(Vol.76 No.8 August 2001) <1> Kekkaku Vol.76,No.8:563-569,2001 TWO-STEP TUBERCULIN TESTING AND BCG VACCINATION IN THE PERSONNEL OF A MEDICAL AND PHARMACEUTICAL UNIVERSITY *Hisashi FUNADA and Yoshitaka ABE *Department of Infectious Prophylaxis, Faculty of Medicine, and Committee on Hospital Infection Control and Prevention, Toyama Medical and Pharmaceutical University In an attempt to cope with recent nosocomial spread of tuberculosis, the tuberculin test with a 0.05ƒĘg of 0.1 ml intradermal dose of purified protein derivative was performed by a two-step procedure on the personnel of a medical and pharmaceutical university, followed by BCG vaccination for non-reactors in the second test. The second test was repeated after two weeks in all but those with erythema of 10 mm or more in diameter associated with double erythema, vesicle formation, and/or necrosis on the initial testing. The first test was done in a total of 935 participants (73% of all personnel) with a median age of 37 (range, 21-67) years. The rate of participation, by occupation, in the hospital personnel ranged from 63% (183/289) for doctors to 98% (351/358) for nurses. The size of erythema showed a unimodal distribution with a peak in the range of 10-19 mm, with a median of 20 mm (range, 0-102). Reactions below 9 mm, which are interpreted as negative, were found in 16% of all participants, and those above 30 mm in 35%. Among participants aged 20-49 years, especially among nurses, reactions tended to be larger with increasing age. Among 539 participants undergoing repeated testing, reactions between the first and second tests correlated well, showing a median increase in size of 10 mm (range, -43-+70) on retesting. Reactions above 30 mm associated with an increase in size larger than 20 mm, among those initially below 29 mm in diameter, were observed in 28% of those retested. Adverse reactions such as vesicle formation with or without hemorrhage, or lymphangitis occurred in 2.5% of all participants on the initial testing and in 1.5% on the retesting, with the highest frequency seen in those aged 30-39 years. BCG was administered to 26 of the 49 participants with a negative reaction on the second test. All vaccinees with a median age of 30 (range, 21-46) years showed tuberculin conversion after two months without developing Koch's phenomenon soon after the vaccination. Incidentally, it is desirable that two-step tuberculin testing such as that in the present study should also be performed using the diameter of induration, particularly that measured transversely, since erythema is not used in any other country than Japan. Key words:Two-step tuberculin testing, BCG vaccination, Medical and pharmaceutical university personnel, Booster effect, Adverse reactions to purified protein derivative *2630 Sugitani, Toyama-shi, Toyama 930-0194 Japan. (Received 13 Feb 2001/Accepted 10 May 2001) <2> Kekkaku Vol.76,No.8:571-579,2001 TUBERCULOSIS IN JAPAN AT PRESENT AND IN NEAR FUTURE *Naohiro NAGAYAMA *Division of Respiratory Diseases, Tokyo National sanatorium Hospital The high incidence of tuberculosis in the elderly people and no decrease in the incidence rates of the young people are two main features of current tuberculosis problem in Japan. To examine the near future prediction of the incidence rate and the rate of clinical break- down by age group, the incidence rates of the newly registered tuberculosis cases of the cohorts born before 1918, in 1919`28, 1929`38, 1939`48, 1949`58 and 1959`68 were studied every ten years. The curves of incidence rate in each cohort were extrapolated to the future to obtain the incidence rates in 2008 and 2018. The numbers of predicted new cases in 2008 and 2018 were estimated to be some 31,000 and 23,000, respectively. The percentage of the cases above 60 y.o. was estimated to be 59%, 59% respectively. As the number of new cases in 1998 was 41,000, 55% of which was above 60 y.o., it will steadily decrease from now on, but the elderly people more than 60 y.o. will continue to occupy high percentage of the new cases. The incidence rate of the new cases will also decrease from 32.4 (per 100,000 populations) in 1998 to 24.5 in 2008 and 19.4 in 2018, and Japan in 2018 will still be a middle prevalence country in the world as now. The rate of clinical breakdown is obtained from dividing the incidence rate by the prevalence of tuberculosis infection. The latter is theoretically calculated from the annual risk of tuberculosis infection assuming that it doesn't depend on age. In Japan the annual risk of infection was supposed to be constant and about 4% till 1947. Since then it declined by some 10% annually till around 1977. Thereafter the annual speed of its decline was estimated to have slowed down. But we cannot know the ture annual risk of tuberculosis infection, as BCG vaccination hinders the interpretation of the result of tuberculin skin testing in Japan. We postulated it declined 5 % annually (Model A) or it was constant to be 0.17 % since 1977 (Model B). Using these models of annual risk of tuberculosis infection, the prevalence of tuberculosis infection by age group was calcu- lated in every calendar year. The incidence rate of each age group was assumed to be equal to that of median age in each age group. For example, the incidence rate of the cohort born in 1919`28 was assumed to be equal to that of the cohort born in 1923. In this way, the annual rates of clinical breakdown of the cohorts born in 1923, 1933, 1943, 1953, 1963 and 1973 were calculated. The