Neisseria meningitides

脑膜炎奈瑟菌
  • 文章类型: Journal Article
    The present article is an update of the literature on bacterial pathogens. Recognizing the interest and scientific and public health importance of infections produced by bacterial pathogens with new virulence mechanisms and/or new mechanisms of resistance to antimicrobial agents, a multidisciplinary group of Spanish physicians and microbiologists organized a joint session and revised the most important papers produced in the field during 2006. Each article was analyzed and discussed by one of the members of the panel. This paper focus on a variety of diseases that pose major clinical and public health challenges today; and include infections produced by community-acquired methicillin-resistant Staphylococcus aureus and S. aureus small colony variants, infections produced by multiply resistant coagulase-negative staphylococci, pneumococcal infections, human listeriosis, meningococcal disease, Haemophilus influenzae, pertussis, Escherichia coli, ESBL-producing organisms, and infections due to non-fermenters. After a review of the state of the art, papers selected in this field are discussed.
    El presente artículo recoge una actualización bibliográfica de patógenos bacterianos. Dado el interés científico y la importancia que tienen para la salud pública las infecciones producidas por patógenos bacterianos con nuevos mecanismos de virulencia y/o nuevos mecanismos de resistencia a los antimicrobianos, un grupo multidisciplinario de microbiólogos y clínicos españoles, con experiencia en enfermedades infecciosas, organizó una reunión en la que se revisaron los artículos más importantes en este campo, publicados en 2006.El contenido de cada uno de los artículos seleccionados fue expuesto y discutido por uno de los miembros del grupo. Este artículo revisa algunas de las enfermedades infecciosas bacterianas que suponen hoy en día algunos de los principales retos para la salud pública e incluye las infecciones producidas por Staphylococcus aureus resistente a meticilina de adquisición comunitaria, las producidas por variantes de colonia pequeña de S. aureus, las relacionadas con estafilococos coagulasa negativa multirresistentes, la infección neumocócica, la listeriosis humana, la infección meningocócica, la tos ferina, las infecciones por Haemophilus influenzae, la diseminación de las bacterias productoras de BLEE, y las infecciones por bacilos gramnegativos no fermentadores. Tras la revisión de la situación actual, se discuten y comentan diferentes artículos relacionados con estos aspectos.
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  • 文章类型: Randomized Controlled Trial
    背景:该分析调查了南澳大利亚州青少年4年以上脑膜炎球菌携带的纵向变化。
    方法:来自“B部分”研究的数据,其中包括一项针对中学生的全州整群随机对照试验(2017年和2018年n=34,489)和针对17-25岁离校者的连续横断面研究(2019-2020年n=4,028).个人每年收集口咽拭子。这项研究包括两个独特的队列:(1)在2019年注册的个人,在2017年,2018年和2019年连续进行了三次年度拭子;(2)在2020年注册的个人,在2017年,2018年和2020年进行了拭子。使用PCR和全基因组测序鉴定疾病相关的脑膜炎奈瑟球菌基因组。单因素分析确定了反复携带(≥2)的危险因素。
    结果:在离校生中,50(1.7%,总计n=2,980)在连续访问中检测到了运输。在连续访问中携带脑膜炎球菌的参与者中,38/50(76.0%)具有通过porAPCR检测到的相同基因组。其中,19具有相同的MLST类型,并且表现出最小的变化,表明他们最有可能持续携带相同的分离株(范围为226到490天,平均持续时间352[SD51]天)。在2019年的离校生队列中,6.7%的人在放学后的第一年获得了马车,而在最后一个学年则为3.3%。与单车检测相比,年龄较大的青少年可能更容易发生复发(16岁与≤15岁相比;OR=1.97(95CI1.0,3.86);p=0.048).
    结论:虽然运输通常是短暂的,一些青少年/年轻人可能有持续性携带,很可能是脑膜炎球菌传播的一个重要群体.
    BACKGROUND: This analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years.
    METHODS: Data from the \"B Part of It\" study, which included a state-wide cluster randomized controlled trial in secondary-school students (n = 34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17-25 years (n = 4028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2).
