[PECULIARITY OF NATIONAL TUBERCULOSIS PROGRAM, JAPAN--Public-Private Mix from the Very Beginning, and Provision of X-ray Apparatus in Most General Practitioner's Clinics].

Modern National Tuberculosis Program (NTP) of Japan started in 1951 when Tuberculosis (TB) Control Law was legislated, and 3 major components were health examination by tuberculin skin test (TST) and miniature X-ray, BCG vaccination and extensive use of modern TB treatment. As to the treatment program, Japan introduced Public-Private Mix (PPM) from the very beginning, and major reasons why PPM was adopted are (1) TB was then highly prevalent (Table 1), (2) TB sanatoria where many specialists are working are located in remote inconvenient places due to stigma against TB, (3) health centers (HCs) in Japan are working exclusively on prophylactic activities, and minor exceptions are treatment of sexually transmitted diseases and artificial pneumothorax for TB cases, however, as it covers on the average 100,000 population, access is not so easy in rural area, (4) Out-patients clinics mainly operated by general practitioners (GPs) are located throughout Japan, and the access is easy. Methods of TB treatment was developing rapidly in early 1950s, however, in 1952, as shown in Table 2, artificial pneumothorax and peritoneum were still used in many cases, and to fix the dosage of refill air, fluoroscopy was needed. Hence, GPs treating TB under TB Control Law had to be equipped with X-ray apparatus. To maintain the quality of TB treatment, "Criteria for TB treatment" was provided and revised taking into consideration the progress in TB treatment. If applied methods of treatment fit with the above criteria, public support is made for the cost of TB treatment. To discuss the applied treatment, TB Advisory Committee was set in each HC, composing of 5 members, director of HC, 2 TB specialists and 2 doctors recommended by the local medical association. In 1953, the first TB prevalence survey using stratified random sampling method was carried out, and the prevalence of TB requiring treatment was estimated at 3.4%, and only 21% of found cases knew their own disease, and more than half of all TB were found above 30 years of age. Based on these results, mass screening was expanded to cover whole population in 1955, and since 1957, cost of mass screening and BCG vaccination was covered 100% by public fund. Unified TB registration system covering whole Japan was introduced in 1961, and in the same year, national government subsidy for the hospitalization of infectious TB cases was raised from 50% to 80%. Hence, Japan succeeded to organize PPM system in TB care, and with 10% annual decline of TB, in 1975, Japan moved into the TB middle prevalence country.

[Speculation on reasons why co-infection of tuberculosis and HIV is rather rare in Japan].

Co-infection of tuberculosis (TB) and HIV is a serious problem in most developing countries and in industrialized countries, co-infection of TB and HIV is seen mainly among migrant population. In case of Japan, the numbers of both new HIV infection and AIDS cases have been increasing except slight decline in both figures in 2012, however, the epidemiological situation of HIV and AIDS is still one of the lowest in the world, and among index diseases of AIDS, TB is 5th among Japanese. Based on prevalence of radiological TB findings in the national TB prevalence survey in 1968 and the coverage of BCG vaccination, the author speculated that most TB primary infection took place among those with rather high delayed type sensitivity, thus formation of typical primary complex was rather rare and the number of tubercle bacilli in primary complex and post-primary early disseminated lesions were few, and less risk of development of active TB even among HIV infected individuals.

[Association between smoking and tuberculosis infection].

