Kekkaku : [Tuberculosis]最新文献

Background: Diagnosis of pulmonary tuberculosis is usually made by diagnostic imaging such as chest X-ray or computed tomography (CT), and sputum test including smear and polymerase chain reaction (PCR) test. However there is difficulty in making diagnose when atypical imaging and negative sputum test are presented, followed by diagnostic delay.

Case: A 26-year-old man from Philippines consulted other clinic because of dry cough and was pointed out mass shadow in right upper lung field in his chest CT. He visited our office because of positive interferon gamma release assay, but repeated sputum test could not find tuberculosis. Bleeding from mass lesion failed to perform biopsy by bronchoscope, and we failed to find tuberculosis by smear and PCR test from bronchial brushing and wash. Transthoracic needle biopsy from his mass lesion revealed multiple non-caseous granuloma, and lead to make a decision about starting medication. Four weeks later sputum culture from his first visit revealed positive, and diagnosis of tuberculosis was made.

Discussion: For avoiding therapy delay it is important to perform invasive diagnostic procedure including histological examination and clinical decision of starting medication, when conservative diagnostic procedure such as sputum test or diagnostic imaging present atypical finding for diagnosing tuberculosis.

We report a 37-year-old patient with latent tuberculosis infection who received isoniazid (INH) antituberculosis chemoprophylaxis. However, he developed fever and productive cough 3 weeks after treatment. Chest radiography and computed tomography showed bilateral infiltrative shadows in upper fields. Bronchoalveolar lavage fluid revealed a high proportion of eosinophils, and histological examination of biopsied lung tissue showed interstitial thickening with eosinocyte infiltration. Based on these findings, the patient was diagnosed with drug-induced eosinophilic pneumonia. His febrile condition and dry cough resolved after discontinuation of INH. Chest X-rays showed improvement of infiltrative shadows. This case report highlights the potential for INH-induced pneumonitis during the course of antituberculosis chemoprophylaxis.

Tuberculosis (TB) case findings from 2012 nationwide TB surveillance data in Japan were reviewed for diagnosis delay, proportion of far-advanced cavitary lesions, coexisting human immunodeficiency virus (HIV) infection and diabetes mellitus (DM), and drug susceptibility'testing (DST). Among 21,283 new TB cases in 2012, 82.4% were detected when patients sought medical attention for TB symptoms or visited medical facilities for other chief complaints. Among 16,432 patients with pulmonary TB, 25.8% had only respiratory symptoms, 31.7% had both respiratory and non-respiratory symptoms, 16.7% had only non-respiratory symptoms, and 0.6% had unknown symptoms. The rest (25.2%) were asymptomatic. The proportion of patient and doctor delays among 12,197 symptomatic pulmonary TB cases was analyzed. A large proportion--approximately 25-30%--of patients aged 35-64 years with symptomatic pulmonary TB exhibited a patient delay of 2 months. Like patient delay, the proportion of patients with a total delay (i.e., the sum of the patient and doctor delays) of ≥ 3 months decreased after 55 years of age. Moreover, the proportion of patients aged ≥ 65 years with a doctor delay of ≥ 1 month was higher than patients aged < 65 years. A large proportion--approximately 30%--of patients with symptomatic smear-positive TB were < 60 years of age with a total delay of ≥ 3 months due to longer patient delays. Meanwhile, the proportion of patients-approximately 15%--with a doctor delay ≥ 1 month was relatively stable across all age groups. The proportion of patients with pulmonary TB with advanced lung cavities increased from 1.5% in 1975 to approximately 2% and remained stable from 1985 to 2007. From 2007 to 2012, 366 patients with HIV infection had newly notified TB, 314 (85.8%) and 52 (14.2%) men and women, respectively, including 76 (20.8%) non-Japanese patients. Newly notified TB cases with DM comprised 14.3% (3,036/ 21,283) of the total cases in 2012 : 16.4% (2,127/12,988) of men and 11.0% (909/8,295) of women. The surveillance system obtained DST results for 8,347 (74.1%) of 11,261 culture-positive pulmonary TB cases in 2012. Among previously untreated cases, the proportions of patients with multi-drug resistant TB, any isoniazid resistance, and any rifampicin resistance were 0.5%, 4.0%, and 0.6%, respectively; the proportions in previously treated cases were 4.0%, 12.1%, and 4.7%, respectively. The proportions in previously untreated cases have remained stable for 6 years (2007-2012).

