(Vol.75 No.2 February 2000)


<1>Kekkaku Vol.75 No.2:65-69,2000

THE VIRULENCE FOR MICE OF NEWLY DESCRIBED 
MYCOBACTERIAL SPECIES 

1*Hajime SAITO, 1Kazuyasu MURAKAMI, 2Mikihisa YAJIMA, 3Norihisa ISHII, 
and 4Hyuk Han KWON 

1*Hiroshima Environment and Health Association, 2National Sanatorium,Tama-Zenshoen  
3Yokohama City University, 4Seoul Health College 

  The virulence for mice of some newly described slowly growing mycobacterial species, 
M.intermedium DSM 44049(Group ‡T), M.lentiflavum ATCC 51985 and M.interjectum 
ATCC 51457(Group ‡U), M.genavense ATCC 51233, M.celatum ATCC 51131, M.branderi 
ATCC 51788 and M.conspicuum DSM 6333(Group ‡V) was compared with the virulence 
of M.intracellulare N-260(virulent strain). 10(6) CFU cultured in Middlebrook 7H9 me- 
dium were given i.v. to the BALB/c mice. Infected animals were sacrificed after one day 
and 56 days, and observed for the incidence and/or degree of gross lesions of visceral or- 
gans. The bacterial load (CFU) in tissue homogenates of the lungs and spleen was 
counted using 7H11 agar plates. Macroscopically, marked enlargement of the spleen and 
numerous small whitish nodules in the lungs of mice infected with M.intracellulare were 
noted, whereas with other test strains no gross disease in the lungs and slight enlarge- 
ment of the spleen of mice infected with M.genavense and M.branderi were noted. The 
average log CFU in the lungs and spleen 56 days after the infection was in the order as 
follows:M.intracellulare(5.90 and 7.57, respectively), M.genavense (4.35, 7.15), M. 
celatum (5.01, 6.00), M.branderi (4.09, 6.33), M.conspicuum (3.11, 5.10), M.intermedium 
(2.26, 4.19), M.lentiflavum (1.70, 3.91), and M.interjectum (1.43, 2.93). Microscopically, 
granulomatous lesions mainly consisted of macrophages with acid-fast bacilli were found 
in the alveolar walls and splenic red pulp of mice infected with M.intracellulare. No 
histopathological changes were produced in the lungs of any of mice infected with other 
test strains, and some milder features were revealed in the spleen of mice infected with 
M.genavense, M.branderi and M.celatum. 
  Thus, we concluded that all of the test strains of the newly described nontuberculous 
slowly growing mycobacteria were less virulent for mice than were M.intracellulare. 
 
Key words:New mycobacterial species, Nontuberculous mycobacteria, 
Slowly growing mycobacteria, Virulence 

*9-1, Hirosekita-machi, Naka-ku, Hiroshima-shi, Hiroshima 
730-8631 Japan 
(Received 5 Aug. 1999/Accepted 20 Oct. 1999) 






<2>Kekkaku Vol.75 No.2:71-77,2000

A STUDY ON THE RISK FACTORS FOR TUBERCULOSIS EPIDEMICS OBSERVED 
FROM THE RESULTS OF EXTRAORDINARY HEALTH EXAMINATIONS 

1*Masanobu FUJIOKA, 2Kaori FUNAHASHI, 3Kimio INUZUKA, 
4Satoru HATTORI, and 5Shinji MARUYAMA 

1*Shinshiro Public Health Center, Aichi Prefecture, 2Kohnan Public Health Center, 
Aichi Prefecture, 3Toyota City Public Health Center, 4Toyohashi City Public 
Health Center, 5Kasugai Public Health Center, Aichi Prfecture 

  In recent years, tuberculosis (tbc) epidemics have been increasing, and have become a 
social problem in Japan. This study was carried out to clarify the current risk factors on 
tbc epidemics. 
  The original reports of a total of 254 tbc patients whose contacts were examined for 
possible tbc infection (extraordinary health examinations) during 1992-97, were investi- 
gated and compared with all new pulmonary tbc cases registered during the same period 
in Aichi prefecture. In addition, from registration cards in each public health center, the 
risk factors for 19 cases of both tbc epidemics (infecting more than 20 contacts) and 
microepidemics infecting 10-19 contacts were further examined. 
  The results obtained were as follows; 
1. Extraordinary health examinations were carried out in 3.2% of total pulmonary tbc cases, 
and were carried out at higher rates among contacts with younger patients and with those 
having severer tbc by radiographical (p<0.01) and bacteriological findings (p<0.01). 
2. 11 tbc epidemics (3.4%) and 34 microepidemics (14.3%) were identified among 254 ex- 
aminations over 6 years. They were frequently observed in groups with abundant bacilli 
discharge and long lasting cough, and also in young age groups. 
3. All of the 19 cases causing epidemics or microepidemics had multiple risk factors; the 
main factors being late diagnosis, inadequate health managements in schools and offices 
and poor quality of patients' living environments. 
  Therefore, it is necessary for public health centers to work more closely with schools 
and industrial circles for the prevention of tbc epidemics. 
  
