[Objective] A nationwide anti-tuberculosis drug resistance survey for Mycobacterium tuberculosis was conducted by the Tuberculosis Research Committee (Ryoken) in Japan, 2002, to clarify the recent trend of drug resistant M. tuberculosis. The drug susceptibility testing (DST) results by participating laboratories were compared with the test results by the reference laboratory, in order to evaluate the quality of DST by the participating laboratories.
[Method] Mycobacterium strains were collected from patients who were admitted to the 99 participating hospitals between June and November in 2002. For each isolate, DST was performed at participating facilities and also at the reference laboratory (Research Institute of Tuberculosis: RIT) for four first-line anti-tuberculosis drugs, i. e., isoniazid (INH), rifampicin (RFP), streptomycin (SM) and ethambutol (EB). Each participating laboratory performed the DST with its routine method. The DST method for M. tuberculosis performed at the reference laboratory was the simplified proportion method on the standard 1% Ogawa medium as described in the national guidelines, and the results were regarded as the judicial ones. The DST results of each isolate from the participating laboratories were compared with the judicial results from the reference laboratory. The accuracy of DST done by the participating laboratories was evaluated in terms of the following indices; sensitivity for detecting drug resistant strains, the specificity for susceptible strain, the overall agreement, and kappa coefficient were calculated to evaluate the performance of local laboratories.
[Results] A total of 3, 122 M. tuberculosis strains were obtained out of 4, 134 mycobacterial strains collected from the participating facilities. Fifty, 23 and 17 local laboratories used Bitspectre-SR (Kyokuto pharmaceuticals), Welpack S (Nichibi) and Ogawa media for DST, respectively. MGIT (Becton Dickinson) and BrothMIC MTB-I (Kyokuto pharmaceuticals)were used in four laboratories each. The sensitivity, specificity, efficiency and kappa coefficient for INH were 84.5%, 98.7%, 98.0%, and 0.798, respectively. Similarly for RFP, they were 90.3%, 99.7%, 99.5%, and 0.894, respectively, False susceptible results were frequently observed (2, 1%)for SM compared with false resistance (0.5%), whereas the efficiency of SM was 97.4%. Similarly for EB, false resistances were frequently observed (2.6%) compared with false susceptibles (0.4%), whereas the efficiency of EB was 96.9%. The kappa coefficient for EB (0.470) was obviously lower than the others. The DST results with Ogawa method at local laboratories showed significantly lower sensitivity than those with Welpack S and MGIT.
[Discussion] The DST methods used at local laboratories were still mainly microtitre methods with egg-based solid media, but the number of laboratories using liquid DST methods increased in 2002 compared to 1997. The overall specificity and efficiency of DST for each anti-tuberculosis drug was over 95%, but the sensitivity was below 90.3%. Because of the frequency of drug resistance (up to 7.9% for SM in 2002), the efficiency and specificity may not be useful indicators for the quality assessment. The kappa coefficient for the agreement between local and reference laboratories'DST was clearly low in the case of EB, except for the laboratories using MGIT where kappa coefficient was higher than 0.8. The quality improvement of DST for EB could be achieved through the standardisation and automatisation.

View full abstract

[Purpose] To investigate the accuracy of clinical diagnosis of TB in Japan in recent years and to compare them with previous studies.
[Method] D ata (sex, age, clinical diagnosis, pathological diagnosis as cause of death) on deceased cases clinically or pathologically diagnosed ante mortem as having tuberculosis was collected from annual reports of the pathological autopsy cases in 1984, 1989, 1994, and 1999-2004. Information on TB death from population statistics in those 9 years also was collected and compared with data of autopsied cases.
[Result] Autopsy rate in these years was sta bly around 10%. Comparison of gender ratio and mean age between the tw o surveys showed similar numbers. During 1999-2004, 1725death cases were diagnosed as TB clinically or pathologically. Number of pathologically proven pulmonary TB cases was 429 and that of miliary TB was 283.55.7% of pulmonary tuberculosis and only 21.9% of miliary tuberculosis were correctly diagnosed before death. Out of 156 cases clinically diagnosed as non-TB diseases but proven as TB pathologically, 30.8 % of clinical diagnosis was pneumonia and/or bronchitis, followed by diagnoses of interstitial pneumonia, respiratory failure, pneumoconiosis and lung cancer. However, the main clinical diagnoses of 175 miss-diagnosed miliary TB cases were diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis.
[Conclusion] In order to reduce un diagnosed pulmonary TB cases and to prevent nosocomial TB infection, differential diagnosis among pneumonia and/or bronchitis cases should be done. In case of miliary TB, not only pneumonia but also diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis should be included in the list differential diagnosis.