PURPOSE: Several reports show smoking as a risk factor of tuberculosis (TB) infection, especially in prisoners, emigrants, the homeless, or people in areas where TB is endemic. These reports mostly used the tuberculin test to detect TB. However, there is no report evaluating smoking as a risk factor of TB infection among people coming into contact with TB with the use of the Interferon-Gamma Release Assays (IGRA) test. MATERIAL & METHOD: We compared TB infection in smokers and non-smokers who came into contact with TB infection by using the IGRA test. We retrospectively collected information about people coming into contact with TB who visited the Daiichi Dispensary from July 1, 2011 to June 30, 2012. They were divided into 2 groups (IGRA positive or negative) and smoking (present/past or never). RESULT: Out of 390 subjects who came into contact with TB examined, 229 were male and 161 were female. The mean age was 39.0 years, 98 were present smokers, 69 were past smokers, and 223 were never-smokers. There were 19 IGRA-positive and 371 IGRA-negative subjects. The IGRA positive rate was 4.9%. Out of 19 IGRA-positive subjects, 13 were smokers or ever-smoker (68.4%). Out of 371 IGRA-negative subjects, 154 cases were smoker or ever-smoker (41.5%). Smoking experience (present and past) was statistically significant in the IGRA-positive group. There were no significant differences in sex, age, drinking habits, and level of contact. Multivariate analysis showed smoking was only one independent risk factor for being IGRA-positive (odds ratio 3.06, 95% confidence interval: 1.14-8.21, p = 0.027). DISCUSSION: Our results suggest that smoking experience in subjects coming into contact with TB is a risk factor for TB infection. TB cases in smokers are reported to be more severe and have delayed detection of disease. They are also more likely to infect those who come in contact with them. If TB source cases and their contacts are both smokers and co-exist in a narrow and limited area, the contacts might be at higher risk of exposure to TB-contaminated air than non-smokers.

[Considerations on uses of newly developed anti-tuberculosis drugs for multi-drug resistant tuberculosis].

We, group of tuberculosis experts, made discussions over how to improve the quality of treatment of multidrug resistant tuberculosis using a newly developed anti-tuberculosis drug, and at the same time, how to prevent the disadvantages of the treated patients and also that of persons who would be infected with newly produced drug-resistant bacilli, by preventing the emergence of resistance to the new drug. A series of proposals are made.

[Impact of introducing rifampicin for the treatment of tuberculosis during the 1970's in Japan].

SETTING: The average duration of tuberculosis chemotherapy in Japan increased year by year throughout the 1960's and reached 49 months by 1973. It then began decreasing slowly in the 1970's and more rapidly after the 1980's. PURPOSE: To clarify the significant factors contributing to the prefectural variation of changes in the average duration of chemotherapy that occurred from 1973 to 1979. METHOD: Multiple regression analysis was conducted with the slopes of the average duration of chemotherapy of tuberculosis in prefectures throughout Japan from 1973 through 1979 as the dependent variable and with parameters related to treatment and patient characteristics of the prefectures as independent variables. RESULTS: The variables, including uses of rifampicin, proportion of bacteriologically confirmed patients among newly registered cases, and average duration of chemotherapy as of 1973, contributed significantly to the slope of change in chemotherapy duration of the prefectures; the duration decreased faster in prefectures where there were more bacteriologically confirmed patients, and where the duration had been shorter at the beginning of the study period. DISCUSSION: Short-course chemotherapy had not been established in the study period, but confidence in the potency of antibacterial activity of the new drug seems to have facilitated the departure from unnecessarily long treatment. The recognition of the importance of bacteriology in the clinical practice of tuberculosis worked in the same way against dependence on X-ray findings causing long-term treatment. Also, the prefectures that had been less affected by the long-term treatment could depart faster from it.

[Liver dysfunction during treatment of latent tuberculosis infection].

PURPOSE: The indications for treatment for latent tuberculosis infection were revised in 2007 to reflect that any subject with a higher risk of tuberculosis regardless of age should be treated. We worried about the incidence of liver dysfunction due to isoniazid (INH) in patients older than 30 yrs. of age. We evaluated the frequency of liver dysfunction due to INH according to age and discussed the possibility of its prevention. METHODS: We reviewed the clinical records of 99 patients younger than 29 yrs. and 229 patients older than 30 yrs. who were treated for latent tuberculosis infection from August 2007 to December 2008 at our clinic. The liver function tests (AST and ALT) were performed before the treatment, one and a half months after the start of the treatment, and almost every month during the treatment. We defined liver dysfunction as an AST and/or ALT greater than 100 IU/L. RESULTS: Seven out of the 99 younger patients (7.1%) and 42 out of the 229 (18.3%) older patients developed liver dysfunction. The difference between the two age groups was statistically significant according to the chi-square test (p < 0.01). After the occurrence of liver dysfunction, 35 out of 49 patients (71%) completed the treatment by maintaining the same or a decreased dose of INH, while the medication was discontinued in 9 patients who were then followed up by chest X-ray examination. Two of these 49 patients discontinued the medication by themselves. CONCLUSIONS: The frequency of liver damage due to INH was higher in persons older than 30 yrs. In this group, 3 persons developed severe liver damage with ALT and/or AST higher than 1000 IU/L. Early detection is required to avoid serious damage. Thus, we decided to perform liver function tests more often, i.e., at 2 weeks after the onset of treatment and every month thereafter.

