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。     

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.     

How to: Diagnose inborn errors of intrinsic and innate immunity to viral,bacterial, mycobacterial,and fungal infections

BackgroundInborn errors of intrinsic and innate immunity constitute the focus of a growing research field that investigates the molecular mechanisms underlying susceptibility to infections previously not considered part of the spectrum of inborn errors of immunity. These so-called nonconventional inborn errors of immunity often occur as infections caused by a narrow spectrum of microorganisms in otherwise healthy subjects.ObjectivesThis review aimed to provide a framework for identifying and evaluating patients with viral, bacterial, mycobacterial, and fungal infection needing further assessment for inborn errors of intrinsic and innate immunity.SourcesA literature search was performed using PubMed, from inception until 1 May 2022. The search included the following keywords: “inborn errors of immunity”; “inborn errors of innate immunity”; “primary immune deficiency”; “primary immunodeficiency”; “infections”; “infectious susceptibility”; “virus”; “pyogenic bacteria”; “mycobacteria”; “fungi”. All article types were considered.ContentWe review the definition of what can be considered an inborn error of immunity and how the definition changed over the last ～25 years. We further provide criteria to rule out secondary immunodeficiencies, identify patients needing further clinical and laboratory immunological assessment, and suspect and diagnose an inborn error of intrinsic and innate immunity. These steps are proposed as part of an algorithm.ImplicationsPatients with unexplained life-threatening infections, including otherwise healthy subjects, should be systematically screened for known inborn errors of immunity. The early diagnosis can prevent recurrence of life-threatening infections in the patients and reduce the total burden of infectious diseases.     

氟喹诺酮类药物抗分枝杆菌作用的实验研究

摘要：目的 研究氟喹诺酮类药物抗分枝杆菌的作用。方法 分别测定9种氟喹诺酮类药物对23种分枝杆菌（包括结核、牛分枝杆菌和21种非结核分枝杆菌）的试管内最低抑菌浓度。结果 不同药物显示不同的试管内抗菌作用谱。结论 氟喹诺酮类药物是临床非结核分枝杆菌病治疗可选择的药物。     

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette–Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone.