(Vol.76 No.4 April 2001) <1>Kekkaku Vol.76, No.4:357-362, 2001 COMPARISON OF IN VITRO ANTIMICROBIAL ACTIVITIES OF OFLOXACIN, LEVOFLOXACIN, CIPROFLOXACIN, AND SPARFLOXACIN AGAINST VARIOUS MYCOBACTERIA 1*Shin KAWAHARA, 1Atsuhiko TADA, and 2Hitoshi NAGARE 1*Department of Internal Medicine and 2Department of Clinical Laboratory, National Minami-Okayama Hospital In vitro antimicrobial activities of ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), and sparfloxacin (SPFX) were compared against various mycobacteria using the agar dilution method with 7H11 medium, and the following results were obtained. (1) These four new quinolones showed excellent antimicrobial activities against M. tuberculosis, M. kansasii, and M. fortuitum. (2) SPFX was most active against slowly growing mycobacteria. The activity against M. tuberculosis was in the order of SPFX>CPFX>LVFX>OFLX. The activity against M. kansasii was in the order of SPFXLVFXOFLXCPFX.@ @(3) On the other hand, CPFX was most active against rapidly growing mycobacteria. The activity against M. fortuitum was in the order of CPFX>SPFX>LVFX>OFLX. Considering the in vitro antimicrobial activities and the pharmacokinetics of these four drugs, they could achieve favorable clinical outcomes for all the patients with pulmonary infection due to M. tuberculosis or M. fortuitum and some of the patients with pulmo- nary infection due to M.kansasii or M. chelonae. Key words:Ofloxacin, Levofloxacin, Ciprofloxacin, Sparfloxacin, Various mycobacteria, Antimicrobial activity *4066, Hayashima, Hayashima-cho, Tsukubo-gun, Okayama 701-0304 Japan. (Received 7 Sep. 2000/Accepted 27 Dec. 2000) <2>Kekkaku Vol.76, No.4:363-370, 2001 A NUTRITIONAL INVESTIGATION OF HOMELESS PATIENTS WITH TUBERCULOSIS 1*Katsumi YAMANAKA, 2Shuzo SAKAI, 2Fumio NOMURA, 3Tomi AKASHI, and 4Toshio USUI 1*Nagoya City Central School of Nursing, 2*Department of Respiratory Medicine, Japanese Red Cross Nagoya First Hospital, 3Department of Health, Health and Welfare Bureau, Nagoya City, 4Nagoya City Nakamura Health Center A retrospective case-control study was performed with TB patients who were admitted to our hospital over the two years from Jan. 1997 to Dec. 1998 and healthy men who underwent a health screening in April 2000 in the same hospital. Thirty-two non-home- less TB patients (the first control group) and 32 healthy men (the second control group) were matched with 32 homeless TB patients according to age. All 3 groups were male. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and lymhocyte count on admission were significantly lower in the homeless patients than in the non- homeless patients and healthy men. Albumin, cholesterol, cholinesterase, hemoglobin level, white blood cell count and lymphocyte count on admission were significantly lower in non-homeless patients than healthy men. Height, weight and body mass index were significantly lower in the homeless patients than in the healthy men. Howerver, ther were no significant differences in these body characteristics between the homeless and non- homeless patients. Twenty-five percent of homeless patients died during hospitali- zation, compared with 6.3 percent of non-homeless patients. Lymphocyte counts among homeless patients who died during hospitalization were significantly lower than among those who survived during hospitalization. Total protein, albumin, cholesterol, cholines- terase, hemoglobin level and weight were lower in patients who died than in those who survived, although the differences were atatistically not significant. Key words:Tuberculosis, Homeless, Nutrition *1-4-7, Aoi, Higashi-ku, Nagoya-shi, Aichi 461-0004 Japan. (Received 6 Oct. 2000/Accepted 26 Jan. 2001) <3>Kekkaku Vol.76, No.4:371-375, 2001 ANALYSIS OF FACTORS RELATED TO THE HIGH INCIDENCE OF TUBERCULOSIS IN THE CITY OF WAKAYAMA -Analysis According to Age Groups, and Sputum Test Results- *Mie KASAMATSU, Junko SHIOTSU, Kumiko SHIMAZAKI, Naoko NAGAI, and Junko KINOSHITA *Wakayama City Public Health Center Over the last 20 years, the decrease in the incidence of Tuberculosis (TB) in Japan has slowed down. As of 1999, the incidence rate was 34.6 per 100,000 population in Japan, which was haigher than that of the other developed countries, and the incidence rate in the city of Wakayama, one of the prefectural capital cities in Japan, during the same peiod was 42.9 per 100,000 population. We investigated the causes of this high incidence rate of TB in Wakayama City according to the analysis by age groups and sputum test results when patients are newly registered. Comparing our data during tha peiod from 1. 