[Mass health examination for tuberculosis].

Miniature radiography or radiophotography (RP) was first developed independently by de Abreu M of Brazil and Koga Y of Japan in 1936, and because of its utility, it was used as a tool of mass health examination for TB all over the world soon after its development. The idea of RP is to take a picture of the chest X-ray image on a fluorescent screen set in a dark box, and this idea was materialized through development of a camera with a small F-number. Through application of RP as a tool for mass health examination, many TB cases had been detected, and most of these had been previously unknown cases. In the TB Control Law legislated in 1951, the three major components were (1) early detection of TB cases by mass miniature radiography (MMR), (2) prevention of TB by BCG vaccination, and (3) distribution of adequate TB treatment. MMR first covered the population below 30 years of age, as it was thought that the prevalence of TB was high among young adults. However, based on the results of the TB Prevalence Survey in 1953, it was expanded to the whole population in 1955, and since 1957, all MMR, tuberculin skin tests, and BCG vaccinations have been carried out free of charge for community residents in Japan. The expenses are shared, in equal thirds, by the central government, the prefectural government, and the community office. The numbers of persons examined by MMR are shown in Fig. 1, and the detection rate of TB cases by MMR and other health examinations are shown in Fig. 2. In accordance with the decline in TB, the number of MMR subjects has gradually been reduced, starting with primary and junior high school students and then with senior high school students, to a point where cases are now confined to those 65 years of age and above and inhabitants living in TB high-incidence areas. The most marked outcomes had been obtained in big enterprises, in which twice yearly MMR had been carried out. These efforts had resulted in a significant rapid decline in cases of TB requiring absence from work as shown in Fig. 3. As sick leave and cost for medical care were secured for 3 years for TB cases in big enterprises in Japan, this rapid decline contributed to the rise of productivity of big enterprises and ultimately to rapid growth of the GNP of Japan. In big enterprises in Japan, in contrast to the rapid decline of TB, the incidence of cancer and other lifestyle-related diseases had increased, and annual examinations for new diseases were introduced as a control measure without thorough analysis of the effectiveness of these examinations. In the case of MMR for TB, before its use as a control measure, procedures including detailed examinations and post-examination management were fully tested, and outcomes were evaluated, and such procedures were needed for health examinations for cancer and other lifestyle-related diseases. The contribution of MMR to the rapid decline of TB in Japan has been highly evaluated, however, success of MMR has resulted in the decline of detection rate of TB, thus deteriorate the cost-effectiveness of MMR. Timing of reducing its use has not been sufficiently examined, and it might be done a little bit earlier.

[Control of cattle TB in Japan].

Traditional food custom of Japan changed after the opening of the country in late 19th century, and habit of eating beef and of drinking milk was introduced, and the control of cattle TB had become one of major topics of veterinary medicine in Japan. Old tuberculin (OT) prepared by Koch R in 1890 initially intended to cure TB, however, it was found ineffective against TB, while local and general reactions after the introduction of OT were found to be useful to detect TB infection, and OT was first applied in veterinary medicine to detect TB infection in cattle. Cattle TB Control Law was legislated in Japan in 1901, and cattle was subjected to health checking including tuberculin test, and TB cattle had to be slaughtered, and TB suspects had to be isolated. Several trials had been done to improve the implementation of the Law by increasing the number of experts in health checking of cattle including tuberculin test and compensation for cattle slaughtered during isolation, and they were partly achieved in the revision of the Law in 1933. However, no marked progress was achieved up to 1945 because of war conditions. In 1948 during the occupation period by the US, tuberculin test method was changed to intradermal skin test method by the strong recommendation of the GHQ, and some lawsuits were raised to slaughter cattle based on tuberculin positive reaction by the newly introduced intradermal method. Autopsy was done for slaughtered cattle due to tuberculin positive test results, and as shown in Table 1, TB lesions were found in the majority of autopsied cattle, and thereafter, no more lawsuits were raised. Annual examination including tuberculin test has been continued hard thereafter, and as shown in Fig. 3, the prevalence of TB cattle has dropped down rapidly, and only one or few TB cattle were found by the annual examination, and TB has been nearly eliminated from cattle in Japan. The efforts made by those engaged in the fight against TB in cattle in Japan were highly appreciated.