    RESULTS: Among school leavers, 50 (1.7%, total n = 2980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤15 years; OR = 1.97 (95%CI 1.0, 3.86); p = 0.048).
    CONCLUSIONS: Whilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.
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  • 文章类型: Journal Article
    脑膜炎和脑膜炎球菌败血症是潜在的危及生命的疾病;教育机构中的年轻人反复暴露于脑膜炎球菌感染的爆发。由于侵袭性脑膜炎球菌病之前是脑膜炎奈瑟菌的咽部携带,确定该人群中脑膜炎球菌携带的患病率至关重要。这项研究的目的是确定ShahidBeheshti医科大学学生的脑膜炎球菌携带率。这项横断面研究是从2019年11月起对251名健康无症状学生的咽拭子标本进行的,为期一年。使用问卷调查来发现奈瑟氏球菌的分离之间的相关性。和居住地,室友的数量,上个月使用抗生素,和吸烟。来自每个学生的一个样品用于在奈瑟菌的一般和选择性培养基上培养。聚合酶链反应用于最终诊断脑膜炎奈瑟菌。该研究的参与者包括222名医学生(88.4%),23名护理学生(9.2%)和6名放射科学生(2.4%)。学生的平均年龄(IQR1)为23岁,134名学生是女性,(53.4%);234名学生单身,(93.2%)。92名学生(36.7%)住在宿舍中。从18个标本中分离出奈瑟菌(7.2%),其中11例(4.4%)为色素沉着细菌。PCR检测在任何样品中均未检测到脑膜炎奈瑟菌。这项研究表明,在一年的研究期间,在参与研究的学生的任何口咽标本中均未检测到脑膜炎球菌。
    Meningitis and meningococcal septicemia are potentially life-threatening illnesses; young people in educational institutions have been repeatedly exposed to outbreaks of meningococcal infections. Since invasive meningococcal disease is preceded by pharyngeal carriage of Neisseria meningitidis, ascertaining the prevalence of meningococcal carriage in this population is of utmost importance. The aim of this study was to determine the rate of meningococcal carriage in students of Shahid Beheshti University of Medical Sciences. This cross-sectional study was conducted on pharyngeal swab specimens of 251 healthy asymptomatic students from November 2019 for one year. A questionnaire was used to find correlation between isolation of Neisseria spp. and the place of residence, number of roommates, antibiotic use in the last month, and smoking. One sample from each student was used for culture on general and selective culture media for Neisseria spp. Polymerase chain reaction was used for the final diagnosis of Neisseria meningitidis. Participants in the study included 222 medical students (88.4%), 23 nursing students (9.2%) and 6 radiology students (2.4%). Mean (IQR1) age of students was 23 years, 134 students were female, (53.4%); 234 students were single, (93.2%). 92 students (36.7%) lived in dormitories. Neisseria were isolated from 18 specimens (7.2%), of which 11 (4.4%) were pigmented bacteria. PCR assay did not detect Neisseria meningitidis in any of the samples. This study showed that meningococcal bacteria were not detected in any of the oropharyngeal specimens from students participating in the study during the one-year study period.
