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1 ) Toman K: What is the additional yield from repeated spu-tum examinations by smear microscopy and culture? In: Tuberculosis case fi nding and chemotherapy. WHO, Geneva, 1979, 40 43.

2 ) WHO Guidelines Approved by the Guidelines Review Committee: Implementing the WHO Stop TB Strategy: A Handbook for National Tuberculosis Control Programmes. World Health Organization, Geneva, 2008.

3 ) Miller DL, Jones R: The bacterial fl ora of the upper respira-tion tract and sputum of working men. J Pathol Bacteriol. 1964 ; 87 : 182 186.

4 ) Harries AD, Mphasa NB, Mundy C, et al.: Screening tuber-culosis suspects using two sputum smears. Int J Tuberc Lung Dis. 2000 ; 4 : 36 40.

5 ) Deun A, Salim A: Optimal tuberculosis case detection by direct sputum smear microscopy: how much better is more? Int J Tuberc Lung Dis. 2002 ; 6 : 222 230.

6 ) Andrew CW, Willem AS : Microbiological testing for

My-cobacterium tuberculosis. Tuberculosis. Saunders Elsevier, London, 2009, 171.

7 ) Mathew P, Kuo YH, Vazirani B, et al.: Are three sputum acid-fast bacillus smears necessary for discontinuing tuber-culosis isolation? J Clin Microbiol. 2002 ; 40 : 3482 3484. 8 ) Ito K: Number of concentrated sputum smears needed to

adequately assess infectivity of patients with pulmonary tuberculosis. Kekkaku. 2006 ; 81 : 357 362.

9 ) Al Zahrani K, Al Jahdani, Poirier L, et al.: Yield of smear, culture and amplifi cation tests from repeated sputum induc-tion for the diagnosis of pulmonary tuberculosis. Int J Tuberc Lung Dis. 2001 ; 5 : 855 860.

10) Gilpin C, Kim SJ, Lumb R, et al. for the Working Group on Sputum Smear Microscopy: Critical appraisal of current recommendations and practices for tuberculosis sputum smear microscopy. Int J Tuberc Lung Dis. 2007 ; 11 : 946 952.

Abstract [Objective] To determine whether three sputum examinations with fl uorescent staining are necessary to diag-nose tuberculosis (TB) in our hospital.

 [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital.

 [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami-nations. The positivity rate of fi rst sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation.

 [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the fi rst sputum smear (79.2%). The positivity rate of the fi rst sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%).

 Cavity formation, and sputum extraction procedures were

not related to the positivity rate of the fi rst sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test signifi cantly rose, but did not rise in the third test.

 [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

Key words: Three sputum smear examinations, Fluorescent staining, Positivity rates of sputum smears

Department of Pulmonary Medicine, National Hospital Orga-nization Matsue Medical Center

Correspondence to: Kanako Kobayashi, Department of Pul-monary Medicine, National Hospital Organization Matsue Medical Center, 5_8_31, Agenogi, Matsue-shi, Shimane 690_ 8556 Japan. (E-mail: kanako.kobayashi@mmedc.jp) −−−−−−−−Original Article−−−−−−−−

THE MINIMUM NUMBER OF SPUTUM SMEAR SAMPLES NEEDED

FOR THE DIAGNOSIS OF TUBERCULOSIS

Kanako KOBAYASHI, Shuichi YANO, Emiko NISHIKAWA, Shinichi IWAMOTO, Mitsuhiro TADA, Toru KADOWAKI, Masahiro KIMURA, and Toshikazu IKEDA

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結核 第 92 巻 第 1 号 2017 年 1 月 10

Abstract [Objectives and Materials] Based on the tuber-culosis (TB) surveillance database, the incidence rates of TB infection and active disease among healthcare workers were observed for female nurses and male doctors in 2010 in comparison with those of the general population.

 [Results] The relative risk (RR) of active TB among female nurses aged 20_69 years was 4.86 (95% confi dence interval: 4.31_5.45) for 2010, which has increased from 2.30 observed in 1987_1997. The RR was highest for nurses aged 20_29 years at 8.84 and declined with age until 3.60 for those aged 50_59 years that was still signifi cantly higher than 1. For male doctors the RR was signifi cantly higher than 1 only for those aged 39 years or younger.

