Dressed not to kill: CD16+ monocytes impair immune defence against tuberculosis

Monocytes are blood leukocytes that can differentiate into several phagocytic cell types, including DCs, which are instrumental to the inflammatory response and host defence against microbes. A study published in this issue of the European Journal of Immunology by Balboa et al. [Eur. J. Immunol. 2013. 43: 335‐347] suggests that a shift of the CD16^? monocyte population toward a CD16⁺ subpopulation may represent an immune evasion strategy that ultimately favors persistence of Mycobacterium tuberculosis. Together with other recent reports, the article by Balboa et al. sheds new light on the function of CD16⁺ monocytes in health and disease; in this commentary, we discuss the implications stemming from these findings.     

Detailed analysis of the radiographic presentation of Mycobacterium kansasii lung disease in patients with HIV infection

BACKGROUND: Published criteria for the diagnosis of Mycobacterium kansasii lung disease require the presence of clinical symptoms, positive microbiologic results, and radiographic abnormalities. In patients with HIV infection, the radiographic findings of M kansasii lung disease are not well described. METHODS: Medical records and chest radiographs of all patients with HIV infection and at least one respiratory specimen culture positive for M kansasii at San Francisco General Hospital between December 1989 and July 2002 were reviewed. RESULTS: Chest radiographic results were abnormal in 75 of 83 patients (90%) included in the study. Radiographic abnormalities were diverse, with consolidation (66%) and nodules (42%) as the most frequent findings. The mid or lower lung zones were involved in 89% of patients. The pattern of radiographic abnormalities did not differ based on acid-fast bacilli smear status, the presence or absence of coexisting pulmonary infections, or CD4+ T-lymphocyte count. In multivariate Cox regression analysis, cavitation was the only radiographic abnormality independently associated with mortality (hazard ratio, 4.8; 95% confidence interval, 1.2 to 19.6). CONCLUSION: Patients with HIV infection and M kansasii lung disease present with diverse radiographic patterns, most commonly consolidation and nodules predominantly located in the mid and lower lung zones. This finding is in contrast to the upper-lobe cavitary presentation described in patients without HIV infection. Although rare, the presence of cavitary disease in patients with HIV infection and M kansasii independently predicts worse outcome. The diversity in the radiographic presentation of M kansasii lung disease implies that clinicians should obtain sputum mycobacterial culture samples from any patient with HIV infection and an abnormal chest radiograph finding.     

链置换扩增技术在结核病诊断中的应用

目的探讨链置换扩增（SDA）技术检测结核分枝杆菌复合群（MTBC）的临床意义和可信性。方法应用SDA技术与荧光定量聚合酶链反应（FQ—PCR），直接检测了453份结核性样本，其中痰标本332份、胸腔积液78份、脑脊液43份。结果332份痰标本培养阳性131份，其中110株（涂阳88份）为MTBC，21株（涂阳20份）为非结核分枝杆菌。在110份证实有MTBC、21份证实有非结核分枝杆菌生长的样本中，SDA和FQ-PCR的敏感性分别为99．1％和95．2％，特异性分别为94．6％和95．2％。在311例结核分枝杆菌感染的患者中，SDA和FQ-PCR的阳性率分别为55．3％（172／311）和47.0％（146／311）。121份结核性胸腔积液、脑脊液样本中，分枝杆菌阳性20例，经鉴定其中19例为结核分枝杆菌，1例为非结核分枝杆菌，SDA和FQ—PCR检测的阳性率分别为43．4％（52／120）和33．4％（40／120）。SDA技术设立的内扩增质量控制（IAC）可确保检测结果的准确性。结论自动检测分析系统能快速、特异地检测临床样本中MTBC，设立IAC可提高结果的可信性。     

分枝杆菌菌株库建设模式与实践研究

目的建立生物安全保证、菌种资源丰富、相应资料齐全、操作流程顺畅、资源共享便捷的分枝杆菌菌株库,为结核病临床诊疗与科学研究提供基础性平台。方法主要依照二级生物安全(BSL-2)实验室管理要求和"中国医学微生物菌种保藏管理办法"、"人间传染的病原微生物名录"等法规构建分枝杆菌菌株库生物安全保证体系;根据菌株库的功能作用结合结核病临床诊疗与科学研究的最新成就及未来发展要求确立分枝杆菌菌株库建设的内涵与外延;以临床分离菌株、专项研究收集菌株为操作对象制定适宜的菌株资料、相应病例资料收集及信息库建设流程;采用网络通讯和数据库技术建立分枝杆菌菌株库信息系统以提高建库工作效率和提供便捷的资源共享服务。结果①构建了包括生物安全管理领导机构、实验技术生物安全水平标准、实验室生物安全管理与防护、菌株库生物安全管理等在内的分枝杆菌菌株库生物安全保证体系;②分枝杆菌菌株库包括菌株保存库、菌株资料库及相应病例资料库、菌株库信息系统三大主要部分,保存菌株的资料收集以相应的1个治疗周期为界限,菌株保存周期为10年;③临床分离菌株的菌株资料、相应病例资料收集及信息库建设流程按时间序列包括收集菌株库外暂存、菌株资料录入、病例资料录入、菌株保存价值判定、菌株入库保存、特定菌株取用及研究信息补充录入等重大步骤,专项研究收集菌株则按其特定的要求建立相应的工作流程;④采用SQL SERVER大型数据库和Delphi7开发工具开发了基于C/S体系结构包含保藏管理、质控管理、文档管理、资源管理、系统管理等五大子系统的分枝杆菌菌株库信息系统。结论在分枝杆菌菌株库建设中,生物安全保证是前提、丰富内涵建设是中心、合理流程设置是关键、信息系统开发是基础。     

