(Vol.77 No.10 October 2002) <1> Kekkaku Vol.77, No.10: 629-637,2002 Original Article IS6110 RESTRICTION FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS ISOLATED IN OKAYAMA PREFECTURE 1Ritsuko OHATA and 2Atsuhiko TADA Abstract Similarity of restriction fragment length polymorphism (RFLP) patterns of Mycobacterium tuberculosis isolated in Okayama Prefecture from December 1999 to December 2001 was investigated. The RFLP patterns showed diversity, 342 different RFLP patterns were found among 395 strains. There were 34 identical clusters (84 strains). The source of infection in the identical clusters was the same in 20 percent, however, in patients younger than 60 years old, the identical rate was 60 percent. These results suggest that, in comparatively younger patients, the identical RFLP pattern is an important index. In general, 40 percent strains including organized 4 main prevalent strains showed similar patterns. Because the patterns shown in these prevalent strains agreed with the patterns often found in the strains from patients in the other areas of Japan, it was revealed that they were endemic strains not only in Okayama Prefecture but also in many areas of Japan. Key words:RFLP analysis, Measure against tuberculosis, RFLP pattern, Similarity, Prevalent strain 1Department of Microbiology, Okayama Prefectural Institute for Environmental Science and Public Health, 2National Minami-Okayama Hospital Correspondence to:Ritsuko Ohata, Department of Microbiology, Okayama Prefectural Institute for Environmental Science and Public Health, 739-1, Uchio, Okayama-shi, Okayama 701-0298 Japan. (E-mail:ritsuko_oohata@pref.okayama.jp) <2> Kekkaku Vol.77, No.10:639-645,2002 Original Article PROBLEMS ABOUT TUBERCULIN SKIN TEST RAISED FROM CONSULTATIONS AND COUNTERMEASURES -Influence to the Interpretation of Tuberculin Skin Test in Case of the Stoppage of BCG Revaccination Abolition and the Introduction of Induration Measurement- 1Keiko NISHIO, 1Kiminori SUZUKI, 1Yuko SUNAMI, 1Akimitsu SHIMURA, 2Hidetoshi IGARI, and 3Keiichi NAGAO Abstract Since people have very limited access to informations on TB, Chiba Anti-TB Association started "Chiba Kekkaku Dial 110", free TB consultation service through telephone, fax and e-mail, since October 1997. We received 1453 consultations during three years by September 2000. The most frequent consultations was about tuberculin skin test(TST) that amounted to 383, 26.4% of the all consultations. We reviewed the consultations on TST to know why consultations of TST are so frequent and what are problems clients want to know. We categorized the consultations according to the professions of clients and three periods of TST, that is, before testing, during testing and reading, and post reading. There were 178(46.5%) consultations from health professionals, 134(35.0%) from general citizens and the rest of them were from those unknown job. The health professionals were 94 physicians, 34 public health nurses, 23 school nurses, 19 nurses, 2 medical technicians, 2 radiographers and 4 others. Consultation after tuberculin reading was the most frequent: 93 out of 178 consultations from health professionals and 97 out of 134 from general citizens. Especially, difficulty in the interpretation of the reading results was common reason of the consultations in both health professionals (69/93) and general citizens (89/97). They feel difficulties in TST result because of widely practiced BCG revaccination and booster phenomenon due to the repetition of TST. Furthermore, TST reading results vary very much between readers especially in double redness (erythema), and it sometimes affects the diagnosis of tuberculosis infection. Therefore, if repeated TST and BCG revaccination practices in children are abolished, most of those consultations might be solved. When induration measurement is used in TST according to the international standard, the complexity of the classifications of the result seems to be dissolved. Considering the current practices in Japan, we recommend that the size of TST induration should be measured and recorded as we measure and record erythema. And induration should be referred in interpretation when they diagnose TB infection with TST. Key words:Tuberculin skin test, Reading the tuberculin skin test, Reading the induration of tuberculin skin test, Abolition of BCG revaccination 1Chiba Anti-Tuberculosis Association, 2Department of Respirology, Graduate School of Medicine, Chiba University, 3Health Sciences Center, Chiba University Correspondence to:Keiko Nishio, Chiba Anti-Tuberculosis Association, 1-1-20, Miyako-cho, Chuo-ku, Chiba 260-0001 Japan. (E-mail:inf-cent@cata.or.jp) <3> Kekkaku Vol.77, No.10:647-658,2002 Original Article PREVENTIVE THERAPY IN MIDDLE-AGED AND ELDERLY PERSONS SELECTED FORM THE POPULATION-BASED SCREENING BY MASS MINIATURE RADIOGRAPHY -Methodological Aspect and Adverse Reactions- 1Masako OHMORI, 