Yoshihiro Kobashi

Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients

The usefulness of the tuberculin skin test (TST) and the QuantiFERON TB-2G (QFT-TB) test were compared in immunocompromised patients. The subjects consisted of 252 immunocompromised patients who were clinically suspected of tuberculosis (TB) infection between April 2005 and December 2006. Regarding the underlying diseases, 74 subjects had malignant diseases, 72 were undergoing immunosuppressive treatment, 52 had diabetes mellitus, 50 had chronic renal failure and four had HIV infection. While the positive rate of the QFT-TB test for the diagnosis of TB infection (TB disease or latent TB infection) was 78.1%, that of TST for TB infection was 50.0%. The QFT-TB test was significantly better than TST. However, 32 (13%) patients had an indeterminate QFT-TB result. Indeterminate findings were significantly more frequent in patients receiving immunosuppressive treatment (28%), especially with lymphocytopaenia in the peripheral blood, than in those who had other underlying diseases. While TST-positive and QFT-TB test-negative results were recognised in immunocompromised patients with bacille Calmette–Guérin vaccination or nontuberculous mycobacterial disease, TST-negative and QFT-TB test-positive results were recognised in immunocompromised patients with a past history of TB infection. It was concluded that the QuantiFERON TB-2G test is a more useful diagnostic method for tuberculosis infection than tuberculin skin test for immunocompromised patients suspected of tuberculosis disease. However, because the results of the QuantiFERON TB-2G test show an indeterminate response for patients receiving immunosuppressive treatment, especially for those with lymphocytopaenia due to severe underlying diseases, care must be taken in the interpretation of the QuantiFERON TB-2G test for these patients.

Clinical and Microbiological Differences between Mycobacterium abscessus and Mycobacterium massiliense Lung Diseases

ABSTRACT In recent years, many novel nontuberculous mycobacterial species have been discovered through genetic analysis. Mycobacterium massiliense and M. bolletii have recently been identified as species separate from M. abscessus. However, little is known regarding their clinical and microbiological differences in Japan. We performed a molecular identification of stored M. abscessus clinical isolates for further identification. We compared clinical characteristics, radiological findings, microbiological findings, and treatment outcomes among patients with M. abscessus and M. massiliense lung diseases. An analysis of 102 previous isolates of M. abscessus identified 72 (71%) M. abscessus, 27 (26%) M. massiliense, and 3 (3%) M. bolletii isolates. Clinical and radiological findings were indistinguishable between the M. abscessus and M. massiliense groups. Forty-two (58%) patients with M. abscessus and 20 (74%) patients with M. massiliense infections received antimicrobial treatment. Both the M. abscessus and M. massiliense groups showed a high level of resistance to all antimicrobials, except for clarithromycin, kanamycin, and amikacin. However, resistance to clarithromycin was more frequently observed in the M. abscessus than in the M. massiliense group (16% and 4%, respectively; P = 0.145). Moreover, the level of resistance to imipenem was significantly lower in M. abscessus isolates than in M. massiliense isolates (19% and 48%, respectively; P = 0.007). The proportions of radiological improvement, sputum smear conversion to negativity, and negative culture conversion during the follow-up period were higher in patients with M. massiliense infections than in those with M. abscessus infections. Patients with M. massiliense infections responded more favorably to antimicrobial therapy than those with M. abscessus infections.

Clinical Reevaluation of the QuantiFERON TB-2G Test as a Diagnostic Method for Differentiating Active Tuberculosis from Nontuberculous Mycobacteriosis

INTRODUCTION We reevaluated the usefulness of a whole-blood interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON TB-2G [QFT-TB]; Cellestis) in obtaining a differential diagnosis between active tuberculosis (TB) and nontuberculous mycobacteriosis (NTM). METHODS The subjects were 50 healthy volunteers, 50 patients with active TB, and 100 patients with NTM who satisfied the diagnostic guidelines of the American Thoracic Society from April 2005 through June 2006. The tuberculin skin test (TST) and the QFT-TB test were performed for all subjects. The QFT-TB test was performed every 2 months. RESULTS Of the healthy volunteers, 64% had a negative TST result and 94% had a negative QFT-TB test result. Of the patients with active TB, 64% had a positive TST result and 4% had a negative QFT-TB test result. Of the patients with pulmonary Mycobacterium avium complex disease, 60% had a positive TST result and 7% had a positive QFT-TB test result. The QFT-TB test had a mean sensitivity of 86% and a mean specificity of 94%. The QFT-TB test results for patients with active TB transiently decreased during treatment involving antituberculous drugs. The rate of positive QFT-TB test results was 86% at the initiation of treatment, 48% 6 months later, and 33% 12 months later. CONCLUSIONS We confirmed that the QFT-TB test is a useful diagnostic method for differentiating active pulmonary TB from NTM, compared with the TST. However, because it is possible that the effect of the QFT-TB test may be long lasting after treatment and may not be resolved over time, even with treatment, as in this study, it may not provide any level of certainty regarding cure of infection.

