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Toru Mori

Publications and source records attributed to Toru Mori.

At least 19 recordsLinked to original sources
PubMed2007

Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a high school.

BACKGROUND AND OBJECTIVE: QuantiFERON-TB Gold (QFT-G) was employed in a contact investigation in a high school to evaluate its performance in adolescents. METHODS: Students of the same school grade as the index case were screened with tuberculin skin test (TST) and CXR examination as an initial contact investigation. QFT-G was performed for students demonstrating a positive TST (erythema larger than 30 mm). RESULTS: Of 349 students whose TST was completed, 95 had positive TST responses, although the distribution of TST responses was similar for both high and low exposure groups. In contrast, only four of the 88 TST-positive students tested with QFT-G were positive by this test, and three of these were from the high exposure group. Chemoprophylaxis was provided to only those four QFT-G-positive students. Follow up of the 91 students who were TST-positive, but QFT-G-negative (or not tested), for more than 3.5 years revealed that none have developed active tuberculosis. CONCLUSIONS: QFT-G appears more specific than TST as contacts with positive TST and negative QFT-G responses were not offered prophylaxis and none developed tuberculosis during 3.5 years of follow up. The replacement of TST with QFT-G, or perhaps combined use of TST and QFT-G, may be more useful in diagnosing true infection and thus reducing the number of subjects indicated for chemoprophylaxis.

Adolescent↗
PubMed2006

Detection of multidrug resistance in Mycobacterium tuberculosis.

We developed a DNA sequencing-based method to detect mutations in the genome of drug-resistant Mycobacterium tuberculosis. Drug resistance in M. tuberculosis is caused by mutations in restricted regions of the genome. Eight genome regions associated with drug resistance, including rpoB for rifampin (RIF), katG and the mabA (fabG1)-inhA promoter for isoniazid (INH), embB for ethambutol (EMB), pncA for pyrazinamide (PZA), rpsL and rrs for streptomycin (STR), and gyrA for levofloxacin, were amplified simultaneously by PCR, and the DNA sequences were determined. It took 6.5 h to complete all procedures. Among the 138 clinical isolates tested, 55 were resistant to at least one drug. Thirty-four of 38 INH-resistant isolates (89.5%), 28 of 28 RIF-resistant isolates (100%), 15 of 18 EMB-resistant isolates (83.3%), 18 of 30 STR-resistant isolates (60%), and 17 of 17 PZA-resistant isolates (100%) had mutations related to specific drug resistance. Eighteen of these mutations had not been reported previously. These novel mutations include one in rpoB, eight in katG, one in the mabA-inhA regulatory region, two in embB, five in pncA, and one in rrs. Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively. Our sequencing-based method was also useful for testing sputa from tuberculosis patients and for screening of mutations in Mycobacterium bovis. In conclusion, our new method is useful for rapid detection of multiple-drug-resistant M. tuberculosis and for identifying novel mutations in drug-resistant M. tuberculosis.

Antitubercular Agents↗
PubMed2006

Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers.

OBJECTIVE: To examine the hypothesis that results of the QuantiFERON-TB Gold assay (QFT-G), a whole-blood test for detection of tuberculosis infection, are more significantly related to known risk factors for tuberculosis infection in healthcare workers (HCWs) who have received bacille Calmette-Guerin vaccine than are results of the Mantoux tuberculin skin test (TST). DESIGN: All HCWs (approximately 510) from a 370-bed general hospital in Tokyo where patients with and patients without tuberculosis are treated were invited to participate in the study. All study participants completed a questionnaire about their Mycobacterium tuberculosis infection risk factors as HCWs at the general hospital. They were then tested for LTBI by means of the QFT-G, followed by the TST. Statistical analyses were performed to compare results of each test with M. tuberculosis infection risk factors (age, length of employment in the healthcare industry, history of working with tuberculosis-positive patients in a tuberculosis ward or in the outpatient department of the hospital's tuberculosis clinic for more than 1 year, chest radiograph evidence of healed tuberculosis, history of performing bronchoscope procedures, and job classification), and for TST-positive HCWs, to compare the QFT-G result with the TST induration diameter. RESULTS: A total of 332 HCWs (95% of whom had been vaccinated with BCG) participated in the study, and 33 had positive QFT-G results, suggesting a prevalence of LTBI of 9.9%. Of 304 HCWs who underwent TST, 283 (93.1%) had an induration diameter of 10 mm or more. Multiple logistic regression analysis revealed that positive QFT-G results were significantly associated with age and with a history of working in a tuberculosis ward or an outpatient department of a tuberculosis clinic. TST results were not correlated with any of the tuberculosis infection risk factors we evaluated. CONCLUSIONS: Positive QFT-G results were closely associated with the presence of risk factors for LTBI in a hospital setting, suggesting that the QFT-G can detect LTBI in a population composed predominantly of BCG vaccinees. Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.

