The compromised host is generally defined as a patient who has a primary underlying disease or is receiving therapy that impairs resistance to infection. It is considered that anergy (loss of delayed hypersensitivity to tuberculoprotein) in the compromised hosts is associated with severe, uncontrolled tuberculous infection due to loss of resistance which may seed mycobacteria into bloodstream, resulting in generalized dissemination and/or tuberculous meningitis.
The changing pattern and present status of disseminated and/or miliary tuberculosis were examined in autopsy cases in relation to the role of the compromised states in causing disseminated tuberculosis. Three hundred and forty seven cases of disseminated tuberculosis were compiled by reviewing the Annual of Pathological Autopsy Cases in Japan (APACJ), 1982-1983. All the organs preserved in fixative were grossly reexamined in detail and microscopic slides were made again in 43 cases autopsied in Kyushu. In addition to these slides, the original microscopic slides obtained at autopsy and urotocol were reviewed together.
The overall incidence of disseminated tuberculosis recorded in APACJ was 0.44% (347/78, 341). Patients of 50 years of age and over occupied 85 % of study subjects. The incidence of disseminated tuberculosis was 0.17% (84/48, 740) in cases with malignant neoplasms, 1.43% (10/699) in cases with collagen diseases, and 1.06% (12/1, 138) in cases with diabetes mellitus. The prevalence of dissemination did not always correlate with any malignancy in this study but with corticosteroid therapy, especially in cases with collagen diseases.
Only 11% of cases with disseminated tuberculosis and/or tuberculous meningitis were correctly diagnosed before autopsy.
Examination of the lung and draining hilar and paratracheal lymph nodes showed old hyalinized granulomas with central or peripheral necrosis containing many mycobacteria. These lesions were considered to represent a nidus of chronic persistent tuberculosis and to be the source of the late dissemination in 84% of Kyushu cases. Histopathologically, corticosteroid therapy seemed to produce more severe, and often non-reactive disease.
Reactivation of tuberculosis may occur at any time presumably whenever defenses are lowered in the course of various underlying diseases in the older age groups, many of which are associated with immunosupressive therapy. Therefore, all physicians should have a basic understanding on the present status of tuberculosis, and should keep in mind possible incidence of tuberculosis, especially if the patient develops unexplained pyrexia. Accuracy in diagnosis could be greatly improved by maintaining awareness of physicians on tuberculosis and broadening the scope of differential diagnosis to include tuberculosis among patients at high risk, especially in the older age groups.

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BCG vaccination against tuberculosis has been carried out for more than half century since the birth of BCG vaccine. The progress and problems of BCG vaccination in the world were briefly reviewed here in two aspects, protective effectiveness and complications, especially during recent 10 years.
1. General status of BCG vaccination today
In most countries, intradermal injection with freeze-dried BCG vaccine is being performed in young children, particularly new-borns and infants in developing countries. Percutaneous BCG vaccination, now being conducted in a few countries, has less complications but varied effectiveness. The BCG strain, dosage and viability of the vaccine have carefully been selected in each country, especially for young children, as these factors were found to be closely related to the effectiveness and complications of the BCG vaccination.
2. Effectiveness of BCG vaccination
It is surprising that the efficacy of BCG vaccination has extensively been disputed up to the present, because the most reliable controlled trials carried out since 1930, had shown very much disparate results of protective effectiveness from none to some 80 %. A well-designed large-scale controlled trial with the secured freeze-dried BCG vaccine was carried out recently in South Indian in order to verify the efficacy of BCG vaccination. However, the South Indian trial gave no protection against bacillary pulmonary tuberculosis in children and young adult throughout 15 years of follow up.
Explanations and hypothesis have been proposed so far for the unexpected results of the South Indian trial, and vaccine dose (viability), infectious with atypical mycobacteria and weak pathogenicity of infectious tubercle bacilli in local area were taken up for the possible causes. Although until present any hypothesis has not yet been confirmed, it can be said that the BCG vaccination may not always be effective in some area of the world.
As the South Indian trial gave no direct information on the efficacy of BCG vaccine in child hood type tuberculosis, a policy to continue BCG vaccinaion in young children was recommended. Also a number of the retrospective studies had shown the protective effect of BCG vaccine against childhood tuberculosis. However, the controlled BCG trial in infants was desired in the future and recently the case-control study in children was carried out to prove the efficacy of BCG vaccination in tuberculosis contacts.
3. The complications of BCG vaccination
The BCG vaccine should be highly effective with less complications. However, the stronger the BCG strain used the more the complications in terms of the suppurative lymphadenitis in young children, as shown in the comparison of vaccine strains between French and J apanese in the field study. As a result, the vaccine of stronger strain which may be more immunogenic, had to be adjusted in the dosage to expect acceptable complications.
More serious complications such as disseminated BCG infectious had never been systematically determined on a world-wide scale. On behalf of IUAT, A. Lotte et al had the first time systematically calculated the incidence of serious complications of BCG vaccinaion on a world scale. The number of disseminated BCG infectious (non-fatal and fatal) and post-BCG diseases were disclosed in the comprehensive study. Although the incidence of the serious BCG complications was extremely low, this survey is very useful for decision of BCG vaccination policy in the future along with the protective effectiveness of BCG vaccination in the area.

