clean data,最后获得每株菌株的contigs序列文件。
将组装好的fasta数据文件上传至Pub MLST(https://pubmlst.org/)网站,分别进行菌株多位点序列分型(multilocus sequence typing, MLST)和外膜蛋白PorA分型;蛋白疫苗相关蛋白基因序列分析,主要包括相关3种蛋白成分:FHbp(H因子结合蛋白)、NadA(奈瑟菌黏附蛋白A)、NHBA(奈瑟菌肝素结合蛋白A)。
采用Pyani软件(版本0.2.12)将2株(病例菌株和密接菌株)与国内2024年5株(包括河北省内1株和河北省外4株)CC4821克隆群B群Nm菌株共同分析平均核苷酸一致性(average nucleotide identity, ANI),并采用ChiPlot(https://www.chiplot.online/)网站将分析结果做成可视化热图。
采用MUMmer软件(版本3.23)将河北省张家口2株分离株与在PubMLST网站上下载的国内外B群Nm所有CC4821克隆群共163株B群Nm菌株共同分析单核苷酸多态性(single nucleotide polymorphism, SNP),并以FastTree软件构建系统进化树,同样利用ChiPlot网站美化处理进化树。
病例阳性血培养样本分离到1株可疑菌株,经质谱仪鉴定为Nm(HE2024ZJK001),鉴定分值>2.20;经玻片凝集试验和实时荧光定量PCR血清群鉴定均为B群。13份密切接触者样本中分离出1株Nm(HE2024ZJK002),该分离株来自月嫂,血清群鉴定结果同样为B群。
2株Nm药敏情况基本一致,对头孢噻肟、头孢曲松、美罗培南、阿奇霉素、米诺环素、氯霉素和利福平7种药物敏感,对环丙沙星、左氧氟沙星、复方新诺明、氨苄西林和青霉素耐药不敏感。
张家口2株分离株(HE2024ZJK001、HE2024ZJK002)分子分型在PubMLST数据库中属于一个新的序列型(sequence type, ST)即ST-18512,均属于同一克隆群(clonal complex, CC)CC4821克隆群。HE2024ZJK001和HE2024ZJK002的PorA型别一致为P120, 23。河北省2024年分离株PorA蛋白型别基本情况为:15株B群Nm菌株共有10种PorA型别,PorA 2个变异区(VR1和VR2)分别各有10种不同的型别。不同克隆群Nm菌株PorA型别有差异,CC4821克隆群常见的PorA型别为P1.20, 23,其余克隆群PorA型别多态性高。不同来源的PorA型别分布明显不同。HE2024ZJK001和HE2024ZJK002的FHbp型别均为变异2型(variant2, v2),亚变型均是v2.16。总体上看河北省2024年Nm菌株除衡水分离株(HE2024HS001)是变异1型(variant1, v1),其余菌株均是v2,最常见的型别是v2.16(53.3%,8株)。CC4821克隆群FHbp型别均为v2.16。来源为病例的分离株优势型别为v2.16(75%,3株)。NHBA型别从地区、来源和克隆群上来看,分布明显不同,均具有多态性。张家口2株NHBA氨基酸型均为Peptide669。纳入分析的河北省菌株均不含有NadA基因。
张家口2株分离株和2024年国内CC4821克隆群B群Nm分离株ANI值均≥98.73%。HE2024ZJK001与HE2024ZJK002的ANI值为99.99%,提示这2株菌株可能为同一来源菌株;山东省威海的病例分离株(SD24WH0038NM)与密接分离株(SD24WH0084NM~SD24WH0086NM)ANI值均≥99.83%,提示可能为同一来源菌株。聚类结果显示HE2024ZJK001和HE2024ZJK002、SD24WH0038NM和SD24WH0084NM~SD24WH0086NM、HB2024BD006分别聚集成簇。聚类分析分为两大分支,一支是河北张家口(HE2024ZJK001、HE2024ZJK002)与河北保定(HE2024BD006)的菌株,显示亲缘关系较密切;另一支由山东威海(SD24WH0038NM和SD24WH0084NM~SD24WH0086NM)菌株相聚成簇,其关系更为紧密。
HE2024ZJK001、HE2024ZJK002与大多数国内菌株相聚成簇,关系密切。HE2024ZJK001和HE2024ZJK002在同一分支,河北石家庄分离株(HE12NME031)、广东省分离株(Nm441107)与HE2024ZJK001、HE2024ZJK002亲缘关系最紧密。其次,湖北省分离株(421007)与HE2024ZJK001、HE2024ZJK002亲缘关系较为密切。HE2024ZJK001和HE2024ZJK002相差0个SNP,提示其为同一来源菌株。
流脑是我国重点监测的呼吸道传染病,随着A群和C群流脑疫苗常规接种,河北省A群和C群的流脑病例逐年下降。2011年河北省首例B群流脑病例被发现[8],紧接着B群流脑病例占比开始逐渐增加。目前,B群Nm已经成为全球最流行的菌群,报告B群比例最高的地区为欧洲,其次是北美洲、亚洲和非洲地区,国际上主要流行的克隆群有CC41/44、CC32、CC269、CC213等[9]。不同于国际上流行的克隆群,中国B群主要流行的克隆群为CC4821。本研究分析的张家口2株Nm菌株克隆群均为CC4821,且纳入研究的河北省B群Nm菌株在MLST可分群部分中,CC4821占比最高,与相关文献报道的中国B群最流行的克隆群为CC4821的结论一致[10]。
