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Abstract [Purpose] Mycobacterium tuberculosis (MTB) infection should be detected in all patients before progressing to active tuberculosis (TB) ; however, interferon-γ release assays (IGRAs) and serological assays cannot accurately detect TB infection in all patients. Therefore, we conducted a prospective study to determine whether TB infections in patients with active pulmonary TB could be reliably detected by combined use of both tests. [Methods] We consecutively enrolled 186 patients suspected of having pulmonary TB referred to our institute between October 2008 and March 2010 in this study. All patients underwent IGRA and serological assays at first visit and subjected for differential diagnoses. [Results] MTB infections could be detected in 49 of 50 patients with active pulmonary TB using tests of humoral and cellular immune responses. However, false-positive serological tests and IGRAs using TB-specific antigens were observed in patients with nontuberculous Mycobacterium (NTM), old TB, or other respiratory diseases. [Conclusion] MTB infections were detected in nearly all patients with active pulmonary TB using tests of humoral and cellular immune responses. However, these assays need to be improved in order to differentiate the active MTB infection from latent MTB infection or NTM infection using combined other separate antigens.

Key words:Mycobacterium tuberculosis infection, Interferon-γ release assay, Serological assay, Tuberculous glycolipid, Lipoarabinomannan polysaccharide

1Graduate School of Health Care Science, Jikei Institute, 2Department

of Respiratory Medicine, National Hospital Organization Toneyama Hospital, 3Department of Bacteriology, Graduate School of Medical

and Dental Sciences, Niigata University

Correspondence to : Ryoji Maekura, Graduate School of Health Care Science, Jikei Institute, 1_2_8, Miyahara, Yodogawa-ku, Osaka-shi, Osaka 532_0003 Japan. (E-mail: mae.ryoji@gmail.com)

(Received 17 Feb. 2017/Accepted 16 Jun. 2017) Kekkaku Vol. 92, No. 9 : 551_558, 2017

−−−−−−−−Original Article−−−−−−−−

CONSIDERATION OF IMPROVEMENT MEASURES FROM LIMITATIONS

OF IMMUNOLOGICAL TESTS―INCLUDING INTERFERON-γ RELEASE

AND ANTIBODY-BASED DETECTION ASSAYS―FOR

MYCOBACTERIUM TUBERCULOSIS INFECTION

1

Ryoji MAEKURA,

2

Seigo KITADA,

3

Yoshitaka TATEISHI,

2

Keisuke MIKI,

2

Mari MIKI,

2

Kenji YOSHIMURA,

2

Kenya FUJIKAWA, and

3

Sohkichi MATSUMOTO

INTRODUCTION

 The gold standard method to diagnose active Mycobac- terium tuberculosis (MTB) disease is either culture-based isolation or the detection of MTB-specific nucleic acids by molecular methods1) 2). Active tuberculosis (TB) disease de-

velops in about 10% of infections, mostly within 1_2 years after exposure3). Remaining individuals enter into a state of

latency (latent TB infection [LTBI]). Active TB developed as a result of MTB infection; therefore, MTB infection should be detected in all patients before progressing to active TB. Generally, the immunological method of detection for MTB infection can be grouped into two categories : serological (antibody detection) assays based on humoral immune re- sponses and tests of cellular immune response (tuberculin skin tests and in vitro interferon [IFN]-γ release assays [IGRAs]). However, MTB infections cannot be detected using individual serological assays and IGRAs in all patients with pulmonary TB4). Commercial serological tests are not recommended for

use in the diagnosis of pulmonary TB, and the use of IGRAs is discouraged for active pulmonary TB diagnosis in low- and middle-income countries.

 We previously reported that the combined use of sero- logical tests with three separate antigens, i.e., tuberculous glycolipid (TBGL) antigen, lipoarabinomannan polysaccha- ride (LAM) antigen, and antigen 60, which was prepared from purified protein derivatives, maximizes the effectiveness of serodiagnosis for pulmonary TB5). The sensitivity increased

to 91.5% in patients with active pulmonary TB and to 86.0 % in smear- and culture-negative patients, and the specificity was 87.5% in the healthy control groups. However, the combined use of IGRAs and serological tests with separate antigens has not been evaluated to determine its effectiveness and limitation for diagnosis of pulmonary TB. So, we conducted a prospective study to determine whether MTB infections in patients with active pulmonary TB could be reliably detected by both serological tests and IGRAs in clinical practice. We also discussed the limitations and improvement measures of

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結核 第92巻 第 9 号 2017年 9 月

566

Abstract A 76-year-old man was referred to our hospital for further examination of infiltrative shadow in the right lower lung field, bilateral pleural effusion and he got a follow-up examination. One-year after the first admission, he emergently admitted to our hospital for dyspnea. Massive pleural effusion with the left side predominance was observed on chest X-ray. Left pleural effusion was exudative with lymphocyte predominance and high adenosine deaminase level, but acid-fast bacteria were negative. Bacteriological examination and cytology of left pleural effusion were also negative. As transbronchial lung biopsy of infiltrative shadow in the right inferior lobe did not yield the definitive diagnosis, we performed left lung and pleural biopsy via video-assisted thoracic surgery. Histopathological examination showed pleural hypertrophy and inflammatory cell infiltration, but Langhans’ giant cells were found in pleural effusion. Although acid-fast bacteria culture of pleural effusion was negative, the culture of the sputum and the bronchoalveolar lavage fluid were positive for M.avium. Taken together, the diagnosis of pleurisy due to M.avium was made. After treatment with clarithromycin+rifampicin+ethambutol, left pleural effusion was decreased. Past studies showed that

several cytokines induced multinucleated giant cells in vitro. This case showed the elevated level of IL-6 in pleural effu- sion, indicating the involvement in the giant cell formation. While the frequency of pleurisy in patients with nontuber- culous mycobacteriosis (NTM) is much rarer than those with pulmonary tuberculosis, we should consider NTM as the putative cause of pleurisy. The appearance of Langhans’ giant cells in pleural effusion would assist the diagnosis of pleurisy due to NTM.

