Management of extra-pulmonary tuberculosis (excluding miliary and meningeal) in south and west Wales (1976-8).

In a retrospective survey of the management of extrapulmonary tuberculosis lymph node and genitourinary tuberculosis were found more commonly than bone and joint or gynaecological disease. Only 29% of patients received 18 moths'' chemotherapy while 31% received nine to 12 months'' treatment with rifampicin and isoniazid regimens and 34% had short-course chemotherapy with other regimens. Five patients were not offered any chemotherapy after diagnosis, and in five patients the diagnosis was overlooked because of administrative errors. One patient died from tuberculosis (renal). Poor drug compliance appeared less of a problem than in pulmonary tuberculosis. Only 14% of patients had their disease managed solely by consultants who were not specialists in chest disease. Liaison with a chest consultant did not necessarily ensure chemotherapy for 18 moths.     

Short-course chemotherapy for mycobacteriosis kansasii?

The success of short-course chemotherapy for tuberculosis, the similarity between Mycobacterium tuberculosis and M. kansasii and the effectiveness of rifampin against the latter organism prompted a comparison of the diseases due to these organisms to assess the feasibility of a prospective trial of short-course chemotherapy in patients with mycobacteriosis kansasii. The two groups of patients were matched for age, sex and time of diagnosis. The patients with mycobacteriosis kansasii more frequently had underlying obstructive pulmonary disease. The clinical course of mycobacteriosis kansasii was more indolent, with a slower rate of improvement according to the chest x-ray films and a longer time before sputum smears and cultures became negative. M. kansasii was significantly more resistant to all the antibiotics, including rifampin. Although these differences from tuberculosis suggest that an equally short course of therapy may not be effective for patients with mycobacteriosis kansasii, the outcome was good in compliant patients who were given the three most effective major drugs for 12 months after the sputum smears and cultures had become negative. Therefore, a trial of modified short-course chemotherapy is recommended for patients with mycobacteriosis kansasii.     

Population-Level Impact of Shorter-Course Regimens for Tuberculosis: A Model-Based Analysis

Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6–3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care (“default”) over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.     

Optimization of tuberculosis complex chemotherapy with the use of moxifloxacin]

It was shown in vitro that moxifloxacin by its activity against Mycobacterium tuberculosis (susceptible and resistant to the main antituberculosis agents) was highly superior to lomefloxacin (by 2 to 4 times by the MIC and by 4 times by the MBC). In murine lung tissue culture the highest effect was observed with the use of moxifloxacin in combination with isoniazid and pirazinamide. The efficacy of the regimens with the use of moxifloxacin was estimated in the treatment of 152 patients with pulmonary tuberculosis diagnosticated for the first time. The use of moxifloxacin was shown to be most advantageous in complex therapy of patients with extended and progressive tuberculosis due to polyresistant Mycobacterium tuberculosis strains or patients with concomitant nonspecific inflammatory diseases of the respiratory tracts due to a great variety of grampositive and gramnegative organisms, acid fact bacteria, atypical bacteria and a great variety of anaerobes. The tolerance of the treatment regimens with the use of moxifloxacin was mainly satisfactory.     

Failure of diagnosis as a factor in tuberculosis mortality.

In British Columbia between January 1970 and December 1974 active tuberculosis was diagnosed only after death in 69 cases; this was more frequent for miliary tuberculosis (31% of reported cases) than for advanced pulmonary tuberculosis (3% of cases). Although 28% of the patients were more than 75 years old, some were much younger, and 38% of the latter were alcoholics. More than 50% of the patients had been hospitalized before death, for a mean of 14.5 days; they were most frequently thought to have pneumonia or cancer at the time of death. Clearly, increased awareness of the continuing presence of tuberculosis in our society is needed.     

Chromosome analyses in man in the course of chemoprophylaxis against tuberculosis and of antituberculosis chemotherapy with isoniazid

Summary Cytogenetic analyses were carried out in lymphocytes of 37 persons before and during a primary chemoprophylaxis or a preventive chemotherapy with isoniazid as weil as of 30 patients suffering from active pulmonary tuberculosis before and during a chemotherapy with isoniazid in combination with two other antimycobacterial drugs. The results of the four participating research groups consistently reveal no indication for a chromosome damaging activity of isoniazid, of its metabolites in the human organism and of the administered drug regimens.     