Purpose: On the basis of actual field data, we investigated the importance of monitoring the drug dosage and treatment duration for the supportive care of patients with tuberculosis who were being treated at public health centers.

Patients & methods: Data of the drug dosage of principal anti-tuberculosis drugs and the treatment duration for the registered patients with tuberculosis at the Shinjuku-ku Public Health Center were analyzed.

Results: The actual dosage of rifampicin and isoniazid according to the "recommended" dosage was administered to 57.3% (67/117) and 82.0% (114/139), respectively, patients with tuberculosis registered at the Shinjuku-ku Public Health Center. In contrast, in patients with tuberculosis who were treated at a highly specialized tuberculosis hospital, the rates were 81.0% (98/121) and 93.5% (86/92), respectively; for both drugs, the rates were significantly higher in this hospital than in the Shinjuku-ku Public Health Center. For the treatment duration, of 92 patients registered at the Shinjuku-ku Public Health Center who could have completed standard treatment in the standard duration, the actual treatment durations were shorter than the standard duration in 15.2% of the patients (14/92; -32 to -1 days), and longer than the standard duration in 77.2% (71/92; 2 to 146 days); the total superfluous treatment days for the latter 71 patients were 1,877 days. The treatment durations were more than 2 weeks shorter or longer than the standard duration for 31 patients, and in 71.0% (22/31) of these patients, no specific reason could be determined as to why the treatment durations were not standard.

Conclusion: In a significant number of patients, the drug dosage and treatment duration were not according to the standard values. By using this data about the management of the drug dosage and treatment duration for the supportive care of patients with tuberculosis treated at public health centers, we may improve quality of the provided supportive care.

Four years has passed since QuantiFERON TB-Gold In-Tube (QFT-GIT), the third generation test, has replaced QuantiFERON-Gold in Japan. The QFT-GIT test detects interferon-gamma (IFN-γ), which is released from lymphocytes present in blood after exposure to the M. tuberculosis complex antigens ESAT-6, CFP-10 and TB7.7. These proteins are absent from all Bacille-Calmette-Guérin (BCG) strains and from most non-tuberculosis mycobacteria, resulting in fewer false positive reactions as seen with the tuberculin skin test (TST). We had various experiences with QFT-GIT during these four years. So, we discussed the usefulness and its limitation of QFT-GIT as follows: 1. Development of the principle of QuantiFERON-GIT: Nobuyuki HARADA (Research Institute of Immune Diagnosis (RIID)). QuantiFERON (QFT) was originated from diagnostic system for bovine in Australia. Although the first generation of QFT, in which PPD had been used as stimulating antigens, was approved in USA, its diagnostic value was not recognized in Japan where most of Japanese are vaccinated with BCG. By combining M. tuberculosis-specific antigens with QFT system, the second generation of QFT, QFT-Gold, was developed, and approved in Japan in 2005. QFT-Gold was soon incorporated in several guidelines such as contact investigations and nosocomial infection measures. Now, QFT-Gold was superseded by the improved QFT-Gold, the current QFT-GIT. However, since QFT-GIT may contain unstable factors including blood volume and shaking methods of blood collection tubes, development of the more improved version is strongly expected. 2. Evaluating the result of QFT-GIT in patients treated with dialysis and immunosuppressive agents: Hidetoshi IGARI (National Hospital Organization Chiba-East National Hospital) The effectiveness of QuantiFERON TB-Gold In-Tube was analyzed in the patients with chronic kidney disease (CKD) and rheumatoid arthritis (RA). QFT positive was 7% and 11% respectively, and indeterminate was 5% and 2% respectively. QFT positive was 2% in hemodialysis patients, significantly lower than that of CKD. QFT positive after biological drug was administered was 8% in RA patients, significantly lower than 15% of RA without biological drug. The rate of latent tuberculosis patients in CKD was as well as health care workers (HCWs) of 8% of QFT positive. On the other hand that of RA might be higher than HCWs. Hemodialysis and biological drug administration might attenuate QFT result with lower rate of positive. The rate of indeterminate was less than 5%. This results was improved in compared with former generation QFT. 3. QFT in Vietnam: Naoto KEICHO (Research Institute of Tuberculosis, JATA). We have promoted collaborative research on tuberculosis with Vietnamese institutes since 2002. NCGM-BMH Medical Collaboration Center plays an important role in the clinical research projects. We report 1) quality assessment of QFT for tuberculosis infection, 2) prevalence and risk factors for tuberculosis

