Efficacy of vaccination strategies against intranasal challenge with Brucella abortus in BALB/c mice

Brucellosis is a zoonotic disease affecting 500,000 people worldwide annually. Inhalation of aerosol containing a pathogen is one of the major routes of disease transmission in humans. Currently there are no licensed human vaccines available. Brucella abortus strain RB51 is a USDA approved live attenuated vaccine against cattle brucellosis. In a mouse model, strain RB51 over-expressing superoxide dismutase (SOD) administered intraperitoneally (IP) has been shown to be more protective than strain RB51 against an IP challenge with B. abortus pathogenic strain 2308. However, there is lack of information on the ability of these vaccine strains to protect against intranasal challenge. With the long-term goal of developing a protective vaccine for animals and people against respiratory challenge of Brucella spp., we tested a number of different vaccination strategies against intranasal infection with strain 2308. We employed strains RB51 and RB51SOD to assess the efficacy of route, dose, and prime-boost strategies against strain 2308 challenge. Despite using multiple protocols to enhance mucosal and systemic protection, neither rough RB51 vaccine strains provided respiratory protection against intranasal pathogenic Brucella infection. However, intranasal (IN) administration of B. abortus vaccine strain 19 induced significant (p ≤ 0.05) pulmonary clearance of strain 2308 upon IN challenge infection compared to saline. Further studies are necessary to address host-pathogen interaction in the lung microenvironment and elucidate immune mechanisms to enhance protection against aerosol infection.     

内蒙古兴安盟地区布鲁氏菌流行株种型鉴定和体外药物敏感性分析

目的 了解内蒙古兴安盟布鲁氏菌流行株的主要种型,分析布鲁氏菌流行株的体外药物敏感性,指导临床治疗。方法 选择内蒙古兴安盟布病发病率较高的旗县和人口密集的旗县,采集临床诊断的布病患者200份血液样本,用全自动血液培养仪培养分离出28株布鲁氏菌,用全自动生化鉴定系统、BCSP31-PCR及传统经典的方法进行种型鉴定,最后用肉汤微量稀释法对其中的25株布鲁氏菌进行13种抗生素的体外药敏试验。结果 28株布鲁氏菌中羊种3型18株(64.29%)和羊种1型10株(35.71%),进行药敏试验的25株菌中,100%菌株对多西环素、庆大霉素、链霉素、四环素均敏感,16%的菌株对利福平、头孢曲松的药物敏感性可能降低,20%的菌株对复方新诺明耐药,100%的菌株对阿奇霉素耐药。结论 内蒙古兴安盟布鲁氏菌流行株主要是羊种3型和羊种1型,目前对一线方案药物较为敏感,在布病的急性期治疗上,宜规范化治疗,首选一线方案药物:多西环素、庆大霉素、链霉素、利福平。     

浙西南非疫区布鲁菌病患者临床特点分析

目的:分析布鲁菌病患者临床特征,提高对布鲁菌病的认知及诊断水平。方法:回顾性分析2014年1月至2019年3月本院明确诊断的11例布鲁菌病患者的流行病学特点、临床表现、实验室检查和流行病学资料。结果:确诊患者中,有明确牛羊动物及不熟生肉接触史者6例;临床表现为发热10例、关节痛4例、畏寒3例、头晕3例及乏力1例;实验室检查结果显示,11例确诊患者C-反应蛋白、红细胞沉降率结果均增高,谷丙转氨酶升高8例,降钙素原增高7例,血白细胞总数降低7例,淋巴细胞增高6例,血小板总数降低6例,血红蛋白降低5例;血培养送检11例,阳性8例,骨髓培养送检3例,阳性2例;随访结果表明该11例患者经内科积极治疗后均治愈。结论:对长期不明原因发热患者结合流行病学特点应考虑布鲁菌病可能,并应早期送检血培养和骨髓培养,避免漏诊和误诊,同时增强高危人群防护意识,防止暴发流行的可能。     

Brucella canis in Commercial Dog Breeding Kennels,Ontario, Canada

We evaluated the prevalence of Brucella canis seropositivity in a convenience sample of dogs from commercial breeding kennels in Ontario, Canada. Overall, 127/1,080 (11.8%) dogs from 23/63 (37%) kennels were seropositive. The prevalence of positive dogs within kennels with >1 positive dog ranged from 3.9% to 100% (median 33%).     