Key words:Tuberculosis epidemic, Microepidemic, Extraordinary health 
examination, Risk factor, Public health center 

*6-1, Nakano Aza Shinshiro-shi, Aichi 441-1326 Japan.
(Received 12 Aug. 1999/Accepted 9 Nov. 1999) 






<3>Kekkaku Vol.75 No.2:79-88,2000

A STUDY ON TUBERCULOSIS CASES AMONG OVER-STAYING FOREIGNERS 

*Jumpei YAMAMURA and Takashi SAWADA 

*Minatomachi Medical Center 

  An analysis was made on eighty-four cases of tuberculosis (TB) among over-staying 
foreigners during the past 9 years at Minatomachi Medical Center. All of them did not 
enroll in any health insurance system because they were illegal immigrants. Most of them 
were in their twenties and thirties. The ratio of male to female was four to one. By eth- 
nic origin, the proportion was highest among Filipinos (30%), followed by Koreans 
(23%), Pakistanis (13%) and Indians (7%). Half of them had been in Japan for more 
than two years. Most patients sought care due to symptoms rather than as a result of 
the efforts of public health centers to screen foreigners. 
  The proportion of extrapulmonary TB among all types of TB was 35% overall. Com- 
pared with pulmonary TB cases, patent's as well as doctor's delay was more marked 
among extrapulmonary TB cases. 
  Forty cases were treated at Minatomachi Medical Center and forty-four cases were 
referred to another hospitals. The default rate including repatriation was as high as 41%, 
and the reasons for this high defaulting rate were as follows: ‡@Language barrier, 
‡AWorry for loosing work during treatment, ‡BWorry for high medical costs because of 
no coverage by a health insurance scheme, ‡CLack of information on medical systems and  
TB, ‡DWorry for forced repatriation by the immigration office. 
  In additon, some cases were not followed up due to unkind behaviour of attending phy- 
sicians. 
  The following measures are needed to prevent the epidemic of tuberculosis among over- 
staying foreigners and our societies. 
a)To provide free medical check-ups 
b)To provide easy access to medical facilities 
c)To utilize the tuberculosis prevention law 
d)To follow up patient thoroughly and strictly 
e)To explain TB in their mother languages 
f)To change the immigration law and its system 
g)To make liaison with other organizations such as medical facilities and NGOs, includ- 
  ing foreign ones, and exchange informations 
h)To build good human relations with patients 

Key words:Tuberculosis, Over-staying 
foreigner, Extrapulmonary tuberculosis, 
Defaulting 

*7-6, Kinko-cho, Kanagawa-ku, Yokohama-shi, 
Kanagawa 221-0056 Japan. 
(Received 1 Jul. 1999/Accepted 11 Nov. 1999) 






<4>Kekkaku Vol.75 No.2:89-96,2000

EVALUATION OF TL-201 LUNG UPTAKE AND IMPAIRMENT OF PULMONARY 
PERFUSION ON SCINTIGRAPHIES IN PULMONARY TUBERCULOSIS 

1*Tadashige FUJII, 2Masao TANAKA, 2Tomonori KOIZUMI, and 2Keishi KUBO 

1*School of Allied Medical Sciences, Shinshu University, 2Department of Internal Medicine, 
Shinshu University School of Medicine 