[Start of TB case-registration and case-management system in Japan].

TB control in Japan started in 1951 through legislation of TB Control Law, consisting of three major components; mass health examination, vaccination and promotion of adequate methods of treatment for TB cases. Mass health examination was first targeted for younger generation below 30 years of age as it was believed that TB was highly prevalent among them, however, it was expanded to cover whole population based on the results of TB Prevalence Survey in 1953 revealing high prevalence of TB in all age groups except children and low awareness of TB cases. Methods of treatment for TB were developing rapidly in late 1950s and early 1960s; initially artificial pneumothorax, then surgical collapse treatment such as thoracoplasty, then pulmonary resection, and finally long term combined use of INH, SM and PAS. Up to surgical treatment era, most TB patients earnestly followed doctor's instruction, however, in chemotherapy era, as most symptoms improved rapidly after the initiation of chemotherapy, patients felt as if they were cured, and it had become difficult to maintain high adherence to treatment. Such behavior was found oftener in patients detected in early stage through mass health examinations. 1947, it was legislated for all doctors to report all diagnosed TB cases to an adjacent health center, and the cases are registered at the health center covering his (her) residence, however, standardized formula of registration was not indicated. In accordance with the progress of TB control program, the number of TB registered cases increased, and the need for standardized registration and case-management had become apparent in mid 1950s, and some preliminary trials had been done. In response to this request, the Ministry of Health and Welfare organized a research group headed by Dr. Misonou K, and the staffs of prefectural health department and enthusiastic staffs working in health centers (HCs), staffs of NIPH (National Institute of Public Health) and RIT (Research Institute of Tuberculosis) to study how to register TB cases, how to collect information and how to improve patients' adherence to treatment. Registration index cards were prepared in each HC arranged alphabetically to avoid double register. The formula of registration card was indicated in Fig. 1 and 2. Small hollows were made in the lower part of the card, and registration card container with 45 metal bars in the bottom as shown in Fig. 3 was prepared. By setting 30 cards dislocating one each hollow as shown in Fig. 3, in one card container with 30 rows, altogether 600 registration cards were stored. In most right part of the card, important information such as activity of the case, treatment status, expected time of next home visit, expiring time of public support for TB treatment, etc. are indicated by different color metal signals. This new system was applied in 216 HCs, about one fourth of all HCs in Japan in 1959, another 200 HCs were added in 1960, and finally from 1961, the new system of registration and case-management started in the whole country after making minor amendments based on experience in 1959 and 1960. Quality of TB case-management improved much after the introduction of new system, and annual statistics not only newly registered TB cases but also on prevalence of active as well as registered cases was available since then, and this was the starting point of TB surveillance system started in 1986.

[Tuberculosis prevalence survey in Japan].