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  • 文章类型: Journal Article
    鉴定用于开发脑膜炎球菌疫苗的合适动物模型一直是一个挑战,因为人类是脑膜炎奈瑟菌的唯一天然宿主。已经开发了小动物模型并广泛用于研究针对各种疾病产生的疫苗制剂的功效或免疫原性。这里,我们描述了用于评估候选四价脑膜炎球菌多糖(MenACYW-TT)蛋白偶联疫苗免疫原性的小鼠模型的开发和优化.三个近交(BALB/c[H-2d],C3H/HeN[H-2k],或C57BL/6[H-2b])和一个近交(ICR[H-2g7])小鼠品系使用连续两倍剂量稀释(每个血清群每剂多糖2µg至0.03125µg)的候选脑膜炎球菌结合疫苗进行评估。10只小鼠的组间隔14天接受两剂候选疫苗,最后一次给药后14天获得血清样品,用于通过ELISA评估血清群特异性抗多糖IgG,并通过血清杀菌测定(SBA)评估杀菌抗体。与BALB/c和C57Bl/6小鼠相比,C3H/HeN和ICR小鼠对所有四个血清群具有更剂量依赖性的抗体应答。总的来说,ICR小鼠对所有四种血清群具有最大的抗体剂量-反应范围(抗多糖IgG和杀菌抗体),并选择作为选择的模型。选择每个血清群0.25μg剂量作为最佳剂量,因为这在大多数评估的小鼠品系中处于血清群特异性剂量反应曲线的动态范围内。我们证明,优化的小鼠免疫原性模型足够敏感,可以区分缀合的多糖,对抗未结合的游离多糖,疫苗制剂的降解。优化后,此优化的小鼠免疫原性模型已用于评估不同缀合化学对免疫原性的影响,并对各种候选脑膜炎球菌结合疫苗进行筛选和分层,以确定具有最理想特征的疫苗,以进行临床试验。
    The identification of an appropriate animal model for use in the development of meningococcal vaccines has been a challenge as humans are the only natural host for Neisseria meningitidis. Small animal models have been developed and are widely used to study the efficacy or immunogenicity of vaccine formulations generated against various diseases. Here, we describe the development and optimization of a mouse model for assessing the immunogenicity of candidate tetravalent meningococcal polysaccharide (MenACYW-TT) protein conjugate vaccines. Three inbred (BALB/c [H-2d], C3H/HeN [H-2k], or C57BL/6 [H-2b]) and one outbred (ICR [H-2g7]) mouse strains were assessed using serial two-fold dose dilutions (from 2 µg to 0.03125 µg per dose of polysaccharide for each serogroup) of candidate meningococcal conjugate vaccines. Groups of 10 mice received two doses of the candidate vaccine 14 days apart with serum samples obtained 14 days after the last dose for the evaluation of serogroup-specific anti-polysaccharide IgG by ELISA and bactericidal antibody by serum bactericidal assay (SBA). C3H/HeN and ICR mice had a more dose-dependent antibody response to all four serogroups than BALB/c and C57Bl/6 mice. In general, ICR mice had the greatest antibody dose-response range (both anti-polysaccharide IgG and bactericidal antibodies) to all four serogroups and were chosen as the model of choice. The 0.25 µg per serogroup dose was chosen as optimal since this was in the dynamic range of the serogroup-specific dose-response curves in most of the mouse strains evaluated. We demonstrate that the optimized mouse immunogenicity model is sufficiently sensitive to differentiate between conjugated polysaccharides, against unconjugated free polysaccharides and, to degradation of the vaccine formulations. Following optimization, this optimized mouse immunogenicity model has been used to assess the impact of different conjugation chemistries on immunogenicity, and to screen and stratify various candidate meningococcal conjugate vaccines to identify those with the most desirable profile to progress to clinical trials.
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  • 文章类型: Journal Article
    布隆阿哈福地区贾曼北部地区脑膜炎爆发的描述性分析。
    描述性二次数据分析。
    从基于病例的表格和行列表中提取脑膜炎病例的记录。
    爆发的来源和模式。
    2016年1月至3月期间,共有367例疑似病例,其中44例确诊。受影响者的平均年龄为58±13岁。病死率为0.82%,男女比例为1:1.3(160/207)。受影响最大的年龄组为15-29岁(54.7%),最少为45-49岁(3.0%)。肺炎链球菌占确诊病例的77.3%,而脑膜炎奈瑟菌占20.5%。脑膜炎奈瑟菌病例来自科特迪瓦的一个边境城镇。
    发生了延续性传播性脑膜炎爆发;确诊病例中的优势菌株是肺炎链球菌。病例主要是女性,最脆弱的群体是15-29岁的人。
    这项工作由作者资助。作者BKD在CDC(前线FETP)-CDCCoAg6NU2GH001876赞助下。
    UNASSIGNED: Descriptive analysis of meningitis outbreak in Jaman North districts of Brong Ahafo Region.