Adult↗
PubMed2006

[The new Tuberculosis Control Program of Japan].

The 1951 Tuberculosis Control Law of Japan was amended extensively and has been in effect since April, 2005. The revision of the National Tuberculosis Program (NTP) is to respond to the tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation. In this review, the main points and framework of the revisions were summarized and the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation is discussed. Also, challenges of Japan's NTP in the recent future are discussed, including the controversies over the proposed abolishment of the Tuberculosis Control Law. 1. IMMUNIZATION: In the revision of NTP, the BCG vaccination of elementary school and junior-high school entrants was discontinued. In order to strengthen the early primary vaccination for infants, the new Law has adopted the direct vaccination scheme omitting tuberculin testing prior to immunization. This program is implemented to young babies, i.e., less than six months old, as defined by the decree. It is a heavy responsibility for the municipalities to ensure the high coverage of immunization when the period of legal vaccination is rather strictly limited practically to the fourth to sixth months after birth. The safe direct vaccination is another new challenge where appropriate management of the Koch's phenomenon or similar reactions should be warranted. 2. CHEMOPROPHYLAXIS: Though unfortunately suspended for some legal reason currently, the expansion and improvement of chemoprophylaxis, or treatment of latent tuberculosis infection, to cover anyone with higher risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. The technical innovations in diagnosis of TB infection such as QuantiFERON will be very helpful. Development of new drugs or drug regimens for this purpose is also expected. 3. CASE DETECTION: The "indiscriminate" screening scheme in the periodic mass health examination has been replaced with a selective one. Only subjects aged 65 or older are eligible for the screening, supplemented with selected occupational groups who are considered to become source of infection, should they develop tuberculosis, such as health-care providers and school teachers. Local autonomies are also responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses, as decided by the autonomies at their disposal. Another important mode of active case-finding, i.e., contact investigation has been legally enforced so that anybody cannot refuse to be examined by the Health Center. This investigation service will be greatly enhanced by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection. Regarding the clinical service of the symptomatic patients that detect 75% of new cases currently will be improved in its quality by introducing an external quality assurance system of commercial bacteriological laboratory services. 4. TREATMENT AND PATIENT SUPPORT: The revised NTP clearly states the government's responsibility for treating TB patients in close cooperation with a doctor, in the framework of the DOTS Japan version. While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issues of improper practice of treatment, as well as the government's slow process for approving drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses, such as quinolones, macrolides and others. 5. PREFECTURAL TB CONTROL PLAN: In order to respond to the specific issues of tuberculosis problem in the respective prefectures in terms of epidemiology or in available resources, the Law requests every prefecture to develop and implement its own TB control plan. The rather abruptly proposed argument of abolishing Tuberculosis Control Law and merging the NTP to Infectious Disease Control Law threatens us with the government's premature departure from active commitment in the tuberculosis control. This reminds us of the United States' remarkable experience of the tuberculosis resurgence in the late 1980's and early 1990's, after 15 years of abandonment of the governmental efforts during 1970s.

Government Programs↗
PubMed2006

Evaluation of a 1 step TRAb assay for the detection of high-affinity components to hTSHR: evidences indicating superiority of the assay in the lower TRAb range.

