TUBERCULOSIS COMPLICATED WITH LIVER CIRRHOSIS

465

TB with LC / A. Saito et al.

−−−−−−−− Original Article −−−−−−−−

TUBERCULOSIS COMPLICATED WITH LIVER CIRRHOSIS Akira SAITO, Naohiro NAGAYAMA, Osamitsu YAGI, Nobuharu OHSHIMA, Atsuhisa TAMURA, Hideaki NAGAI, Shinobu AKAGAWA, Yoshiko KAWABE, Kazuko MACHIDA, Atsuyuki KURASHIMA and Hideki YOTSUMOTO Abstract [Objectives] The aim of this study is to examine the clinical characteristics of tuberculous patients complicated with liver cirrhosis. [Materials and Methods] 44 patients (39 males and 5 females) admitted to Tokyo National Hospital since 1991 till 2005 were analysed. [Results] Eighteen patients died and liver failure was the leading cause of death (N＝10). Hepatitis C viral infection (N＝17), and excessive alcohol consumption (N＝13) were the major causes of liver cirrhosis. Twenty five patients followed-up for more than 3 months were further selected for the detailed analyses. Multi-drug combination chemotherapy including isoniazid, rifampicin and ethambutol was administered in 22 patients. Adverse effects were seen in 20 patients. The numbers of patients with leukopenia, thrombocytopenia and hyperbilirubinemia were 10, 9 and 3, respectively. They recovered following the alteration of chemotherapeutic regi-

men or drug desensitization. [Conclusion] Tuberculous patients with liver cirrhosis are characterized with higher mortality rate and higher frequency of adverse effects of antituberculous chemotherapy. Multidrug combination regimen could be tolerable under adequate surveillance of side effects even in the situation of preexisting liver dysfunction. Key words : Tuberculosis, Liver cirrhosis, Side effect, Antituberculous drug, Drug induced liver dysfunction, Leukopenia Department of Respiratory Disease, National Hospital Organization Tokyo National Hospital Correspondence to : Akira Saito, Graduate School of Medicine, University of Tokyo, 7_3_1, Hongo, Bunkyo-ku, Tokyo 113_0033 Japan. (E-mail : asaitou-tky＠umin.ac.jp)

467

Kekkaku Vol. 81, No. 7 : 467_474, 2006


DECENTRALIZED DOTS SHORTENS DELAY TO TB TREATMENT SIGNIFICANTLY IN CAMBODIA

1

Saint SALY, 2Ikushi ONOZAKI, 2Nobukatsu ISHIKAWA

Abstract [SETTING] Rural districts in Cambodia with and without decentralized health center based DOTS program. [OBJECTIVE] To compare delays to treatment and behavior of patients up to diagnosis, between the pilot districts where DOTS is decentralized through the health centers, and the control districts where DOTS is provided through hospitals. [DESIGN] A cross sectional study with structured questionnaire interviews to all new smear-positive TB patients aged 15 years or older who were registered in the study sites from May 1st to July 31st in 2002. [RESULTS] The total delay in the pilot districts was significantly shorter than that in the control districts (median 58 days vs. 232 days, p＜0.01). The median doctors’delay within TB service in the pilot districts was 10 days and that in the control was 6 days. The period between first consultation to any health care provider and first visit to a TB service center, subsequent contact delay, was longer than any other type of delay and significantly different (24 days in pilot vs. 185 days in control, p＜0.01). The distance and travel costs to a TB service center were the factors associated with delay in seeking diagnosis of tuberculosis. No other variables had any significant association with the delay. [CONCLUSION] Decentralizing DOTS to primary care health centers is highly effective in reducing the delay to TB treatment in Cambodia. Key words : Tuberculosis, DOTS, Delay analysis, Cambodia, Decentralization

Introduction Cambodia is one of the 22 countries with the highest burden of tuberculosis (TB) in the world. The annual incidence rate of smear-positive pulmonary TB was estimated at 241 per 100,000 inhabitants in 1997 1). The international strategy for TB control, known as DOTS (Directly Observed Treatment, Short-course), has been adopted in Cambodia since 1994. Up to 1998, DOTS was provided through a hospital-based approach in which TB diagnosis and treatment were available through provincial and district hospitals. The World Health Organization (WHO) acknowledged that Cambodia achieved a remarkable success with a high cure rate, increasing from 68％ in 1994 to 89％ in 1998, but case detection rate was still low at only 51％ in 1998 1). Moreover, a long delay in TB diagnosis has been common. The reason might be due to the TB Control Program not being available in rural areas, including in the health centers (HC), which constitute the core of primary health care services 2) 3). 1