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We have already reported an outbreak of swine mycobacterial lymphadenitis caused by Mycobacterium avium - M. intracellulare complex.
In the present study we investigated the distribution of mycobacteria in the environment of swine breeding.
M. avium - M. intracellulare complex was isolated from the fresh saw-dust prepared for bedding of pigs and from the old saw-dust used for bedding.
Serotypes of the strains isolated from the lymphonodes of the swine and the fresh saw-dust were compared. Serotypes were determined by agglutination reaction according to Schaefer's method.
The distribution of serotypes of the strains isolated from swine were limited in a few types. Out of 14 isolates, ten strains (71. 4 %) were serotype 8, two were serotype 9 and one was serotype 6. All of these strains belong to the “intermediate” group of Anz.
On the other hand, the serotypes of the strains isolated from the saw-dust were widely distributed. Out of 18 isolates, six strains (33.3 %) were in the “intermediate” group, eight strains (44.4 %) were in the “authentic ” group and two strains (11.1 %) were in the “other” group.
From these observations, it is suggested that swine which were bred on saw-dust spread on the floor, swallowed a lot of mycobacteria and killed most of them in their bodies. A few strains of serotype 8, 9 and 6 survived and produced tuberculous lesions in swine.
Nemoto et al. reported that serotypes of the strains isolated from Japanese patients caused by M. intracellulare were widely distributed and the serotype 8 was found rarely.
From the present study, the results are summarized as follow:
1) Saw-dust is a source of mycobacterial infection of swine.
2) Swine is not a significant source of human mycobacterial infection.

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1. In Vivo Experiment
Antituberculosis activity of ofloxacin in mice was observed using Mycobacterium bovis strain Ravenel, which was expected to be more virulent for mice than M. tuberculosis strain H 37 Rv. Effect of pyrazinamide was also examined, as the effect of pyrazinamide was not yet studied in mice challenged by M. bovis. Female mice, weighing 26 ± 2 g, of the ddY-strain were challenged by an intraperitoneal injection of M. bovis strain Ravenel, 1. 5 × 10⁷ viable units per mouse. Eighty mice were divided into four groups: (1) control group mice received daily intraperitoneal injection of a 0.2 ml sample of a 0.067 M phosphate buffer solution (pH 7.1); (2) pyrazinamide group mice received daily intraperitoneal injection of 1 mg of pyrazinamide; (3) ofloxacin group mice received daily intraperitoneal injection of 1 mg of ofloxacin; (4) ofloxacin-pyrazinamide group mice received daily intraperitoneal injection of 1 mg ofloxacin and 1 mg pyrazinamide. These treatments were begun from the next day of the challenge. At one week-intervals, three mice of each group were sacrificed and the number of viable bacteria in the livers and the lungs were measured. The effects of the treatment were determined by the number of viable bacteria in the liver and the lungs of one mouse.
As reported previously (Tsukamura, M: Am. Rev. Respir. Dis., 132: 915, 1985), ofloxacin was eliminated most rapidly from the lungs and, therefore, the number of viable bacteria in the lungs was not influenced by the ofloxacin treatment. However, the number o f viable bacteria in the liver was reduced markedly by the treatment with ofloxacin. The number of viable bacteria were never decreased by the treatment with pyrazinamide alone. In the mice treated with.ofloxacin and pyrazinamide, the numbers of viable bacteria in the liver increased after 3-4 weeks. Pyrazinamide appeared to act antagonistically against the in vivo effect of ofloxacin.
2. In Vitro Experiment
In vitro growth-inhibitory activity of ofloxacin against M. tuberculosis and M. bovis were lowered in pH 6.2 (“3% Ogawa egg medium”) than in pH 6.8 (“1% Ogawa egg medium”). Pyrazinamide alone did not show any activity in egg media even at a concentration of 500 μg/ml. It did not show any combined effect with ofloxacin in the in vitro.experiment.

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