The aim of this study was to develop an assay to selectively detect high-affinity components among TRAb. Using an rhTSHR-coated tube system, a 1 step TRAb assay method was developed that included 1) co-incubation with (125)I-bTSH, 2) a 50 microl serum sample, 3) an increased incubation volume (450 microl), and 4) a 1 hour incubation time. Sixty-one TRAb positive Graves' sera were studied. When the regular TRAb assay (Reg) results were quantitatively compared to the 1 step assay (1 step) results, certain dispersions and overestimations using the latter were seen. Further, some 1 step positive results were observed in the low Reg range. Overestimations were considered mostly due to the differences between TRAb standard and patients' serum TRAb in the binding competition against co-incubated (125)I-bTSH, which was shown from a modified assay mimicking the 1 step conditions. Therefore, the 1 step results were decided to be expressed by % inhibition against (125)I-bTSH. As for data dispersions, TRAb absorptions during the regular 1st incubation were studied. Individually, the absorption rates varied from 11 to 69%, and higher absorptions were observed in lower Reg range, especially in those negative by the 1 step. Observed 1 step positive results in the low Reg range were of interest, and 1 step/Reg ratios were calculated. The ratios with 1 step negative samples were significantly lower than those of 1 step positive samples. In conclusion, the 1 step assay was proved to detect a particular and biologically active TRAb, especially in those with low TRAb. The clinical significance of the 1 step results should be of future interest.

Antibody Affinity↗
PubMed2005

Correlation between suspended particles in the environmental air and causes of disease among inhabitants: cross-sectional studies using the vital statistics and air pollution data in Japan.

To identify the diseases that correlate with suspended particle concentration in the ambient air, a cross-sectional epidemiological study was conducted using the annual vital statistics and air pollution estimates of 1881 points throughout Japan. The concentration of suspended particulate matters (SPMs) 10 microm or less in diameter were hypothetically converted to PM(2.5) values (converted PM(2.5) or cPM(2.5)) by using a conversion factor obtained from 25 estimates in Japan. Among various causes of death, a significant correlation was observed between both the SPM and cPM(2.5) (SPM/cPM(2.5)) levels and the age-adjusted death rates of ischemic heart disease or hypertensive heart disease in both genders. Correlation was noted with pneumonia, asthma, chronic bronchitis/emphysema, or lung cancer only in females. Unexpectedly, breast, endometrial, and ovarian cancer also showed significant increases in mortality rates related to the SPM/cPM(2.5) level, suggesting a role for suspended particles in the ambient air with or without gaseous component as a possible endocrine-disrupting, estrogenic agent. Multivariate regression analysis of confounding factors, smoking rate, population density, and hormone-related factors revealed consistent significance of SPM/cPM(2.5) in these diseases.

Air↗
PubMed2005

Survey of human immunodeficiency virus (HIV)-seropositive patients with mycobacterial infection in Japan.

OBJECTIVE: To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. METHODS: Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis (n=78) were analysed with the use of IS6110 and (CGG)(5) or IS1245 and IS1311, respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients (n=87). RESULTS: Of 86 mycobacterial strains, M. tuberculosis, M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium. CONCLUSIONS: This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Adolescent↗
PubMed2005

Differences in TSH receptor binding and thyroid-stimulating properties between TSH and Graves' IgG. Slowly-acting TSH receptor antibody moieties in Graves' sera affect assay data.

We analyzed TSH receptor (TSHR) effects, both binding and thyroid-stimulation, of TSH and Graves' IgG. A new TRAb assay system utilizes rhTSHR coated tubes and is comprised of two step incubation, the first incubation with patient serum followed by a second incubation with 125I-bTSH. We called TRAb measured by this method as hTRAb. 125I-bTSH binding capacity of the tube was found close to saturation at 1 hr with 200 microl of 125I-bTSH. Up to 5 hr of first incubation for hTRAb assay revealed significant increases in all hTRAb activities. hTRAb was not affected by second incubation time or dose of 125I-bTSH. When 1 step incubation with 125I-bTSH and Graves' serum was performed, hTRAb again increased significantly with time. A simple competitive equilibrium model could not be applied to these ligands. Second, Graves' IgG and bTSH were compared for in vitro thyroid-stimulation sequentially up to 24 hr, measuring cAMP generation from cultured porcine thyrocytes. While bTSH yielded peak cAMP generation by 8 hr, TSAb revealed more cAMP generation by 24 hr than at 8 hr. We concluded that individual Graves' sera contain heterogeneous TRAb of variable avidities, and that slow-acting TRAb, which may lack biological activity, can be detected by prolonged incubation.

Animals↗
PubMed2005

[Usefulness of QuantiFERON TB-2G in contact investigation of a tuberculosis outbreak in a university].