Short-course therapy for tuberculosis in infants and children. Infectious Diseases and Immunization Committee,Canadian Paediatric Society.

OBJECTIVE: To improve efficacy of and compliance with therapy for tuberculosis in children. OPTIONS: Short-course (6-month) multi-drug therapy, either non-supervised or directly supervised, versus long-course (more than 6-month) multi-drug therapy. OUTCOMES: Success (more than 90% of cases cured without relapse or serious side effects), development of drug resistance and compliance with treatment. EVIDENCE: Review of published reports of efficacy trials of tuberculosis therapy in children, side effects and compliance studies; consensus of expert opinion. VALUES: Values were assigned to the evidence by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society through review of the data and consensus. BENEFITS, HARMS AND COSTS: Improved efficacy and compliance with short-course protocols should lower the rate of treatment failure among children in Canada and the cost of tuberculosis care. RECOMMENDATIONS: A short-course (6-month) protocol of four drugs for the first 2 months and two drugs for the subsequent 4 months is recommended to treat pulmonary tuberculosis or extrapulmonary disease causing lymphadenopathy. Tuberculous meningitis, disease involving bones and joints and tuberculosis with HIV infection require longer courses of treatment. Asymptomatic tuberculosis should be treated with daily doses of isoniazid for 9 months. Intermittent directly observed therapy is recommended if compliance cannot be ensured. Routine liver function testing is not recommended for prepubescent children taking isoniazid, but monthly assessment for clinical symptoms and periodic liver function evaluation is advised in adolescent women, especially post partum. VALIDATION: This report was reviewed by the directors of the Canadian Paediatric Society, the Hepatitis and Special Pathogens Division of the Laboratory Centre for Disease Control and the Canadian Thoracic Society. The recommendations are similar to those of the American Academy of Pediatrics. SPONSOR: The recommendations were developed and endorsed by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society.     

Long term efficacy of DOTS regimens for tuberculosis: systematic review

Objective To identify published studies assessing tuberculosis recurrence after successful treatment with standard short course regimens for six months to determine the strength and sufficiency of evidence to support current guidelines.Design Systematic review.Data sources Medline, Embase, Cochrane clinical trials register, specialist tuberculosis journals, and reference lists. Only English language publications were eligible.Review methods Studies were included irrespective of methodology or quality. Abstracted information included inclusion and exclusion criteria for participants, duration of follow-up, and definitions of treatment success and disease recurrence. The primary outcome was the proportion of successfully treated patients recorded with recurrent tuberculosis during the follow-up period.Results 17 study arms from 16 studies met the inclusion criteria; 10 were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes. Although several clinical trials supported the use of daily treatment regimens, studies reporting tuberculosis recurrence after intermittent regimens were limited. Few studies carried out under routine programmatic conditions reported disease recurrence. Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence.Conclusions Despite DOTS (directly observed treatment, short course) being implemented for more than 10 years and millions of patients treated for tuberculosis, few studies have assessed the ability of standard DOTS regimens to result in lasting cure for patients treated under routine programmatic conditions.     

Detection of in vitro and in vivo released antigens of diagnostic interest in Mycobacterium tuberculosis by immunoblotting

Identification of in vitro and in vivo released mycobacterial antigens are of considerable interest in diagnosis of Mycobacterium tuberculosis. Isolation of in vitro released antigen from M. tb excretory-secretory culture filtrate protein and in vivo released circulating tuberculous antigen from smear positive pulmonary tuberculosis sera by ammonium sulphate precipitation is reported. The antigens were resolved by SDS-PAGE and immunoblotting was performed using pooled serum of smear positive, smear negative pulmonary tuberculosis sera and normal sera to identify reactive tuberculous antigens. In vitro and in vivo released mycobacterial antigens showed reactivity at 100, 31, 43 and 20 kDa with smear positive and smear negative pulmonary tuberculosis patients. Further, the in vitro released antigen showed strong reactivity exclusively at 55 kDa antigen with smear positive and 24 kDa antigen with smear negative pulmonary tuberculosis sera. In vivo released antigen reacted exclusively at 170 and 16 kDa with smear positive and 19 kDa antigen with smear negative pulmonary tuberculosis patients. Antigens of 24 and 19 kDa which are reactive with sputum negative sera will be of diagnostic interest and need further study in patients with low bacillary load. The in vitro and in vivo released mycobacterial 100, 31,43 and 20 kDa antigens, reactive with patients sera are of diagnostic interest in tuberculosis.     

