(Vol.75 No.11 November 2000) <1> Kekkaku Vol.75,No.11:629-641,2000 COST EFFECTIVENESS ANALYSIS OF ISONIAZID PREVENTIVE THERAPY TO THE CONTACTS OF TUBERCULOSIS PATIENTS UNDER JAPANESE SETTINGS *Takashi YOSHIYAMA *Epidemiology Division, Department of Applied Research, Research Insititute of Tuberculosis The target for isoniazid preventive therapy against tuberculosis in Japan has been con- tact persons of tuberculosis patients with the age of less than 30. This paper discusses about the cost effectiveness analysis of preventive therapy with the mathematical model. The effectiveness was measured with averted tuberculosis cases, averted death, averted loss of DALY (disability adjusted life years), averted loss of healthy years of life. With all indicators, isoniazid preventive therapy was effective if preventive chemotherapy is given to persons younger than 70 years old and with the higher probability of new infec- tion than 20%, and if it is given following the present criteria of tuberculin testing for preventive therapy in Japan. The total medical cost is cheaper among persons with the preventive therapy than those without the preventive therapy, if the probability of new infection among the contact persons is more than 29% at the age of 40. The isoniazid preventive therapy for health care workers, whose prevalence of infection is higher than the average population, was also effective in both cases with and without baseline tuber- culin testing. However, the positive predictive value of criteria of preventive therapy highly depends on the probability of new infection. Key words:Tuberculosis, Isoniazid preventive therapy, CEA(cost effectiveness analysis), Contact tracing *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 10 May 2000/Accepted 6 Jul. 2000) <2> Kekkaku Vol.75,No.11:643-648,2000 TWO STEP TUBERCULIN TESTING AMONG ELDERLY JAPANESE ADMITTED TO IN RESIDENTIAL HOMES 1*,2Masaaki MIKAMI and 2Yuji KAWASAKI 1Department of Internal, Medicine, Kurayoshi Hospital, 2Department of Respiratory Medicine, National Sanatorium Matsue Hospital This study was carried out to know the prevalence and determinants of tuberculin reac- tors and the size of booster phenomenon in 211 Japanese residents of a provincial nursing home for eldery. The age of the study subjects ranged from 65 to 99 (mean 83.2), and no subjects were foreign born, and had any history of BCG vaccination. The prevalence of TB infection in this aged group was estimated 70% or higher. Testing was done according to the standard method used in Japan. Results showed that 35.1% of subjects were positive by the initial test, and 27.0% converted to positive by the second test, thus altogether 52.6% were positive by two step test. No association was found between the prevalence of tuberculin positive rate and the age or the preformance status. Lower body mass index, Lymphocytopenia, hypoalbuminemia and PNI (prognostic untritional index) were seen to relate with the weaked tuberculin skin reaction. Key words:Two-step tuberculin test, Booster phenomenon, Body mass index, Nutrition, Elderly, Residential home *43, Yamane, Kurayoshi-shi, Tottori 682-0023 Japan. (Received 18 Feb. 2000/Accepted 21 Jul. 2000) <3> Kekkaku Vol.75,No.11:649-659,2000 THE INVASION OF MYCOBACTERIUM TUBERCULOSIS INTO NON-PHAGOCYTIC CELLS 1*Kazue HIGUCHI, 1Nobuyuki HARADA, 2Hiroyuki YAMADA, 3Kazuo KOBAYASHI, and 4Minoru TAKEDA 1*Divisions of Immunology and 2Molecular Pathology, Department of Basic Research, Research Institute of Tuberculosis, 3Department of Host Defense, Osaka City University Medical School, 4Department of Biochemistry, Showa Universtiy School of Medicine To explore the ability of tubercule bacilli to invade and survive within non-phagocytic cells, we used in this study a human fibroblast cell line, WI-38, derived from normal embryonic lung and a human epithelial cell line, SQ-5, derived from lung squamous cell carcinoma. Live M.tuberculosis Erdman and M.tuberculosis H37Rv invaded WI-38 cells more efficiently than live M.tuberculosis H37Ra, M.bovis Ravenel, M.bovis BCG Tokyo and M.bovis BCG Pasteur. The capability of tubercle bacilli to invade WI-38 cells was Erdman†H37Rv„BCG PastureàM.bovis RavenelàBCG Tokyo„H37Ra. A similar in- vasive ability was observed using SQ-5 cells. In contrast with live bacilli, heat-killed bacilli failed to invade WI-38 cells, whereas they were detected within