A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements

BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) is an important component of any tuberculosis control programme and depends largely on tuberculin skin testing. The appropriate interpretation of skin test results requires knowledge of the possible confounding factors such as previous BCG vaccination. Uncertainty about the effect of BCG vaccination on tuberculin skin testing and the strength with which recommendations are made to individual patients regarding treatment of LTBI have identified a need to analyse the available data on the effect of BCG on skin testing. A meta-analysis of the evidence for the effect of BCG vaccination on tuberculin skin testing in subjects without active tuberculosis was therefore performed. METHODS: Medline was searched for English language articles published from 1966 to 1999 using the key words "BCG vaccine", "tuberculin test/PPD", and "skin testing". Bibliographies of relevant articles were reviewed for additional studies that may have been missed in the Medline search. Articles were considered for inclusion in the meta-analysis if they had recorded tuberculin skin test results in subjects who had received BCG vaccination more than 5 years previously and had a concurrent control group. Only prospective studies were considered. The geographical location, number of participants, type of BCG vaccine used, type of tuberculin skin test performed, and the results of the tuberculin skin test were extracted. RESULTS: The abstracts and titles of 980 articles were identified, 370 full text articles were reviewed, and 26 articles were included in the final analysis. Patients who had received BCG vaccination were more likely to have a positive skin test (5 TU PPD: relative risk (RR) 2.12 (95% confidence interval (CI)1.50 to 3.00); 2 TU RT23: 2.65 [corrected] (95% CI 1.83 to 3.85). The effect of BCG vaccination on PPD skin test results was less after 15 years. Positive skin tests with indurations of >15 mm are more likely to be the result of tuberculous infection than of BCG vaccination. CONCLUSIONS: In subjects without active tuberculosis, immunisation with BCG significantly increases the likelihood of a positive tuberculin skin test. The interpretation of the skin test therefore needs to be made in the individual clinical context and with evaluation of other risk factors for infection. The size of the induration should also be considered when making recommendations for treatment of latent infection.     

IFN-γ酶联免疫斑点法与结核菌素皮试在附睾结核检测中的应用比较

目的:将新兴的结核特异性IFN-γ酶联免疫斑点法(ELISPOT)应用于附睾结核检测,并比较其与传统的结核菌素皮试(PPD)在附睾结核及健康对照组中检测的差异,探讨ELISPOT在附睾结核诊断中的应用前景。方法:采用自主研制的ELISPOT试剂盒对13例附睾结核患者进行检测;采用PPD对11例附睾结核患者检测。同时采用2种方法对57例健康男性志愿者进行平行检测。结果:附睾结核患者,ELISPOT阳性率92.3%(12/13),PPD阳性率90.9%(10/11),2种方法差异无显著性(P>0.05)。健康志愿者中ELISPOT阳性率14.0%(8/57),PPD阳性率49.1%(28/57),两者差异有极显著性(P<0.01)。结论:附睾结核检测中ELISPOT在敏感性上与PPD一致,在区分附睾结核与健康人方面特异性优于PPD,在附睾结核诊断上有较好的应用前景。     

Mycobacterial isolations in young adults with cystic fibrosis.

In 223 patients admitted to hospital with cystic fibrosis mycobacteria were found in the sputa of seven. All of these cases were identified over a six year period after the introduction of routine examination and culture of sputum for acid fast bacilli in patients with cystic fibrosis. The organisms isolated were Mycobacterium tuberculosis in three patients, M chelonei in one, M fortuitum in one, and unidentified mycobacteria in two. The diagnosis was not suspected on clinical grounds in any of the cases; in one patient, however, night sweats were a prominent feature before diagnosis. In four of the patients direct sputum smear examination did not reveal the organism, which was grown subsequently in culture. An unusual phenomenon of liquefaction of the Lowenstein-Jensen culture medium was encountered in five of the seven patients described, which in one case made identification and sensitivity testing of the organism impossible. This phenomenon has been observed in sputum cultures from other patients with cystic fibrosis but not in other pulmonary diseases. Immunological studies performed in three of the patients showed normal numbers of peripheral blood T and B lymphocyte in all three; in vitro lymphocyte transformation to tuberculin PPD was, however, reduced in the patient with extensive M fortuitum infection, which proved fatal. Mycobacteria may be present in the sputa of patients with cystic fibrosis more often than previously recognised and therefore sputum examination and culture for mycobacteria should be performed periodically in these patients.     

Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay

BACKGROUND: Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting Mycobacterium tuberculosis DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. METHODS: Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested for M tuberculosis using PCR, acid fast staining (AFS), and culture. RESULTS: Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. CONCLUSIONS: Urine based nested PCR for M tuberculosis may be a useful test for identifying HIV patients with pulmonary tuberculosis.     

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation.     

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

BackgroundEarly signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk.MethodsA retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984–2015.ResultsThree-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40–100) and specificity 77% (95% CI 72–81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay.ConclusionsAntibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.     

The value of tuberculin skin testing in haemodialysis patients.

BACKGROUND: Chronic haemodialysis patients are at increased risk for developing tuberculosis (TB). Appropriate screening methods to detect latent Mycobacterium tuberculosis infection are required. The aim of this prospective multi-centre study was to evaluate the tuberculin skin test (TST) as a screening method for detection of M.tuberculosis infection in haemodialysis patients. METHODS: A total of 224 patients in two haemodialysis centres were prospectively tested, using 2 units of tuberculin PPD RT23. Up to three booster injections were given with a 7 day interval to patients not responding to the previous test. The results were compared with clinical and radiological data. RESULTS: The cumulative prevalence of a positive TST was 14.7% for the first test, 27.8% for the second test and 32.6% for the fourth test. There was no influence of age, gender, haemodialysis centre, dialysis efficiency, nutritional state, levels of zinc, vitamin D therapy, primary renal disease, (previous or active) immunosuppressive therapy or response to hepatitis B vaccination. There was a significant, but weak, correlation between TST positivity and a history of positive TST or TB. Chest radiography and positive TST were not correlated, yet a positive chest X-ray increased the detection of patients with latent M.tuberculosis infection up to 47.8%. CONCLUSIONS: In haemodialysis patients, a positive response of >30% to repeated TST was obtained. Two consecutive TSTs were sufficient to recruit most of the booster reactions. Since only a weak correlation was found with anamnestic data, regular TST evaluation in combination with a chest X-ray, is a useful tool to detect infection with M.tuberculosis in haemodialysis patients.     

Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients

BACKGROUND: Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection. METHODS: One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing. RESULTS: Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6. CONCLUSION: Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.     

Tuberculin skin test and anergy in dialysis patients of a tuberculosis-endemic area

BACKGROUND/AIM: Uremic patients are at an increased risk of being affected by tuberculosis (TB). Periodical tuberculin skin tests were suggested to detect TB-infected patients. These were replaced by chest radiographs in endemic areas like Taiwan. However, almost 50% of the TB incidence in dialysis patients was extrapulmonary. In this study, we tried to investigate the value of tuberculin tests in dialysis patients in endemic areas. METHODS: The patients were recruited from our dialysis unit. Purified protein derivative (PPD) and control tests with antigens for Candida and toxoid were performed using the Mantoux method. PPD with >10-mm induration will be considered positive. Skin anergy meant that the indurations of all antigens were less than 5 mm. A follow-up was done 12 months after the tests. RESULTS: A total of 177 patients were evaluated. Anergy was found in 40 patients (22.6%). A positive predictor of anergy was age >45 years (p = 0.03), while a negative predictor was prealbumin >20 mg/dl (p = 0.04). Fifty-three patients (30%) had positive PPD tests. Seven of the positive PPD patients (13.2%) developed active TB during the following years. Among the 40 patients with skin anergy, 6 (15%) were found to have active TB. Of the 48 patients (21.1%) with indurations of the PPD tests between 5 and 10 mm, none was found to have active TB. CONCLUSION: Although anergy will influence the sensitivity of PPD tests, these tests in combination with anergy tests could help to establish the diagnosis of TB in uremic patients, even in TB-endemic areas.     

Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection

BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. METHODS: Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes were separated, cytocentrifuged onto glass microscope slides, and reacted with anti-gamma/delta monoclonal antibody. The percentage of gamma/delta positive cells was determined by microscopic counting of 300 lymphocytes. RESULTS: No difference was found in the percentage of gamma/delta T lymphocytes between patients and controls. However, when the patients were divided into two groups according to reactivity or non-reactivity in the Mantoux skin reaction a higher percentage of gamma/delta T lymphocytes was found in the peripheral blood of patients with tuberculin anergy than in tuberculin positive patients or controls. CONCLUSIONS: Higher gamma/delta T cell counts are found in tuberculin negative patients with tuberculosis than in tuberculin positive patients or tuberculin positive controls. The high gamma/delta T cell counts in tuberculin anergic patients may reflect a shift in the immune response in a Th2 direction characterised by increased antibody production and decreased cell mediated responses.


