Two hundred eighty one cases of the lung disease due to mycobacteria other than tubercle bacilli (atypical mycobacteria) were found at the seven National Chest Hospitals in Japan during the past ...several years. Eighteen of 281 cases were the disease due to M. kansasii, 3 due to M. scrofulaceuni, 247 due to M. intracellulare, 11 due to M. chelonei, and 2 due to M fortuitum. The first chest radiograms were observed, and the radiographic features of the disease due to various species of atypical mycobacteria were compared. The results were summerized as follows: (I) Minimal cases and cases without any previous pathological changes in the respiratory organs (primary infection cases) were found more f requently among persons of middle age and younger than among the older persons in the disease due to all the species of atypical mycobacteria. (II) There was no statistically significant difference in the ratio of cavitary cases to the total cases among the various species (83 to 100%). (III) The difference in the radiographic features among various species were as follows. i) In the case of the disease due to group IV organisms (M. chelonei and M. fortuitum), single solitary cavity was found in the lung field, and its shape was round, thin-walled and less than 40mm in diameter in almost all cases. In the case of the disease due to M. kansasii, round, thin-walled cavitary lesions were observed which were similar to that of the disease due to group IV organisms, however, the proportion of cases with multiple (3 and more) cavitations amounted to 16.6% of the total cases, and giant cavity (over 40mm in diameter) was found occasionally. ii) In the case of the disease due to M. intracellulare, subpleural cavitary lesions were found in many cases, while in the case of the disease due to M. kansasii, M. scrofulaceum and M. chelonei, cavitary lesions were found in the lung field in the majority of the cases. iii) In the cases with the lesions localized in one lobe, the lesions were found more frequently (2.7 times) in the right lung than in the left, and the number of cases with the lesions localized in the upper lobes amounted to approximately 90% of the total cases. The number of cases with the lesions localized in the middle lobe was only 2% in the case of M. intracellulare infections. iv) The majority of non-cavitary lesions were infiltrative. Only in the case of the disease due to M. intracellulare, various lesions (diffuse nodular lesions, bronchiectasis and pleural empyema, etc.) were observed. In the case of the disease due to group IV organisms, non-cavitary lesions were not found in most of cases (61.5%). v) The previous pathological changes in the respiratory organs were found in many cases of M. intracellulare infection, but they were found in a few cases of M. kansasii and group IV organisms infection. In the case of the disease due to M. scrofulaceum, pneumoconiosis was found in 2 of 3 cases. (IV) Even among the disease due to the same species of atypical mycobacteria (111. intrace llulare), the radiographic findings differed in different hospitals.
Sixty seven cases with pulmonary atypical mycobacteriosis (2 by M. kansasii, 62 by M. intracellulare, 2 by M. fortuitum and 1 by a possible new pathogen of group III mycobacteria) died in 9 Japanese ...national sanatoria up to October 1976. Of these 67 cases, 40 died of atypical mycobacterial disease, and the remaining 27 cases died of other diseases. Roentgenological aggravation was found in 44 cases (1 by M. kansasii, 1 by M. fortuitum and 42 by M. intracellulare). There were various types of roentgenological aggravation. Spread of non-cavitary foci, infiltrate and pneumonia were found most frequently (40/44, 90.9%). Enlargement of cavity was found in 12 cases (27.2%), appearance of pleural effusion in 5 cases (11.4%), and spontaneous pneumothorax in 3 cases. Infection of bulla was found in 11 out of 22 cases with bullae as the underlying disease. The first roentgenological aggravation was found in 20 (45.5%) out of 44 cases within 12 months; 13 cases (29.5%) between 13 to 24 months; and 11 cases (25%) over 2 years after the discovery of the disease. From the results mentioned above, in the fatal cases, progression of the disease was predicted by the appearance of the roentgenological aggravation within 2 years after the discovery of the disease. There were various courses of the progression of the lesions as shown in Figures 2a and 2b. One of the typical course of the progression was devided into the following 5 stages: The first stage: localized cavitary lesion. The second stage: spread of foci around cavity. The third stage: spread of foci in contralateral lung. The fourth stage: enlargement of cavity (appearance of giant cavity). The fifth stage: extensive pneumonia in the lower lung field. Another typical course of the progression was the repeated infections of bullae. Roentgenological aggravation found in patients with atypical mycobacterial disease was not rarely due to the mixed infection with various organisms (gram-negative bacilli, fungi and also human type tubercle bacilli). The majority of the patients with underlying pulmonary disease (extensive emphysema, chronic bronchitis and bronchiectasis) died of pulmonary insufficiency in the relatively early stage of atypical mycobacteriosis. The patients with the mixed infection have died, in spite of the negative conversion or the dicrease of the excretion of atypical mycobacteria. There were two cases (M. intracellulare infection) complicated with pulmonary tuberculosis.