1Masako WADA, 2Kenji NISHII, 3Tomoaki NAKAZONO, 4Hidenori MASUYAMA, 1Takashi YOSHIYAMA, 5Keiko INABA, 1Kunihiko ITOH, 1Kazuhiro UCHIMURA, 3Mihoko SAEGUSA, 1Satoshi MITARAI, 1Moriyo KIMURA, and 6Akira SHIMOUCHI Abstract The notification rate of tuberculosis in Japan was 31.0per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.5per 100,000 among those over 65 years of age. We conducted a study of preventive therapy in middle-aged and elderly persons selected from the population-based screening by the mass miniature radiography. The eligible criteria were 50-79 years of age, fibrous lesion which were compatible with healed tuberculosis and showed no change for at least one year, no previous treatment for tuberculosis, normal liver function tests, and no serious disease at the time of study. The eligible criteria for liver function tests in this study was less than 50 IU/L of AST and ALT value, and less than 1.5 mg/dl of T-bil level. A total of 13,219 people underwent TB screening in 4 cities in 1997 and 2 cities in 1998. Among them, 440 persons fulfilled the above criteria based on the screening records and chest X-ray films. The municipal offices sent letters to 418 people, except 22 whose addresses were unknown, to obtain permission to use their addresses and results of screening in our study. Permission was obtained from 137 persons and we sent them invitation letters for cost-free physical checkup service. Ninety-five persons visited us, and we offered them physical checkup and explained about our study. After obtaining the informed consent, we performed chest X-ray and sputum examination for 3 consecutive days. Finally 29 people were enrolled in the study. They were divided into 4 groups by sex and age, and were randomly assigned to one of two treatment groups. One group took 300 mg of INH per day for 6 months and the other group was only followed up by chest X-ray. Fourteen out of 29 persons began to take INH and received monthly liver function test. All the subjects were scheduled to follow by medical checkup every 6 months for 5 years. The proportion of taking INH tablets was estimated to range from 94% to 100%, based on the calendar for record of taking medication and the number of remaining tablets each month. Six (42.9%) of 14 persons reported adverse reactions. Two of 6 persons complained some of diarrhea, vomiting and gastrointestinal disturbance within 2 weeks, and discontinued taking INH, although none of them showed abnormal liver function tests. Two of 6 persons who reported some kinds of symptoms and 2 of 8 persons who did not complain of any symptoms showed abnormal liver function tests. The abnormal liver function tests had developed from 2 months after the beginning of INH taking in most of the persons and the abnormality improved after the completion of 6-month treatment. We have followed them for a maximum duration of 2.5 years, and 3 cases dropped out from the study. These defaulted cases had completed 6 months of INH. One person (69 y.o. male) was diagnosed as active TB by his chest X-ray film at the 6th month medical checkup, although it was not confirmed bacteriologically. One person (62 y.o. female) had the mastectomy for breast cancer 7 months before the entry to this study and relapsed at the 8th month after the entry. One person (73 y.o. female) was diagnosed as lung cancer at the medical checkup on 2.5 years. Besides them, 4 persons were suspected of worsening the abnormal shadows on chest X-ray films;one was from the INH group and three were from the follow-up group. However none of them was diagnosed clinically and bacteriologically as active tuberculosis. Key words:Population-based screening, Middle-aged and elderly, Isoniazid, Preventive therapy, Informed consent, Adverse reactions 1Research Institute of Tuberculosis, 2Branch Hospital, Okayama Institute of Health and Prevention, 3Health Care Center, Fukujuji Hospital, 4Dai-ichi Dispensary, Japan Anti-Tuberculosis Association, 5Regional Office for the Eastern Mediterranean, World Health Organization, 6Office for Infectious Disease Control, Bureau of Health & Welfare, Osaka City Correspondence to:Masako Ohmori, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (E-mail:ohmori@jata.or.jp) <4> Kekkaku Vol.77, No.10:659-664,2002 Original Article REPEATED TUBERCULIN SKIN TESTS IN NURSE STUDENTS -Observation for 3 years- 1Eriko SHIGETOH, 1Akihiro MAEDA, 1Hiroshi OIWA, 1Yasuyuki YOKOSAKI, and 2Isao MURAKAMI Abstract In Japan, two-step tuberculin skin test (two-step TST) is recommended for health care workers (HCWs) if the diameter of erythema in the first test is less than 30mm, and to detect new infection if there is 10mm or more increase from the base-line diameter. We observed TST in nurse students from the entrance to the graduation for 3 years, and analyzed the change of TST reaction to discuss the usefulness of two-step TST and the criteria for detecting new tuberculous infection among BCG vaccinated HCWs. Mean}S.D.