分枝杆菌快速变色液体培养基临床应用的评价

目的 :评价快速变色液体培养基对分枝杆菌的检测与肺结核病早期诊断的临床应用和推广价值。方法 :对 14 5例疑似肺结核痰标本在痰厚涂片萋尼氏染色法抗酸染色镜检后分别接种于变色液体培养基和 L - J培养基 37℃培养并观察结果。变色液体培养基接种后于两周前和两周后分别每天观察一次和隔天观察一次 ,若培养基变为紫红色 ,或底层有紫红色颗粒沉淀时 ,作抗酸染色镜检 ,证实有分枝杆菌则为分枝杆菌培养阳性。改良 L - J培养基接种后按操作常规观察结果 ,八周未见细菌生长则为分枝杆菌培养阴性。结果 :变色液体培养基培养阳性率 4 4 .8% ,略高于 L - J培养基 35 .9% (P>0 .1) ;痰标本接种 15 d时 ,变色液体培养基培养阳性率 98% (6 4 /6 5 ) ,L - J培养基 19% (10 /5 2 ) ;分枝杆菌平均生长天数前者 10 d,后者 2 5 d。上述两组数据经统计学分析 ,差异均有显著性 (P<0 .0 0 5 )。污染率变色液体培养基为 6 .9% ,L - J培养基 4 % ,差异无显著性 (0 .2 5 相似文献   

Turnaround time of whole genome sequencing for mycobacterial identification and drug susceptibility testing in routine practice

ObjectivesUntil recently whole genome sequencing (WGS) for mycobacteria has been restricted mostly to the research setting. However, in 2017 Public Health England has implemented WGS for routine mycobacterial identification and susceptibility testing for Mycobacterium tuberculosis. Our objective was to evaluate the impact of this change on the laboratory turnaround times and availability of results.MethodsOver the years 2016 and 2017, the period 1 January to 30 April was selected to represent before and after implementation of WGS. Prior to 2017, line probe assays were used for mycobacterial species identification. Turnaround times for the different steps of the diagnostic process were evaluated for all positive mycobacterial cultures that were sent from our hospital to the Reference Laboratory during the study period.ResultsA total of 161 positive mycobacterial cultures were sent to the Reference Laboratory. Half of the isolates (n=81/161, 50%) were M. tuberculosis and 80/161 (50%) were non-tuberculous mycobacteria. The median number of workdays for mycobacterial species identification was 1 day (interquartile range (IQR) 1-3) in 2016 and 6 days (IQR 5-7) in 2017, p <0.001. For M. tuberculosis complex, the median time to drug susceptibility testing results, either molecular or phenotypic, was 12 days (IQR 11-18) in 2016 and 8 days (IQR 7-10) in 2017, p <0.001.ConclusionsRoutine WGS performed well in this setting for mycobacterial identification and susceptibility testing for M. tuberculosis and decreased time to drug susceptibility testing results. There was an increase in turnaround times for species identification using WGS, when compared with the previous methods.     

Shaping the niche in macrophages: Genetic diversity of the M. tuberculosis complex and its consequences for the infected host

Pathogenic mycobacteria of the Mycobacterium tuberculosis complex (MTBC) have co-evolved with their individual hosts and are able to transform the hostile environment of the macrophage into a permissive cellular habitat. The impact of MTBC genetic variability has long been considered largely unimportant in TB pathogenesis. Members of the MTBC can now be distinguished into three major phylogenetic groups consisting of 7 phylogenetic lineages and more than 30 so called sub-lineages/subgroups. MTBC genetic diversity indeed influences the transmissibility and virulence of clinical MTBC isolates as well as the immune response and the clinical outcome. Here we review the genetic diversity and epidemiology of MTBC strains and describe the current knowledge about the host immune response to infection with MTBC clinical isolates using human and murine experimental model systems in vivo and in vitro. We discuss the role of innate cytokines in detail and portray two in our group recently developed approaches to characterize the intracellular niches of MTBC strains. Characterizing the niches and deciphering the strategies of MTBC strains to transform an antibacterial effector cell into a permissive cellular habitat offers the opportunity to identify strain- and lineage-specific key factors which may represent targets for novel antimicrobial or host directed therapies for tuberculosis.