Clinical Utility of the QuantiFERON TB-2G Test for Elderly Patients With Active Tuberculosis

OBJECTIVE To evaluate the response to the QuantiFERON-TB-2 Gold (QFT-2G) test (Cellestis Ltd; Carnegie, VIC, Australia) in elderly patients with active tuberculosis (TB) to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in this group of patients. METHODS The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens. RESULTS Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB. CONCLUSION We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.

Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice

The present authors assessed risk factors that can promote indeterminate results of QuantiFERON TB-2G (QFT-2G; Cellestis Ltd, Carnegie, Australia) tests. The subjects were 704 patients with suspected tuberculosis (TB) and latent TB infection between January 2005 and December 2007. The QFT-2G test and the tuberculin skin test (TST) were performed for all subjects. If the results of the QFT-2G test were indeterminate, the test was repeated within 1 month. In total, 72 (10.2%) patients showed indeterminate results on the QFT-2G test. Indeterminate results were due to positive control failure in 68 (88.9%) patients and negative control failure in four patients. The results of the TST were negative for 64 patients showing indeterminate results, the remaining eight patients showed a positive response to the TST. Indeterminate results were significantly associated with elderly and immunocompromised patients. Lymphocytopaenia and hypoalbuminaemia were significantly associated with indeterminate laboratory findings. When the QFT-2G test was repeated for all patients showing indeterminate results, 12 (16.7%) patients demonstrated determinate results on the subsequent test. Indeterminate results of the QuantiFERON TB-2G test under routine clinical practice are not infrequent. When scoring QuantiFERON TB-2G test results for elderly and immunocompromised patients, one must be careful because the possibility of obtaining determinate results may be low even if the test is repeated.

The Microbiological and Clinical Effects of Combined Therapy according to Guidelines on the Treatment of Pulmonary Mycobacterium avium Complex Disease in Japan – Including a Follow-Up Study

Background: The difficulty of treatment for pulmonary Mycobacterium avium complex (MAC) in Japan. Objectives: To investigate the clinical and microbiological effects of treatment according to the guidelines proposed by the American Thoracic Society and the Japanese Society for Tuberculosis and prospective follow-up studies after the completion of treatment of patients with pulmonary MAC disease. Methods: Analysis of the microbiological effects with regard to sputum conversion rate and the sputum relapsing rate and the clinical effects with regard to clinical symptoms and radiological findings for patients with pulmonary MAC disease treated with a regimen consisting of rifampicin, ethambutol, streptomycin, and clarithromycin over 24 months and follow-up over 12 months. Results: Sixty-five patients with pulmonary MAC disease were enrolled in this trial. In 39 patients, negative sputum conversion was observed within 6 months after the initiation of this regimen, 16 relapsed, and 20 experienced clinical worsening within 1 year after the completion of treatment. Although retreatment with the same regimen or a regimen including new quinolones was carried out for these patients, we could not achieve negative sputum conversion and/or clinical improvement. Conclusions: We believe that the dose of clarithromycin for pulmonary MAC disease may be increased and recommend surgery for patients with a localized lesion at early-stage MAC disease to prevent a high rate of relapse.

Transitional changes in T-cell responses to Mycobacterium tuberculosis-specific antigens during treatment

