April

Utility of T-SPOT for TB Diagnosis / K. Nemoto et al. 449

3 : e2489.

7 ） Kobashi Y, Shimizu H, Ohue Y, et al.: False negative results of QuantiFERON TB-2G test in patients with active tuber-culosis. Jpn J Infect Dis. 2009 ; 62 : 300 302.

8 ） Hang NT, Lien LT, Kobayashi N, et al.: Analysis of factors lowering sensitivity of interferon-γγ release assay for tuber-culosis. PLoS ONE. 2011 ; 6 : e23806.

9 ） Cho K, Cho E, Kwon S, et al.: Factors associated with indeterminate and false negative results of QuantiFERON-TB GOLD In-Tube test in active tuberculosis. Tuberc Respir Dis. 2012 ; 72 : 416 425.

10） Liao CH, Lai CC, Tan CK, et al.: False-negative results by enzyme-linked immunospot assay for interferon-gamma among patients with culture-confi rmed tuberculosis. J Infect. 2009 ; 59 : 421 423.

11） Lee YM, Park KH, Kim SM, et al.: Risk factors for false-negative results of T-SPOT.TB and tuberculin skin test in extrapulmonary tuberculosis. Infection. 2013 ; 41 : 1089 1095.

12） Lenders LM, Meldau R, van Zyl-Smit RN, et al.: Com-parison of same day versus delayed enumeration of TB-specifi c T cell responses. J Infect. 2010 ; 60 : 344 350. 13） Wang SH, Stew S, Cyktor J, et al.: Validation of increased

blood storage times with the T-SPOT.TB assay with T-Cell

Xtend reagent in individuals with different tuberculosis risk factors. J Clin Microbiol. 2012 ; 50 : 2469 2471.

14） Talbot EA, Maro I, Ferguson K, et al.: Maintenance of sensitivity of the T-SPOT.TB assay after overnight storage of blood samples, Dar es Salaam, Tanzania. Tuberc Res Treat. 2012 ; 2012 : 345290.

Abstract [Background] T-SPOT.TB (T-SPOT), an inter-feron-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the fi eld. However, limited data is available on the usefulness of T-SPOT with TCX as a fi eld test for diagnos-ing active TB.

 [Purpose] To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB.

 [Methods] A total of 57 patients with active TB who under-went the T-SPOT test with TCX prior to treatment were en-rolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the fi nal analysis. The basic characteristics and clinical fi ndings were compared between the true-positive and false-negative T-SPOT groups.

 [Results] Of the 56 patients, 40 (71.4％), 13 (23.2％), 3 (5.4 ％) had true-positive, false-negative, and borderline T-SPOT

results, respectively. This study did not reveal any signifi cant risk factors for a false-negative T-SPOT result.

 [Conclusion] In this clinical study, the proportion of pa-tients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient’s background. Key words : Active tuberculosis, False-negative, T-Cell Xtend, T-SPOT.TB

1_{Department of Respiratory Medicine,} 2_{Department of}

Tho-racic Surgery, National Hospital Organization Ibarakihigashi National Hospital

Correspondence to : Kenji Nemoto, Department of Respira-tory Medicine, National Hospital Organization Ibarakihigashi National Hospital, 825, Terunuma, Tokai-mura, Naka-gun, Ibaraki 319_1113 Japan.

(E-mail: nemoken1124@yahoo.co.jp) −−−−−−−−Original Article−−−−−−−−

CLINICAL UTILITY OF T-SPOT

_{.TB ASSAY WITH T-Cell Xtend}

REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS

IN THE FIELD TEST AT OUR HOSPITAL

1_{Kenji NEMOTO,} 1_{Shuji OH-ISHI,} 1_{Masato TAGUCHI,} 1_{Kentaro HYODO,} 1_{Jun KANAZAWA,} 1_{Yukiko MIURA,} 1_{Takio TAKAKU,} 2_{Shingo USUI,}

