Kekkaku : [Tuberculosis]最新文献

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of. certain types of suppressor macrophage populations. During the course of infections due to pathogenic mycobacteria, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This review describes the immunological properties of M1- and M2-type macrophages generated in hosts with certain microbial infections including mycobacteriosis and those generated in tumor-bearing animals. Particularly, this paper highlights the immunological and molecular biological characteristics of M1 and M2 macrophage populations, which are induced by mycobacterial infections

Purpose: QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis.

Methods: Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases.

Results: (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001).

Discussion: Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G-positive contacts.

Purpose: In response to a case of endotoxin contamination of tubes used in QuantiFERON® TB Gold (QFT-3G) testing in Japan in 2013, the effect of this contamination on QFT-3G test results was investigated.

Methods: We analyzed QFT-3G results from 4,258 participants in a tuberculosis contact investigation in Yamagata, Japan from September 2010 to April 2015. Of these, 2,488 samples were collected before the endotoxin contamination, while 1,770 samples were collected after the contamination.

Results: Negative control values in the group tested after the contamination were significantly lower than those in the group tested before the contamination (P < 0.0005). The proportion of positive controls that exceeded the calculated limit (10IU/ml) in the group tested after the contamination (87.8%) was lower than that in the group tested before the contamination (96.8%; P < 0.0005). The proportion of intermediate results in the group tested after the contamination (3.2%) was markedly lower than that in the group tested before the contamination (6.6%).

Discussion: Differences in QFT-3G test results were found to be related to a difference in blood collection before or after endotoxin contamination of blood collection tubes. Values resulting from QFT-3G testing were lower in blood samples that were collected after the contamination relative to those collected before the contamination.

Purpose: The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) can be challenging. A serodiagnosis enzyme immunoassay (EIA) kit, which detects the serum anti-glycopeptidolipid (GPL) core IgA antibody, has been commercialized recently; however, its clinical usefulness in the diagnosis of MAC-PD is still unclear. This study aimed to evaluate the availability of this kit and identify factors affecting testing accuracy.

Methods: We performed a retrospective study of 195 patients who were evaluated with an EIA kit at Nagasaki University Hospital between November 2012 and March 2014.

Results: 12 of 16 (75.0%) MAC patients have underlying diseases ; 8 of 16 (50%) had complications associated with respiratory diseases. There were no significant differences between the seropositive and seronegative background of patients with confirmed MAC-PD. Regarding the accuracy of serodiagnosis EIA kit, its sensitivity and specificity were 81.3% and 88.3% (with a cut-off value of 0.7 U/ml), respectively. Of false-positive patients with bronchiectasis, 28.6 % demonstrated a good response to anti-MAC treatment, indicating that the sensitivity of the EIA kit might be higher than that of culture-based diagnosis because patients with clinically diagnosed MAC-PD were included in the false-positive population.

Conclusions: In the current study, the serodiagnosis EIA kit demonstrated good sensitivity and specificity for the diagnosis of MAC-PD. Further clinical investigations are necessary to clarify the role of this kit in definitively diagnosing MAC infections.

A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases.

A 72-year-old man presented with fever, dyspnea, and weight loss. He was referred to our hospital for further examination of the cause of the pleural effusions. Chest computed tomography showed pleural effusions, a pericardial effusion, and enlarged lymph nodes in the carina tracheae. We administered treatment for heart failure and conducted analyses for a malignant tumor. The pericardial effusion improved, but the pericardium was thickened. Positron emission tomography-computed tomography (PET-CT) showed fluorine-18 deoxyglucose accumulation at the superior fovea of the right clavicle, carina tracheae, superior mediastinum lymph nodes, and a thickened pericardium. Because these findings did not suggest malignancy, we assumed this was a tuberculous lesion. Echocardiography confirmed this finding as constrictive pericarditis; therefore, pericardiolysis was performed. Pathological examination showed features of caseous necrosis and granulomatous changes. Hence, the patient was diagnosed with tuberculous constrictive pericarditis. PET-CT serves as a useful tool for the diagnosis of tuberculous pericarditis.

This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed.

An 86-year-old woman with severe dementia had been treated with oral prednisolone at 2 mg/day for autoimmune bullous dermatosis for several years. One year ago, she referred to our hospital due to an ulcerative skin lesion over the right tibial tuberosity. The lesion was treated by an iodine-containing ointment, but did not heal. Subsequently, a new skin lesion appeared in the right popliteal fossa. One month ago, the patient had increased sputum production that was accompanied by fever, anorexia, and dyspnea; consequently, she visited our department. Chest computed tomography revealed diffuse micronodules with ground-glass attenuation. Acid-fast bacteria staining of the sputum was positive and the polymerase chain reaction detected Mycobacterium tuberculosis. In addition, the bacilli were also found in the skin lesions of the right limb. Therefore, a diagnosis of cutaneous, and miliary tuberculosis was made. Although the anti-tuberculous combination chemotherapy consisting of isoniazid, rifampicin, and ethambutol was immediately initiated, her condition did not improve. She died on day 19 of hospitalization. Drug susceptibility testing revealed no resistance to all the three drugs; hence, it was concluded that the time-delay in diagnosis of cutaneous tuberculosis lead to the progression to miliary tuberculosis and subsequent death.

Background: Pulmonary disease caused by nontuberculous mycobacteria has a variable clinical course. Although this is possibly the result of not only host factors, but also bacterial factors, many questions remain to be answered regarding these manifestations.

Methods: To assess the relationship between the progression of pulmonary Mycobacterium avium disease and bacterial factors we performed variable number tandem repeats (VNTR) typing analysis of M. avium tandem repeats (MATR) in M. avium isolates from 46 patients with different clinical courses, and furthermore, examined the association between disease progression and a pMAH135 plasmid derived from M. avium.

Results: In patients whose treatment was initiated because of worsenedchest radiograph findings and/or clinical symptoms within 18 months after being diagnosed with pulmonary M. avium disease, the detection rate of 6 genes located in pMAH135 was 35.3-47.1% for 17 isolates. However, in untreated patients with a stable condition, these rates were 10.3-13.8% in 29 isolates. MATR-VNTR typing analysis showed that isolates from patients with worsened disease and those with stable disease are clustered differently. In cluster III, the number of isolates from patients with worsened disease was higher than that from patients with stable disease (p = 0.019), and furthermore, the number of isolates carrying pMAH135 genes was higher than that not carrying pMAH135 genes (p ≤ 0.001).

Conclusion: These results indicate an association between the progression of pulmonary M. avium disease and pMAH135. The presence of pMAH135 genes might be a useful prognostic indicator for pulmonary M. avium disease and may serve as one criterion for treatment initiation.

The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept in mind, while in the treatment of lung cancer, the possibility of concurrent PTB should also be considered.