BACKGROUND Currently, there is no available test for monitoring the clinical effect of active tuberculosis (TB) disease treatment. Therefore, we studied the usefulness of two commercial IFN-gamma assays (QuantiFERON TB-2G (QFT-2G) and T-SPOT.TB tests) for monitoring clinical efficacy. METHODS The subjects were 40 patients with active TB disease. These two commercial IFN-gamma assays were carried out every three months during active TB disease treatment. RESULTS While the positive response rate of QFT-2G test significantly decreased from 83% at treatment initiation to 58% at treatment completion, that of T-SPOT.TB decreased from 90% at treatment initiation to 63% at treatment completion. Although there was a significant decrease in patients with TB infection showing positive responses for ESAT-6 only or CFP-10 only antigens on both IFN-gamma assays, there was no significant decrease in patients showing positive responses for both ESAT-6 and CFP-10 antigens on both IFN-gamma assays. On both QFT-2G test and T-SPOT.TB test, the mean values of the IFN-gamma levels in the pre- and post-treatment responses showed significantly decreased responses to CFP-10. On the other hand, smear conversion results of clinical specimens were obtained in all patients at treatment completion. CONCLUSIONS Antituberculous treatment induced a significant decrease in T-cell responses to separate ESAT-6 and CFP-10 antigens as measured by both IFN-gamma assays. Although IFN-gamma assays might be later than smear conversion results of clinical specimens, the quantitative responses especially to CFP-10 may be one of the useful monitoring markers of clinical efficacy for active TB disease treatment.

Chronic necrotizing pulmonary aspergillosis as a complication of pulmonary Mycobacterium avium complex disease.

Objective and background:  To investigate the characteristic clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) as a complication of pulmonary Mycobacterium avium complex (MAC) disease.

Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis and performance timing.

BackgroundThe Japanese Respiratory Society guidelines propose a differential diagnosis for atypical pneumonia and bacterial pneumonia using a scoring system for the selection of appropriate antibiotic. In order to improve this scoring system, the guidelines are seeking new specific parameter. The purpose of this study was to clarify the pattern of abnormalities with Mycoplasma pneumoniae pneumonia on chest computed tomography (CT) and whether the radiographic findings could distinguish M. pneumoniae pneumonia from Streptococcus pneumoniae pneumonia.MethodsA retrospective review was performed of the CT findings of 64 cases and 68 cases where M. pneumoniae and S. pneumoniae, respectively, were the only pathogen identified by the panel of diagnostic tests used.ResultsOf the 64 patients with M. pneumoniae pneumonia, bronchial wall thickening was observed most frequently (81%), followed by centrilobular nodules (78%), ground-glass attenuation (78%), and consolidation (61%). Bronchial wall thickening and centrilobular nodules were observed more often in M. pneumoniae patients than in S. pneumoniae patients (p < 0.0001). The presence of bilateral bronchial wall thickening or centrilobular nodules was only seen in patients with M. pneumoniae pneumonia. Using the scoring system of the Japanese Respiratory Society guidelines and chest CT findings, 97% of M. pneumoniae patients were suspected to be M. pneumoniae pneumonia without serology. When comparing the CT findings between early stage and progressed stage in the same patients with severe pneumonia, the radiographic features of early stage M. pneumoniae pneumonia were not observed clearly in the progressed stage.ConclusionThe present results indicate that the diagnosis of M. pneumoniae pneumonia would appear to be reliable when found with a combination of bronchial wall thickening and centrilobular nodules in the CT findings. However, these CT findings are not observed in progressed severe M. pneumoniae pneumonia patients.

Evaluating the Use of a Streptococcus pneumoniae Urinary Antigen Detection Kit for the Management of Community-Acquired Pneumonia in Japan

Background: The urinary antigen detection kit for Streptococcus pneumoniae was tested. Objectives: It was our aim to evaluate the usefulness of the immunochromatographic membrane test by doing a large prospective study of community-acquired pneumonia (CAP) in Japan. Methods: We prospectively evaluated the use of the S. pneumoniae urinary antigen detection kit and analyzed the treatment and clinical effect seen in patients with positive test kit results. One hundred and fifty-six patients with CAP admitted to our hospital between October 2001 and September 2003 were evaluated. Results: In 49% of these CAP patients, the causative microorganisms were isolated. S. pneumoniae was suspected to be the causative microorganism in 15%, but positive results of the urinary antigen detection kit indicated S. pneumoniae to be a probable microorganism in 28%, even though antibiotics had previously been administered to half of the patients. The kit was particularly useful for diagnosing patients with poor quality sputum in whom antibiotics treatment nevertheless had to be selected. Antibiotics appropriate for S. pneumoniae (mainly penicillin) were given. The treatment was found to have excellent clinical results in 89% of the CAP patients. Conclusions: The S. pneumoniae urinary antigen detection kit was considered to be useful in selecting treatment since there was a high level of clinical effectiveness when the most suitable antibiotics were immediately administered to positive patients. The use of the S. pneumoniae urinary antigen kit is rapid and simple compared with conventional microbiological procedures.