Chest X-ray examination had been used rather soon after the discovery of X-ray by Rontgen K in 1895 as it was possible to detect chest abnormality by simple radiography. After the discovery of radiophotography independently by Abreu M and Koga Y in 1936, it was applied as a method of mass screening for TB in Japan, and Imamura A made a special lecture on "The mass screening for TB" using radiophotography in 1940 in the Annual Meeting of the Japanese Society for TB. From experiences of mass screening, it was found that there were many cases of TB who do not aware of their own disease, and to know the prevalence of TB, the screening of survey subjects by X-ray examination is indispensable. Noticing the importance of mass health examination by chest X-ray, Dr. Tanaka S, then director of information division, JATAHQ, edited a book entitled "How to carry out mass health examination for TB" in 1951, then he moved to the Ministry of Health and Welfare and engaged in the preparation of the first TB prevalence survey. Random sampling technique was already developed, and health center network covering the whole country was already completed in early 1950s. Using these background, the first TB prevalence survey was conducted in 1953. TB Prevalence Survey Committee was organized asking cooperation of experts in TB, epidemiology and statistics, and the survey in sampled area was carried out by a survey team headed by the director of health center in charge of the sampled area. The survey teams engaged in the survey with enthusiasm, and the rate of response to the survey was 99.3%. The result of this survey was published in the WHO Bulletin, 1955. After the survey in 1953, the following prevalence surveys were carried out in 1958, 1963, 1968 and 1973. Outline of these surveys was shown in Table 1, and the rate of examination was high in all, except the survey in 1973. In this year, TB prevalence survey was carried out in conjunction with the national nutritional survey and the national mental health survey, and unfortunately, there were some opponent groups against the national mental health survey, which affected the rate of response to the TB survey, too. In addition to the 5 prevalence surveys, one thirds of the survey population in 1953, 1958 and 1963 was surveyed in the next year to know the incidence of TB. Follow-up survey on active TB cases found in the 1953 and 1958 survey was carried out in 1964, and similar follow-up survey was carried out in 1968 for active TB cases found in 1953, 1958 and 1963 surveys. Moreover, survey subjects excluding active TB cases in 1968 were followed up until 1973, and the incidence of newly registered TB cases during this period was surveyed. Summarized results of TB prevalence surveys are reported. The first survey was carried out in 1953, and had been repeated every 5 years until 1973. As national TB control program (NTP) under new TB Control Law had been implemented since 1951, the results of 5 surveys clearly indicated the outcome of NTP of Japan. Age-specific prevalence of active TB in 5 surveys is shown in Fig. 1. Due to advances in chemotherapy, there was certain difference in the definition of active TB in 1953 and 1958, and chemotherapy was indicated more widely for those with TB pathology in lung in 1958. Comparing the age-specific prevalence of active TB in 1953 and 1958, the prevalence decreased in 1958 below 35 years of age, and increased above 35 years. The decline in the prevalence of active TB in age groups below 35 in spite of widening of definition of active TB in 1958 indicated the efficacy of TB control with mass screening and BCG vaccination and treatment for detected cases. As the definition of active TB had been unchanged since 1958 up to 1973, the decline in the prevalence of active TB seen in all age groups clearly indicated the achievements of NTP. Overall trend of prevalence of active TB, cavitary TB, bacillary TB and smear+PTB in 5 surveys is shown in Fig. 2 together with epidemiological figures obtained from vital registration, namely incidence of TB, prevalence of active TB at the end of the year and TB mortality. In analyzing the results, we have to take note of the difference in bacteriological examination methods. As laryngeal swab method was used in 1963 and 1968, culture positive rate was lower and no information about smear examination, however, from 1958 to 1973, all indices had declined exponentially with similar speed including prevalence of smear +PTB and bacillary TB if results in 1958 and 1973 were connected directly. Based on this results and the fact that marked decline in the prevalence of active TB requiring much larger sample size for the survey, TB prevalence survey was stopped, and data from vital register has been used since then to evaluate the TB situation. Results of 3 incidence surveys were shown in Fig. 3. Shift of higher incidence from younger age groups to higher age groups was clearly shown from 1954 survey to 1964 survey. The results of routine follow-up by vital registration of 1968 survey population excluding TB cases found in 1968 survey were shown in Table 2, and high risk groups were clearly shown in this table. As routine X-ray examination was done by radiography in 1963 survey, it was possible to pick up any slight TB pathology, and the age-specific prevalence of any TB finding, that of healed findings and of calcified lesions were shown together with BCG vaccination coverage in Fig. 4. In the age groups above 40, the prevalence of any TB finding, as well as of healed and calcified findings was very high, while the coverage of BCG vaccination was below 20%. BCG vaccination was started in Japan in 1943, and those above 40 years of age in 1963 were then already 20 years of age or above, and only few were vaccinated with BCG when BCG vaccination was expanded to cover higher age groups thereafter. TB prevalence survey has now come to be used as one of methods to estimate the incidence of TB under the impact of HIV/AIDS epidemic, and its significance is now re-evaluated.

[Spanish flu related data].