     

Tuberculin positivity: A serious problem before transplantation in Turkey

Chronic renal failure (CRF) patients are at increased risk of tuberculosis. Detecting latent tuberculosis infection is essential before transplantation. The tuberculin skin test is the only validated method for the diagnosis of latent tuberculosis infection and for screening for hypersensitivity. The aim of this study was to assess the tuberculin test status (5 Todd units tuberculin) of 164 asymptomatic transplant candidates and correlate it with anamnestic data and laboratory values of patients awaiting transplantation. Skin test positivity was higher among older age subjects (r = .294, P = .0001). The cumulative prevalence rates of tuberculin positivity and anergy were 42.1% (69 patients) and 43.3% (71 patients), respectively. Only 14.5% of the positive patients had a previous tbc history; 15.9% had a family history of tbc. Among peritoneal dialysis (PD) patients, the rate of anergic skin tests was higher, while positivity was higher among patients who were preparing for preemptive renal transplantation (P = .009). In conclusion, there was a high prevalence of tuberculin positivity and anergy among asymptomatic pretransplant CRF patients. CRF patients who are awaiting transplantation especially should meet evaluations for previous tbc anamnesis and family history. Elderly subjects showed a higher risk for purified protein derivate positivity.     

Tuberculin testing of kidney allograft recipients and donors before transplantation

Immunocompromised patients such as those with chronic renal failure requiring hemodialysis (HD) are at increased risk of developing tuberculosis (TB). The gold standard screening tool used to detect tuberculosis is the tuberculin test, which owes its popularity to its ease of administration and high sensitivity. This study was done to identify the incidence of tuberculin test positivity among dialysis patients before transplantation and also in volunteer living kidney donors. PATIENTS AND METHODS: This cross-sectional, comparative study was done on 308 kidney allograft recipient candidates, 80 potential living unrelated and related donors within a few months before transplantation, and 855 control cases before employment. Patients were tuberculin-tested using the Mantoux technique. The PPD (purified protein derivative)-positive dialysis patients were compared with PPD-negative subjects, regarding age, gender, dialysis duration, cause of chronic renal failure, and nutritional state as well as PPD test results in potential donors. Patients were divided into <10 mm versus > or =10 mm induration. Statistical analysis was performed using SPSS 11.0. RESULTS: The mean age of the donors was 26.6 +/- 4.6 years with a male:female ratio of 87.5%:12.5%. The tuberculin test was positive in 11.25% of cases, all of whom were males with with induration >10 mm. There was no significant difference regarding the PPD results and age. The mean age of recipients was 40.1 +/- 14.7 years with a male/female ratio of 1.3:1. The tuberculin test was positive in 33.6% of recipient candidates. Mean duration on dialysis was 2.5 +/- 1.2 years. No significant correlation existed regarding the dialysis duration, cause of renal failure, c-reactive protein, erythrocyte sedimentation rate, and response to tuberculin test. There was a direct relationship between age and PPD test results (Pearson correlation +192). CONCLUSION: Our results showed that more dialysis patients were PPD positive compared with donors.     

Superior Sensitivity of Ex Vivo IFN‐γ Release Assays as Compared to Skin Testing in Immunocompromised Patients

Comparative assessment of the tuberculin skin testing (TST) and commercial IFN‐γ release‐assays (IGRAs) is hampered by the use of different antigens (tuberculin PPD in TST vs. ESAT‐6/CFP‐10 in IGRAs). Thus, PPD was used as a common stimulus to compare performance of the TST and three IGRAs in 72 controls, 101 hemodialysis patients and 100 renal transplant recipients. Results of the TST were compared with PPD‐induced IFN‐γ induction in vitro detected by ELISPOT, ELISA or a flow‐cytometric FACS assay. Percentages of positive tests were significantly lower in TST (9.2%) compared to ELISA (55.3%), ELISPOT (45.3%) and FACS (44.9%, p < 0.0001). Agreement between TST and IGRAs was highest for controls (κ = 0.19–0.32) and poor in immunocompromised patients (κ = 0 for transplant patients, κ = 0.06–0.13 for hemodialysis patients). Discrepant results were largely TST negative and IGRA positive. Among IGRAs, agreement was highest between ELISPOT and FACS (κ = 0.61). Unlike TST, all IGRAs were associated with variables of mycobacterial exposure. Among IGRAs, the FACS assay was least affected by the level of immunosuppression. In conclusion, both the percentage of positive results and between‐test‐agreement were higher with IGRAs as compared to TST. This indicates superiority of IGRAs in detecting a PPD‐specific immune response which may also apply for immunity toward Mycobacterium tuberculosis–specific antigens.     