PURPOSE: This study examined the usefulness of QuantiFERON TB-2G (QFT) i.e., a novel technique for detecting tuberculosis infection based on the whole blood interferon-gamma response to specific antigens, in the investigation of a tuberculosis outbreak among university students. SUBJECTS AND METHOD: One university student was diagnosed as smear-positive pulmonary tuberculosis. In order to determine the extent of tuberculosis infection among contact students, tuberculin skin tests and QFT were performed on the close-contact group (220 people), as well as on the non-close-contact group (242 people). RESULTS: Nine students were found to be TB either clinically or on the X-ray screening in the contact investigation. In the close-contact group, the QFT-positive rate was 32.7%. The proportion of those exhibiting tuberculin reactions with erythema diameters of 30 mm or larger was 57.7%. In the non-close-contact group, the QFT-positive rate was only 0.8 %, as expected from the current healthy Japanese youths of this age. In contrast, strong tuberculin reactions with erythema of 30 mm or larger were seen in 18.2% in the latter group, most likely due to the previous history of BCG vaccination. CONCLUSION: QFT was clearly demonstrated to be a useful method for diagnosing tuberculosis infection, especially among subjects who show tuberculin reactivity due to past BCG vaccination. At the same time, the current criteria for the indication of chemoprophylaxis based on the strong tuberculin reaction were considered to be unreliable, causing many subjects with strong reactions to be given unnecessary preventive medications.

Adult↗
PubMed2005

[Detection of tuberculosis infection using a whole blood interferon gamma assay in a contact investigation--evaluation using quantiFERon TB-2G].

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a novel method of detecting tuberculosis infection, QuantiFERON TB-2G (QFT), in a large scale contact investigation when an outbreak of mass tuberculosis infection was suspected. SUBJECTS AND METHODS: The index case was a health-care worker who worked in a maternity hospital. The investigated contacts were categorized as follow according to the grade of closeness of contact; the "very close" contact group (11 subjects), the "close" contact group (33 subjects), and the "non-close" contact group (3,791 subjects). For the former two groups, tuberculin skin test (TST), chest X-ray examination and QFT were conducted. For the last contact group, TST and chest X-ray examination were conducted only to subjects who aged less than 29 years old, while only chest X-ray examination was conducted to those aged 30 years or older. The QFT test, i.e., a whole blood interferon-gamma assay using Mycobacterium tuberculosis-specific antigens, was performed to the "very close" and "close" contacts, and for strong tuberculin reactors among the "non-close" contacts. RESULTS: The number of infected subjects in the "very close" contact group, the "close" contact group, and the "non-close" contact group were 7, 7, and 277, respectively, based on TST results. On the other hand, the number of infected subjects in each group were 3, 2, and 5, respectively, based on the QFT test. CONCLUSION: If the indication of chemoprophylaxis was determined based on TST test, this case would have been regarded a large tuberculosis outbreak. However, the use of the QFT test greatly reduced the number of the infected persons, so that the possibility of such massive TB outbreak was denied. Thus, the use of QFT, with which TB infection could be detected more accurately, seems to be very beneficial in contact investigations.

Adult↗
PubMed2005

[Cost-effectiveness analysis of QuantiFERON-TB 2nd generation used for detection of tuberculosis infection in contact investigations].

PURPOSE: QuantiFERON-TB-2nd Generation (QFT) has recently been developed as an accurate tool for detecting tuberculosis infection regardless of past history of BCG vaccination. A cost-effectiveness analysis was made on the usefulness of QFT that was used in the contacts investigation of a group of subject exposed to tuberculosis infection. METHODS: A model was built assuming that a group of youngsters was exposed to an infection source with different degrees of intensity. The distribution of the tuberculin reaction of this group was assumed to be variable according to the history of BCG vaccination and tuberculin testing. Also, the distribution of tuberculin reaction size after the recent exposure is assumed to be different, as has been observed previously. The strategies for investigating this group included giving QFT to subjects having erythema size exceeding 30 mm, 20 mm, and 10 mm as compared with the strategy with the tuberculin test only, or the QFT only. The outcome variables calculated for each strategy were sensitivity and specificity, and predictive values in detecting tuberculosis infection; the number of indications for chemoprophylaxis, the number of tuberculosis patients averted, and the costs incurred in treating tuberculosis patients and chemoprophylaxis cases and testing with tuberculin and QFT were also considered. The sensitivity (specificity) of the QFT employed in the analysis was 89% (98%) based on our observations. RESULTS & CONCLUSION: It was confirmed that the additional use of QFT would greatly reduce the number of indications for chemoprophylaxis cases that have never been infected and that the use of QFT is cost effective in spite of its relatively high unit cost. It will be useful to decide on the eligibility of QFT testing, i.e., the minimal tuberculin reaction size of subjects to whom QFT is given, based on the assumption of pre-exposure distribution of tuberculin reaction size of the group.