 The rates of those who were indicated for treatment of latent TB infection (LTBI) were clearly higher among healthcare workers; for female nurses the RR was 32.7 (95% CI: 30.5_35.0), ranging from the highest level of 62.8 among those aged 20_29 years down to 11.6 for those aged 60_69 years. For male doctors also, the RR was high at 9.7 (7.9_ 11.7) for 20_69 years, ranging from 14.5 for those aged 20_ 29 years down to 5.3 for those aged 60_69 years.

 [Discussion] TB cases of nurses and doctors were more likely to be detected by the active case fi nding measures such as periodic screening and contact investigations than cases in the general population, which indicates the current effort of addressing the occupational exposure in the healthcare set-tings. The high level of risk of TB disease as well as LTBI among healthcare professions and its possibly increasing trend as seen in female nurses warrants further strengthening of monitoring of the problem and overall countermeasures in their workplaces.

Key words : Tuberculosis, Incidence rate, Relative risk, Healthcare worker

Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association

Correspondence to: Yuko Yamauchi, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.

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

RISK OF TUBERCULOSIS INFECTION AND DISEASE

AMONG JAPANESE FEMALE NURSES AND MALE DOCTORS

IN RECENT YEARS

Yuko YAMAUCHI, Yoko NAGATA, Noriko KOBAYASHI, and Toru MORI

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Abstract [Objectives] To investigate the adverse reactions of antimicrobial drugs in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients.

 [Results] Sixty-six patients with MDR-TB who have been treated from 2010 through 2014 were evaluated in the retro-spective analysis. Variety of adverse reactions including psy-chological reaction, central nervous system toxicity, ophthalmic toxicity, peripheral neurotoxicity, gastrointestinal reactions, hematologic abnormalities, musculoskeletal adverse effects, and endocrine disorder, were observed. However, there was no fatal case due to the adverse reactions of the anti-tubercu-losis drugs in this observation.

 [Conclusions] Drugs for MDR-TB and XDR-TB treatment are limited and the adverse reactions of drugs for MDR-TB

and XDR-TB are not well-known. Therefore, the treatment may fail due to inappropriate management of adverse events. MDR-TB and XDR-TB should be treated by the experts of the adverse reactions of all anti-tuberculosis drugs.

Key words : Tuberculosis, Multidrug-resistant tuberculosis (MDR-TB), Treatment, Adverse reaction

Respiratory Medicine Division, Fukujuji Hospital, Japan Anti-Tuberculosis Association

Correspondence to: Yuka Sasaki, Respiratory Medicine Di-vision, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8522 Japan. (E-mail: sasakiy@fukujuji.org)

−−−−−−−−Original Article−−−−−−−−

THE FREQUENCIES AND MANAGEMENT OF ADVERSE REACTIONS

IN MULTI-DRUG RESISTANT TUBERCULOSIS TREATMENT

Yuka SASAKI, Takashi YOSHIYAMA, Masao OKUMURA, Kouzo MORIMOTO, Maki MIYAMOTO, IRINA, Kouzo YOSHIMORI, Atsuyuki KURASHIMA,

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結核 第 92 巻 第 1 号 2017 年 1 月 26

Abstract [Objective] To contribute to countermeasures against pulmonary tuberculosis in patients with HIV infection through analyzing and evaluating its treatment outcomes and patient management.

 [Methods] The subjects were pulmonary tuberculosis patients newly registered between 2008 and 2014 in whom concomitant HIV infection was detected. For the control, sex- and generation-matched pulmonary tuberculosis patients newly registered in Osaka City between 2012 and 2014 were adopted. On analysis, the χ2 test and Fisher’s exact test were used, and a signifi cance level below 5% was regarded as signifi cant.

 [Results] 1) There were 25 pulmonary tuberculosis patients complicated by HIV. All were male and the mean age was 43.2 years old.