Swine flu epidemic is a current topic, and data relating to Spanish flu pandemic from 1918 to 1920 were presented for your information. Monthly trend of number of deaths due to influenza, acute bronchitis, pneumonia and bronchopneumonia together with PTB, other TB and TB of all forms from 1917 to 1920 was presented in Table 1 and Fig. 1. Flu epidemics in early 1917 and from winter 1917 to spring 1818 were so-called common seasonal flu epidemic, however, new pandemic started from October 1918, and the number of deaths due to flu increased 14 times compared with previous month in October, 19 times in November, and the pandemic reached the summit, and started to decrease from December, however, marked decline was seen only after April 1919. The number of deaths due to flu started to increase again from November 1919, and reached its summit again in January 1920, and the pandemic ended in July. The age- and sex-specific mortality rate due to influenza in 1918 was shown in Fig. 2. The rate was high among infants, 20s and 30s and elderly, and by sex, the rate of female was higher below 35 and lower above 35. The number of deaths due to acute bronchitis and pneumonia and bronchopneumonia fluctuated in parallel with that of influenza, and deaths due to these conditions were very difficult to differentiate, and the impact of flu could better be evaluated by summing up all these three conditions, the sum of deaths due to three conditions was expressed as influenza related death. The proportion of deaths due to three conditions by age group was shown in Fig. 3. The proportion of acute bronchitis was high in infants and elderly, and in the other age groups, influenza occupied around 30% and pneumonia and bronchopneumonia around 70% of influenza related death. Total number of deaths due to influenza related diseases from 1918 to 1920 was 816,884, and the annual rate was 489.4 per 100,000. Annual age- and sex-specific mortality rate due to influenza related diseases was shown in Fig. 4, and it showed similar pattern with that of influenza. Because of huge excess death of TB patients due to influenza and related diseases, TB mortality in Japan, which had been increasing since 1884, started to decrease since 1919, and TB mortality which had been decreasing slowly since the beginning of 20th century in European countries and the US, the decline was accelerated since 1919.

[Tuberculosis primary infection].

Since the introduction of mass BCG vaccination program, it has become difficult to know how TB primary infection takes place. Based on data before the introduction of mass BCG vaccination, the author tried to overview TB primary infection. Most TB primary infection takes place via lung as shown in Table 1. Soon after TB primary infection, primary focus in the lung and regional glandular changes were formed, and they were named primary complex, which is the morphological sign of TB primary infection. Comparing the location of primary focus in right and left lung, it was 56.6% vs. 43.4%, which just correspond to the right and left lung volume as shown in Table 2. Observing by the location of primary focus in different lung lobes, it was found more frequently in upper lobe than in middle and lower lobe after adjustment for volume of different lung lobes as shown in Fig. 1 and Table 2, however, chronic pulmonary TB is found much more frequently in apex or upper part of the lung. The number of primary foci was 1 in the majority of cases, however, 2 or more foci were found in some cases. Several weeks after TB primary infection, TB immunity started to work, and primary focus be never formed thereafter. The fact indicates that multiple primary foci were seen only repeated TB infection taking place in short period soon after primary infection. The distribution of number of primary foci should follow Poisson's distribution if repeated infection takes place by chance, and it should follow Polya-Eggenberger's distribution if chance of repeated infection takes place cumulatively, and observed figure matched with the latter as shown in Fig. 2. Location of primary complex is useful sign to determine invasion place of tubercle bacilli in epidemiological survey of TB infection in medical accident cases. If major pulmonary lesions are found in middle or lower part of lung, we have to suspect onset of TB soon after primary infection among immunity attenuated cases such as HIV/AIDS, diabetics and cases using steroid, and if cavities are found more likely diabetes is suspected, and no cavity with or without adenopathy more likely HIV/AIDS.

[Start of PTB (Phthisis) mortality statistics in Japan (2)].

