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Murase Y.,The Research Institute of Tuberculosis
Nihon rinsho. Japanese journal of clinical medicine | Year: 2011

This review summarized recent findings on lineage-specific characteristics of Mycobacterium tuberculosis. M. tuberculosis is more generically diverse than previously assumed, and it is expected that such genetic diversity may influence on both clinical and epidemiological aspects of tuberculosis diseases. In Japan, approximately 75% of clinical isolates belongs to the Beijing family genotype, which is highly prevalent throughout East Asia. Beijing strains have been emerging in some other areas with drug resistance and genetic homogeneity, suggesting their selective advantages over other lineages of M. tuberculosis. More frequent distribution of modern type of Beijing strains among both younger and homeless people in Japan may reflect their recent epidemics. Further studies are needed to reveal the mechanisms underlying the lineage-specific characteristics, and these will offer new insights into future tuberculosis control. Source


Higuchi K.,The Research Institute of Tuberculosis
Nihon rinsho. Japanese journal of clinical medicine | Year: 2011

At present, there are only two methods to diagnose tuberculosis infection in the world, tuberculin skin test (TST) and interferon gamma release assays (IGRAs). Since TST could show positive responses due to BCG vaccination or infection of non-tuberculous mycobacterium and BCG vaccination is widely done in Japan, TST has a critical problem in its specificity. QuantiFERON-TB Gold (QFT-G/QFT-3G) is one of IGRAs and uses M. tuberculosis-specific antigens (ESAT-6, CFP-10, TB7.7) for stimulation of whole blood to induce IFN-gamma production by antigen-specific T cells. Produced IFN-gamma is measured by ELISA system. IFN-gamma is produced by individuals with TB infection but not by BCG-vaccinated individuals without TB infection. As QFT can detect TB infection among BCG vaccinated individuals more accurately than TST, it is possible to diagnose TB infection efficiently in contact investigation so on. However, as same as TST, QFT cannot discriminate between remote infection and recent infection, nor between progressive infection and controllable recent infection. Since QFT is newly development TB diagnosis test, there are many subjects in the QFT test system. For example, one subject is that accurate QFT results among immunocompromised populations are difficult to obtain because of weak immune responses. After these many research data are accumulated, we will be able to have many solutions in QFT. Source


Shi R.,Henan Provincial Public Health Clinical Center | Sugawara I.,The Research Institute of Tuberculosis
Tohoku Journal of Experimental Medicine | Year: 2010

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a tenacious and remarkably successfulpathogen that has latently infected one third of the world's population, according to the World Health Organization (WHO) statistics. It is anticipated that 10% of these infected individuals will develop active tuberculosis at some point in their lifetime. The long-term use of the current drug regimen, the emergence of drug-resistant strains, and HIV co-infection have resulted in a resurgence of research efforts to address the urgent need for new anti-tuberculosis drugs. A number of potential candidate drugs with novel modes of action have entered clinical trials in recent years, and these are likely to be effective against antituberculosis drug-resistant strains. They include neuroquinolone derivatives, a modified ethambutol, nitroimidazole groups and so on. This mini-review summarizes the latest information about eight new antituberculosis drug candidates and describes their activities, pharmacokinetics, mechanisms of action, and mechanisms of drug-resistance induced by these drug candidates. © 2010 Tohoku University Medical Press. Source


Wada T.,Japan Institute for Environmental Sciences | Iwamoto T.,Kobe Institute of Health | Hase A.,Japan Institute for Environmental Sciences | Maeda S.,The Research Institute of Tuberculosis
Infection, Genetics and Evolution | Year: 2012

The Beijing family is an endemic lineage of Mycobacterium tuberculosis in eastern Asia. In Japan, five evolutionarily sequential sublineages composing the lineage have predominated. Comparative genomic sequencing based on a microarray technique was conducted for five representative strains of those respective sublineages. Results revealed approximately 200 point mutations specific to each strain. Subsequently, to investigate the genetic diversity of each sublineage, we analysed the phylogenetic divergence of 103 domestic strains belonging to them using genetic markers derived from the mutation information. Results show that the five sublineages have comprised smaller lineages which had diverged at various points. The smaller sub-sublineages have emerged with respective bottlenecks, which are reflected in the excessive monophyletic evolution of the species. Our data provide necessary information to grasp a comprehensive picture of genetic diversity of the lineage constructed in its evolution. © 2012 Elsevier B.V. Source


Ohmori M.,The Research Institute of Tuberculosis
Kekkaku : [Tuberculosis] | Year: 2012

The nationwide computerized tuberculosis (TB) surveillance system was revised in 2007. It was developed to be user-friendly and to allow the evaluation of current TB problems and control issues in Japan. All public health centers in Japan (518 as of April 2007) have system terminals connected to a central computer, and the data entered at these terminals are sent to the online central computer excluding personal identification data. All the figures and tables in this paper were created using the annual report database which are compiled from this system. The revision in 2007 added many new functions to the system, such as a function for automatically sending data upon transfer. The monitoring information for assisting case management of TB patients by the DOTS was also enhanced. The algorithm for classifying treatment outcomes automatically based on data entered regarding cancellations from registration, bacteriological results and drug usage each month was revised. The proportion of "Failed" and "Defaulted" combined was 4.6% among new sputum smear positive pulmonary TB patients newly registered in 2009, while "Died" accounted for as high as 19.3%, due largely to a high percentage of the elderly. A new system for contact examination management is provided as a subsystem. Feedback of data analyses has been strengthened by various methods. This TB surveillance system is indispensable for implementing the evidence-based TB control program in Japan. An important role of the Research Institute of Tuberculosis is to support the planning and execution of TB control with provision of useful epidemiological information from the system. Source

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