  T1-201 lung uptake in 74 patients (85 lesions) and pulmonary perfusion in 105 patients 
were studied to evaluate clinical usefulness of T1-201 lung uptake and perfusion lung 
scintigraphy in pulmonary tuberculosis, using a scintillation camera with a mini-com- 
puter system. As indices of T1-201 lung uptake, lung (lesion)to upper mediastinum 
uptake ratio (L/M) and visual grading were used. 
  L/M in pulmonary tuberculosis was 1.96}0.66, which was significantly larger than 
1.04}0.24 in healthy controls and lower than that in heart diseases with left heart fail- 
ure and idiopathic interstitial pneumonia, and showed no significant differences with that 
in acute pneumonia, pyothorax, primary lung cancer and malignant mediastinal tumor. 
  L/M in pulmonary tuberculosis did not correlate with CRP, erythrocyte sedimentation 
rate, Gaffky number of sputum and body temperature. It correlated with the type of pul- 
monary tuberculosis according to the Gakken Classification reflecting the disease activ- 
ity. It was larger in the exudative type, caseo-infiltrative one, disseminated one, one 
with cavity in infiltrative lesion than the fibro-caseous one. 
  On perfusion lung scintigram, impairment of pulmonary perfusion larger than area of 
the entire unilateral lung was observed in 68 cases (64.8%). Area of hypoperfused lung 
field, which correlated with % vital capacity (r=0.60, p=0.0002)and PaO(2)(r=0.39, p= 
0.0024), was significantly larger in patients with silicosis and those with bilateral 
pleural involvements such as pleural callosity than in those with type ‡V according to 
the Gakkai Classification. Most of the patients showed decreased pulmonary perfusion and 
T1-201 accumulation of which grade reflects the disease activity in active tuberculous 
lesion. Patients with miliary tuberculosis and those with silicotuberculosis showed 
diffuse T1-201 accumulation in the both lungs. 
  T1-201 lung scintigraphy seems to be useful for visualizing active tuberculous lesions, 
particularly the ones that could not be detected by the chest radiograph in patients with 
destroyed lung and with pleural callosity. Joint use of T1-201 and perfusion lung scinti- 
graphies provides useful informations about the pathophysiology and disease process in 
pulmonary tuberculosis. 
   
Key words:Pulmonary tuberculosis, T1-201 lung scintigraphy, 
T1-201 lung uptake, Perfusion lung scintigraphy, 
Pulmonary perfusion 

*3-1-1, Asahi, Matsumoto-shi, Nagano 390-8621 Japan. 
(Received 24 Sep. 1999/Accepted 24 Nov. 1999) 






<5>Kekkaku Vol.75 No.2:97-101,2000

The 74th Annual Neeting Invitation Lecture 

TUBERCULOSIS:RECENT PROGRESS IN BASIC IMMUNITY AND 
VACCINE DEVELOPMENT 

*Ian M. ORME 

*Mycobacteria Research Laboratories, Department of Microbiology, 
Colorado State University 

  Tuberculosis continues to be the most prevalent cause of death from an infectious agent 
globally, and its interaction with HIV is having devastating effects, particularly in Sub- 
Saharan Africa. Over the past decade, my laboratory has developed small animal models 
of pulmonary infection, which have revealed new information regarding the nature of ac- 
quired immunity, and subsequent immunopathology, in the lungs. We propose that cell 
mediated immunity compreses two separate elements;protective immunity, driven by IL- 
12 and IFN;and DTH, mediated by TNF and driven by chemokines. The generation of a 
CD4 response is critical to both processes, but other cells are also involved in the overall 
control of the infection. These include gamma delta T cells, which we believe control the 
inflammatory influx of cells;CD4+NK cells, which may play a role in focussing lym- 
phocytes into lung granulomas;and CD8 T cells, which play a currently undefined role 
after initial expression of immunity and establishment of chronic disease in the lungs has 
ensued. Complex interactions between these populations of cells appear to control the in- 
flux of mediator cells into the lungs and then focus them at sites of infection. Prior to 
adequate expression of protective immunity the correct expression of chemokine and adhe- 
sion molecules is critical. A better understanding of these processes will hopefully in turn 
lead to better vaccine design, a topic witch is also addressed in this paper. 

*Frot Collins CO 80523, USA.
(Received 25 Nov. 1999) 






<6>Kekkaku Vol.75 No.2:103-124,2000

The 74th Annual Meeting Symposium 

‡W. CURRENT STATUS OF TUBERCULOSIS EDUCATION IN UNIVERSITIES 
AND FUTURE TASKS 

Chairpersons:1Nobuhiro NARITA 
             2*Shoji KUDOH 

1Second Department of Internal Medicine, Nara Medical University, 
2*Fourth Department of Internal Medicine, Nippon Medical School 

