(Vol.76, No.5 May 2001) <1> Kekkaku Vol.76, No.5: 407-411, 2001 INFANTS 12 MONTH-OLD OR LESS AS A HIGH RISK GROUP IN TUBERCULOSIS -Comparison of Clinical Data with Those in Children Aged One to Two Years- 1*Shinya KONDO, 1Masaki ITO, and 2Sachiko KAGEYAMA 1*Division of Respiratory Disease, Tokyo Metropolitan Children's Hospital, 2Department of Pediatrics, National Higashi-Utsunomiya Hospital A number of tuberculosis (TB) infants 12 month-old or less is larger than the ones of any other age groups with childhood TB in our hospital. This study was undertaken to elucidate clinically why infants 12 month-old or less suffered from TB most among infants and early children. We studied tuberculin skin reaction, isolation frequency of Mycobacterium tuberculosis (MTB) in gastric aspirates, and frequency of systemic dissemination of TB among 45 TB infants 12 month-old or less, and compared the results with those of 31 control TB infants and children aged 13 to 35 month-old. The frequency distribution of tuberculin skin reaction size among the studied infants was significantly smaller than that among the controls (p<0.05). MTB was positive among 33 out of the 45 studied infants (73%) while 12 out of the 31 controls (39%), and the difference was significant (p<0.005). Miliary TB and/or TB meningitis were seen among 8 out of the 45 studied infants (18%) while 1 out of the 31 controls (3%), and there was marginally significant difference between them (p=0.054). These results suggest that delayed-type hypersensitivity and cell-mediated immunity to MTB among infants 12 month-old or less may be lower than those among infants and children aged 13 to 35 month-old, and the studied infants may be inferior in their capacity to kill mycobacteria and to encapsulate mycobacteria by granuloma formation. Key words:Tuberculosis, Infant, Tuberculin reaction, Delayed-type hypersensitivity, Cell-mediated immunity *From 1-3-1, Umezono, Kiyose-shi, Tokyo 204-0024 Japan. (Received 19 Jun. 2000/Accepted 15 Feb. 2001) <2> Kekkaku Vol.76, No.5: 413-418, 2001 PROFILES OF EXPRESSION OF THE THERAPEUTIC EFFICACY OF KRM-1648 IN MICE INFECTED WTIH MYCOBACTERIUM AVIUM COMPLEX AT DIFFERENT CHALLENGE DOSES 1Toshiaki SHIMIZU, 1,2Keiko OGASAWARA, 1Katsumasa SATO, 1Chiaki SANO, and 1*Haruaki TOMIOKA 1*Department of Microbiology and Immunology and 2Department of Otorhinolaryngology, Shimane Medical University Studied were made on the profiles of the therapeutic efficacy of KRM-1648 (KRM) against Mycobacterium avium complex (MAC) infection, which was induced in mice at different challenge doses, in reducing bacterial growth in the visceral organs and altering the profiles of cytokine mRNA expression at the sites of infection. First, bacterial growth in the lungs of mice infected with either high or low challenge doses of MAC, was reduced due to KRM treatment. This effect was noted even in the early phase of infection (week 4) in mice, that were given a high-dose infection. Second, marked thera- peutic efficacy of KRM was observed in mice, that were given low-dose MAC infection, in terms of the reduction in bacterial loads in the spleen. However, in mice given a high- dose bacterial challenge, KRM did not exhibit such an efficacy. Third, the expression of both proinflammatory cytokines (TNF-CIFN-) and anti-inflammatory cytokines (IL-10, TGF-) in mRNA levels were increased at 4 weeks after infection. Notably, all of the cytokines tested for the mRNA expression levels were higher in mice given a low-dose MAC infection as compared to those in mice given a high-dose infection. KRM treatment increased the mRNA levels of these cytokines at week 4, while TGF- mRNA expression at week 8 was conversely decreased by KRM treatment. These findings suggest that the profiles of the therapeutic efficacy of KRM vary in mice given low- or High-dose MAC infection. Key words:Mycobacterium avium complex, KRM-1648, Cytokine *From 89-1, Enya-cho, Izumo-shi, Shimane 693-8501 Japan. (Received 10 Oct. 2000/Accepted 1 Mar. 2001) <3> Kekkaku Vol.76, No.5: 419-426, 2001 EVALUATION OF RAPIDLY GROWING MYCOBACTERIA ISOLATES IN A GENERAL HOSPITAL:REPORTS FROM THE HOSPITAL MICROBIOLOGY LABORATORY 1*Setsuko TAZAWA, 2Kenji MARUMO, 2Yoshiko NAKAMURA, 3Michiaki NARUSHIMA, and 4Dousei HIGUCHI 1*Division of Central Clinical Laboratory, 2Department of Clinical Pathology, 3Department of Respiratory Medicine, and 4Department of Dermatology, Showa University Fujigaoka Hospital Forty isolates of rapidly growing Mycobacteria, Mycobacterium fortuitum group including M.fortuitum and M. peregrinum and M.chelonae group including