National Center for Tuberculosis Control, Cambodia, 2Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association

The effective involvement of the peripheral health care facilities is imperative to achieve total geographical and patient coverage in TB 4). The National Tuberculosis Control Program (NTP), therefore, developed a new strategy to decentralize DOTS into the district health system through health center networks in 2000 in close collaboration with WHO and the JICA National TB Control Project. In the initial phase of the implementation of this strategy, three pilot districts were selected from three different provinces in rural Cambodia. The duration of the delay to TB diagnosis varies from country to country : two months in Australia 5) and Malawi 6) ; three months in Malaysia 7) and five months in Tanzania 8). A number of studies on delay to TB treatment have explained the delay from two perspectives : patients’delay in seeking care, and doctors’ delay to correct diagnosis and treatment 9) 11) 12). Distance is one of the major causes of patients’delay. Some studies found that distance between the patient’ s home and health facilities could lead to a long patients’delay in Correspondence to : Saint Saly, MD, MSc, National Center for Tuberculosis and Leprosy Control, Cambodia, c/o JICA National TB Control Project, Cambodia, P.O. Box 613, Phnom Penh, Cambodia (E-mail : tb.cam.jica＠online.com.kh salysaint＠yahoo.com) 国内連絡先：小野崎郁史，結核研究所国際協力部 (E-mail :onozaki＠jata.or.jp) （Received 23 Jan. 2006 / Accepted 24 Apr. 2006）

RFP Resistance in M. kansasii / S. Yoshida et al.

479


DETECTION OF rpoB MUTATIONS IN RIFAMPICIN-RESISTANT MYCOBACTERIUM KANSASII 1

Shiomi YOSHIDA, 1Katsuhiro SUZUKI, 1Kazunari TSUYUGUCHI, 4Tomotada IWAMOTO, 2 Motohisa TOMITA, 1Masaji OKADA, 3Mitsunori SAKATANI

Abstract [Purpose] To detect rifampicin-resistant mutations in Mycobacterium kansasii (M. kansasii). [Methods] We examined the M. kansasii isolates from sputum of patients at National Hospital Organization Kinkichuo Chest Medical Center from January 1, 2001 to November 30, 2005 using drug-susceptibility testing, and analyzed 69-bp fragment of rpoB gene in rifampicin-resistant strains. [Results] Three strains from 314 isolates were determined as rifampicin resistant using drug-susceptibility testing. Those strains showed a rise in minimum inhibitory concentration (MIC), and had the mutations in rpoB gene. These point mutations in codons 513 and 516 were common mutations found in rifampicin-resistant clinical isolates of M.tuberculosis. [Discussion] We verified the association between rpoB

gene mutations and rifampicin resistance in M. kansasii. Key words : Mycobacterium kansasii, Rifampicin-resistance, rpoB mutations, Drug-susceptibility test 1

Clinical Research Center, 2Department of Clinical Laboratory, 3 Department of Respiratory Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, 4Kobe Institute of Health Correspondence to: Shiomi Yoshida, Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai-shi, Osaka 591_ 8555 Japan. (E-mail : dustin＠kch.hosp.go.jp)

485

Spatial Distribution of TB in Tokyo / H. Watase et al.


GEOSPATIAL ANALYSIS OF TUBERCULOSIS IN TOKYO 1

Hirotoshi WATASE and 2Yoshiko NAKANISHI

Abstract [Purpose] To assess geographic variations in the incidence of tuberculosis in Tokyo. [Methods] Using information on tuberculosis incidence, 2000 to 2002, from the annual notification report, patients were categorized into 8 groups by sex and age. We then calculated the Standardized Incidence Ratio (SIR) for each of the 23 wards in Tokyo. The SIR map was described by spatial interpolation and evaluated by cross validation. Spatial scan statistics were used to detect the significance of high-risk areas across the region. We compare this with the proportional distribution of those receiving public assistance and according to the SIR. [Results] The geographic variations of SIR did not show a uniform pattern for each group. Spatial scan statistics clearly identified locations, that were significantly high for male groups over 20 years old. Groups under 20 years old and all female groups did not produce high incidence cluster, which are likely to demonstrate spatial features of the proportion of

those receiving public assistance. [Conclusions] The geographic distribution of the proportion of those receiving public assistance should impact upon the geographic distribution of the high incidence clusters. However, considering the results of the young age group and each female group, we suggest that recent infection risk among local habitants was almost uniform, with a slightly higher tendency in urban locations of Tokyo. Key words : Tuberculosis, Spatial interpolation, High risk group, Standardized incidence ratio, Geographic distribution 1