NRS2002评分和血清白蛋白值与门诊肺结核患者病情的相关性

目的 评价NRS2002评分和血清白蛋白（ALB）值与门诊肺结核患者病情的相关性。 方法 选择2017年10月至2018年9月在余姚市人民医院肺结核门诊就诊的290名肺结核患者为研究对象。患者首次就诊时进行NRS2002营养筛查,NRS2002评分≥3分判定为存在营养风险。检测患者血清白蛋白（ALB）值,ALB≤35 g/L判定为营养不足。观察患者NRS2002评分、ALB值与肺结核患者痰液结核分枝杆菌阳性、肺结核空洞等情况的相关性。 结果 NRS2002评分、年龄与肺结核患者的病情相关。NRS2002评分≥3分以及ALB≤35 g/L的患者痰液结核分枝杆菌阳性率和存在肺结核空洞的比例均高于NRS2002评分35 g/L的患者（均P40岁为肺结核患者痰液结核分枝杆菌阳性的危险因素;而年龄、性别、NRS2002评分和ALB值均不是患者肺结核空洞的危险因素。 结论 NRS2002评分≥3分、ALB≤35 g/L的肺结核患者更容易出现痰液结核分枝杆菌阳性情况。肺结核患者营养状况与肺结核患者病情具有一定相关性。     

Large-scale validation of a latex agglutination test for diagnosis of tuberculosis

Large-scale validation of a simple latex agglutination test for the diagnosis of tuberculosis is described. Soluble antigens extracted from a non-pathogenic saprophytic mycobacterium, Mycobacterium w, which shares antigenic determinants with Mycobacterium tuberculosis, were covalently linked to carboxylated polystyrene latex beads. Batch to batch reproducibility of coated latex was ensured. Latex reagents were standardized to overcome non-specific agglutination. Reagents of the test are stable for 1 year at 4 degrees C. A total of 1,058 serum samples of pulmonary and extrapulmonary tuberculosis patients or patients with other pulmonary diseases and healthy controls living in endemic areas were tested. Sensitivity of 94% for pulmonary tuberculosis and 87% for extrapulmonary tuberculosis was obtained. Specificity is 92.2% for healthy controls and patients with other respiratory diseases. We conclude that the latex agglutination test can be utilized for mass screening for both pulmonary and extrapulmonary tuberculosis where diagnosis by existing methods is much more difficult.     

肺结核合并下呼吸道感染患者CT影像特点及IL-23R水平表达的临床意义

摘要 目的：探讨肺结核合并下呼吸道感染患者CT影像特点及IL-23R水平表达的临床意义。方法：选取2015年1月-2018年8月于我院就诊的123例肺结核患者,将所选取的患者按是否合并下呼吸道感染分为单纯肺结核组73例和肺结核合并下呼吸道感染组50例。分析两组组患者临床表现、CT影像学图片、CT影像学表现、血清IL-23R的表达水平的差异。结果：单纯肺结核组患者出现14例低热、11例胸闷、17例消瘦、14例气短、18例痰中带血、14例颈部淋巴结肿大、23例咳嗽、21例胸痛。肺结核合并下呼吸道感染组患者出现16例低热、13例胸闷、21例消瘦、19例气短、20例痰中带血、15例颈部淋巴结肿大、26例咳嗽、23例胸痛,两组患者临床表现差异均无统计学意义（P＞0.05）。单纯肺结核组CT影像学图片显示可见结节影或包块影,呈明显分叶征、短毛刺征、空泡征并发肺不张、棘状突起,边缘较清晰,增强扫描后明显强化。肺结核合并下呼吸道感染组CT影像学图片显示有分叶、毛刺,同时肺内肿物周边存在晕征、血管聚集征、卫星灶征、胸膜凹陷等表现,此外伴纵膈及肺门淋巴结明显肿大,胸壁侵犯。肺结核合并下呼吸道感染组CT影像中毛刺状结节、胸膜凹陷、空洞、分叶征、肿块、条索影比例均高于单纯肺结核组,差异有统计学意义（P＜0.05）。肺结核合并下呼吸道感染组患者IL-23R水平明显高于单纯肺结核组,差异有统计学意义（P＜0.05）。结论：与单纯肺结核患者相比较,肺结核合并下呼吸道感染患者临床表现更为严重,CT影像学特点更为明显,患者血清中IL-23R表达水平明显升高,临床可通过CT影像学结合血清IL-23R检测,以提高肺结核合并下呼吸道感染患者的临床诊断。     