Tuberculosis Due to Defi nite Exogenous Reinfection / S. Iwamoto et al. 455

6 ） Sahadevan R, Narayanan S, Paramasivan CN, et al.: Restric-tion fragment length polymorphism typing of clinical iso-lates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras, India, by use of direct-repeat probe. J Clin Microbiol. 1995 ; 33 : 3037 3039. 7 ） Heldal E, Döcker H, Caugant DA, et al.: Pulmonary

tuber-culosis in Norwegian patients. The role of reactivation, re-infection and primary re-infection assessed by previous mass screening data and restriction fragment length polymorphism analysis. Int J Tuberc Lung Dis. 2000 ; 4 : 300 307. 8 ） 近藤有好, 桶谷典弘, 桑原克弘, 他.：老健施設におけ

る結核の外来性再感染と思われる集団発生について. 結核. 2002 ; 77 : 401 408.

9 ） Murase Y, Mitarai S, Sugawara I, et al.: Promising loci

of variable numbers of tandem repeats for typing Beijing family Mycobacterium tuberculosis. J Med Microbiol. 2008 ; 57 : 873 880.

10） 前田伸司, 村瀬良朗, 御手洗聡, 他：国内結核菌型別の ための迅速・簡便な反復配列多型（VNTR）分析システ ム― JATA（12）-VNTR分析法の実際. 結核. 2008 ; 83 : 673 678.

11） Sola C, Ferdinand S, Mammina C, et al.: Genetic diversity of Mycobacterium tuberculosis in Sicily based on spoligo-typing and variable number of tandem DNA repeats and comparison with a spoligotyping database for population-based analysis. J Clin Microbiol. 2001 ; 39 : 1559 1565. 12） 横山栄二, 岸田一則：結核集団感染における分子疫学

的解析. 微生物生物検出情報. 2006 ; 27 : 262 263.

Abstract [Purpose] We report an outbreak of 64 cases of tuberculosis (TB) that spread in a welfare facility for elderly individuals.

 [Objective and Methods] First, 64 TB patients who had contact with the source patient were screened at our hospital. We examined the time course up to the discovery of symptoms and analyzed the results for variable numbers of tandem re-peats (VNTR) and the drug susceptibility tests. Second, we performed chest computed tomography to examine lesions due to a previous TB infection.

 [Result] The source patient had recurrent aspiration pneu-monia. The delay in doctor consultation was considered day 0, and the delay of diagnosis was 267 days. On examining the contacts, we found that 29 patients had TB while 35 had a latent TB infection. Results of the VNTR and the drug susceptibility tests showed that all the patients who developed TB had the same pattern as that of the source patient. Chest computed tomography showed lesions due to a previous TB

infection in 8 patients.

 [Conclusion] Based on the results of the VNTR and drug susceptibility tests, we concluded that the outbreak was due to an exogenous infection from the same source. All 8 patients who showed lesions due to a previous TB infection were aged ＞81 years, and TB in these patients was found to be due to exogenous re-infection.

Key words: Exogenous reinfection, Mass outbreak, Variable numbers of tandem repeats, Drug susceptibility testing Department of Pulmonary Medicine, National Hospital Orga-nization Matsue Medical Center

Correspondence to : Shinichi Iwamoto, Department of Pul-monary Medicine, National Hospital Organization Matsue Medical Center, 5_8_31, Agenogi, Matsue-shi, Shimane 690_0015 Japan. (E-mail: shinichi.iwamoto@mmedc.jp) −−−−−−−−Original Article−−−−−−−−

AN OUTBREAK OF PULMONARY TUBERCULOSIS DUE TO

DEFINITE EXOGENOUS REINFECTION

AMONG ELDERLY INDIVIDUALS IN WELFARE FACILITIES

結核 第 91 巻 第 4 号 2016 年 4 月 464

Abstract [Setting] We conducted a systematic review of literatures on the prevalence and incidence of latent tuber-culosis infection in correctional settings, with the aim of offer-ing one of the resources to guide establishment of policies on screening for and treating LTBI among prisoners in Japan.  [Objective] Using the keywords latent tuberculosis AND (prison OR jail OR correctional) and tuberculosis infection AND (prison OR jail OR correctional) , we conducted a systematic review of relevant literatures on PubMed and secondary searches from the reference list of primary sources. We limited our search to those original articles published since 1980, and in English.