(mm) in erythema and induration in each occasion were: in a group with single TST at entrance (T(1))and before graduation (T(G))(n=99, group I);T(1)=19.8}11.3, T(G)=23.6}14.3 for erythema and T(1)=12.5}5.3, T(G)=13.8}5.0 for induration:in a group with two-step TST at entrance (T(1) and T(2))(n=40, group II);T(1)=11.9}7.8, T(2)=20.4}10.6, T(G)=22.1}13.5 for erythema and T(1)=8.6}6.1, T(2)=12.0}5.1, T(G)=13.4}5.4 for induration:in a group BCG vaccinated after single negative TST (less than 10mm of erythema and/or less than 5mm of induration)(n=12, group I-B);T(1)=4.0}3.5, T(B)=19.8}5.8, T(G)=16.3}7.6 for erythema and T(1)=0.5}1.5, T(B)=14.1}3.7, T(G)=11.9} 4.4 for induration:in a group BCG vaccinated after two negative TST (n=10, group II-B); T(1)=3.6}3.1, T(2)=6.2}2.4, T(B)=23.9}8.5, T(G)=14.1}6.9 for erythema and T(1)=1.7}2.7, T(2)=3.2}1.8, T(B)=16.0}3.2, T(G)=7.5}7.8 for induration. One student in the group II was diagnosed as tuberculosis before the graduation. If we exclude this case form the group II, mean}S.D.(mm) of T(G) in group II were 20.7}11.2 for erythema and 13.1}5.0 for induration. Booster phenomenon was significant on two-step TST. There was moderate booster phenomenon even after 34 months from the previous single TST. There was also significant waning of reaction 27 to 31 months after BCG vaccination. But there were no significant waning nor booster after two-step TST. Concerning the difference between the reaction before graduation and at entrance, mean}S.D.(mm) in erythema and induration, [T(G)-T(1)] in the group I were +3.8+11.4 and +1.6}5.8, respectively, [T(G)-T(2 or 1)] in the group II were +0.7}11.4 and +0.4}5.6, respectively, [T(G)-T(B)] in the group I-B and II-B were -6.4}9.9 and -5.0}6.5. If we exclude one case who got tuberculosis from the group II, mean}S.D.(mm) in erythema and induration of [T(G)-T(2)] in group II were -0.6}8.1 and +0.2}5.4, respectively. According to the criteria in Japan of more than 10mm increase in erythema and more than 6mm increase in induration, recommended by Menzies, significant values of [T(G)-(T(1), (T(2) or T(B)] was observed in 24(24%) by erythema and 22(22%) by induration in the group I, while in the group II only in 4(10%) by erythema and 5(12.5%) by induration, which included case diagnosed as active tuberculosis. The criterion of 10mm increase in erythema seems to correspond to that of 6mm increase in induration. 95% confidential limit in the differences between two tests were 15.6mm(mean plus 2 standard deviation) in erythema and 11.0mm in induration in the group II. Considering that these data may include some newly infected persons, appropriate criteria for detecting new tuberculosis infection is estimated to be between 10 to 15mm increase in erythema and 6 to 11mm increase in induration from the baseline by two-step TST. Among BCG vaccinated, TST two months after vaccination is useful as the base line. As there is moderate booster phenomenon even after three years from the previous single test and variation is more common, the detection of new tuberculous infection can be made more accurately with the two-step TST in HCWs. Key words:Repeated tuberculin test, Two-step tuberculin test, Nurse student, Diagnosis of tuberculosis infection, Booster phenomenon, Wane of tuberculin reaction 1Respiratory Division, National Hiroshima Hospital, 2Hatsukaichi Nomura Hospital Correspondence to:Eriko Shigetoh, National Hiroshima Hospital, 513 Jike, Saijo-cho, Higashihiroshima-shi, Hiroshima 733-0041 Japan. (E-mail:eriko@hirosima.hosp.go.jp) <5> Kekkaku Vol.77, No.10:665-669,2002 Original Article THE TREND OF M.KANSASII INFECTION IN OKAYAMA PREFECTURE BETWEEN 1994 AND 2000 Kimihiro MIMURA Abstract The first case of pulmonary Mycobacterium kansasii infection in Okayama Prefecture was discovered in the Mizushima industrial area in 1976. Thereafter pulmonary M.kansasii infection spread to neighboring areas and increase in the number of the patients was reported in 1995. In the present study, new patients with M.kansasii infection between 1994 and 2000 were surveyed by questionnaires sent to 32 main hospitals in Okayama Prefecture. The results showed that 110 patients with pulmonary M.kansasii infection were documented by 20 hospitals. The number of new patients was 10 to 20 annually, and the number of new patients was stable after 1995. The new patients were documented in the center of the Mizushima industrial area and the geographic spread to the new neighboring area was not confirmed. Key words:Mycobacterium kansasii, Non-tuberculous mycobacteriosis, Okayama Prefecture, Mizushima industrial area, Epidemiology Division of Respiratory Diseases, Kawasaki Medical School Correspondence to:Kimihiro Mimura, Division of Respiratory Diseases, Kawasaki Medical School, 577, Matsushima, Kurashiki-shi, Okayama 701-0114 Japan. (E-mail:sandman@med.Kawasaki-m.ac.jp)