 2) The sputum smear positivity rate was 76.0% in the pulmonary tuberculosis patients complicated by HIV and 50.8 % in 250 control pulmonary tuberculosis patients, showing a signifi cantly higher rate in the former.

 3) Risk factors for the discontinuation of medication for tuberculosis: In the patients complicated by HIV, the follow-ing risks of the discontinuation of medication were noted in the order of a decreasing frequency:‘Lack of medication helpers’ in 68.0%, ‘Side effects’ in 48.0%, ‘Financial prob-lems’ in 32.0%, and ‘Liver damage’ in 28.0%. Those in the control pulmonary tuberculosis patients were 33.2%, 22.8 %, 16.0%, and 11.6%, respectively, showing a signifi cant difference in each factor.

 4) The DOTS executing rates were 68.0% and 94.8% in the patients complicated by HIV and control patients, respectively, showing that it was signifi cantly lower in the patients complicated by HIV. On comparison of the treatment

outcomes excluding died, on treatment, transferred out, not evaluated, treatment succeeded in 72.7% in the patients complicated by HIV and 92.9% in the control patients, showing a signifi cantly lower success rate in the patients complicated by HIV. The numbers of risk factors of discon-tinuation in 16 and 6 patients complicated by HIV in whom treatment succeeded and treatment failed/defaulted were 3.8 and 2.8, respectively, showing that the number was higher in patients with successful treatment, and the DOTS execution rates were 75.0% and 33.3%, respectively, showing a higher rate in the successful treatment cases.

 [Conclusion] The treatment outcome was signifi cantly poorer in pulmonary tuberculosis patients complicated by HIV than in the control pulmonary tuberculosis patients. More risk factors for the discontinuation of medication were observed and the DOTS execution rate was lower in the patients complicated by HIV, suggesting that risk assess-ment for the discontinuation of medication should be appro-priately performed, and support for medication should be strengthened.

Key words : Pulmonary tuberculosis, HIV, Co-infection, DOTS, Treatment outcome, Risk factors for failed/defaulted 1Osaka City Public Health Offi ce, 2Nishinari Ward Offi ce, Osaka City

Correspondence to : Kenji Matsumoto, Osaka City Public Health Offi ce, 1_2_7_1000, Asahimachi, Abeno-ku, Osaka-shi, Osaka 545_0051 Japan.

(E-mail: ke-matsumoto@city.osaka.lg.jp) −−−−−−−−Original Article−−−−−−−−

TREATMENT SUPPORT AND TREATMENT OUTCOMES OF

PULMONARY TUBERCULOSIS IN PATIENTS WITH HIV INFECTION

IN OSAKA CITY

1Kenji MATSUMOTO, 1Jun KOMUKAI, 1Yuko TSUDA, 1Hideya UEDA, 1Maiko ADACHI, 1Naoko SHIMIZU, 1Kazumi SAITO, 1Hidetetsu HIROKAWA,

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Abstract [Aim] To explore the possible role of social network analysis (SNA) in identifying infected contacts and visualizing data in a tuberculosis (TB) contact investigation.  [Method] We analyzed TB contact investigation data from an outbreak in a Japanese language school in Tokyo, Japan, in 20XX. Information on places which the index case and his contacts commonly shared was collected in line with the data collected routinely in contact investigation. Average hours of exposure to the index case were calculated for each contact by using SNA software, and the relationship to the index case via commonly shared places was visualized as a sociogram. Statistical analysis was performed to compare the exposure hours and TB infection statuses between those infected, including active TB and latent TB infection (LTBI), and non-infected contacts.

 [Result] The data on the index TB case and 41 contacts, of whom 5 and 10 were diagnosed with active TB and LTBI, were analyzed. Contacts with active TB and LTBI had 12.5 and 11.5 times longer median hours of exposure, which were signifi cantly longer compared to non-infected contacts. The sociogram summarized the network of index TB case, contacts characterized by exposure hours and infection statuses, and

the places shared by the index case and the contacts.