 [Results] 55 articles were identifi ed, and 15 were subject to the systematic review. Of the 12 articles on prevalence of LTBI, 5 were from middle and high-burden and 7 from low-burden countries. The average prevalence of LTBI among middle and high-burden countries was 73.0％, and among low-burden countries, 40.3％. Duration of incarceration and

history of previous incarceration were identifi ed as risk factors for high LTBI prevalence which were specifi c to the prison population. Incidence of LTBI among the high-burden country was 61.8 per 100 person years, while 5.9 and 6.3 in

the two reports from low-burden countries.

 [Conclusion] Prevalence and incidence of LTBI were higher than the general population, both in middle/high- and low-burden countries. The fact that duration of incarceration and

history of previous incarceration were identifi ed as risk factors indicate that high prevalence of LTBI among prison population is not just attributable to the characteristics of prisoners themselves, but also to the possibility of TB infec-tion occurring in prison settings.

Key words : Tuberculosis, Incarcerated population, Latent tuberculosis infection (LTBI), Systematic review

Department of Epidemiology and Clinical Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Correspondence to : Lisa Kawatsu, Department of Epide-miology and Clinical Research, Research Institute of Tuber-culosis, Japan Anti-Tuberculosis Association, 3_ 1_ 24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.

(E-mail: kawatsu@jata.or.jp) −−−−−−−−Original Article−−−−−−−−

A SYSTEMATIC REVIEW ON THE PREVALENCE AND INCIDENCE OF

LATENT TUBERCULOSIS INFECTION AMONG PRISON POPULATION

結核 第 91 巻 第 4 号 2016 年 4 月 468

Abstract [Objective] We analyzed the use of QFT®_{-TB Gold}

in Tube and T-SPOT®_{.TB in diagnosing patients with}

suspect-ed pulmonary tuberculosis.

 [Subjects and Methods] We evaluated 122 patients with suspected pulmonary tuberculosis (where chest X-ray showed consolidation or tumor shadow in predilection sites of pul-monary tuberculosis and through contact investigation). QFT®

-TB Gold and T-SPOT®_{.TB were performed for all the}

pa-tients. The positive response rate and history of pulmonary tuberculosis in patients who showed positive results for the tests were evaluated.

 [Results] Ninteen patients showed positive results for QFT®

-TB Gold, and 9, for T-SPOT®_{.TB. Four patients showed}

positive results for QFT®_{-TB Gold, and 3, for T-SPOT}®_{.TB in}

4 patients with active tuberculosis. The patients without active tuberculosis whose IGRAs were positive (old pulmonary tuberculosis, Mycobacterium avium cmplex, pneumonia, lung cancer, pulmonary sequestration, bronchiectasis) had a past

history of pulmonary tuberculosis.

 [Conclusion] The positive result rate of QFT®_{-TB Gold was}

higher than that of T-SPOT®_{.TB in the subjects with suspected}

pulmonary tuberculosis. We think that QFT®_{-TB Gold refl ected}

the past history of pulmonary tuberculosis.

Key words: Interferon-gamma release assay, QuantiFERON®

-TB Gold in Tube, T-SPOT®_.TB

Department of General Internal Medicine 1, Kawasaki Hos-pital, Kawasaki Medical School

Correspondence to: Niro Okimoto, Department of General Internal Medicine 1, Kawasaki Hospital, Kawasaki Medical School, 2_1_80, Nakasange, Kita-ku, Okayama-shi, Okayama 700_8505 Japan.

(E-mail: n.okimoto@med.kawasaki-m.ac.jp) −−−−−−−−Short Report−−−−−−−−

USE OF QuantiFERON

_{-TB Gold in Tube AND T-SPOT}

_{. TB FOR DIAGNOSING}

PATIENTS WITH SUSPECTED PULMONARY TUBERCULOSIS

Mycobacterium abscessus Pulmonary Disease / Y. Tsunoda et al. ₄₇₃

Abstract [Introduction] Mycobacterium abscessus pulmo-nary disease is common in patients with bronchiectasis. However, the underlying disease that is more likely to be present in patients with M.abscessus pulmonary disease remains poorly understood.