rates of clinical breakdown for the cohorts born in 1923, 1933 and 1943 were similar with each other and were approximately 100 per 100,000 in both models. The rate of clinical each other and were approximately 100 per 100,000 in both models. The rate of clinical breakdown at 25 years old for the cohort born in 1953 was 0.64 times smaller than that for the cohort born in 1943. It might due to the improvement of nutritional state and the effectiveness for adult tuberculosis of compulsory BCG vaccination which has been done after World War II in Japan. But for the cohort born after World War II, the later the cohort was born, the larger its rate of clinical breakdown was in both models. And, for example, the rate of clinical breakdown at age 25 years old for the cohort born in 1973 was 2.4 times (in Model A) or 1.7 tunes (in Model B) larger than that for the cohorts born in 1953. This may imply that there has been some factor(s) which facilitates tuberculous disease after tuberculous infection in young people in modern Japan. One explanation for this is the possibility that immune ability to tuberculosis might be weak- ened in young generations by some factor(s) such as environmental pollution. Key words:Prediction of tuberculosis incidence, Annual risk of tuberuclosis infection, Risk of clinical breakdown, BCG vaccination, Tuberculosis in elderly people, Tuberculosis in young people *3-1-1, Takeoka, Kiyose-shi, Tokyo 204-8585 Japan. (Received 24 Jan. 2001/ Accepted 14 May 2001) <3> Kekkaku Vol.76,No.8:581-587,2001 TWO-STEP TUBERCULIN SKIN TEST IN NURSE STUDENTS 1*Takayoshi TASHIRO, 1Hideko URATA, 2Katsunori YANAGIHARA, 2Yoshitsugu MIYAZAKI, 2Kazunori TOMONO, and 2Shigeru KOHONO 1*Department of Nursing, School of Allied Medical Sciences, Nagasaki University, 2Second Department of Internal Medicine, Nagasaki University School of Medicine The tuberculin skin test (TST) was conducted in 243 nurse students (19.4}1.3 years old). The second TST were carried out in 240 students who did not show blister or necrosis in the first TST. The size of erythema was 16.5}9.4 mm in the first TST (T1) and 24.3}15.6 mm in the second TST (T2). The negative reactors, whose size of erythema was below 10 mm, were decreased from 53 to 25, whereas, the strong reactors, whose size of erythema was more then 30mm, were increased from 11 to 71. The difference of the size of erythema (T2-T1) was 9.7}11.9mm in the group I(190 students) who received the latest TST in junior high school, whereas, that was 0.5}9.2mm in the group II (50 students) who received the latest TST 14 months before this study. T2-T1 in the group I was weakly correlated with T1. Twenty-four negative reactors received BCG vaccination, and 23 of them converted to positive. Seventy-one strong reactors were checked by chest X-ray, and none showed the findings of tuberculosis, and required the administration of anti-TB drug. The two-step TST is an essential means to know the baseline reactivity to TST, and to distinguish newly infected tuberculosis form booster phenomenon. Key words:Tuberculosis, Two-step tuberculin skin test, Booster phenomenon, BCG vaccination, Nurse students *1-7-1, Sakamoto, Nagasaki-shi, Nagasaki 852-8520 Japan. (Received 16 Mar. 2001/ Accepted 17 May 2001) <4> Kekkaku Vol.76,No.8:589-592,2001 CLINICAL EVALUATION OF PATIENTS WITH PULMONARY TUBERCULOSIS DURING THE PAST 10 YEARS IN OUR HOSPITAL *Shuichi YANO, Shinji SHISHIDO, Kanako KOBAYASHI, Hiroko NAKANO, Masaaki MIKAMI, and Yuji KAWASAKI *Department of Pulmonary Medicine, National Sanatorium Matsue Hospital The background of patients who died of active pulmonary tuberculosis during 10 year's period (1989 to 1998). Of 973 tuberculosis patients, 76 patients died, of which 56 died of non-tuberculosis, and 20 died of tuberculosis. A total of 12 patients died within 3 months after being hospitalized. The period from hospitalization to death was signifi- cantly shorter in tuberculosis patients with independent gait failure, original treatment, without tuberculosis medical history, and no drug resistance. We considered that in tuber- culosis death, severe tuberculosis itself is the cause of early death, and recurrence and drug resistance patients are the most serious problems in later deaths. Key words:Pulmonary tuberculosis, Tuberculosis death *5-8-31, Agenogi, Matsue-shi, Shimane 690-8556 Japan. (Received 25 Oct. 2000/ Accepted 16 May 2001) <5> Kekkaku Vol.76,No.8:593-600,2001 The 76th Annual Meeting Educational Lecture BACTERIAL INFECTIONS AND TOLL-LIKE RECEPTORS *Shizuo AKIRA *Department of Host Defense, Research Institute for Microbial Diseases, Osaka University Toll-like receptors are type-1 transmembrane receptors involved in microbial recognition. TLR4 has been shown to function as the lipopolysaccharide signaling receptor, while TLR2 recognizes peptidoglycans from Gram-positive bacteria, and lipoproteins. TLR9 is involved in the recognition of bacterial DNA (CpG DNA). Although various microbial cell wall components are recognized by different receptors, all of these responses are abrogated in MyD88-deficient cells. These results show that different TLRs recognize different microbial cell wall components, and that MyD88 is an essential signaling molecule shared among interleukin-1 receptor/Toll family members. However, in LPS signaling MyD88- independent pathway is present in addition to MyD88-dependent pathway. Key words:TLR, LPS, CpG DNA, MyD88, Peptidoglycan *3-1, Yamadaoka, Suita-shi, Osaka 565-0871 Japan. (Received 30 May. 2001)