A case of pulmonary Mycobacterium kansasii infection with pleural effusion is very rare. We report a case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis. A 44-year-old man presented to a clinic with a productive cough, sputum, and loss of appetite for several months. Chest X-ray and chest computed tomography (CT) showed right pleural effusion, centrilobular nodules and infiltrative shadows with cavities in the bilateral lung fields. The direct smear examination showed positive acid-fast bacilli (Gaffky 5). He was referred to our hospital for suspected recurrent pulmonary tuberculosis. We started anti-tuberculosis drugs because pulmonary tuberculosis complicated with pleurisy was first suspected from the findings of high ADA level (78.6 IU/l) of the effusion and positive result of interferon-gamma release assay (QuantiFERON TB-2G). But Mycobacterium tuberculosis and M. avium complex was not identified by the polymerase chain reaction method and the culture of the sputum was negative. At a later date, Mycobacterium kansasii was detected by sputum culture. The patient was diagnosed as pulmonary Mycobacterium kansasii infection and treatment with anti-tuberculosis drugs including RFP resulted in a good clinical response. This case was a rare case of pulmonary Mycobacterium kansasii infection with pleural effusion, distinguished from pulmonary tuberculosis.

Purpose: To investigate a new treatment outcome index that may be useful in the Japanese tuberculosis surveillance system.

Objective and method: For sputum smear-positive primary tuberculosis patients, we estimated (a) treatment completion rates at the end of the next year of registration, and (b) treatment completion rates within 1 year from starting treatment in cases in which ≥ 1 year of treatment are indicated. For (a), we estimated treatment completion rates for newly registered cases during 2009 in the Japanese tuberculosis surveillance system, specifically at Fukujuji Hospital, which has a highly specialized tuberculosis treatment unit. For (b), we estimated the above-mentioned cases as well as those of "A" Public Health Center.

Result: (a): The treatment completion rate at the end of the next year of registration was estimated to be 88.7% for newly registered cases during 2009 in the Japanese tuberculosis surveillance system. Among 66 jurisdictions, the highest and lowest completion rates were 100% and 58.3%, respectively, with a standard deviation of 6.7%. For Fukujuji Hospital cases, the completion rate was 93.1%. (b): The treatment completion rate within 1 year from the start of treatment was estimated to be 76.4% for newly registered cases during 2009 in the Japanese tuberculosis surveillance system. Among 66 jurisdictions, the highest and lowest completion rates were 90.9% and 44.1%, respectively, with a standard deviation of 8.8%. For Fukujuji Hospital and "A" Public Health Center cases, the completion rates were 91.1% and 80.0%, respectively.

Conclusion: As a new treatment outcome index, treatment completion rates within 1 year might be more accurate than the treatment completion rate at the end of the next year of registration.

Objectives: The coexistence of lung cancer and pulmonary Mycobacterium avium complex (MAC) infection has not been well reported. This study illustrated the clinical characteristics of pulmonary MAC infections complicated with lung cancer.