Role of some representatives of opportunistic microflora in development of secondary infection in patients with pulmonary tuberculosis]

The results of the laboratory diagnosis of secondary (mixed) infection of the respiratory tracts in patients with respiratory tract tuberculosis were summarized. The study was performed for 12 months in a Tuberculosis Clinic. The species of the pathogens and the frequency of their detection in various clinical specimens from pulmonary tuberculosis patients were determined. The data on resistance of the strains of Streptococcus viridans group isolated from the pulmonary tuberculosis patients to various antimicrobials including new fluoroquinolones are presented.     

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model

Background

Availability of an ultra-short-course drug regimen capable of curing patients with tuberculosis in 2 to 3 mo would significantly improve global control efforts. Because immediate prospects for novel treatment-shortening drugs remain uncertain, we examined whether better use of existing drugs could shorten the duration of treatment. Rifapentine is a long-lived rifamycin derivative currently recommended only in once-weekly continuation-phase regimens. Moxifloxacin is an 8-methoxyfluoroquinolone currently used in second-line regimens.

Methods and Findings

Using a well-established mouse model with a high bacterial burden and human-equivalent drug dosing, we compared the efficacy of rifapentine- and moxifloxacin-containing regimens with that of the standard daily short-course regimen based on rifampin, isoniazid, and pyrazinamide. Bactericidal activity was assessed by lung colony-forming unit counts, and sterilizing activity was assessed by the proportion of mice with culture-positive relapse after 2, 3, 4, and 6 mo of treatment. Here, we demonstrate that replacing rifampin with rifapentine and isoniazid with moxifloxacin dramatically increased the activity of the standard daily regimen. After just 2 mo of treatment, mice receiving rifapentine- and moxifloxacin-containing regimens were found to have negative lung cultures, while those given the standard regimen still harbored 3.17 log₁₀ colony-forming units in the lungs (p < 0.01). No relapse was observed after just 3 mo of treatment with daily and thrice-weekly administered rifapentine- and moxifloxacin-containing regimens, whereas the standard daily regimen required 6 mo to prevent relapse in all mice.

Conclusions

Rifapentine should no longer be viewed solely as a rifamycin for once-weekly administration. Our results suggest that treatment regimens based on daily and thrice-weekly administration of rifapentine and moxifloxacin may permit shortening the current 6 mo duration of treatment to 3 mo or less. Such regimens warrant urgent clinical investigation.     

Polymorphism of the tumor necrosis factor alpha gene in patients with infiltrative tuberculosis and from the Bashkorstan populations

The polymorphism at position -308 of the TNF-alpha gene promoter was analyzed in three ethnic groups and in patients with infiltrative pulmonary tuberculosis from Bashkortostan. No interethnic difference in allele or genotype frequency distribution was observed. The frequency of allele TNF2 in tuberculosis patients was significantly higher than in controls (chi 2 = 11.69, p = 0.001), suggesting an association of this allele with higher risk of pulmonary tuberculosis or a disturbed immune response.     

Potential use of Amplicor PCR kit in diagnosing pulmonary tuberculosis from gastric aspirate.

