我国脑膜炎奈瑟菌孔蛋白PorA、PorB的多态性分析

目的以蛋白质组学研究为基础,分析2003—2005年我国流脑暴发流行期间C群脑膜炎奈瑟菌菌株特征,建立以致病性相关蛋白多态性为目标的新分型方法。方法利用双向电泳和MALDI-TOF质谱鉴定分析2003—2005年流脑流行期内分离的66株C群脑膜炎奈瑟菌菌株及2株参考菌株的蛋白表达,重点分析与致病性相关的蛋白多态性特征。结果根据孔蛋白PorA、PorB在双向电泳中的多态性,建立了12个特征菌型。安徽菌株的PorA和PorB蛋白电泳谱型显示出了高度的一致性,而其他地区的菌株则显示出高度的多态性。结论PorA和PorB蛋白2-DE电泳谱型可以作为一种新的菌株分型方法,可能在菌型变迁检测和流脑暴发预警中具有重要应用前景。     

Gram-negative bacteria induce proinflammatory cytokine production by monocytes in the absence of lipopolysaccharide (LPS)

Tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-6 production by human monocytes in response to a clinical strain of the Gram-negative encapsulated bacteria Neisseria meningitidis and an isogenic lpxA- strain deficient in LPS was investigated. Wild-type N. meningitidis at concentrations between 105 and 108 organisms/ml and purified LPS induced proinflammatory cytokine production. High levels of these cytokines were also produced in response to the lpxA- strain at 107 and 108 organisms/ml. The specific LPS antagonist bactericidal/permeability-increasing protein (rBPI21) inhibited cytokine production induced by LPS and wild-type bacteria at 105 organisms/ml but not at higher concentrations, and not by LPS-deficient bacteria at any concentration. These data show that proinflammatory cytokine production by monocytes in response to N. meningitidis does not require the presence of LPS. Therapeutic strategies designed to block LPS alone may not therefore be sufficient for interrupting the inflammatory response in severe meningococcal disease.     

Restricted genetic defects underlie human complement C6 deficiency

Complement C6 homozygous deficiency (C6D) has been rarely observed in Caucasians but was reported at higher prevalence among African-Americans. We report on the molecular basis of C6D in seven unrelated black individuals of North or Central Africa descent who live in France. These patients have presented Neisseria meningitidis infection (four cases), focal and segmental glomerulosclerosis with hyalinosis (one case), systemic lupus erythematosus (one case) or Still's disease (one case). All patients exhibited undetectable antigenic C6 by using a sensitive ELISA assay. An additional four cases of complete C6 deficiency with no associated disease have been characterized after family studies. Exons 6, 7 and 12 have been described recently as the location of molecular defects on the C6 gene in randomly chosen black Americans. Genomic DNA from the seven patients were subjected to direct polymerase chain reaction amplification of these three exons. Nucleotide sequencing analysis of the amplified DNA fragments revealed a homozygous single-base deletion (1936delG) in exon 12 in three cases and four compound heterozygous deletions for a single base in exon 7 (1195delC) or in exon 6 (878delA) associated with the same deletion in exon 12 (1936delG). Our observations further establish the restricted pattern of genetic defects associated with homozygous C6 complement deficiency in individuals of African descent.     

Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine

Individuals with properdin, C3 or late complement component deficiency (LCCD) frequently develop meningococcal disease. Vaccination of these persons has been recommended, although reports on efficacy are scarce and not conclusive. We immunized 53 complement-deficient persons, of whom 19 had properdin deficiency, seven a C3 deficiency syndrome and 27 had LCCD with the tetravalent (ACYW) meningococcal capsular polysaccharide vaccine. Serological studies were performed in 43 of them. As controls 25 non-complement-deficient relatives of the complement-deficient vaccinees and 21 healthy non-related controls were vaccinated. Post-vaccination, complement-deficient individuals and controls developed a significant immunoglobulin-specific antibody response to capsular polysaccharides group A, C, Y, W135, but a great individual variation was noticed. Also, the proportion of vaccinees of the various vaccinated groups with a significant increase in bactericidal titre (assayed with heterologous complement) was similar. Opsonization of meningococci A and W135 with sera of the 20 LCCD individuals yielded in 11 (55%) and eight (40%) sera a significant increase of phagocytic activity after vaccination, respectively. Despite vaccination, four complement-deficient patients experienced six episodes of meningococcal disease in the 6 years post-vaccination. Four episodes were due to serogroup B, not included in the vaccine. Despite good response to serogroup Y upon vaccination, disease due to serogroup Y occurred in two C8β-deficient patients, 3.5 and 5 years post-vaccination. These results support the recommendation to vaccinate complement-deficient individuals and to revaccinate them every 3 years.     

