Yutsuki Nakajima

Screening for Tuberculosis Infection Using Whole‐Blood Interferon‐γ and Mantoux Testing Among Japanese Healthcare Workers

OBJECTIVE To examine the hypothesis that results of the QuantiFERON-TB Gold assay (QFT-G), a whole-blood test for detection of tuberculosis infection, are more significantly related to known risk factors for tuberculosis infection in healthcare workers (HCWs) who have received bacille Calmette-Guerin vaccine than are results of the Mantoux tuberculin skin test (TST). DESIGN All HCWs (approximately 510) from a 370-bed general hospital in Tokyo where patients with and patients without tuberculosis are treated were invited to participate in the study. All study participants completed a questionnaire about their Mycobacterium tuberculosis infection risk factors as HCWs at the general hospital. They were then tested for LTBI by means of the QFT-G, followed by the TST. Statistical analyses were performed to compare results of each test with M. tuberculosis infection risk factors (age, length of employment in the healthcare industry, history of working with tuberculosis-positive patients in a tuberculosis ward or in the outpatient department of the hospitals tuberculosis clinic for more than 1 year, chest radiograph evidence of healed tuberculosis, history of performing bronchoscope procedures, and job classification), and for TST-positive HCWs, to compare the QFT-G result with the TST induration diameter. RESULTS A total of 332 HCWs (95% of whom had been vaccinated with BCG) participated in the study, and 33 had positive QFT-G results, suggesting a prevalence of LTBI of 9.9%. Of 304 HCWs who underwent TST, 283 (93.1%) had an induration diameter of 10 mm or more. Multiple logistic regression analysis revealed that positive QFT-G results were significantly associated with age and with a history of working in a tuberculosis ward or an outpatient department of a tuberculosis clinic. TST results were not correlated with any of the tuberculosis infection risk factors we evaluated. CONCLUSIONS Positive QFT-G results were closely associated with the presence of risk factors for LTBI in a hospital setting, suggesting that the QFT-G can detect LTBI in a population composed predominantly of BCG vaccinees. Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.

Diagnosis of Active Tuberculous Serositis by Antigen-Specific Interferon-γ Response of Cavity Fluid Cells

BACKGROUND To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens. METHODS Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology. Culture was performed for 18 h with fluid mononuclear cells in the supernatant of the effusion together with saline or Mycobacterium tuberculosis-specific antigenic peptides, early secretory antigenic target 6 and culture filtrate protein 10. IFN-gamma concentrations in the culture supernatants were measured. RESULTS In patients with active tuberculous serositis, antigen-specific IFN-gamma responses of cavity fluid samples were significantly higher than those of nontuberculous effusion samples. Area under the receiver operating characteristic (AUROC) curve was significantly greater for cavity fluid IFN-gamma response (AUROC curve, 0.996) than for cavity fluid adenosine deaminase and whole-blood IFN-gamma responses (AUROC curve, 0.882 and 0.719, respectively; P = .037 and P < .001, respectively). Although the AUROC curve was greater for cavity fluid IFN-gamma response than for background cavity fluid IFN-gamma level (AUROC curve, 0.975), the AUROC curves were not statistically significantly different (P = .74). However, multivariate logistic regression analysis revealed that cavity fluid IFN-gamma responses were significantly associated with the diagnosis, even after adjustment for background IFN-gamma level (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P < .001). CONCLUSIONS The cavity fluid IFN-gamma assay could be a method for accurately and promptly diagnosing active tuberculous serositis.

Reversion rates of QuantiFERON-TB Gold are related to pre-treatment IFN-gamma levels

OBJECTIVE The quantitative interferon (IFN)-gamma in response to Mycobacterium tuberculosis-specific antigens declines in tuberculosis patients after starting treatment, however, in some cases remains high despite clinical improvements. Our aim was to evaluate clinical parameters associated with remaining QuantiFERON-TB Gold (QFT-G) positive after treatment. METHODS A prospective cohort study of 101 culture-positive, positive QFT-G, HIV-uninfected patients with pulmonary tuberculosis. QFT-G was performed at diagnosis, at the end of intensive phase, at treatment completion, and 5-7 months post-treatment completion. RESULTS There were 80 patients with complete results, 34 (43%) remaining QFT-G positive and 46 (58%) reverting to QFT-G negative at the 5-7 month post-treatment time point. There was a significant decline in IFN-gamma levels in response to both CFP-10 and ESAT-6 with tuberculosis treatment. Multivariate analysis revealed significant associations between IFN-gamma levels detected before treatment and remaining QFT-G positive post-treatment after adjustment for smear status, presence of cavitation, and positive sputum culture two months after starting treatment. CONCLUSIONS Quantitative QFT-G responses drop significantly in active tuberculosis patients undergoing treatment, with almost 60% becoming test negative. Reversion to a negative QFT-G result was closely associated with the magnitude of the IFN-gamma response prior to treatment and increasing age.

Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations

Background. The detection of latent tuberculosis (TB) is essential for TB control, but T-cell assay might be influenced by degree of immunosuppression. The relationship between immunocompetence and interferon (IFN)-γ response in QuantiFERON-TB Gold (QFT) is uncertain, especially in HIV-negative populations. Methods and Results. QFT has been performed for healthy subjects and TB suspected patients. Of 3017 patients, 727 were diagnosed as pulmonary TB by culture. The absolute number of blood lymphocyte in TB patients was significantly associated with QFT. Definitive TB patients were divided into eight groups according to lymphocyte counts. For each subgroup, receiver operating characteristic curve analysis was conducted from 357 healthy control subjects. The optimal cut-off for the patient group with adequate lymphocyte counts was found, but this was reduced for lymphocytopenia. Conclusions. The lymphocyte count was positively associated with QFT. Positive criteria should be calibrated in consideration of cell-mediated immunocompetence and risk of progression to active TB.

Combined typical carcinoid and acinic cell tumor of the lung

We report a case of combined typical carcinoid and acinic cell tumor of the lung in a 55-year-old female. A chest radiograph revealed an abnormal shadow. Computed tomography (CT) showed a tumor in the S3 segment of the right lung. The transbronchial biopsy yielded a diagnosis of non-small-cell lung cancer. Radical surgery was performed. The pathological diagnosis was combined typical carcinoid and acinic cell tumor of the right lung. This is third case of this tumor which has been reported.