    UNASSIGNED: Descriptive secondary data analysis.
    UNASSIGNED: records of meningitis cases were extracted from case-based forms and line list.
    UNASSIGNED: The source and pattern of outbreak.
    UNASSIGNED: A total of 367 suspected cases with 44 confirmed were recorded from Jaman North during the period of January to March 2016. The mean age of those affected was 58 ± 13 years. The case fatality rate was 0.82% and the proportion of males to females was 1:1.3 (160/207). The age group most affected was 15-29 years (54.7%) and the least was 45-49 years (3.0%). Streptococcus pneumoniae formed 77.3% of confirmed cases whilst Neisseria meningitides was 20.5%. Cases with Neisseria meningitides came from a border town in La Cote d\'Ivoire.
    UNASSIGNED: A protracted propagated meningitis outbreak occurred; and the predominant bacteria strain among confirmed cases was Streptococcus pneumoniae. Cases were mainly females and the most vulnerable group were people aged 15-29 years.
    UNASSIGNED: This work was funded by the authors. Author BKD was sponsored under CDC (Frontline FETP)-CDC CoAg 6NU2GGH001876.
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  • 文章类型: Journal Article
    The four-component meningococcal serogroup B vaccine (4CMenB) contains antigens present in the majority of meningococci causing invasive meningococcal disease (IMD) and may potentially offer protection against strains belonging to non-B serogroups.This study aimed to evaluate the ability of 4CMenB-induced antibodies to kill, in a human serum bactericidal assay (hSBA), non-B meningococci belonging to the main genotypes responsible for IMD in Italy.Meningococci, collected between 2015 and 2017, was characterized for PorA, FetA and sequence type, and for clonal complex. Twenty non-B isolates, representative of the most frequent genotypes, were molecularly characterized for 4CMenB antigens and tested in hSBA with sera from 4CMenB-vaccinated infants and adolescents.Among twenty isolates, eleven were serogroup C, five were Y, two W and two X. All isolates contained genes encoding for fHbp and NHBA antigens and four harbored the NadA full-length encoding gene. Positive hSBA titers were obtained against all serogroup W, X and Y isolates and against five serogroup C isolates.These data show that the 4CMenB vaccine can induce bactericidal antibodies against genetically representative meningococcal W, Y and X strains from Italy. For serogroup C, different susceptibilities to killing were observed for strains with similar antigenic repertoires.
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  • 文章类型: Journal Article
    由于能够在原子水平上理解蛋白质-配体相互作用,因此计算机研究吸引了相当大的兴趣。这种计算机模拟分析的主要主要工具是分子对接和分子动力学(MD)模拟。本文研究了如何从丹参中提取的天然化合物来阻断奈瑟菌粘附A调节蛋白(NadR)。在分子对接分析中,在10个候选物中,只有4个化合物与NadR具有较高的结合亲和力(TanshinolB,TanshinolA,紫精酸和Tournefolal分别为-7.61,-7.56,-8.22和-7.81kcal/mol,分别,与-7.23kcal/mol的天然配体相比)。吸收,分布,新陈代谢,排泄(ADME)和毒性特性,药物化学简介,和物理化学特征显示,tournefolal具有良好的性能,可以作为安全和良好的抗粘连药物。因此,对这四种配体与NadR蛋白的复合物进行了100ns的MD模拟。RMSD,RMSF,RG和氢键显示出Tournefolal与NadR蛋白具有稳定的结合亲和力和分子相互作用。鉴于这些结果,现在有必要进行更多的体外和体内研究,关于tournefolal的疗效。由RamaswamyH.Sarma沟通。
    In silico studies are attracting considerable interest due to their ability to understand protein-ligand interactions at the atomic level. The main principal tools of this in silico analyses are molecular docking and molecular dynamic (MD) simulation. This paper examines how can natural compounds that are derived from Salviae miltiorrhizae to block Neisseria adhesion A Regulatory protein (NadR). In molecular docking analysis, only four compounds were found in higher binding affinity with NadR among 10 candidates (tanshinol B, tanshinol A, lithospermic acid and tournefolal were -7.61, -7.56, -8.22 and -7.81 kcal/mol, respectively, compared to -7.23 kcal/mol of native ligand). Absorption, distribution, metabolism, excretion (ADME) and toxicity properties, medicinal chemistry profile, and physicochemical features were displayed that tournefolal contains good properties to work as a safe and good anti-adhesive drug. Therefore, the complexes of these four ligands with NadR protein were subjected to 100 ns of MD simulation. RMSD, RMSF, RG and hydrogen bonding exhibited that tournefolal showed stable binding affinity and molecular interaction with NadR protein. In light of these results, there is now a need to conduct much more in vitro and in vivo studies about the efficacy of tournefolal.Communicated by Ramaswamy H. Sarma.