1. 1998 to 12. 31. 1999 with data during the same peiod in the whole country and the rest of Wakayama Pref., the following results were obtained. Observing by age-groups, the incidence of TB in Wakayama City as well as in the rest of Wakayama Pref. and in the whole coutry was highest in the age-group above 70 years of age, thought the rate of Wakayama City was significantly higher (146.2 per 100,000 population) than that in the rest of Wakayama Pref. (98.5 per 100,000 popu- lation) and that in the whole country (90.3 per 100,000 population). Furthermore, the incidence rate of cases diagnosed as TB without bacteriological proof in Wakayama City (57.1 per 100,000 population) was significantly higher than that of the whole country (33.7 per 100,000 population). Therefore, we concluded that one of the causes of high incidence of TB in Wakayama City was due to inappropriate method of diagnosing TB. More extensive use of sputum examination and strict evaluation of cases without bacteriological proof are desirable to increase the accuracy of TB diagnosis in Wakayama City. Key words:Wakayama City, Incidence of Tuberculosis, Sputum test-negatuve pulmonary tuberculosis, Aged population *5-2-15, Fukiage, Wakayama-shi, Wakayama 640-8137 Japan. (Received 5 Oct. 2000/Accepted 9 Feb. 2001) <4>Kekkaku Vol.76, No.4:379-383, 2001 A CASE OF DRUG-RESISTANT PULMONARY TUBERCULOSIS TREATED SUCCESSFULLY FOLLOWING DISAPPEARANCE OF RIFAMPICIN RESISTANCE AFTER 17 YEARS' CHEMOTHERAPY *Eriko SHIGETO, Isao MURAKAMI, and Yasuyuki YOKOSAKI *Department of Respiratory Diseases, National Hiroshima Hospital A female who first acquired pulmonary tuberculosis in 1962 when she was 25 years old, admitted to the National Hiroshima Hospital in 1982. Her sputum has been smear positive for acid-fast bacilli for 3 years before admission in spite of continuous anti- tuberculous chemotherapy, and were resistant to isoniazid (INH) and rifampicin (RFP). She was treated with a regimen containing ethambutol (EB), prothionamide (TH) and enviomycin (EVM) but continued to be culture positive. Though she was treated with various regimens which include one to three sensitive drugs, her sputum continued to be positive for M.tuberculosis in the following 14 years. During the course, resistance to EB, TH, cycloserine (CS) and streptomycin (SM) emerged. Resistance to RFP temporarily retracted in 1988, but her sputum was bacilli negative only for 2 months after the addition of RFP to previous regimen, and followed by resurgence of RFP resistance. In 1992, data of drug sensitivity tests showed sensitivity to TH, CS and RFP in turn, which were not used for 3 to 5 years. In 1993, she was treated with RFP, TH and EVM successfully and continued to be bacteriologically negative for 7 years so far. Drug resistance to M. tuberculosis is induced by inappropriate chemotherapy as seen in this case. Regimens with less than three drugs without RFP and INH was not only insuf- ficient to get cure but, what was worse, also induced additional resistance to used drugs. The reason of successful chemotherapy in this case was spontaneous disappearance of drug resistance to RFP and TH. This case suggests that the disappearance of drug resis- tance is possible, when drugs are not used for more than a few years, hence the successful treatment could be expected. However is must be emphasized that the drug resistance is produced by incorrect treatment as seen in this case, and its prevention is of the prime importance. Key words:Drug-resistant tuberculosis, Rifampicin, resistance induction, Disappearance of drug resistance *513, Jike, Saijo-cho, Higashihiroshima-shi, Hiroshima 739-0041 Japan. (Received 18 Sep. 2000/Accepted 5 Feb. 2001) <5>Kekkaku Vol.76, No.4:385-397, 2001 The 75th Annual Meeting Special Lecture WHERE DO WE STAND WITH BCG VACCINATION PROGRAMME IN JAPAN? *Toru MORI *Tuberculosis Research Institute, Japan Anti-Tuberculosis Association The current BCG vaccination program of Japan is critically discussed based on recent knowledge, especially with regard to its epeidemiological aspects, in order to put the problem into perspective for Japan's future tuberculosis control program. 