SQ-5 cells. These results and incorporation of latex beads suggest that SQ-5 cells, but not WI-38 cells, possess phagocytic activity. H37Rv multiplied most actively within WI-38 cells when compared to H37Ra and BCG Tokyo, suggesting that the ability to invade and survive within non-phagocytic cells reflects the more active invasion of virulent M.tuberculosis than avirulent M.tuberculosis. The assay system used in this study may help us to clarify the virulence of tubercle bacilli in vitro. Key words:Invasion, M.tuberculosis, Non-phagocytic cells, Lung cells, Virulence *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 20 Jun. 2000/Accepted 23 Aug. 2000) <4> Kekkaku Vol.75,No.11:661-664,2000 A CASE REPORT OF PULMONARY MYCOBACTERIUM KANSASII INFECTION FOUND REGULAR MEDICAL EXAMINATION IN OUR MEDICAL COLLEGE OF NURSING *Keiko INATOMI *Department of Health Care, Juntendo Medical College of Nursing A 20-year-old female was checked by chest X-ray film just before starting practical nurse training in the hospital. She was diagnosed as tuberculosis in the initial phase of treatment. In Japan, the num- ber of newly registered tuberculosis has been increasing since 1997, and the stop tubercu- losis campaign is organized by the Ministry of Health and Welfare. The incidence rate of tuberculosis announced officially by the Ministry of Public Welfare was 33.9 per 100,000 in 1997, while that of nontuberculous mycobacteriosis has been increasing year by year, and it was 2.45 in 1997. The one out of 4 nontuberculous mycobacteriosis is cansed by M. kansasii. Six colonies of Mycobacterium kansasii were detected by gastric juice culture from this patient. Untreated strains of M.kansasii are susceptible to rifampicin, isoniazid, ethambutol, ethionamide, streptomycin and cycloserine at concentrations readily available in the serum with usual therapeutic doses. Isolates are usually resistant to available serum level of pyrazinamide. The patient was treated with rifampicin, isoniazid and ethambutol for 6 months. Pyrazinamide was stopped at 1 month and 10days treatment due to liver dysfunction and resistance to the organism. Pulmonary infiltration with cavity disappeared during follow up examination. Nowa- days we must take into account not only tuberculosis but also primary nontuberculous mycobacteriosis at regular medical check of young female. Key words:Nontuberculous mycobacteriosis, Mycobacterium kansasii, Regular medical check, Nurse student *2-2, Takasu, Urayasu-shi, Chiba 279-0023 Japan. (Received 29 Mar. 2000/Accepted 30 Aug. 2000) <5> Kekkaku Vol.75,No.11:665-673,2000 Commemorative Lecture of Receiving Imamura Memorial Prize THE EFFECTIVENESS OF PYRAZINAMIDE-CONTAINING SIX-MONTH SHORT COURSE CHEMOTHERAPY *Masako WADA *Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Incidence of tuberculosis worldwide will increase progressively unless the effective program is implemented immediately. In Japan, the decreasing of tuberculosis incidence has been very slow since 1977 and this trend has not been improved till now. Six-month regimens for the treatment of tuberculosis were recommended by IUATLD, ATS, CDC, and WHO and have been adopted in most developed countries since late 1980s, but not adopted in Japan till April, 1996. We studied effectiveness of 6-month regimen including pyrazinamide (2HRZE or E/4HRE) on newly diagnosed pulmonary tuberculosis who started the treatment in the Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA). From January 1991 to December 1997, 726 newly diagnosed pulmonary tubercu- losis patients started treatment with 6-month regimen. Bacillary negative conversion rate among 424 patients whose bacilli were susceptible to both isoniazid and rifampicin, was 92.9% after 2 months of treatment and who completed treatment without change of treatment regimen. Among 726 cases, 593 (81.7%) succeeded, 48 (6.6%) defaulted, 53 (7.3%) were referred to other doctors, and 32 (4.4%) died. The relapse rate after completion of the treatment was 3.2 percent among 345 patients whose bacilli were susceptible to both isoniazid and rifampicin and who completed the treatment without change of regimen. The relapse rate among the patients complicated with diabetes mellitus (DM) was higher than that among non-DM patients (6.31/100 person-years vs 0.90/100 person-years)(Pƒ0.001). When drug-induced hepatitis was defined as the elevation of