Contact Tracing↗
PubMed2005

[Variation in yield of needle scars with multipuncture BCG vaccination].

PURPOSE: BCG vaccination using the multipuncture percutaneous method has long been employed in Japan. The purpose of this study is to clarify whether the number of needle scars achieved the BCG vaccination differs with the vaccinating physician. METHODS: A total of 218 babies who were vaccinated at the age of 4 months by different physicians at the Public Health Centres of Katsushika-Ward, Tokyo, were examined at the age of 3 years, in the three-year-old health check-up programme. The BCG vaccination with the multipuncture method generates 18 needle scars at a maximum. We examined each child for how many needle scars after BCG vaccination were visible, with reference to the vaccinating physician. RESULTS: The mean number of the visible scars was 9.23 (SD 6.11), and significantly smaller (P < 0.01) than that for all 22 Wards (12.18 +/- 5.64) investigated with the same method. The mean number of needle scars of the babies in Katsushika Ward was the third smallest among the 22 Wards and significantly smaller (P < 0.05) than the national average as determined in the nationwide survey conducted in 2000. Significant differences were evident among the 7 physicians performing the vaccination, the best and second best means being 15.26 (SD3.62) and 14.59 (SD3.58) respectively, and significantly larger (P < 0.01) than the means for the 7 physicians. The worst mean was 3.43 (SD4.46), significantly smaller (P < 0.01) than the mean for the 7 physicians. CONCLUSION: The mean number of needle scars after BCG vaccination of babies significantly differed with the 7 physicians in the present study. Poor technique was presumed responsible for small numbers of scars and technical training is therefore necessary in order to improve the BCG vaccination outcome.

BCG Vaccine↗
PubMed2004

Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens.

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.

Adolescent↗
PubMed2004

[Reform of Japan's NTP and its technical perspectives].

The 1951 Tuberculosis Control Law of Japan is now faced with tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation. The law is also challenged with the shift of the paradigm for the National Tuberculosis (TB) Programme. In order to respond properly to these changes, the Tuberculosis Panel of the Health Science Council of the Ministry of Health, Labor and Welfare submitted its report for the amendment of the law in March 2002. Based on this report, a new Tuberculosis Control Law was passed in Parliament last June, and related decrees of the Cabinet and the Ministry are now being revised in preparation for it's enactment in April 2005. In this special lecture, the main points and framework of the revisions were discussed with the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation. 1. Case detection. There will be a shift from the current "indiscriminate" screening scheme to a selective one regarding periodic mass health examination. Only subjects aged 65 or older will be eligible for the screening, supplemented with selected occupational groups who are considered to be at a higher risk of TB, or may be a danger to others if they develop TB, such as health-care providers and school teachers. In addition, local autonomies are responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses. This means that the efforts of the autonomies are critical for the new system to be effective. The extra-ordinary examination will be limited to only the patient's contacts, and will be mandatory for those contacts so they cannot refuse to be examined by the Health Center. The public services used in the contact investigations will be greatly facilitated by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON). The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services. 2. Chemoprophylaxis. Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. These technical innovations in diagnosis of TB infection will be very helpful. Development of new drug regimens for the preventive treatment is also badly needed. 3. Immunization. Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned. In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing. This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree. It is essential to maintain the high level of vaccination coverage under the new program. The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years). To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination. A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted. 4. Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor. This is an important legal basis for the expansion of the DOTS Japan version. While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issue of improper practice of treatment, as well as the government's slow process for approving new drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses. 5. Prefectural TB Control Plan: In order to resolve the problems specific to the respective prefectures in terms of epidemiological parameters or available resources, the new Law requests every prefecture to develop its own TB control plan. In order for the new TB Control Law to be effective, strong government commitment supported by technological innovation is mandatory. It is for that reason that the Japanese Society of Tuberculosis should aggressively join the global movement to stop TB along with the general public of Japan.