Patients and methods: We conducted a retrospective analysis of the clinical characteristics of patients with pulmonary MAC infections complicated with newly diagnosed lung cancer between 2006 and 2012.

Results: Of 530 patients with pulmonary MAC infections, 13 (2.4%) were complicated with lung cancer. Six men and 7 women with a mean age of 73 years were also diagnosed with cancer, and 5 had a smoking history. Six patients were diagnosed concurrently, and 7 patients were diagnosed with pulmonary MAC infections prior to being diagnosed with cancer. Histological examination revealed adenocarcinoma, small cell carcinoma, and other cancer types in 9, 2, and 2 patients, respectively. Eleven of 13 patients had cancers of stages I-IIIA, and 10 underwent cancer resection. Analysis of the anatomical relationship between lung cancer and MAC revealed that both diseases were present in the same lobe in 10 patients. The disease extent was within one-third of a single lung field in 9 patients. Anti-MAC treatment was initiated in 7 patients, but was discontinued in 2 patients owing to side effects. Six patients did not receive anti-MAC treatment.

Conclusion: In this study, lung cancer was frequent among patients with pulmonary MAC infections, and both diseases tended to be in the early stages. Physicians should consider coexisting lung cancer when managing MAC infections.

An 88-year-old woman with rheumatoid arthritis who had started etanercept treatment in July 2011 was referred to our hospital in February 2012 for right-sided pleural effusion. Chest computed tomography showed right pleural effusion, partial swelling of a calcified mediastinal lymph node, and mid-esophageal thickening of the mucosal wall. Gastroendoscopy showed mid-esophageal ulceration. Histological examination of biopsy specimens from this ulceration revealed noncaseating granulomas with Langhans giant cells. Ziehl-Neelsen staining of this section was positive for acid-fast bacilli. Polymerase chain reaction analysis of gastric juice was positive for Mycobacterium tuberculosis; we therefore diagnosed the patient with esophageal tuberculosis. However, since abdominal computed tomography showed swelling of mesenteric lymph nodes, we also suspected intestinal tuberculosis. Colonoscopy showed multiple ileal erosions; histological analyses of biopsied specimens revealed granulomas with Langhans giant cells, similar to the esophageal findings. We finally diagnosed the patient with both esophageal and intestinal tuberculosis. After anti-tuberculosis treatment, the right pleural effusion disappeared and the abdominal lesions improved. Although mycobacterial involvement of both the esophagus and intestine is rare in immunocompromised and immunocompetent hosts, differential diagnosis of these diseases is likely to become more important.

Objective: To evaluate COBAS TaqMan MAI test misidentification of Mycobacterium lentiflavum as Mycobacterium intracellulare.

Materials and methods: Preliminary comparative analysis identified 13 clinical isolates used in this study as COBAS Amplicor MAV and MIN-negative but COBAS TaqMan MAI-positive. The COBAS TaqMan MAI test limit of detection and reproducibility were evaluated by tenfold dilution series from 3 x 10(8) CFU/mL. Isolate 16S rDNA nucleotide sequences were compared with Mycobacterium avium and M. intracellulare.

Results: Discrepancies were observed between isolates identified as M. lentiflavum by 16S rDNA sequencing and as M. intracellulare by the COBAS TaqMan MAI test. The false-positive results were verified by sequence comparison of a randomly sampled clinical isolate and the M. intracellulare reference strain. Sequence analysis of M. lentiflavum and M. intracellulare 16S rDNA amplification products showed at least 3 mismatches between species. The high identity in the sequence was found for M. intracellulare by COBAS TaqMan MAI.

Conclusion: In Japan, commercially available nucleic acid probe- and amplification-based tests cannot identify M. lentiflavum. Correct identification, though challenging, is possible using standard cultivation procedures for colony growth. Misleading results using the COBAS TaqMan MAI kit may lead to erroneous diagnoses.