M.chelonae subsp. chelonae and M.chelonae subsp. abscessus at Showa University Fujigaoka Hospital collected between February 1981 and December 1997 were investigated in this study. These isolates were from the patients who were not infected with HIV. The average age of fourteen patients, from whom M.fortuitum group was isolated, was 58 years, ranging from 17 to 80 years old. One patient (71-year-old) with chronic myelogenous leukemia and another (64-year-old) with chronic diabetes mellitus were diagnosed with skin abscesses of M.fortuitum group, which were located on the right site of the neck and in the scar after injecting insulin (injection abscess), respectively. The average age of twenty-six patients, from whom M.chelonae group was isolated, was 57 years, ranging from 32 to 84 years old. One patients (75-year-old) with articular rheumatism was diag- nosed with a lung infection of mixed M.chelonae group and Pseudomonas aeruginosa, and another (74-year-old) with diabetes mellitus and kidney failure was strongly suspected of a lung infection. The isolates of the two mycobacteria form the remaining patients were due to colonization, while these patients had the following underlying diseases contributing to infections:pulmonary emphysema;diabetes mellitus;leukemia;collagen diseases;lung cancer ;chronic kidney diseases;systemic lupus erythematosus;carcino- matous pleurisy;bronchiectasis;post-tuberculosis. Most isolates of the two mycobacteria were separated from the specimens of patients' respiratory tracts, but since M.chelonae group was a contaminant in the tap-water for diluting concentrated chlorhexidine, the organism happened to be isolated with the mucous membranes of the 6 patients' colons that were picked up while using the washed fiber-scope. These findings suggest that M. fortuitum and M. chelonae groups, in spite of the fact that they rarely cause infection, have a significant risk of infecting aged patients in general hospitals with various under- lying diseases attributable to infections. As only a few colonies were isolated from patients' specimens in the majority of cases, it took time to carry out these clinical examinations, and to improve this "laboratory's delay", it is needed to make faster report to clinicians. Key words:Mycobacterium fortuitum group, Mycobacterium chelonae group, Underlying disease, Skin abscess, Lung infection *From 1-30, Fujigaoka, Aoba-ku, Yokohama-shi, Kanagawa 227-8501 Japan. (Received 21 Aug. 2000/Accepted 1 Mar. 2001) <4> Kekkaku Vol.76, No.5: 427-436, 2001 CLINICAL STUDY ON THE CASES IN WHICH INH OR RFP WAS DISCONTINUED DURING TREATMENT FOR PULMONARY TUBERCULOSIS Cooperative Study Unit of Chemotherapy of Tuberculosis of National Sanatoria in Japan (CSUCTNS) (Chairman:Masashi MOHRI) 1*Susumu HARADA, 1Masahiro TAKAMOTO, 1Tsuneo ISHIBASHI, 2Masashi MOHRI, 2Koji SATO, 3Fumio YAMAGISHI, 3Yuka SASAKI, 4Kiyokatsu TANABE, 4Reiko SATO, 5Tadahiko FUJINO, 6Masao TANO, 6Makoto TANIZAWA, 7Mitsunori SAKATANI, 8Tadaaki MORIMOTO, 9Shin KAWAHARA, 9Naokatsu HOTTA, 10Eriko SHIGETO, 11Kazutaka NISHIMURA, 11Takahiro ABE, 12Tomoaki IWANAGA, 13Toshiyuki OE, 14Kazuyasu SHIMAZU, 14Momoko EBIHARA, 15Shojyu NAKAGAWA, and 16Mutsuo KUBA 1*National Omuta Hospital, 2National Tokyo Hospital, 3National Chibahigashi Hospital, 4National Minamiyokohama Hospital, 5National Kanagawa Hospital, 6National Higashi- nagoya Hospital, 7Natiolal Kinkichuo Hospital, 8National Toneyama Hospital, 9National Minamiokayama Hospital, 10National Hiroshima Hospital, 11National Ehime Hospital, 12National Minamifukuoka Hospital, 13National Higashisaga Hospital, 14National Kumamoto- minami Hospital, 15National Nishibeppu Hospital, 16National Okinawa Hospital Short course regimens;2HRZ(E)(S)/4HR(E), 6HRS(E)/3`6HR and 6`9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuber- culosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospitals in 1996. Results were as follows. 1. In 47(7.9%) of the 597 patients, either INH (19;3.2%)or RFP(33;5.5%) was discontin- ued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s(10.9%), 60s(11.7%) or 70s(11.4%). 21(13.6%) of 154 female patients and 26(5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33;5.5%), drug resis- tance (10;1.7%) and complications or underlying diseases (8;1.3%). 4. Fever or eruption (19;3.2%) and drug induced hepatitis (12;2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance. Key words:Pulmonary tuberculosis, INH, RFP, Side effect, Discontinuation of standard chemotherapy *From 1044-1, Tachibana, Omuta-shi, Fukuoka 837-0911 Japan. (Received 20 Oct. 2000/Accepted 2 Mar. 2001)