 [Method] From 2001 through 2010, all patients, whose sputum or bronchoscopic lavage cultures yielded

M.absces-sus, were included in the study.

 [Results] Among the 11 patients included (male/female: 4/7), 4 male patients had a history of smoking. All 11 patients presented with bronchiectasis on computed tomography before the detection of M.abscessus, and most patients demonstrated nodular bronchiectasis on chest computed tomography.  Six patients (54.5％) developed M.abscessus pulmonary disease during treatment for non-abscessus non-tuberculous mycobacterial disease: M.avium complex pulmonary disease in 5 and M.kansasii infection in 1. Although laboratory exam-ination yielded negative fi ndings for non-abscessus mycobac-terium when M.abscessus was detected, radiographic deterio-ration was observed in 4 of 6 patients.

 Five patients received drug therapy, 3 of whom were treated with multi-drug therapy including clarithromycin, ethambutol, and rifampicin, and the remaining 2 patients received low-dose macrolide therapy. However, M.abscessus was detected con-sistently in all patients, and deteriorated chest CT fi ndings were

observed in 4. Among the remaining 6 patients untreated with drugs, sputum cultures yielded M.abscessus with radiographic deterioration in 4 patients.

 [Conclusion] Our results indicated that M.abscessus infec-tion developed during the treatment for non-abscessus myco-bacterial disease, which was mainly due to M.avium complex pulmonary disease in most patients. M.abscessus infection thus occurred via microbial substitution. This phenomenon should be considered an important issue during the treatment for non-abscessus mycobacterial disease, which requires long-term medication.

Key words: M.abscessus, Underlying disease, MAC, Micro-bial substitution, Non-tuberculous mycobacteria

1_{Department of Respiratory Medicine,} 2_{Department of Clinical}

Laboratory, National Hospital Organization Ibarakihigashi National Hospital

Correspondence to: Yoshiya Tsunoda, Department of Respi-ratory Medicine, National Hospital Organization Ibaraki-higashi National Hospital, 825, Terunuma, Tokai-mura, Naka-gun, Ibaraki 319_1113 Japan.

(E-mail: chabo448@yahoo.co.jp) −−−−−−−−Short Report−−−−−−−−

MYCOBACTERIUM ABSCESSUS

PULMONARY DISEASE:

IMPORTANT PATHOGEN INVOLVED IN MICROBIAL SUBSTITUTION DURING

THE TREATMENT OF NON-ABSCESSUS MYCOBACTERIAL DISEASE

1_{Yoshiya TSUNODA,} 1_{Akimasa SEKINE,}1_{Yuki SUMAZAKI,} 1_{Toru TANAKA,} 1_{Shih-Yuan LIN,} 1_{Hiroyuki TAKOI,} 1_{Kenji HAYASHIHARA,}

Reactivation of Tuberculosis after R-CHOP / T. Yuba et al. 479

Abstract A 79-year-old man with a history of tuberculosis was found to have chronic empyema in the right lung and was diagnosed with malignant diffuse large-cell lymphoma (Ann Arbor stage IIE). After completion of one course of rituximab plus cyclophosphamide, pirarubicin, vincristine, and pred-nisolone (R-CHOP) chemotherapy, the patient developed lung abscess and sepsis caused by Streptococcus intermedius. This condition was treated with antimicrobial agents, and therapy was resumed. After the second course, the chemo-therapy regimen was continued without prednisolone, and after administration of the third course, a chest wall mass was found in the right lung. An acid-fast bacillus smear test of the abscess aspirate was positive, and Mycobacterium

tuber-culosis was detected in a polymerase chain reaction assay, leading to a diagnosis of perithoracic tuberculosis. Chemo-therapy for the lymphoma was discontinued, and treatment with four oral antitubercular agents was started. This treat-ment led to remission of perithoracic tuberculosis. In Japan,

tuberculous scar and chronic empyema are relatively com-mon fi ndings, and relapse of tuberculosis should always be considered for patients with these fi ndings during chemo-therapy and immunosuppressive chemo-therapy.