γ-干扰素释放反应与PPD皮试在肾结核诊断应用比较

目的：采用结核分枝杆菌特异性IFN-γ免疫酶联斑点法（Elispot）与传统的结核菌素（PPD）皮试对肾结核患者及健康人群结核分枝杆菌感染现状进行检查,并比较两种方法的差异。方法：采用自主研制的Elispot试剂盒和PPD皮试,对14例肾结核患者及133例健康志愿者进行平行检测。结果：14例肾结核患者检测中,13例PPD阳性,12例Elispot阳性,差异无统计学意义。133例志愿者中86例PPD阳性,22例Elispot阳性,差异有统计学意义。结论：Elispot试剂盒在健康人群中检测阳性率远低于PPD皮试,而在肾结核的检测中差异无统计学意义。Elispot在区分肾结核患者与健康人方面价值优于PPD皮试。在肾结核的诊断有较好的发展前景。     

Tuberculosis screening in dialysis patients--is the tuberculin test effective?

AIM: Patients with end-stage renal disease are at increased risk for tuberculosis (TB). The Centers for Disease Control and Prevention (CDC) has recommended annual skin testing for TB, with tuberculin-purified protein derivative (PPD), in patients with chronic renal failure. The aim of this study was to identify the incidence and prevalence oftuberculin positivity and assess the utility of the tuberculin test in an inner city dialysis population. METHODS: All patients on chronic hemodialysis at a center affiliated to the University of Chicago, who were tuberculin-tested between 1997 and 2000 or had previously documented PPD positivity precluding retesting, were included. Demographics, comorbidity, and tuberculin and anergy reactivity were recorded. A positive PPD was an induration of > 10 mm in response to 5 tuberculin units of PPD, and anergy an induration of < 2 mm in response to the anergy antigens (Candida and Mumps), at 48 h. PPD-positive patients were compared with PPD-negative patients; Fisher's exact test and t-test were used, p < 0.05 was considered significant. RESULTS: Of 131 patients at the dialysis center, 118 were studied. The remaining 13 refused consent to PPD testing. 41 (35%) were PPD-positive, 77 (65%) were negative. Of the 77 PPD-negative patients, 62 (81%) were anergic. None of the PPD-positive patients had clinical or radiographic signs of active TB. Only 20 patients received INH prophylaxis, the others refused or had contraindications to therapy. The conversion rate ranged from 3 - 8% per year. Demographics, nutritional parameters, comorbidity and adequacy of dialysis did not help predict PPD positivity. CONCLUSION: There is a high prevalence of PPD positivity and anergy among dialysis patients. As the diagnostic utility of the time-tested PPD test is unclear in an anergic dialysis population, the need for a high index of suspicion for active tuberculosis and timely diagnostic work up should be reinforced and not replaced by total dependence on the tuberculin test.     

Lack of skin test reactivity to common mycobacterial antigens in human immunodeficiency virus infected individuals with high CD4 counts.

BACKGROUND: T cell response to mycobacterial antigens may be directed against those antigens common to all mycobacteria (group i), those restricted to slow (group ii) or fast growers (group iii), or those which are species- or subspecies-specific (group iv). These responses were assessed by skin testing patients infected with the human immunodeficiency virus (HIV) and healthy controls with reagents derived from different strains of mycobacteria. METHODS: Skin test responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium serotypes 4 and 8, and either M intracellulare or M flavescens antigens were evaluated prospectively in 51 HIV infected patients and 67 healthy controls. RESULTS: Assessment of induration at 72 hours showed absence of skin test response to common mycobacterial antigens in all 27 HIV positive patients with CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27% reactivity in controls; complete anergy was demonstrated in 24 patients with CD4 counts of < 400/mm3. By contrast, no difference in species or subspecies-specific responses was found between healthy controls and HIV positive patients with CD4 counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are instrumental in determining the balance between cell-mediated and humoral immunity. One T helper subset (TH1) produces cytokines that increase cellular immunity and is stimulated by group i common mycobacterial antigens. Lack of this response, but preservation of responses to species-specific antigens while CD4 counts are near normal, may indicate an early failing of TH1 immunity and explain the increased susceptibility of HIV positive patients to mycobacterial infection early on in the evolution of their HIV infection.     

