Genetic diversity of Mycobacterium tuberculosis isolates from Tochigi prefecture, a local region of Japan.

BACKGROUND: Foreign-born patients with tuberculosis (TB) may introduce globally disseminated isolates of Mycobacterium tuberculosis into large cities in Japan. The risk of dissemination of these isolates into local regions, however, has not been determined. This study analyzed the molecular epidemiology of M. tuberculosis isolates obtained from TB patients living in a local region of Japan. METHODS: Whole genome sequences of 169 M. tuberculosis isolates, obtained from 148 Japanese-born and 21 foreign-born patients living in Tochigi, Japan, were analyzed using the Comprehensive analysis server for the Mycobacterium t u b erculosis complex (CASTB). RESULTS: The 169 isolates were clustered into four clades; Lineage 2 (111 isolates 65.7%), Lineage 4 (43 isolates, 25.4%), Lineage 1 (13 isolates, 7.7%), and Lineage 3 (2 isolates, 1.2%). Of the 111 isolates belonging to Lineage 2, 79 (71.2%) were of the atypical Beijing sub-genotype. Of the 13 Lineage 1 isolates, nine (69.2%) were from foreign-born patients. The isolates belonging to Lineage 4 were further clustered into three clades, two containing isolates shared by both Japanese- and foreign-born patients. The two isolates belonging to Lineage 3 were obtained from foreign-born patients. CONCLUSIONS: The genotypic diversity of M. tuberculosis in a local region of Japan is increased primarily by the presence of isolates obtained from foreign-born patients.

Molecular Epidemiology of Drug-Resistant Mycobacterium Tuberculosis in Japan.

Clinical isolates of drug-resistant (isoniazid and/or rifampicin-resistant) Mycobacterium tuberculosis were obtained from 254 patients diagnosed with drug-resistant tuberculosis in Japan from April 2015 to March 2017 in National Hospital Organization hospitals. The 254 patients were approximately 32% of all 795 patients who were diagnosed with culture-confirmed drug-resistant tuberculosis from 2015 to 2016 nationwide in Japan. The whole-genome sequences of all the isolates from the 254 patients and the lineages of these isolates were determined, and phylogenetic trees were constructed based on single nucleotide polymorphism concatemers. Of these patients, 202 (79.5%) were born in Japan and 52 (20.5%) were born elsewhere. Of the 254 drug-resistant isolates, 54 (21.3%) were multidrug resistant, being resistant to both isoniazid and rifampicin. The percentages of multidrug-resistant isolates were significantly higher in foreign-born (38.5% [20/52]) than Japanese-born patients (16.8% [34/202]). Of the 54 multidrug-resistant isolates, nine were extensively drug resistant, which were all obtained from Japanese-born patients. Five extensively drug-resistant isolates were obtained from patients with incipient tuberculosis. A significant number of multidrug-resistant M. tuberculosis strains were isolated from foreign-born patients from Asian countries that have a high tuberculosis burden. Foreign-derived isolates affect the nationwide genetic diversity of drug-resistant M. tuberculosis in Japan. Extensively drug-resistant M. tuberculosis isolates were transmitted among the Japanese population. IMPORTANCE The incidence rate of tuberculosis (TB) in Japan was 11.5 per 100,000 of the population in 2019. Of TB patients in Japan, 61.1% were aged >70 years, and 10.7% were born outside Japan, mostly in Asian countries with a high burden of tuberculosis. Of the tuberculosis patients in the present study, 5.4% and 1.0% showed resistance to isoniazid and rifampicin, respectively, and 0.7% were multidrug resistant. The objective of this study was to clarify the molecular epidemiological properties of drug-resistant tuberculosis in Japan. Molecular epidemiology provides several clues to inform potential measures to control drug-resistant tuberculosis in Japan.