View full abstract

[Objectives] We described clinical features of pulmonary Mycobacterium scofulaceum disease.
[Materials and methods] We desc ribed 15 cases of pulmonary Mycobacterium scrofulaceum infection admitted to National Hospital Organization Omuta National Hospital from 1989 to 2003 and reviewed the clinical feature, the findings of chest radiograph, and clinical course.
[Results] Sex ratio was 8 m ale cases and 7 female cases, and the average age was 65.9 years old. Smoking history was found in 8 patients and occupational history of the dust inhalation was found in 7 patients with pulmonary M. scrofulaceum infection. There were 11 cases of tuberculosis-like form and 4cases of nodular-bronchiectasis form according to the NTM Research society classification based on the findings of chest radiography. Improvement of the findings of chest radiography was seen in 4 patients by therapy, while no change or aggravation in 11 patients. Five patients died and among them, 3 died due to aggravation of pulmonary M. scrofulaceum infection.
[Discussion] Cases showing tuberculosis-like form were dominant, and most of them showed extensive lesions when they were diagnosed, and these facts were considered to be major factors of difficulty in the treatment of this infection. The facts that 7 cases had occupational exposure to the dust, obstructive pulmonary disease in 3 cases, and 6 cases showed sputum culture positive for other nontuberculous mycobacteriosis, suggest that local resistance of lung might be attenuated, and this could be one of factors of onset and development of this infection. Only 4 cases showed improvement, while 5cases died (primary disease death in 3 cases) and it was thought that the prognosis of the disease was in general poor.

View full abstract

[Purpose] To ascertain tuberculosis (TB) infection control measures and incidence of TB in nursing homes for elder.
[Subjects and method] The questionnaire on TB infection control was distributed to all nursing homes in Osaka City in 2005.
[Results] The questionnaire was returned from 197 (90%)out of 219 facilities. In more than half of facilities, infection control committee was organized (57%) and automated ventilation system was installed (59%). In almost all facilities, residents had annual chest X-ray screening (94%). Respiratory symptoms were checked for residents and “day service” users in majority of facilities.100% of employees had annual chest X-ray screening. However TB education session for employees was held annually in only 40% of facilities. Education materials on TB were distributed in 19%. Tuberculin skin test (TST)was conducted for new employees in 31%. TB patients were diagnosed in 22% of facilities in the past 3 years from 2002to 2004. Incidence rate of TB is 75.2 per 100, 000 for residents and 24.1 per 100, 000 for employees. Analysis showed that TB incidence rate is higher in facilities with larger number of residents and in facilities where infection control committee is organized, and facilities where TST is conducted for new employees.
[Discussion] In Osaka City, TB infection control was more often implemented in facilities where TB patient was diagnosed. When age structure is taken into consideration, TB incidence rate of employees or residents was lower than general population. Nosocomial TB infection does not seem to be occurring in nursing homes. However, as TB patients were diagnosed occasionally, TB infection control measures should be strengthened in Osaka City.