Long-term survival and nutritional data in patients with cystic fibrosis treated in a Danish centre.

BACKGROUND: Adequate nutrition and optimal treatment of bronchopulmonary infections are both of critical importance in maintaining the health of patients with cystic fibrosis. The cystic fibrosis centre in Copenhagen has followed a regimen of very early and aggressive antimicrobial treatment, especially against Pseudomonas aeruginosa infection. An unrestricted diet of low fat and high protein without hyperalimentation was recommended before 1985 which was then changed to a high fat, high calorie intake. METHODS: The overall impact of the treatment regimen was evaluated by a cross sectional analysis of all 223 patients who attended the centre in 1989. Growth and nutritional parameters were combined with lung function parameters and with a retrospective analysis of chronic P aeruginosa infection and its duration. Survival curves for all 313 patients treated at the centre since 1949 were calculated. RESULTS: All the patients with cystic fibrosis had normal height, although the final height was achieved a little later than in healthy controls. Body weight was lower than normal in males above 15 and in females above 10 years of age. The body mass index (BMI), which was approximately 98% of normal in the younger patients, declined to 90% in adult men and to 83% in adult women with cystic fibrosis, and was strongly correlated with lung function parameters. In 1989 the median age of survival of all patients treated in the centre since 1949 was 30 years (32 years in males and 29 years in females). CONCLUSIONS: The overall treatment regimen in the cystic fibrosis centre in Copenhagen is associated with growth and survival rates that are at least equal to those in other cystic fibrosis centres in other countries.     

酶联免疫斑点法在快速诊断活动性肺结核中的应用

目的探讨酶联免疫斑点法（ELISPOT）在临床快速诊断活动性肺结核病中的应用价值。方法：采用T—SPOT．TB试剂盒对36例明确诊断为活动性肺结核的初治患者、30例健康体检者的外周血中结核分枝杆菌特异性T淋巴细胞进行检测,同时对26例活动性肺结核患者做结核菌素（PPD）试验。结果在36例活动性肺结核初治患者和30例健康对照者中,T-SPOT检测的阳性率分别为80．6％与6．7％,此技术用于诊断初治活动性肺结核患者的敏感性为80．6％,特异性为93．3％,阳性预测值为93．5％,阴性预测值为80．0％。在26例同时做PPD试验的活动性肺结核患者中,T-SPOT检测的阳性率略高于PPD试验（80．6％vs61．5％）,但差异无明显统计学意义（P〉0．05）。结论酶联免疫斑点法是一种具有较高敏感性和特异性的检测结核感染的技术,在活动性肺结核病的快速诊断中有较大应用价值。     

Clinical characteristics of tuberculous infection following renal transplantation

ObjectiveThis study investigated the clinical characteristics of patients with tuberculosis (TB) following renal transplantation (RT) in order to identify markers or signs that can facilitate early diagnosis.MethodsA retrospective analysis was performed on 12 cases of Mycobacterium tuberculosis infection treated at our hospital between 2005 and 2020.ResultsThe incidence of TB after RT at our hospital was 0.9%, and the median postoperative onset time was 22 months. The average age of patients included in our analysis was 44.2 ± 9.4 years; 11 of the 12 patients were male, and most patients had (low) fever as the first or only manifestation. Five patients had respiratory symptoms; 5 had typical computed tomography (CT) presentation; and 2 had a confirmed history of TB. Two sputum smears from 12 patients were positive by acid fast staining, and M. tuberculosis was detected in peripheral blood samples by metagenomic next-generation sequencing (NGS). One patient had a positive result in the purified protein derivative (PPD) test, 7 were positive with the interferon gamma release assay (IGRA), 8/12 patients were confirmed to have TB infection by NGS and 1 was confirmed positive by lung biopsy.ConclusionBecause of the use of immunosuppressive agents, most patients with TB following RT have atypical clinical symptoms and CT findings, and may have a high probability of a false negative result with the traditional PPD test and a low probability of M. tuberculosis detection, making early diagnosis difficult. Therefore, in RT recipients with prolonged fever of unknown origin and unusual clinical manifestations, especially those who are unresponsive to antibiotic treatment, a diagnosis of TB should be considered. The interferon gamma release assay and NGS are relatively new detection methods with high sensitivity and specificity; these along with regular, repeated testing by various approaches can aid the early diagnosis of TB.