一起流行性脑脊髓膜炎疫情病例密切接触者及周围人群的脑膜炎奈瑟菌菌属类型及抗体检出情况调查

目的 对流行性脑脊髓膜炎患者的密切接触者及周围人群进行脑膜炎奈瑟菌菌属类型及抗体检测调查,为流脑防控工作提供科学依据。方法 采集病例密切接触者和周围人群的血清和咽拭子进行带菌及抗体检测。结果 共采集流脑患者密切接触者30人和周围人群147人,其中密切接触者共3人检出脑膜炎奈瑟菌阳性,且均为C群;周围人群共19人检出脑膜炎奈瑟菌阳性,其中B群17人,W135群2人。在抗体检测中,其中周围人群的检出率高于密切接触者（χ2 = 7.885,P＜0.05）;密切接触者中Y群检出率高于周围人群（χ2 = 12.638,P＜0.05）。在疫苗接种与抗体检出中,密切接触者的A群流脑多糖疫苗、A + C脑膜炎球菌结合疫苗的接种率与周围人群比较均无统计学上差异（P＞0.05）,同时A群与A + C群抗体检测在统计学上也无差异（P＞0.05）。但在未全程接种的A + C群抗体检测中,未全程接种的周围人群抗体阳性率高于密切接触者（χ2 = 6.021,P＜0.05）。结论 本起疫情检测菌属以B群为主,抗体检出以为A群为主,且疫苗接种率越高,抗体阳性检出率越高。     

Fulminant meningococcal septic shock in a boy with combined inherited properdin and protein C deficiency.

A 7-year-old patient with fulminant septic shock due to Neisseria meningitidis of the uncommon serogroup Y developed extensive gangrene of the limbs. Multiple amputations were necessary and a pulmonary embolism occurred within 2 days post-operatively. Complement and haemostatic system studies, done after recovery, showed a complete absence of properdin antigen and a low protein C antigen and activity level in plasma. Defective haemolytic activity in gel by the alternative pathway of complement activation could be restored with purified properdin, indicating a properdin deficiency type 1. Protein C antigen level as well as activity were in agreement with a protein C deficiency type I. The polymerase chain reaction (PCR) product of exon five of the protein C gene showed a substitution of 72Gly by Arg. Both deficiencies were traced among relatives of the patient. Serum of the father of the patient's mother was also properdin-deficient. Microsatellite haplotyping of the X-chromosome of the patient and his relatives showed that a distinct haplotype cosegregated with the properdin deficiency (Lodscore 2.25; four informative meioses). The protein C type I deficiency was present in the patient's mother and her mother and cosegregated with the mutation found. So far as is known, this is the first patient described with combined inherited properdin deficiency and protein C deficiency.     

Three Outbreak-causing Neisseria meningitidis Serogroup C Clones,Brazil

During 2003–2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates.     

Meningococcal vaccination: a discussion with all adolescents,whether college-bound or not

ABSTRACT

Introduction: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.

Methods: IMD incidence by college attendance status and vaccination rates were analyzed using publicly available surveillance data.

Results: 64/158 IMD cases occurred in non-college 18–24-year-olds during 2015–2017. Among non-college cases, the MenACWY vaccination rates were 38%–57% vs 90%–100% among college cases when vaccination status was known; MenB vaccination was 0% vs 0%–7%, respectively. In 2018, 17.2% of all 17-year-olds received ≥1 dose of multidose MenB vaccines; ≤50% completed the series.

Conclusion: Meningococcal vaccination is emphasized for college-bound adolescents, but non-college adolescents bear much of the disease burden. Low vaccine receipt preserves their risk, underscoring the need to protect all adolescents through vaccination.