View full abstract

A 79-year-old woman was admitted to our hospital because of general fatigue. Chest radiograph and computed tomograph showed bronchiectasis and centrilobular nodules in the right middle lobe and lingula, which had not changed from previous examination. Intrahepatic nodular lesions and swelling of the left cervical lymph nodes, supraclavicular lymph node, abdominal paraaortic lymph nodes and inguinal lymph nodes was observed. Biopsy specimen of the liver lesion demonstrated epithelioid cell granulomas. Biopsy of the right inguinal lymph node demonstrated epithelioid cell granulomas with caseous necrosis and culture of the specimen showed Mycobacterium tuberculosis. The patient was diagnosed as having liver tuberculosis and multiple tuberculous lymphadenitis. Antituberculous treatment with isoniazid, rifampicin, ethambutol and pyrazinamide were started and continued for 6 months. All lesions improved after treatment. This was a rare case of liver tuberculosis that was difficult to distinguish from liver metastasis of cancer.

View full abstract

A 36 year-old female was pointed out of pulmonary abnormal shadows in the annual chest survey. Chest radiograph and computed tomography (CT) disclosed bilateral diffuse infiltrative shadows and tree-in-bud appearance in the right upper lung field and the left lingula. A sputum smear for acid-fast bacilli was negative. Histopathologically, the transbronchial lung biopsy specimen revealed non-caseous epithelioid granulomas with numerous giant cell s. Acid-fast bacilli were cultured from her sputum, however, nontuberculous mycobacteria was not detected by DNA-DNA hybridization method. Mycobacterium mageritense was identified by 16S ribosomal RNA sequencing with 100% matching. The isolated colony of M. mageritense was resistant to nine anti-tuberculous drugs. Follow-up chest CT scan showed a gradual decrease of infiltrative shadows without therapy.
To the best of our knowled ge, M. mageritense infections are rare, and this is the first case report of pulmonary infection in the literature. We conclude that the pulmonary infection of M. mageritense is one of causes of granuloma formation, and in some case it is difficult to differentiate clinically from sarcoidosis.

View full abstract

Chemotherapy of pulmonary MAC (Mycobacterium avium complex) infection has been almost universally agreed with the multidrugs regimen that contains Clarithromycin (CAM), Rifampin (RFP), Ethambtol (EB), and aminoglycoside in case of advanced stage.
One of the reason for the multidrugs regimen which is similar to tuberculous chemotherapy is to inhibit the emersion of resistant MAC strain. The other reasons, enhancement of anti microbial activity and response to polyclonal infection are unique to the MAC chemotherapy. In the current MAC chemotherapy, both CAM and aminoglycoside are main axes because only they can suppress the growth of MAC alone respectively. Efficacy of CAM was revealed through the randomized controlled trials of disseminated MAC infection with HIV and that consequences applied to pulmonary MAC infection treatment. CAM is not effective unless exceed 2 μg/ml blood concentration. RFP decreases CAM blood concentration remarkably, but the regimens contained RFP and CAM are superior clinically to the regimens without RFP. There seemed to be unknown pharmacological mechanisms with RFP. Although the advantage of aminoglycosides is easily achieved high blood concentration, if aminoglycoside dosage is exceed 15 mg/kg, the possibility of auditory disturbance increase.
About the duration of MAC chemotherapy, many guidelines recommended that one year continuation after the negative conversion of sputum culture. It is not the evidence but an expert opinion. We often experience recurrences several months later after the all drugs are ceased. The interval days to positive conversion of sputum culture from the day of completion of chemotherapy are randomly distributed with weibull's equation. It suggests that exogenous re-infec tion may cause the recurrence of pulmonary MAC infection as pointed out by Wallace Jr.
Considering these iss ues, we have the conception of pulmonary MAC infection chemotherapy as follows.
1. full d ose induction chemotherapy (two years)
2. maintenance chemotherapy (one year)
3. preventive chemotherapy (one year)These conceptions have to be the problem validated.
However, these current chemotherapies are not effective adequately, we need the combination treatment with surgical resection when indicated as a localized focus for example. Generally chemotherapy could not cured the destructed bronchial lesion due to MAC infection as like as local bronchiectasis or cavities. Consequently, the chemotherapy just after the surgical resection of destructed focus is most appropriate period.

View full abstract