新疆急慢性布鲁菌病患者炎性细胞因子免疫水平研究

目的 探讨新疆急、慢性布鲁菌病患者细胞因子（IL-4、IL-6、IL-10、IL-17、TNF-α、INF-γ）、炎性因子（PCT、hs-CRP）及RF、ESR、ASO、血培养的临床诊断意义。方法 对布鲁菌病住院患者（病例组）和正常对照人群（对照组）采用多重微球流式免疫荧光发光法和生化等技术检测多种细胞因子及炎性因子,并进行统计学分析。结果 病例组和对照组IL-4、IL-6、IL-10、IL-17、TNF-α和IFN-γ分别为2.74(0.97~6.25)和0.56(0.53~0.64)、34.10(13.05~60.8)和0.78(0.41~2.52)、1.83(1.15~2.75)和0.89(0.77~1.13)、6.77(2.48~13.74)和1.03(0.68~1.20)、35.23(5.79~74.98)和1.33(0.80~2.17)、212.96(42.3~436.72) pg/mL和1.69(1.36~1.89) pg/mL,病例组明显高于对照组,差异均有统计学意义（P<0.05）。急性组和慢性组IL-6、IL-10、IL-17、TNF-α、IFN-γ分别为65.32(36.27~68.60)和29.38(11.30~53.09)、2.38(1.51~3.34)和0.89(0.77~1.13)、11.98(3.92~16.49)和5.27(2.24~12.49)、50.88(16.59~96.69)和28.24（5.30~64.40）、319.00（145.14~588.52）pg/mL和160.52（36.5~418.54） pg/mL,PCT和hs-CRP分别为0.08(0.06~0.12) pg/mL和0.04(0.03~0.06) pg/mL、12.60（5.0~30.8）mg/L和3.30（1.2~16.2） mg/L,差异均有统计学意义（P<0.05）;低抗体滴度组和高抗体滴度组IL-6、PCT 、hs-CRP 、RF、ESR、血培养阳性率分别为30.46(11.30~50.02) pg/mL和46.20(17.72~79.69) pg/mL、0.04(0.03~0.06) pg/mL和0.07(0.04~0.11) pg/mL、3.03(0.85~9.70) mg/L和13.65(2.97~31.43) mg/L、3.0（0.8~9.7）IU/mL和13.6（3.0~31.4）IU/mL、15（7~31）mm/h和27（15~46）mm/h、15.3%和33.3%,差异均有统计学意义（P<0.05）。单因素分析显示6种细胞因子均为布鲁菌病患病程度的危险因素,多因素Logistic回归分析显示IL-6和INF-γ水平是布鲁菌病患病程度的独立危险因素。结论 IL-4、IL-6、IL-10、IL-17、TNF-α、IFN-γ及PCT、hs-CRP等指标不仅能及时准确反映布鲁杆菌感染发病程度和临床分期的免疫状况,而且IL-6和INF-γ表达水平具有独立的临床诊断评估作用,血培养在急性期或高滴度组具有重要的临床诊断价值。     

1例布鲁氏菌感染性腹主动脉假性动脉瘤患者的围手术期护理

总结1例布鲁氏菌感染性腹主动脉假性动脉瘤患者的围术期护理经验。护理要点：做好传染病患者的隔离防护管理和心理建设;手术前控制血压、疼痛和体温,卧床期间做好预防血栓指导;术后严格控制血压和腹内压,做好引流管护理,根据疾病特点做好腹壁疝、下肢动脉栓塞的观察护理和预防布鲁氏杆菌病复发指导。经过40 d精心治疗和护理,患者康复出院。微信、电话随访1年,患者恢复良好。     