Fukagawa Health Consultation Bureau, 2Koto Public Health Center Correspondence to : Hirotoshi Watase, Fukagawa Health Consultation Bureau, 3_4_301, Shirakawa, Koto-ku, Tokyo 135_0021 Japan. (E-mail : h-watase05＠city.koto.tokyo.jp)

結核第 81 巻第 7 号 2006 年 7 月

490

8 ） Jones RS, Fekete T, Truant AL, et al. : Persistent bacteremia due to Tsukamurella paurometabolum in a patient undergo-

文献 1 ）束村道雄, 水野松司：喀痰中に見出される一新菌種 Gordona aurantiaca について. 結核. 1971 ; 46 : 93_98. 2 ） Tsukamura M, Kawakami K : Lung infection caused by Gordona aurantiaca (Rhodococcus aurantiacus). Journal of Clinical Microbiology. 1982 ; 16 : 604_607. 3 ） Collins MD, Smida J, Dorsch, et al. : Tsukamurella gen. nov. harboring Corynebacterium paurometabolum and Rhodococcus aurantiacus. Int J Syst Bacteriol. 1988 ; 38 : 385_391. 4 ） Bergey’ s Manual of Determinative Bacteriology, 9th ed., Holt JG, ed., Williams & Wilkins, Baltimore, 1994. 5 ） Gomez JP : Tsukamurella infection in an Immunocompromised Patient. Chest. 2003 ; 124 (Suppl.) : 255S_256S.

ing hemodialysis. Case report and review. Clin Infect Dis. 1994 ; 18 : 830_832. 9 ） Tsukamura M, Hikosaka K, Nishimura K, et al. : Severe progressive subcutaneous abscess and necrotizing tenosynovitis caused by Rhodococcus aurantiacus. Journal of Clinical Microbiology. 1988 ; 26 : 201_205. 10） Prinz G, Ban E, Fekete S, et al. : Meningitis caused by Gordona aurantiaca (Rhodococcus aurantiacus). Journal of Clinical Microbiology. 1985 ; 22 : 472_474. 11） Almehmi A, Pfister AK, McCowan R, et al. : Implantable cardioverter-defibrillator infection caused by Tsukamurella. WV Med J. 2004 ; 100 : 185_186.

6 ） Alcaide ML, Espinoza L, Abbo L : Cavitary pneumonia secondary to Tsukamurella in an AIDS patient. First case and a review of the literature. J Infect. 2004 ; 49 : 17_19.

12） Granel F, Lozniewski A, Barbaud A, et al. : Cutaneous infection caused by Tsukamurella paurometabolum. Clin Infect Dis. 1996 ; 23 : 839_840.

7 ） Shapiro CL, Haft RF, Gantz NM, et al. : Tsukamurella paurometabolum : A novel pathogen causing catheter-related

Tsukamurella 属を分離した 1 症例（会議録）. 日本臨床

13）伊東ひろ子, 樋口晶子, 小野剛司, 他：血液培養から微生物学会雑誌. 2005 ; 15 : 107.

bacteremia in patients with cancer. Clin Infect Dis. 1992 ; 14 : 200_203.

−−−−−−−− Case Report −−−−−−−−

TSUKAMURELLA TYROSINOSOLVENS CULTURED FROM SPUTUM OF A PATIENT WHO RECEIVED TOTAL GASTRECTOMY FOR GASTRIC CANCER 1

Takemasa MATSUMOTO, 1Motokimi SHIRAISHI, 2Hisae YOSHIMURA, 1Keiji SOGEN, Taishi HARADA, 1Chikara YOSHIMURA, 1Ryutaro ARAMAKI, 1Fumio YAMAMOTO, 1 Takashige KURAKI, and 1Kentaro WATANABE

1

Abstract A 79-year old woman underwent total gastrectomy under the diagnosis of gastric cancer in Feb. 2003. In the beginning of Jan. 2005, she noticed hemosputum and was admitted to our hospital. Chest radiograph and CT disclosed bilateral upper lobe-dominant nodular opacities in the subpleural areas and ground-glass opacities in right S6. Transbronchial lung biopsy was performed, but no useful information for the diagnosis was obtained. Ziehl-Neelsen stain was negative for the smear of the sputum at admission, but weakly stained acid-fast bacilli were grown in the MGIT culture. By the analysis of mycolic acid and menaquinone of the cell membrane, the bacilli were identified as Tsukamurella. Since she was asymptomatic and repeated sputum examination

revealed negative bacilli, she has been observed at the outpatient clinic without any treatment. Key words : Tsukamurella, Nocardia, Mycobacterium, Nontuberculous mycobacteriosis 1

Department of Respiratory Medicine, 2Department of Laboratory Medicine, Fukuoka University Hospital Correspondence to : Takemasa Matsumoto, Department of Respiratory Medicine, Fukuoka University Hospital, 7_45_1, Nanakuma, Jonan-ku, Fukuoka-shi, Fukuoka 814_0180 Japan.