 [Discussion] SNA analysis was considered to be useful in prioritizing contacts in a TB contact investigation, in assist-ing interpretation of indeterminate Interferon-Gamma release assay test results, in estimating places where transmission occurred, and visualizing data accrued in TB contact inves-tigations.

Key words : Social-network analysis, Tuberculosis contact investigation, Tuberculosis outbreak

1Department of Epidemiology and Clinical Research, 2Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-tuberculosis Association (RIT/JATA) ; 3Graduate School of Biomedical Sciences, Nagasaki University ;4Shinjuku City Public Health Center

Correspondence to: Kiyohiko Izumi, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan.

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

THE POTENTIAL ROLE OF SOCIAL NETWORK ANALYSIS

IN TUBERCULOSIS CONTACT INVESTIGATION

1,3Kiyohiko IZUMI, 1Lisa KAWATSU, 4Satoshi MIYAKE, 4Yu WATANABE, 2Yoshiro MURASE, 1Kazuhiro UCHIMURA, and 1,3Akihiro OHKADO

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Subphrenic Abscess with Paradoxical Response / M. Yamada et al. 39

5 ) Smith H: Paradoxical responses during the chemotherapy of tuberculosis. J Infe CT. 1987 ; 15 : 1 3.

6 ) Kasahara K, Fukuoka A, Murakawa K, et al.: Tuberculous peritonitis developing during chemotherapy for pulmonary and intestinal. Respirology. 2005 ; 10 : 257 260.

7 ) 佐藤 博, 大泉耕太郎, 宮本雅吉, 他:強力化学療法に 伴う胸部レ線像の悪化例について. 結核. 1982 ; 57 : 425 427. 8 ) 亀田和彦:結核の悪化 初期悪化の検討. 結核. 1982 ; 57 : 548. 9 ) 小宮幸作, 有賀晴之, 長山直弘, 他:結核性胸膜炎に対 する胸腔ドレーン留置後に発症した胸壁冷膿瘍の 1 例. 結核. 2010 ; 85 : 673 677.

Abstract A 40-year-old woman was admitted to our hos-pital with cough and sputum production. A chest computed tomography (CT) scan revealed a diffuse nodular shadow in the upper lung. The patient was diagnosed with pulmonary tuberculosis, based on a positive T-SPOT®.TB test result of peripheral blood and a positive polymerase chain reaction (PCR) test result for Mycobacterium tuberculosis in gastric aspirates. M.tuberculosis was subsequently isolated from the gastric aspirate specimen. After 2 months of treatment with antituberculous medication, the patient developed a low grade fever and left-sided chest pain. A CT scan revealed a left pleural effusion and a right subphrenic abscess. Tuber-culous pleurisy with paradoxical response was diagnosed on the basis of an increased lymphocyte count and increased adenosine deaminase activity in the pleural fl uid exudate. A percutaneous ultrasound-guided needle biopsy of the sub-phrenic abscess was performed. Histological analysis revealed epithelioid cell granulomas with necrosis and PCR for M. tuberculosis using puncture needle washing fl uid returned

positive results. Based on these fi ndings, a diagnosis of subphrenic abscess with paradoxical response, caused by M. tuberculosis, was made. Subphrenic abscess caused by M. tuberculosis is an important consideration during antituber-culous therapy.

Key words : Pulmonary tuberculosis, Paradoxical response, Subphrenic abscess, Tuberculous pleurisy

1Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Kashiwa Hospital, 2Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine Correspondence to: Masami Yamada, Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Kashiwa Hospital, 163_1, Kashiwashita, Kashiwa-shi, Chiba 277_8567 Japan.

(E-mail: masami-y@jikei.ac.jp) −−−−−−−−Case Report−−−−−−−−

A CASE OF SUBPHRENIC ABSCESS WITH PARADOXICAL RESPONSE

CAUSED BY MYCOBACTERIUM TUBERCULOSIS

1Masami YAMADA, 1Hideaki YAMAKAWA, 1Masahiro YOSHIDA, 1Takeo ISHIKAWA, 1Masamichi TAKAGI, and 2Kazuyoshi KUWANO

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Abstract Rifampicin can induce hypothyroidism. We report a case of pulmonary tuberculosis and tuberculous pleurisy that was complicated by rifampicin-induced hypothyroidism. The patient received rifampicin-based tuberculosis treatment and experienced persistent appetite loss, which led us to pro-vide concomitant hypothyroidism treatment.