Key words:Mycobacterium avium infection, Pleurisy, Lang- hans’ giant cells, IL-6

Department of Respiratory Medicine and Rheumatology, Institute of Biomedical Sciences, Tokushima University Graduate School.

Correspondence to : Yasuhiko Nishioka, Department of Respiratory Medicine and Rheumatology, Institute of Bio- medical Sciences, Tokushima University Graduate School, 3_18_15, Kuramoto-cho, Tokushima-shi, Tokushima 770_ 8503 Japan. (E-mail: yasuhiko@tokushima-u.ac.jp)

−−−−−−−−Case Report−−−−−−−−

A CASE OF

MYCOBACTERIUM AVIUM PLEURISY

WITH A LOT OF LANGHANS’

GIANT CELLS AND HIGH LEVEL IL-6

IN PLEURAL EFFUSIONS

Terumi TAKIKURA, Masaki HANIBUCHI, Yuko TOYODA, Mayo KONDO, Hiroyuki KOZAI, Asami FUKUYA, and Yasuhiko NISHIOKA

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Intractable M.fortuitum Infection/A.Mitsune et al. 571

nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 ; 175 : 367‒416.

2 ) 松永伸一, 倉島篤行, 永井英明, 他:Mycobacterium ab- scessusの感染を合併した外因性リポイド肺炎の1例. 日

呼吸会誌. 2003 ; 41 : 14‒18.

3 ) Goto T, Hamaguchi R, Maeshima A, et al.: Pulmonary resec- tion for Mycobacterium chelonae infection. Ann Thorac

Cardiovasc Surg. 2012 ; 18 : 128‒131.

4 ) Tang SS, Lye DC, Jureen R, et al.: Rapidly growing mycobacteria in Singapore, 2006‒2011. Clin Microbiol Infect. 2015 ; 21 : 236‒241.

5 ) 萩原恵里, 関根朗雅, 佐藤友英, 他:Mycobacterium for- tuitumによる肺感染症の臨床的検討. 日呼吸会誌. 2008 ;

46 : 788‒792.

6 ) Park S, Suh GY, Chung MP, et al.: Clinical significance of

Mycobacterium fortuitum isolated from respiratory speci-

mens. Respir Med. 2008 ; 102 : 437‒442.

7 ) Matsumoto T, Otsuka K, Tomii K:Mycobacterium fortuitum

thoracic empyema: A case report and review of the literature. J Infect Chemother. 2015 ; 21 : 747‒750.

8 ) Suzuki K, Terada J, Sasaki Y, et al.: Pulmonary Myco- bacterium fortuitum infection with cervical lymphadenitis

in a patient carrying autoantibodies to interferon-γ. Intern Med. 2014 ; 53 : 1361‒1364.

9 ) Gondouin A, Manzoni Ph, Ranfaing E, et al.: Exogenous lipid pneumonia: A retrospective multicentre study of 44 cases in France. Eur Respir J. 1996 ; 9 : 1463‒1469. 10) Marchiori E, Zanetti G, Mano CM, et al.: Exogenous lipoid

pneumonia. Clinical and radiological manifestations. Respir Med. 2011 ; 105 : 659‒666.

11) Kanetsuna F: Bactericidal Effect of Fatty Acids on Myco- bacteria, with Particular Reference to the Suggested Mecha- nism of Intracellular Killing. Microbiol Immunol. 1985 ; 29 : 127‒141.

Abstract A 49-year-old woman with refractory pulmonary Mycobacterium fortutium infection was referred to our hos- pital. Bronchoscopy was reexamined in suspect of other diseases, because the disease was progressive and resistant to multidrug antibiotic therapy. However, no new findings were obtained which suggested malignancy or other infec- tions. Since it was difficult to control by medical treatment, pneumonectomy was performed. On the other hand, it turned out that she regularly performed gargling of sesame oil prior to admission. In addition, there were a large number of lipid droplets in the resected lung. We finally reached the diagno- sis of M.fortuitum infection associated with lipoid pneumonia. In case of intractable nontuberculous mycobacterial infec- tion, it is necessary to suspect the possibility of concomitant

lipoid pneumonia.

Key words:Mycobacterium fortuitum, Nontuberculous my- cobacterial infection, lipoid pneumonia

1Center for Respiratory Diseases, 2Department of Pathology,

National Hospital Organization Tokyo National Hospital;

3Department of Respiratory Medicine, Tohoku University

Graduate School of Medicine

Correspondence to: Ayumi Mitsune, Department of Respi- ratory Medicine, Tohoku University Graduate School of Medicine, 1_1, Seiryo-machi, Aoba-ku, Sendai-shi, Miyagi 980_8574 Japan. (E-mail: mitsune@rm.med.tohoku.ac.jp) −−−−−−−−Case Report−−−−−−−−

A CASE OF REFRACTORY PULMONARY

MYCOBACTERIUM FORTUITUM

INFECTION WITH LIPOID PNEUMONIA DUE TO SESAME OIL

1, 3Ayumi MITSUNE, 1Junko SUZUKI, 1Kimihiko MASUDA, 1Hirotoshi MATSUI, 1Hideaki NAGAI, 1Yuuta INOUE, 1Takeshi FUKAMI, 2Masashi KITANI,

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