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  • 文章类型: Journal Article
    在没有疫苗的情况下,目前,在高流行人群中,抗生素依赖的降低淋病奈瑟菌患病率的努力已被证明会导致极高的抗生素消费水平.尚未进行随机对照试验来验证该策略,并且该方法的一个重要问题是它可能引起抗菌素耐药性。为了促进这场辩论,我们评估了相关物种的大规模治疗,脑膜炎奈瑟菌,与抗生素耐药性的出现有关。为此,我们对大规模脑膜炎球菌治疗方案对脑膜炎奈瑟氏球菌患病率和抗菌素耐药性的影响进行了历史回顾.我们发现大量治疗方案与抗菌素耐药性的出现有关的证据。
    In the absence of a vaccine, current antibiotic-dependent efforts to reduce the prevalence of Neisseria gonorrhoeae in high prevalence populations have been shown to result in extremely high levels of antibiotic consumption. No randomized controlled trials have been conducted to validate this strategy and an important concern of this approach is that it may induce antimicrobial resistance. To contribute to this debate, we assessed if mass treatment in the related species, Neisseria meningitidis, was associated with the emergence of antimicrobial resistance. To this end, we conducted a historical review of the effect of mass meningococcal treatment programmes on the prevalence of N. meningitidis and the emergence of antimicrobial resistance. We found evidence that mass treatment programmes were associated with the emergence of antimicrobial resistance.
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  • 文章类型: Journal Article
    背景:猪圆环病毒和猪肺炎支原体可引起猪的呼吸道疾病,给世界养猪业造成了严重的经济损失。目前,这些感染主要通过疫苗接种来预防和控制。市场上的新疫苗主要由亚单位和灭活疫苗组成,但通常具有比传统活疫苗更低的抗原性。因此,越来越需要开发新的佐剂,这些佐剂可以引起快速和持久的免疫力,以增强疫苗的抗原功效。研究表明,脑膜炎球菌孔蛋白PorB可以作为配体与Toll样受体结合,激活免疫投射的产生,并作为疫苗免疫佐剂。
    目的:在本文中,我们表达并纯化了重组PorB蛋白,并验证了其对猪圆环病毒2型和猪肺炎支原体基因工程疫苗的免疫原性。
    方法:在本文中,用原核表达的方法表达并纯化重组PorB蛋白,四种不同浓度的PorB蛋白,将具有两种基因工程疫苗的弗氏佐剂与小鼠皮下免疫相结合。
    结果:我们的研究表明,适当剂量的重组蛋白PorB可以在短时间内增强两种基因工程疫苗在小鼠体内诱导的体液和细胞反应水平。与弗氏的商业佐剂相比,PorB佐剂组可能会导致两种基因工程疫苗在统计学上更高的抗体滴度(P<0.001)。
    结论:重组蛋白PorB可能是提高猪圆环病毒2型和猪肺炎支原体疫苗保护效果的候选佐剂。该蛋白质可用于未来的实际应用。
    BACKGROUND: Porcine circovirus and Mycoplasma hyopneumoniae can cause respiratory diseases in pigs, which cause serious economic loss in the worldwide pig industry. Currently, these infections are mainly prevented and controlled by vaccination. The new vaccines on the market are mainly composed of subunits and inactivated vaccines but usually have lower antigenicity than traditional live vaccines. Thus, there is an increasing need to develop new adjuvants that can cause rapid and long-lasting immunity to enhance the antigenic efficacy for vaccines. Studies have shown that meningococcal porin PorB can act as a ligand to combine with Toll-like receptors to activate the production of immunological projections and act as a vaccine immunological adjuvant.