 An 85-year-old woman with no underlying thyroid-related disease presented to her local hospital with a 3-month history of appetite and weight loss. A chest radiograph revealed pleural effusions and infi ltrative shadows in the lower fi elds of both lungs, and we also detected high levels of lympho-cytes and adenosine deaminase levels (49.6 IU/l) in the pleu-ral effusion, with positive results from a polymerase chain reaction assay of a sputum sample. Thus, we diagnosed the patient with pulmonary tuberculosis and tuberculous pleurisy, and initiated treatment using isoniazid, rifampicin, etham-butol, and pyrazinamide. Her clinical course was good and her anorexia was improved. However, she subsequently experienced recurrent appetite loss, malaise, and bilateral lower-leg edema. Follow-up laboratory testing revealed that she had developed hypothyroidism. We started treatment using levothyroxine without interrupting the tuberculosis

treatment. The loss of appetite and other thyroid-related symptoms were improved. The patient’s thyroid function had been normal at her admission, and there were no fi ndings of Hashimoto’s thyroiditis or other thyroid conditions. Based on the clinical course, we conclude that the rifampicin induced the hypothyroidism.

 Therefore, rifampicin-induced hypothyroidism should be considered in cases with persistent appetite loss, even if the patient appears to be experiencing anorexia as an adverse drug reaction.

Key words : Rifampicin, Adverse reactions, Hypothyroidism, Tuberculosis, Hashimoto’s thyroiditis

1Department of General Internal Medicine, 2Department of Rheumatology, Kameda Medical Center

Correspondence to: Yuto Hamada, Department of Respiratory Medicine, Sagamihara National Hospital, 18_1, Sakuradai, Minami-ku, Sagamihara-shi, Kanagawa 252_0392 Japan. (E-mail: yutohamada1983@gmail.com)

−−−−−−−−Case Report−−−−−−−−

PULMONARY TUBERCULOSIS AND TUBERCULOUS PLEURISY

COMPLICATED WITH RIFAMPICIN-INDUCED HYPOTHYROIDISM :

A CASE REPORT

1, 2Yuto HAMADA, 1Akiyuki SATO, and 2Shinji MOTOJIMA 10) Glaeser H, Drescher S, Eichelbaum M: Infl uence of

rifam-picin on the expression and function of human intestinal cytochrome P450 enzymes. Br J Clin Pharmacol. 2005 ; 59 : 199 206.

11) Christensen HR, Simonsen K, Hegedus L, et al.: Infl uence of rifampicin on thyroid gland volume, thyroid hormones and antipyrine metabolism. Acta Endocrinol (Copenh). 1989 ; 121 : 406 410.

12) Ohnhaus EE, Studer H: A link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol. 1983 ; 15 : 71 76. 13) 深田修司, 中武伸元, 田尻淳一:リファンピシン(RFP 治療中に甲状腺機能が不安定となった慢性甲状腺炎の 一症例. 日本内分泌学会雑誌. 2012 ; 88 : 354. 14) 當時久保正之:リファンピシン(RFP)により甲状腺 機能低下および心嚢液貯留をきたしたと思われる 1 例. 日本内分泌学会雑誌. 2012 ; 88 : 541. 15) 芦澤潔人, 小溝紗耶香, 夫津木要二:リファンピシン RFP 内服中に認めた出産後甲状腺機能低下症の一例. 日本内分泌学会雑誌. 2015 ; 91 (2-Suppl) : 109. 16) 西川光重:薬剤による甲状腺障害. 日本内科学会雑誌. 2010 ; 99 : 776 785.

17) Kasagi K, Kousaka T, Higuchi K, et al.: Clinical signifi cance of measurements of antithyroid antibodies in the diagnosis of Hashimoto’s thyroiditis: comparison with histological fi ndings. Thyroid. 1996 ; 6 : 445 450.

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