As mentioned in the previous report, PTB mortality by prefecture was printed in the "Statistics Annual", however, the population based on which the rate was calculated was not shown in the "Statistics Annual". In Japan, family register system was introduced in 1872, and every Japanese had to be registered at municipality where their family live. Based on this registry, statistics on registered population by sex and age, and by prefecture was available. In case when some family member(s) move to place other than registered place, he/she has to report to the local municipality in which they reside. When they move further to other place, the same procedure was required. Population based on this temporary registration system was named as A-type population, however, it did not show the population actually living in the municipality. Many persons newly register when they move in, however, forget to report to the previous residence when they move out. Overall numbers of move-in always larger than move-out. To adjust for this discrepancy and to estimate actually living population by each prefecture, the difference of move-in and move-out in a certain prefecture was multiplied by the ratio of total move-in and move-out in a certain prefecture and that of the whole country. Thus calculated population was designated as B-type population, and was proximate to actually living population in each prefecture. As B-type population was tabulated by sex in each prefecture, PTB mortality by sex could be calculated by using this B-type population, and the calculated figures were shown in Table 3 by sex for each prefecture. The correlation between PTB mortality by prefecture printed in the "Statistics Annual" and that calculated by using B-type population in 1886, 1892 and 1899 were shown in Fig. 4. Both coincide well nearly in all prefectures, except Tokyo and Hokkaido in 1886 and 1892, and in Tokyo in 1899. It was shown how difficult it was to estimate actually living population in an area where population move was very active, however, in general, in other prefectures both coincided well, and figures shown in Table 3 could be used to estimate PTB mortality in each prefecture by sex. Since 1899, ICD (International Classification of Diseases) was adopted in Japan as causes of death, and TB of all forms were divided into PTB, TB meningitis, intestinal TB and TB of other organs. As phthisis mortality was also available in 1899, correlation between PTB (Phthisis) mortality and that of TB of all forms was shown in Fig. 5 by age groups and by prefecture. The former was higher than the latter, and observing by age groups, correlation was not good in infants and elder population 60 years and over. In large cities like Tokyo and Oosaka, figures of the former were higher than the latter. It was indicated that it was not appropriate to combine and analyze the trend of PTB (Phthisis) mortality with the TB mortality statistics after 1899 adopting ICD.

[Start of PTB (Phthisis) mortality statistics in Japan (1)].

First "Statistics Annual", which included the population and vital statistics was published in Japan in 1882, and the numbers of death classified by major causes of death were tabulated by sex and age groups and by prefecture. Koch R reported the discovery of tubercle bacilli as the pathogen for TB in 1882, and since the latter half of 1883, the numbers of death due to PTB (Phthisis) were tabulated by prefecture, and by sex and age groups since 1884 annually except for 1885. Based on the population statistics and the numbers of PTB death, PTB (Phthisis) mortality was calculated by sex and age groups, and the results were shown in Table 1. PTB mortality per 100,000 increased from 78.2 in 1884 to 171.9 in 1899. Sex- and age-specific PTB mortality in 1884 showed a pattern increasing with age, and the PTB mortality of male was higher than that of female in adult as shown in Fig. 2. In 1889, low peak of mortality was seen in the age groups 15-19 and 20-29, and in these age groups, the PTB mortality was higher in female than in male. Such trend was seen more markedly in 1894 and 1899, while the rate was higher in male than in female in the age groups over 40. Trend of PTB mortality by sex and age groups was shown in Fig. 3. Rapid increase of PTB mortality in the age groups 10-14 and 20-29 could be explained by the rapid increase of young women workers in fast growing silk and spinning industries, but how rapid increase of PTB mortality in infants be explained? In "Statistics Annual", PTB (Phthisis) mortality rate by prefecture was printed, and the summarized table was shown in Table 2. The rates in 1883 and 1884 were calculated from the numbers of PTB death and the B-type population shown in the "Statistics Annual", which will be described in the next issue of this paper.

[Tuberculosis and its control--lessons from the past and future prospect].