serum liver enzyme levels with the clinical symptoms of hepatitis or their elevation over 5 times of normal upper limit, the incidence of drug-induced hepatitis among the patients treated with pyrazinamide-containing 6-month regimen was not higher than that among the patients treated with 9-month regimen without pyrazinamide (6HRS or E/3HR)(7.9% vs 7.3%). The risk factors for drug-induced hepatitis included elderly, history of gastrectomy, hypoalbuminemia, the higher dose of isoniazid over than 7.5mg/kg, higher than 30mg/kg of pyrazinamide and positive HCV antibody. The effectiveness of 6-month regimen on the patients whose organisms were resistant to isoniazid and susceptible to rifampicin was studied. The average duration of the treatment for the patients started 6-month regimen was 3.2 months shorter than for the patients started 9-month regimen (10.2 months vs 13.4 months). I concluded that 6-month regimen containing-pyrazinamide was effective for the patients with isoniazid-rifampicin susceptible tuberculosis patients except the patients complicated with diabetes mellitus. But the frequency of drug-induced hepatitis was higher than that of previous reports, and further studies are needed to elucidate the cause of high frequency of hepatitis among Japanese patients. Key words:6-month short course chemotherapy, Drug-induced hepatitits, Pyrazinamide, Diabetes mellitus, Relapse rate *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 14 Aug. 2000) <6> Kekkaku Vol.75,No.11:675-679,2000 The 75th Annual Meeting Symposium ‡X. COOPERATION BETWEEN PUBLIC HEALTH CENTERS AND HOSPITALS IN TUBERCULOSIS CONTROL -How Should Clinical Nurses and Public Health Nurses Work Together?- Chairpersons:1Mieko TSUJI 2Takeko YAMASHITA 1*Osaka Prefectural Habikino Hospital, 2Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Symposium Topics and Presenters: 1. Hospital nureses' cooperation wtih public health centers:Tazuko KUME(Osaka Prefectural Habikino Hospital) 2. Activity of public health nurses and their cooperation with hospitals:Yuko YAMAUCHI (Chuo Public Health Center, Miyazaki Prefecture) 3. Report on cooperation between public health center and hospitals in the central area of Kyoto Prefecture:Kazuko OKURA(Shuzan Public Health Center, Kyoto Prefecture) 4. Report on cooperation between hospitals and public health center in big cities: Hideko ISHII(Minami Public Health Center, Nagoya City) 5. Comments:Tadayuki AHIKO(Murayama Public Health Center, Yamagata Prefecture) and Isamu TAKAMATSU (Osaka Prefectural Habikino Hospital) The result of cohort analysis of the patients newly registered from Jan. 1, 1994 until Dec. 31, 1995, showed that 49,824(84.2%) patients out of a total of 59,150 patients had been cured or completed. On the other hand, there were 1,527(2.6%) failure cases, 2,521(4.3%) defaulters, and 5,287(8.9%) deaths due to TB or other causes. The tratment outcome for smear positive tuberculosis was less favorable. Thus, the Japan's tuberculosis treatment program has not yet achieved the global target of WHO, i.e., the cure rate of 85% of smear positive patients. The Ministry of Health and Welfare declared gTB Emergencyhon July 26, 1999. It was a warning to the general public of Japan, as well as to the medical and health professions and central and local governments against their neglect of the tuberculosis problem that has been slow in its improvement since long, and recently has been in upsurge, accompanied by the emergence of formidable problems such as outbreaks of tuberculosis, nosocomial infections and multi-drug-resistant tuberculosis. The public health and the clinical service both have their heavy mission to respond to this declaration hand in hand, fulrfilling their respective professional duties to the society. The symposium confirmed that under such situation of the problem, the cooperation between clinical service and public health is very essential and can be very effective in order to improve the results of treatment program for the sake of patients' QOL and for prevention of multi-drug-resistant tuberculosis as well. This was warmly supported by the enthusiasm of the audience with various questions and discussion. Key words:Tuberculosis, Cooperation between public health and clinical service, Treatment failure, Defaulter, Cohort analysis *3-7-1, Habikino, Habikino-shi, Osaka 583-8588 Japan. (Received 21 Aug. 2000)