Polymerase chain reaction (PCR) detection of mycobacteria from gastric aspirate for the diagnosis of tuberculosis is not fully evaluated up to now. A total of 116 gastric aspirate specimens were collected from patients with suspected pulmonary tuberculosis. The breakdown of diagnosis was 67 pulmonary tuberculosis, 16 nontuberculous mycobacterial infection, 5 extra pulmonary tuberculosis, and 28 other lung diseases. The conventional methods were shown to have a sensitivity of 47.8% and a specificity of 79.6%; on the other hand, Amplicor had 34.9% and 97.0%, respectively. The Amplicor provided a more rapid and specific method for diagnosing tuberculosis and was more useful than the conventional.     

多层螺旋CT对肺结核合并肺癌患者的诊断价值

目的:研究多层螺旋CT对肺结核合并肺癌的鉴别诊断价值。方法:选择2013年3月至2015年9月在我院确诊的肺结核合并肺癌患者32例和单纯肺结核患者39例应用多层螺旋CT扫描患者肺部病变情况。结果:肺结核合并肺癌组:陈旧性肺结核28例、活动性肺结核4例;病灶位置经典部位29例、非经典部位3例,合并鳞癌11例、腺癌13例、小细胞癌5例、未分化癌3例;10例结核病灶与肺癌病灶不同侧、13例结核病灶与肺癌病灶同侧不同叶、9例结核病灶于肺癌病灶同侧同叶。单纯性肺结核组胨旧性肺结核36例、活动性肺结核3例;病灶位置经典部位34例(上叶尖段11例、后段9例、下叶背段14例)、非经典部位5例。肺结核合并肺癌组患者分叶征、毛刺征、胸膜凹陷征、阻塞性肺炎及肺不张以及棘状突起比例高于单纯肺结核组,而空泡影比例低于单纯肺结核组,差异具有统计学意义(P0.05);两组钙化、斑片条索影、结节影以及空洞或空腔比较,差异无统计学意义(P0.05)。结论:多层螺旋CT对肺结核合并肺癌具有较高的临床鉴别诊断价值。     

Active tuberculosis in Indochinese refugees in British Columbia.

The incidence of active tuberculosis in 8692 Indochinese refugees admitted to British Columbia between 1979 and 1981 was reviewed. In the first 3 months after entry into the province the rate was extremely high--estimated at 1890/100 000 (126 times the provincial average). A large proportion of these cases were of primary or minimal pulmonary tuberculosis. However, although the proportion of cases of minimal pulmonary tuberculosis was twice the provincial average, the proportion of these cases that were confirmed by culture was only one third the provincial average; this suggests some overdiagnosis in this period. In the subsequent 21 months of residence the incidence of active tuberculosis was also high, at 353/100 000, which was more than 20 times the provincial average. The distribution of cases by severity was closer to the provincial distribution in this period, but advanced disease accounted for a far smaller proportion of cases in both periods than it did in 1980 in the entire province.     

Shifts in the heart left ventricle function in patients with pulmonary tuberculosis during adequate chemotherapy

To investigate the hemodynamics and myocardic contraction of the heart left ventricle, 61 patients with pulmonary tuberculosis (main group) and 26 healthy subjects (control group) were observed. Higher ultimate systolic and diasystolic volumes of the left ventricle and lower levels of the efflux fraction in the patients with active pulmonary tuberculosis were stated. There was shown inverse correlation of the systemic systolic arterial pressure and the left ventricle efflux fraction with ESR, evident of the tuberculosis intoxication. The most pronounced aggravation of the left ventricle function was recorded in the patients with the most severe tuberculosis process. The impairments in the left ventricle in the patients with active pulmonary tuberculosis were of functional nature. Due to intensive therapy of the tuberculosis, the indices of the left ventricle efflux function improved and the systemic arterial pressure came to normal, along with elimination of the tuberculosis intoxication signs.     

Gramnegative opportunistic microflora as etiological factor of secondary infection in patients with pulmonary tuberculosis]

The results of the laboratory diagnoses of respiratory tract secondary infections in patients with pulmonary tuberculosis within a period of 12 months in a tuberculosis clinic were generalized. The species composition of the causative agents of lower respiratory tract secondary infection and the frequency of their detection in various clinical speciments (sputum, bronchial washings) were determined. The data on resistance of the opportunistic gramnegative bacilli (enterobacteria, pseudomonads, Acinetobacter spp.) isolated from the patients with pulmonary tuberculosis to various groups of antibacterials are presented.