It was reported previously by the present group (1-3) that the frequency of isolation of my cobacteria other than tubercle bacilli (‘atypical’ mycobacteria) and the incidence of mycobacterioses due ...to these mycobacteria are higher in the hospitals locating in the South coast of the Honshu island. It was shown also that more than 90% of the mycobacterioses in this country were due to M. avium-intracellulare complex and that the lung disease due to M. kansasii was found only in the Tokyo area and its neighbourhood. In the present study, the prevalence rate of the “atypical” mycobacterioses was compared among the hospitals locating in various places of this country. A morning sputum specimen was added with an equal volume of a 4% NaOH solution and dissolved by shaking at room temperature for 15 to 20 minutes. The sputum was inoculated to the Ogawa egg medium. Growing organisms were screened for ‘atypical’ mycobacteria by the use of the PNB medium (4) or the salicylate medium (5). The acid-fastness and the photochromogenicity were also tested in individual hospitals. The organisms that grew on the PNB or salicylate medium were sent to the Chubu hospital and were identified according to the methods previously described (2). ‘Atypical’ mycobacterioses were defined by the following conditions: (a) The excretion of ‘atypical’ mycobacteria more than three times in the period of the first 6 months after hospitalization; (b) presence of lung lesion in the chest X-ray picture; (c) coincidence of the excretion of ‘atypical’ mycobacteria and clinical symptoms. The location of the 13 participating hospitals are shown in Fig. 1. The prevalence rate was the highest in five hospitals, Tokyo, Chubu, Kinki, Tenryuso, and Kochi, which are located in the Southern Pacific coast of Japan (Table 1). The species of mycobacteria other than tubercle bacilli which caused lung disease in patients are shown in Table 2. Furthermore, it was shown that tuberculous patients who were hospitalized for long time were infected with ‘atypical’ mycobacteria (Table 3). All causative organisms which caused ‘secondary’ infection belonged to M. aviurnintracellulare complex.
Nine cases (8 pulmonary disease and I pleural empyema) of the respiratory disease due to Mycobacterium fortuitum were found in 5 of 13 National sanatoria in Japan during the period from January 1967 ...to August 1980. It was supposed that the respiratory disease due to M. fortuitum occupied about 1 per cent of whole atypical mycobacteriosis and the patients were found all over the country. The patients previously reported in Japan were all over 40-year-old and the patients found in National sanatoria were all over 50-year-old, while patients under 20 years of age have been found not rarely in Europe and America. There were no difierence in the number of patient by sex (5 men and 4 women). Subjective symptoms such as fever, cough, sputum and hemoptysis were observed at the onset of the illness in the majority of the patients. The disease was divided into two types; i.e., the primary infection type without underlying respiratory disease and the secondary infection type with preexisting disease. Three of 9 cases belong to the primary infection type. In the remaining 6 cases which belong to the secondary infection type, plumonary tuberculosis, pleurisy and pneumoconiosis was observed as the underlying disease, but there was no association of achalasia which was found frequently in European and American patients. In the primary infection type sputum culture negative conversion occurred in all cases by antituberculous drug therapy alone and the appearance of their chest X-ray improved, although all strains isolated from the patient were completely resistant to all antituberculous drugs. On the contrary, in the majority of the secondary infection cases the excretion of organisms from sputum continued for extended periods. No patient underwent any surgical treatment. Two patients have died during this period, but both patients died of the disease other than atypical mycobacteriosis.
Screening for atypical mycobacteria (mycobacteria other than tubercle bacilli) were carried out in thirteen participating hospitals by using the p-nitrobenzoic acid-Ogawa egg medium. The subjects ...were the patients who were under hospitalization in June, September and December, 1975 and March, 1976. The isolation of mycobacteria was carried out using Ogawa egg medium which was inoculated with a sputum specimen after treatment with equal volume of a 4% (2%) NaOH solution for 15 minutes. 1. The ratio of atypical mycobacteria (including Gordona) among all mycobacteria was 7.8% in average and the ratio in senso stricto (excluding Gordona) was 7.5% in average (Table 1). The ratio was high in the hospitals located in South coast of Honshu and Shikoku islands facing Pacific Ocean (Fig. 1). 2. The kinds of species of atypical mycobacteria are shown in Table 2. The results agreed well with the results obtained by previous two studies (National Chest Hospital Group: Kekkaku, 48: 203-211, 1973; 51: 99-107, 1976). 3. The number of patients with lung disease due to atypical mycobacteria who were hospitalized in the period April, 1975 to March, 1976 was 128. Out of these, ca. 94% of the patients belonged to the disease due to M. avium-intracellulare omplex, and only 3% to that due to M. kansasii. Two cases showed the disease due to M fortuitum (Table 3). The frequency of occurrence of disease, so far observed using a ratio, the number of patients with disease due to atypical mycobacteria per the number of patients with lung disease (including tuberculosis) under hospitalization per day, as an index, was high in the hospitals located in the South coast of Honshu and Shikoku islands facing Pacific Ocean (Table 4 and Fig. 2). 4. The kinds of species isolated from sputa of patients with cavitary lung disease (mostly tuberculosis) and/or bronchiectasis were almost the same in three studies (Table 5). However, decrease in the ratio of M. nonchromogenicum was observed (1968 7.5%, 1971 4.4%, 1974 2.3%, t975 0.4%). 5. The kinds of species that caused lung disease were almost similar in our three studies (Table 6). Disease due to M. aviwn-intracellulare complex showed 94 to 96% of all atypical mycobacterioses, and disease due to M. kansasii 2 to 4% (Table 6). So far observed from the index used, the ratio of patients with lung disease due to atypical mycobacteria is increasing (Table 6). This increase has been suggested to be due to accumulation of such patients, as our another study (Kekkaku, 51: 447-451, 1976) showed that the prevalence rate of the disease among newly hospitalized patients was almost the same in recent five years (1971 to 1975).