二尖瓣成形术后布鲁氏杆菌感染1例

布鲁氏杆菌病是一种人畜共患传染病,临床表现症状多种多样,多有发热、多汗、关节疼痛,肝、脾、淋巴结肿大等,本文通过对1例二尖瓣成形术后布鲁氏杆菌感染病例进行分析,提高对布鲁氏杆菌的实验室认识,提高诊断水平,做到及时确诊,规范治疗。     

布鲁氏菌A19疫苗株全基因组测序及比较基因组学分析

目的 探索布鲁氏杆菌A19疫苗株全基因组的结构、分子生物学的功能,并对其生物信息学进行研究。方法 采用Illumina Hiseq 4000和PacBio对A19进行全基因组测序,并与GenBank 上的8株菌进行比较基因组学解析。A19基因组3 286 167 bp, 预测3 371个基因,GC含量57.25%。通过注释COG库,对应基因有2 560个,将其归入22类COG中;根据比对KEGG库,得到2 544个基因,共参与33类代谢通路。结果 综合两个数据库结果发现,大多数A19预测基因中的基因功能主要与膜运输、氨基酸转运及碳水化合物代谢有关。结论 通过分析发现, A19和猪羊牛种布鲁氏菌之间存在一定差异,并找出牛种毒力基因。本实验通过测序A19全基因组,为布鲁菌疫苗的研究提供思路。     

布鲁氏菌脊柱炎临床特点分析

目的探讨布鲁氏菌脊柱炎患者的临床特点。方法回顾性分析32例布鲁氏菌脊柱炎患者的临床资料,采用虎红平板凝集法进行布鲁氏菌抗体检测,患者均采用多西环素、利福平、头孢噻肟钠治疗。统计分析患者治疗后的临床表现、影像学表现及布鲁氏菌抗体滴度。结果治疗后,患者逐渐恢复体力,无多汗,无发热,无神经痛,活动自如,无肢体麻木及疼痛。治疗后,影像学显示患者脓肿逐渐吸收,骨质破坏逐渐恢复,炎症过程和骨与组织的纤维化逐渐好转。患者经规范治疗后抗体滴度逐渐下降至1∶100(++)以下或阴转。结论布鲁氏菌脊柱炎多侵犯椎体,造成骨质破坏,伴有骨质增生,可形成小脓肿,患者活动受限,易被误诊为脊柱结核和脊柱肿瘤,经早期、联合、足量、足疗程规范治疗,患者预后良好。     

Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-{gamma} in CD4+ T cells

Immunization of BALB/c mice with killed Brucella abortus (BA)has previously been shown to Increase serum lgG2a levels andlong-term T cell clones from these mice secrete T_h1-associatedcytokines: IFN- and IL-2 but not IL-4 or IL-5. We analyzed cytokinegene expression following primary immunization with BA to determinewhen CD4⁺ T cells first express cytokine genes and whether specifichypothesized cytokine patterns (e.g. T_h precursor, T_h0) couldbe identified prior to a T_h1-like pattern. Our results demonstrateda highly consistent and novel pattern of T_h 1/T_h2 cytokine geneexpression characterized by elevated IL-10 and IFN- in CD4⁺T cells which rapidly manifests itself and is sustained forat least 10 days after immunization. No elevation in IL-2 cytokinegene expression was observed and treatment of BA-immunlzed micewith blocking anti- IL-2 antibodies had no effect on the cytokinegene expression pattern, although treatment with anti-IFN antibodiesresulted in increased IL-4, IL-5, and IL-9 cytoklne gene expression,In the absence of any change In IFN- or IL-10 as early as 4days after immunization. These results suggest that a wholepathogen may trigger sufficient costimulatory signals to rapidlyinduce effector T cells in the absence of elevated IL-2 andthat IL-10 Is specifically elevated in certain T_h1-like responses.