Key words: Malignant lymphoma, R-CHOP chemotherapy, Rituximab, Recurrence of tuberculosis

1_{Departments of Respiratory Medicine, Kyoto First Red Cross}

Hospital, 2_{Internal Medicine, JCHO Kuramaguchi Medical}

Center, 3_{Department of Infectious Diseases, Kyoto Prefectural}

University of Medicine

Correspondence to: Tatsuya Yuba, Departments of Respiratory Medicine, Kyoto First Red Cross Hospital, 15_749 Honmachi, Higashiyama-ku, Kyoto-shi, Kyoto 605_0981 Japan. (E-mail: tyb2001@gmail.com)

−−−−−−−−Case Report−−−−−−−−

REACTIVATION OF TUBERCULOSIS PRESENTING WITH EMPYEMA

DUE TO ANTICANCER CHEMOTHERAPY FOR

DIFFUSE LARGE B CELL LYMPHOMA

1_{Tatsuya YUBA,} 2_{Mayumi HATSUSE,} 3_{Mai KODAMA,} 1_{Sayaka UDA,} 1_{Akihiro YOSHIMURA, and} 1_{Naoko KURISU}

TB Annual Report 2014 (2) 487

−−−−−−−−Report and Information−−−−−−−−

TUBERCULOSIS ANNUAL REPORT 2014

─ (2) Tuberculosis in Pediatric and Elderly Patients ─

Tuberculosis Surveillance Center (TSC), RIT, JATA Abstract In 2014, 49 pediatric tuberculosis (TB) patients

aged 0_14 years were newly notifi ed in Japan, with a notifi cation rate of 0.30 per 100,000 population. Since 2006, the number of pediatric TB patients notifi ed each year has been less than 100. Of the 49 patients, 17 (34.7％) were aged 0_4 years, 15 (30.6％) were 5_9 years, and 17 (34.7％) were 10_14 years. Until recently, the proportion of those aged 0_4 years was higher than those aged 10_14 years, but this year the proportions have become equal.

 Of these 49, fi ve had meningeal TB and two had miliary TB. In terms of case detection, 19 (38.8％) sought health care, while 25 (51.0％) were identifi ed through contact investigations.

 Since 2000, the number of all elderly patients (aged 65 years or older) with TB decreased rapidly, and remained stable until recently. However, the number of such patients has declined gradually since 2012. The proportion of TB patients aged 65 years or older has consistently increased to as high as 65.4％ in 2014; notably, the proportion of TB patients aged 80 years or older has also increased to 37.7％. Since 1999, the TB notifi cation rates in Japan have been consistently higher among patients aged 85 years or older than among those aged 65_84 years. The rate of notifi cation for TB patients aged 65 years or older decreased by 3.1％ from 2013 (13,227 patients) to 2014 (12,823 patients).  The proportion of bacteriologically positive TB patients among the general population of pulmonary TB (PTB) patients was higher among those aged 65 years or older than among those aged 15_64 years. Among all symptomatic patients,

the proportion of PTB patients with only non-respiratory symptoms increased with age to 28.5％ among those aged 85 years or older. The proportion of TB patients with a patient delay of two months or longer was lower among patients aged 65 years or older than among those aged 15_64 years (14.5 ％ vs. 28.2％), whereas the proportion of TB patients with a doctor delay of one month or longer was slightly higher among patients aged 65 years or older than among those aged 15_64 years (22.6％ vs. 19.5％).

 Among TB patients aged 65 years or older who were newly notifi ed in 2013, 31.4％ died within one year after the initia-tion of TB treatment; of these patients, 18.8％ died within three months. The proportion of deaths within three months after the initiation of TB treatment increased substantially with age, from 8.8％ of those aged 65_69 years to 35.6％ of those aged 90 years or older.

Key words: Tuberculosis, Notifi cation rate, Pediatric tuber-culosis, Tuberculosis in the elderly, Annual trend

Research Institute of Tuberculosis (RIT), Japan Anti-Tuber-culosis Association (JATA)

Correspondence to: Mayumi Suenaga, Department of Techni-cal Assistance, RIT, JATA; Kazuhiro Uchimura, Department of Epidemiology and Clinical Research, RIT, JATA, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.