Koch R reported the discovery of tubercle bacilli on March 24, 1882, and the numbers of death from phthisis were collected in the vital statistics from the latter half of 1883 in Japan. Tuberculosis death was officially adopted in the Japanese vital statistics from 1899, and there was certain disagreement existed between the numbers of death from TB and phthisis in 1899, the analysis on the trend of TB in Japan was done based on TB death. Trend of TB in Japan in the past 100 years could be divided into five phases. In phase 1 (1899-1918), TB mortality had increased with the first industrialization of Japan with main focus on the weaving industry. During this period, TB mortality of female was higher than that of male and then major victims of TB were young girls born from 1890 to 1925. In phase 2 (1918-1930), TB mortality decreased through excess death of TB cases by the influenza pandemic in 1918. This decline due to influenza pandemic was seen all over the world, and in the European countries and the U.S., the decline continued up to 1945 while in Japan, TB had increased again in the phase 3 (1930-1945) mainly due to second industrialization with main focus on heavy industry and the impact of quasi-war and war conditions. In phase 4 (1945-mid 1970s), TB started to decline fast due to the excess death of TB cases during the World War II and then, the application of modern TB control started from early 1950s. In phase 5 (from mid 1970s until now), decline of TB has showed down. Increase or slowdown of TB decline was seen nearly all countries of the world, however, its causes were different from country to country. In case of Japan, slowdown was caused by the rapid ageing of the population, in developing countries mainly by the impact of HIV epidemic and in industrialized countries, mainly by the migration of the population and partly by the HIV epidemic. Contribution of phthisiology in Japan to the global progress of phthisiology could be summarized as follows: elucidation of the pathogenesis of TB when TB was highly prevalent in Japan by high incidence of TB from primarily infected youth, the development of mass screening for TB using radiophotography technique developed in Japan, completion of the interpretation method of chest X-ray findings, first success in the mass production of freeze-dried BCG vaccine in the world, the first implementation of the TB prevalence survey using random sampling method in 1953, and the development of a new drug for TB, kanamycin. Phthisiology also contributed to the progress of international health. As the objective index to measure the magnitude of TB problem, the concept of annual risk of TB infection (ARTI) was introduced by Sutherland and Styblo, and by using ARTI, the epidemiological situation of TB could be divided into 3 categories; high prevalence country with ARTI above 1%, low prevalence country below 0.05-0.1%, and middle prevalence country inbetween. To reduce the burden of TB in high prevalence countries, so-called DOTS strategy of TB control was introduced and has been applied in most developing countries, and the gap between high and low prevalence countries has reduced in the past decade. Cooperation in global TB control has also been done actively from the government and NGOs of industrialized countries under the strong leadership of WHO. For the success of TB control, the transmission of tubercle bacilli in a community should be cut either infection, onset of TB or the progress of TB. Prevention of TB infection could be achieved by the early detection of TB cases and their cure by the treatment. To encourage early visit to doctors for those with symptoms suggesting TB and adequate examinations at medical institutions for these persons would be a major tool of early detection of TB cases in Japan in the future. In addition, there is no doubt to intensify contacts examinations and source investigations. It is hoped to elucidate recent pathogenesis of TB by applying new technologies such as QFT and RFLP. Prevention of onset of TB will be focused on the preventive use of TB drugs, however, development of new vaccine better than BCG is also encouraged for the developing countries where the risk of TB infection is remained high. TB is now a curable disease, and the duration of treatment has been shortened to 6 months. If new more potent TB drugs were developed, and the total duration of treatment could be shortened, the global TB control could be done much more easily, and also most MDRTB cases could be cured. Otsuka Pharmaceutical Company is now developing a new potent drug which has no cross resistance with existing TB drugs. This new drug is now on the clinical trial phase II, and it is hoped that Japan can make another great contribution to the global TB control. It is my sincere wish that the government continues to assist the research to develop new TB drugs and new technologies used in TB control, and in future, if it is needed to change the current policy of TB control, a new policy should be tried in a pilot area before its introduction on national level. The Japanese Society for TB is a key organization in developing further research and the training of new personnel engaging in TB research and control, and I sincerely hope further development of the Society.

[Mortality rate of pulmonary TB in the late 19th century].

Statistics Annual of Japan was first published in 1882, and it covered all aspects of statistics in Japan including demography. Sex- and age-specific population and the population in each prefecture were available, and the number of death classified by major causes of death was also shown. R Koch reported the discovery of tubercle bacilli in 1882, and from the latter half of 1883, the number of death due to pulmonary tuberculosis (phthisis) were collected and tabulated together with the death due to meningitis and apoplexy, and the collection of data on death due to pulmonary tuberculosis had continued until 1906 except 1885. Industrialization took place in the late 19th century in Japan, and in accordance with the industrialization, the new epidemic of TB started. Mortality statistics on TB was available since 1899 classified as TB of all forms, pulmonary TB, TB meningitis, intestinal TB and other TB, and official statistics on TB was said to be started from 1899. The data on death due to pulmonary tuberculosis in the late 19th century was found out by the author from the old Statistics Annual of Japan, and the mortality rate due to pulmonary tuberculosis was tabulated and calculated for the first time, and the secular trend of mortality from pulmonary TB in 47 prefectures in Japan from 1983 and that of sex- and age-specific rate from 1984 until 1899 were shown in this paper.