Symposium Topics and Presenters: 
1. Education of tuberculosis in medical school:Kaoru SHIMOKATA (Department of 
   Clinical Preventive Medicine, Nagoya University Daiko Medical Center) 
2. From Medical University holding Tuberculous ward:Shosaku ABE (Third Depart- 
   ment of Internal Medicine, Sapporo Medical University School of Medicine), et al. 
3. Necessity and Significance of Sanatorium ward associated with University Hospital: 
   Saburo SONE, et al. (Third Department of Internal Medicine, The University of 
   Tokushima School of Medicine) 
4. A proposal on education and training for tuberculosis in medical school from 
   aspect of sanatoriums:Takeshi OGURA (Toneyama National Hospital) 
5. How to avoid infecting TB and to prevent contracting TB while medical and nurs- 
   ing practices:Keiichi NAGAO (Health Sciences Center, Chiba University), et al. 
6. Special speech:A review of the year since TB patient rooms were included in a 
   common ward as a part of ministry of welfare's model project:Shuji KURANE 
   (Fourth Department of Internal Medicine, Nippon Medical School) 

  Tuberculosis began to rank first in mortality rate in Japan in the Meiji Era, and espe- 
cially since it did not confrom to the "national wealth and military strength" that was 
the national policy of the time due to the high mortality rates in the early decades of 
life, it was referred to as the "disease that was destroying the country" and the "pan- 
demic disease." Even after entering the Showa Era, tuberculosis long occupied first place 
as the cause of death in Japan, and it raged unchecked for a period after World War 
‡U. However, the prognosis of tuberculosis as a whole improved considerably as a result 
of the development of antituberculosis agents, such as streptmycin, and the advent of 
rifampicin made it a curable disease. Its rank as a cause of death subsequently fell pre- 
cipitously, and many of the TB wards that had been established in universtiy hospitals 
were closed as the numbers of patients rapidly declined. 
  At the present time, only 22 of the 80 university hospitals in the country have TB 
wards or TB beds, and 18 of the hospitals that had TB wards have closed them. Two of 
them closed them prior to 1964, 6 between 1965 and 1974, 4 between 1975 and 1984, 4 
between 1985 and 1994, and 2 since 1995. Thus, it would be no exaggeration to say that 
there has been a steady decline in the TB wards of university hospitals. 
  It is fairly easy to surmise that the result has been a decrease in the opportunities and 
time available for educating medical students about tuberculosis. Today, university hospi- 
tals not only accept medical students, but 80% of clinical residents as well, and they too 
have lost opportunities for education concerning tuberculosis. We would hope that the 
concern of Japanese physicians regarding tuberculosis has not diminished in proportion to 
the decrease in TB wards in our university hospotals. However, as is truly revealed by the 
expression "doctor's delay" in the diagnosis and treatment of tuberculosis, it is a fact 
that physicians no longer bear pulmonary tuberculosis in mind when diagnosing and 
treating patients with respiratory disease, and that as a result diagnosis is delayed, 
treatment is drawn out, and in the worst-case scenario, we see scattered instances of a 
tragic outcome. 
  When we consider the recent conditions in society, as reported in recent newspapers, tu- 
berculosis is not a disease that is on the declien at all in Japan today. However, as 
stated above, but if the concern of ordinary physicians has drifted away from tuberculo- 
sis, it is fair to say that it is not only a major problem medically, but socially as well. 
Consideration of the tuberculosis education in university medical schools seems to be op- 
portune at this time. Professor Shimokata of Nagoya Universtiy, who is chairperson of 
the Japan Tuberculosis Education Committee, outlined the problems of tuberculosis edu- 
cation in his speech at this symposium. We also heard about the current status of tuber- 
culosis education in universities from Professor Sone of Tokushima University, as a 
university that has a tuberculosis wing, and from Professor Abe of Sapporo Medical Uni- 
versity, as a university that has a tuberculosis ward. From the standpoint of accepting 
medical students as physicians we heard hospital director Ogura of Toneyama National 
Hospital call for tuberculosis education. In addition, Professor Nagao of Chiba Univer- 
sity reported on education of medical students and nursing students in regard to the pre- 
vention of infection with tuberculosis, and lecturer Kurane of Nippon Medical School 
reported on experience with the establishment of tuberculosis beds in a general ward as 
a model project of the Ministry of Health and Welfare as a special speech. 
  The problems that this topic connotes are quite large, and they can hardly be said to 
have been solved by this symposium, nevertheless, it may provide a considerable degree 
of direction in terms of considering the tuberculosis education of medical students in the 
future.  

Key words:Tuberculosis education, University hospital, 
Tuberculosis ward 

*1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602 Japan. 
(Received 13 Dec. 1999)