流行病学调查发现,本次张家口B群Nm病例患儿,所接触场所只有出生医院与月子中心,未接触过疑似病例,可以判定为本地感染病例。在密接人员月嫂咽拭子样本中检出B群Nm菌株,分子分型与病例B群Nm菌株完全一致,ANI和SNP分析结果为同一来源菌株,推断可能是月嫂传染给了患儿;由于健康人可以正常携带Nm菌株,所以作为成年人的月嫂可表现为无任何症状,但对于刚出生的婴儿来说,其免疫系统尚未发育完全,所以感染后极易出现临床症状。
药物敏感性实验结果表明,张家口病例患儿分离株(HE2024ZJK001)对环丙沙星、左氧氟沙星、复方新诺明、氨苄西林和青霉素表现为不敏感,但对第3代头孢菌素、美罗培南、阿奇霉素等抗菌药物敏感,可提示临床医生选择合适抗生素进行治疗。河北省早在2011年已经出现了对青霉素不敏感的B群Nm菌株[11],2014年中国首次报道从B群流脑病例分离出对青霉素耐药的菌株[12]。首选药物的敏感性降低,提示今后应加强对B群Nm菌株耐药情况的监测,从而指导临床合理用药。
本研究对于HE2024ZJK001与HE2024ZJK002菌株的病原学特征采用两种基因组亲缘关系分析方式,首先是对2024年全年国内B群CC4821菌株进行ANI分析,其次是对自PubMLST数据库录入首株CC4821的B群Nm菌株(1976—2025年)以来的国内外B群CC4821菌株共同进行SNP分析。ANI分析从基因组水平,通过计算基因组的相似性评估物种间的亲缘关系,相同物种的基因组ANI大于95%,不同物种的基因组ANI小于95%,因此常以95%的ANI作为物种划分与物种聚类的标准,对于近源物种间有较高的区分度[13]。SNP分析从基因的核苷酸水平对菌株进行分型鉴定,具有更高的分辨率,对于菌株的遗传进化和流行病学溯源调查等方面有重要作用[14]。经基因组分析发现,张家口2株分离株ANI值为99.99%,说明HE2024ZJK001与HE2024ZJK002基因组几乎完全相同,差异可能来源于测序误差[13],因而提示这2株Nm为同一来源株菌;同时SNP研究结果HE2024ZJK001与HE2024ZJK002之间相差0个SNP,进一步证明二者为同一来源株菌。SNP分析结果中B群CC4821克隆群分为3个分支(Ⅰ、Ⅱ和Ⅲ),其中菌株来源大多为国内,在3个分支上均有分布,国外菌株则主要聚集于分支Ⅱ。位于分支Ⅰ的分离株均为国内菌株且大多来自上海市,主要流行的型别为ST-5789;分支Ⅱ上国外菌株和国内菌株均有分布,流行的型别主要为ST-3200;分支III除一支越南菌株外,其余均为国内菌株,主要流行的型别为ST-5664和ST-4821。以上结果表明不同地区B群Nm菌株的型别分布呈现多元化,重点关注各地区菌株的流行特征,对于制定适合本地的流脑防控策略至关重要。
当前国际交流越发密切,为传染病病原传播提供了便利条件,由B群脑膜炎奈瑟菌引发的流脑疫情增多,尤其是小年龄儿童,研发符合我国流行特征的B群流脑疫苗意义重大。A、C、W、Y群脑膜炎球菌疫苗成分是基于细菌表面的荚膜多糖或者将荚膜多糖和载体蛋白共价结合,已成功上市应用多年[1]。B群Nm荚膜多糖与人神经细胞分子结构相似,作为疫苗成分,人体可能会导致自身免疫性疾病[15–16]。目前在国内B群疫苗尚未上市,国外已经有针对B群流脑上市的疫苗,该疫苗是基于多个蛋白抗原成分[17–19]。本次SNP分析可知B群CC4821克隆群在国内外均有流行,国内主要流行的型别为ST-5798,同时ST-5664、ST-3200和ST-4821也有多数分布;国外主要流行的型别为ST-3200,其次为ST-3469和ST-6595,说明国内外B群CC4821克隆群流行特征不一致,相关研究也支持此结论[20]。国内外流行的B群Nm菌株存在基因型别和抗原表达的差异,导致国外的现有的B群流脑疫苗不能直接在国内应用。因此需要依据我国B群Nm流行株的抗原基因特点研发适合实际情况的B群流脑疫苗,从而有效防控我国B群流脑可能出现的新流行态势。
本研究是对1例月嫂传染给婴儿的散发型流脑病例进行流行病学调查和病原学特征分析。近年来,母婴密集场所的流脑病例时有发生,我国现有免疫程序的流脑疫苗无法覆盖B群Nm,因此有必要加强重点场所健康人群Nm携带情况的调查,及时掌握本地流脑菌群的变迁和流行菌株的病原学特征,尽早采取针对性的措施预防和控制流脑的发生,也提示应加强月嫂市场的健康监管。

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2026年第42卷第3期
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doi: 10.11847/zgggws1147830
  • 接收时间:2025-05-06
  • 首发时间:2026-10-23
  • 出版时间:2026-03-10
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  • 收稿日期:2025-05-06
  • 修回日期:2025-08-04
  • 录用日期:2025-09-03
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    1华北理工大学公共卫生学院,唐山 063210
    2河北省疾病预防控制中心 河北省传染病病原鉴定分析与流行病学重点实验室,石家庄 050021
    3张家口市疾病预防控制中心,张家口 075000

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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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