    OBJECTIVE: In this article, we expressed and purified the recombinant PorB protein and verified its immunogenicity against porcine circovirus type 2 and Mycoplasma hyopneumoniae genetically engineered vaccine.
    METHODS: In this article, we used prokaryotic expression to express and purify recombinant PorB protein, four different concentrations of PorB protein, Freund\'s adjuvant with two genetically engineered vaccines were combined with subcutaneous immunization of mice.
    RESULTS: Our study shows that the appropriate dose of the recombinant protein PorB can enhance the levels of humoral and cellular responses induced by two genetically engineered vaccines in a short period of time in mice. The PorB adjuvant group may cause statistically higher antibody titers for both genetically engineered vaccines compared to Freund\'s commercial adjuvant (P<0.001).
    CONCLUSIONS: The recombinant protein PorB may be a good candidate adjuvant for improving the protective effect of vaccines against porcine circovirus type 2 and Mycoplasma hyopneumoniae, and the protein can be used for future practical applications.
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  • 文章类型: Journal Article
    几十年来,有效淋病疫苗的潜在线索是否一直潜伏在国际疾病监测数据中?尽管尚未开发出临床有效的淋病疫苗,但我们提供了直接和间接的证据,表明疫苗不仅是可能的,但可能已经存在。来自古巴的经验,新西兰,和加拿大建议,为控制特定类型的脑膜炎球菌疾病而开发的含有B组脑膜炎奈瑟菌外膜囊泡(OMV)的疫苗也可以预防很大比例的淋病。这种现象的机制尚未阐明,但我们提出了一些策略,通过利用临床试验中储存的血清和用脑膜炎球菌B组OMV疫苗(MeNZB)引发的个体来揭示潜在的交叉保护性抗原和效应子免疫反应。阐明这些将有助于持续开发淋病的高效疫苗选择。虽然在新西兰使用的疫苗,在那里收集了最强有力的经验证据,不再可用,OMV已包含在多组分重组脑膜炎球菌疫苗4CMenB(Bexsero)中,该疫苗现已获得许可并在许多国家/地区使用。一些证据表明,它有可能影响淋病的患病率。控制淋病的疫苗不需要是完美的,并且建模支持即使是中等有效的疫苗也可以对疾病患病率产生重大影响。我们如何使用现成的疫苗来减轻淋病的负担?在疫苗犹豫不断增长的世界中,有哪些潜在的社会障碍?我们总结了证据并考虑了一些剩余的问题。
    Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cuba, New Zealand, and Canada suggest that vaccines containing Group B Neisseria meningitides outer membrane vesicles (OMV) developed to control type-specific meningococcal disease may also prevent a significant proportion of gonorrhea. The mechanisms for this phenomenon have not yet been elucidated but we present some strategies for unraveling potential cross protective antigens and effector immune responses by exploiting stored sera from clinical trials and individuals primed with a meningococcal group B OMV vaccine (MeNZB). Elucidating these will contribute to the ongoing development of high efficacy vaccine options for gonorrhea. While the vaccine used in New Zealand, where the strongest empirical evidence has been gathered, is no longer available, the OMV has been included in the multi component recombinant meningococcal vaccine 4CMenB (Bexsero) which is now licensed and used in numerous countries. Several lines of evidence suggest it has the potential to affect gonorrhea prevalence. A vaccine to control gonorrhea does not need to be perfect and modeling supports that even a moderately efficacious vaccine could make a significant impact in disease prevalence. How might we use an off the shelf vaccine to reduce the burden of gonorrhea? What are some of the potential societal barriers in a world where vaccine hesitancy is growing? We summarize the evidence and consider some of the remaining questions.
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