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Radiological Findings of Mycobacterial Infection / J. Fujita

8 ） Choi D, Lee KS, Suh GY, et al. : Pulmonary tuberculosis

文献 1 ）岩崎龍郎：「改訂結核の病理」, 日経印刷, 東京, 1997. 2 ） Aschoff L : Lectures on Pathology. Hoeber, New York, 1924, 42_43, 53_57. 3 ） Fujita J, Ohtsuki Y, Suemitsu I, et al. : Pathological and radiological changes in resected lung specimens in patients with Mycobacterium avium intracellulare complex disease. Eur Respir J. 1999 ; 13 : 535_540. 4 ） Poey C, Verhaegen F, Giron J, et al. : High resolution chest CT in tuberculosis : evolutive patterns and signs of activity. J Comput Assist Tomogr. 1997 ; 21 : 601_607. 5 ） Hatipoglu ON, Osma E, Manisali M, et al. : High resolution computed tomographic findings in pulmonary tuberculosis. Thorax. 1996 ; 51 : 397_402. 6 ） Wang YH, Lin AS, Lai YF, et al. : The high value of high-

presenting as acute respiratory failure : radiologic findings. J Comput Assist Tomogr. 1999 ; 23 : 107_113. 9 ） Fujita J, Bandoh S, Kubo A, et al. : High-resolution CT shows a variety of appearance in disseminated tuberculosis in adults. Int J Tuberc Lung Dis. 2006 ; 10 : 222_226. 10） Fujita J, Ohtsuki Y, Shigeto E, et al. : Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex. Respir Med. 2003 ; 97 : 933_938. 11） Griffith DE, Brown-Elliott BA, Wallace RJ Jr. : Diagnosing nontuberculous mycobacterial lung disease. Infect Dis Clin North Am. 2002 ; 16 : 235_249. 12） American Thoracic Society : Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am J Respir Crit Care Med. 1997 ; 156 : S1_S20. 13） Obayashi Y, Fujita J, Suemitsu I, et al. : Clinical features of non-tuberculous mycobacterial disease : comparisons

resolution computed tomography in predicting the activity of

between smear-positive and smear-negative cases, and

pulmonary tuberculosis. Int J Tuberc Lung Dis. 2003 ; 7 : 563_568. 7 ） Kosaka N, Sakai T, Uematsu H, et al. : Specific highresolution computed tomography findings associated with

between Mycobacterium avium and Mycobacterium intracellulare. Int J Tuberc Lung Dis. 1998 ; 2 : 597_602. 14） Lynch DA, Simone PM, Fox MA, et al. : CT features of pulmonary Mycobacterium avium complex infection. J Comput Assist Tomogr. 1995 ; 19 : 353_360.

sputum smear-positive pulmonary tuberculosis. J Comput Assist Tomogr. 2005 ; 29 : 801_804.

−−−−−−−− The 81st Annual Meeting Educational Seminar −−−−−−−−

CLINICORADIOLOGICAL DIAGNOSIS OF RESPIRATORY INFECTIONS : ESTIMATE OF PATHOGENS BY RADIOLOGICAL FINDINGS AND THE STRATEGY FOR TREATMENT Jiro FUJITA Abstract This review discusses the clinicoradiological findings of pulmonary tuberculosis as well as non-tuberculous mycobacteria. To make a differential diagnosis between pneumonia and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal anatomical structures. If clinicoradiological analyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and respiratory bronchioles is very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures, estimation of causative pathogens could be possible. To differentiate infections caused by Mycobacterium tuberculosis from non-tuberculous mycobacteria, several important criteria have been demonstrated. Briefly, in MAC respiratory infection, right middle lobe and left lingula are frequently involved

and centrilobular nodules and diffuse bronchiectases are characteristic radiological findings. Key words : Lobulus, Acinus, Pulmonary tuberculosis, Nontuberculous mycobacteria Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus Correspondence to : Jiro Fujita, Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903_0215 Japan. (E-mail : fujita＠med.u-ryukyu.ac.jp)