Antitubercular Agents↗
PubMed2004

[Usefulness of a novel diagnostic method of tuberculosis infection, QuantiFERON TB-2G, in an outbreak of tuberculosis].

OBJECTIVE: The purpose of this study was to evaluate QuantiFERON TB-2G (QFT), a novel method of detecting tuberculosis infection among contacts of a tuberculosis patient by determining the whole-blood interferongamma response to the specific antigens. SUBJECTS AND METHODS: A teacher of a college who had been coughing for the preceding two months was diagnosed with smear-positive tuberculosis. About 270 students of the college were considered to have been exposed to tuberculosis infection, of whom 73 were in closer contact with the index case because they participated in a one-week group excursion attended by the teacher. Two of the contact students developed active tuberculosis shortly thereafter. Tuberculin tests were conducted to almost all students, and QFT was performed for only those with tuberculin reactions having erythema diameters of 30 mm or larger. RESULTS: Tuberculin tests of students, all of whom had been vaccinated with BCG at least once, revealed that the distribution of the close contact group was slightly shifted to right (larger side) than those with less close contacts. The QFT positive rate for close contacts was 45.5%, while that for less close contacts was only 7.1%, which obviously indicates that QFT is hardly affected by the tuberculin allergy due to past BCG vaccination. The distribution of interferon-gamma measurements (log-transformed) of the close contacts showed typical bimodality, one mode representing the infected, another the non-infected. This was not clear for the less close contacts. The correlation of interferon-gamma measurements (log-transformed) with tuberculin reaction erythema size was weak, if not non-significant. CONCLUSION: It was concluded that QFT was a useful method for diagnosing tuberculosis infection and was unaffected by the BCG-caused tuberculin allergy. In the case of the outbreak mentioned above, QFT greatly reduced the indication of chemoprophylaxis, from 28% of all the contacts solely based on tuberculin test to only 7%. Although there remains some problems to be overcome for QFT to be widely used with high confidence, this technology will provide a high possibility for wider and more accurate indication of chemoprophylaxis and will be one of the essential tools of tuberculosis control of the 21st century in Japan.

Adolescent↗
PubMed2004

[Basic characteristics of a novel diagnostic method (QuantiFERON TB-2G) for latent tuberculosis infection with the use of Mycobacterium tuberculosis-specific antigens, ESAT-6 and CFP-10].

PURPOSES: To determine the optimum cut-off level of a newly developed method for diagnosing tuberculosis infection based on whole-blood interferon-gamma measurement, and to study the basic characteristics of the method. STUDY SUBJECTS: 1) A total of 220 young, healthy individuals having no apparent exposure to tuberculosis infection, most of whom have had a vaccination with BCG vaccine. 2) One hundred eighteen tuberculosis patients who were diagnosed by positive Mycobacterium tuberculosis on culture. 3) A group of 75 youngsters exposed to an infectious tuberculosis patient and who showed a strong tuberculin reaction (with erythema diameter of 30 mm or more). METHOD: Whole-blood specimens of donors were stimulated with antigens, i.e., ESAT-6 and CFP-10, and then cultured. Plasma concentrations of interferon-gamma discharged were then determined with QuantiFERON-CMI. Correlation between interferon-gamma concentrations in response to ESAT-6 and CFP-10, and their correlation with Mantoux test results were analyzed for various categories of donors. The Receiver Operating Characteristics analysis was performed considering the loss due to misclassification. [ RESULTS AND DISCUSSION: The optimum cut-off level was determined as 0.35 IU/ml for both ESAT-6 and CFP-10. This gave the test a sensitivity of 89.0% and specificity of 98.1% in detecting tuberculosis infection. The correlation of interferon-gamma response with tuberculin tests among BCG-vaccinated individuals was low, which suggested that the test was not influenced by previous BCG vaccination. The low correlation between ESAT-6 and CFP-10 tests suggested that the simultaneous use of the two tests was beneficial. As in the case of clinical tests in general, the cut-off should be set at a lower level when the test is applied to high prevalence situation and vice versa.

Adolescent↗