1. Efficacy and Overall Effectiveness:Various indicators of BCG efficacy have been proposed, and the meticulous analysis on the variability and the quality of these indicators seems to have formed a consensus on the efficacy, as seen in the recent meta-analysis studies. However, much has been left unanswered concerning the conditious under which the efficacy is guaranteed. The impact of the vaccination program on the population should also be considered in order to make decisions on the program. Comparing the age-specific tuberculosis notification rate between japan and the USA, where there has been no BCG vaccination program, shows that the rate for 0 to 4 year olds is clearly lower in Japan than in the USA, while it is more than five times higher for all ages in Japan than in the USA. The statistics for Japanese children are superior to those of US children with respect to the speed of decline in notification rate as well. Thoes observations support the overall effectiveness of BCG vaccination in Japan. 2. Mechanisms of BCG Vaccination Efficacy and Its Duration:Two possible mecha- nisms of how BCG works to prevent tuberculosis were proposed. Epidemiological models based on each mechanism were subsequently tested by simulating 20 years' development of cases in the BCG vaccination trial by BMRC. In mechanism 1, the BCG-induced immunity is assumed to boost TB immunity in inhibiting the clinical breakdown of tuberculosis during the 10 to 15 years after the vaccination. In mechanism 2, the immunity markes the infection process abort (presumably, at 90%, during the seven years after infection, for example), leading to a smaller risk of future clinical development. So far, most epidemiological models implicitly assume mechanism 1 above. In animal experimental models, however, it has been difficult to simulate the mechanisms differentially, which has been one of the drawbacks to this argument. 3. Effectiveness of Revaccination:Revaccination with BCG Vaccine aims to restore or to endow immunological resistance through repeating vaccination to those who have par- tially or totally lost the immunity acquired from the primary vaccination. Although some animal experiments support the efficacy of revaccination with BCG, studies in humans have been rare and the results are variable. The observation of Polish infants and schoolchildren is suggestive of the efficacy, but it is not randomized and of question- able value. The recent study of Malawi is a randomized trial. It demonstrated that BCG revaccination protects against leprosy, but does not protect significantly against tubercu- losis. It is possible, however, that it does protect aginst tuberculous lymphadenitis. The two above-mentioned possible mechanisms of BCG immunity were applied to a model analysis of BCG revaccination. It was known that revaccination effectiveness is very limited under any assumption, given the current Japanese epidemiological situation of tuberculosis, so that the demerits due to revaccination, such as strong local reactions, must not be neglected but should be carefully considered. At the same time, we should remember that this model analysis assumes that the primary vaccination is given to new borns with advanced and uniform techniques, which is not always true, and revaccination may supplement the technical failure of the primary vaccination. 4. Deciding on the Total Discountinuation of BCG Vaccination Programme Japan:The recommendations of WHO or IUATLD on the discontinuation of the BCG vaccination program are just conventional ones and the theoretical reasonings is difficult to accept. After all, the decision making should depend on the lay decision makers' subjective judg- ment balancing benefit and loss in terms of costs and health incurred by the policy, as shown by Waaler and Rouillon. The current Japanese BCG vaccination program is very expensibe, but brings about some, though very small, benefit. This balance was compared with that of Sweden around 1975, when the program was discontinued. The comparison clearly showed that the cost-effectiveness of the program in Japan today in superior to that of Sweden in 1975. Key words:BCG vaccination, BCG vaccine, Tuberculosis control, Epidemiology, Preventive medicine *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 20 Feb. 2001)