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ML phylogenetic trees based on SNP concatenated sequence alignments of clinical isolates. ML phylogenetic trees of the 169 clinical isolates based on whole genome analysis. Radial rectangular tree layouts are shown for Lineages 1 (a), 2 (b) and 4 (c). Bootstrap values are shown in the phylogenetic trees. Clades show Lineage 2 Modern/typical (orange) and Ancestral/atypical (yellow). Scale bars indicate nucleotide substitutions per site. Black circles indicate foreign-born TB patients
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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 p...
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The study aims to describe the clustering characteristics of Mycobacterium tuberculosis ( M.tb ) strains circulating in eastern China and determine the ratio of relapse and reinfection in recurrent patients. We recruited sputum smear-positive pulmonary tuberculosis cases from five cities of Jiangsu Province, China, during August 2013 and December 2...
Citations
... The large databases built with WGS data allow to develop a precise and comprehensive knowledge of L2 diversity [4,26,31,37]. Computational genomics now allows to study in-depth both the global and the local L2 history [6,24,26,32,35,[38][39][40][41][42]. The evolutionary history of L2 isolates is still debated as is their precise dating of emergence and their geographical origin [26,34]. ...
... Skeletal evidence of tuberculosis during the Bronze age was found in Korea and Japan [46,47]. In Japan, one of the main characteristics of the tuberculosis history, especially in aged people that were not vaccinated by BCG, is the presence of still poorly characterised ancestral L2 strains [22,26,39,42,48]. MIRU-VNTR diversity had been shown earlier to be quite important in L2 isolates from Japan [44]. ...
... We are currently developing the TB-Annotator project, a new computational genomics pipeline whose aim is to perform datamining of MTBC genomic diversity using Sequence Read Archives (SRAs). We studied a set of L2 isolates from central Japan Honshu prefecture, Tochigi [42]. The 169 clinical isolates of M. tuberculosis we studied were from TB patients diagnosed in 2007 and in 2013 [42]. ...
By gathering 680 publicly available Sequence Read Archives from isolates of Mycobacterium tuberculosis complex (MTBC) including 190 belonging to the lineage 2 Beijing , and using an in-house bioinformatical pipeline, the TB-Annotator , that analyses more than 50 000 characters, we describe herein a new L2 sublineage from 20 isolates found in the Tochigi province, (Japan), that we designate as asia ancestral 5 (AAnc5). These isolates harbour a number of specific criteria (42 SNPs) and their intra-cluster pairwise distance suggests historical and not epidemiological transmission. These isolates harbour a mutation in rpoC , and do not fulfil, any of the modern Beijing lineage criteria, nor any of the other ancestral Beijing lineages described so far. Asia ancestral 5 isolates do not possess mutT2 58 and ogt 12 characteristics of modern Beijing , but possess ancestral Beijing SNPs characteristics. By looking into the literature, we found a reference isolate ID381, described in Kobe and Osaka belonging to the ‘G3’ group, sharing 36 out of the 42 specific SNPs found in AAnc5. We also assessed the intermediate position of the asia ancestral 4 (AAnc4) sublineage recently described in Thailand and propose an improved classification of the L2 that now includes AAnc4 and AAnc5. By increasing the recruitment into TB-Annotator to around 3000 genomes (including 642 belonging to L2), we confirmed our results and discovered additional historical ancestral L2 branches that remain to be investigated in more detail. We also present, in addition, some anthropological and historical data from Chinese and Japan history of tuberculosis, as well as from Korea, that could support our results on L2 evolution. This study shows that the reconstruction of the early history of tuberculosis in Asia is likely to reveal complex patterns since its emergence.
... The prevalence rate of TB in large Japanese cities such as Tokyo is more than twice that in rural areas, which is likely due to larger populations of foreignborn TB-positive immigrants in those cities (2). TB-positive individuals from countries with a high TB burden may introduce globally disseminated isolates of Mycobacterium tuberculosis, not only into large cities such as Tokyo (2), but into rural areas such as Tochigi prefecture (3). ...
... Foreign-born TB patients from countries with a high TB burden are thought to enhance the risks of M. tuberculosis spread in countries with a low incidence of TB (5). That is, foreign-born TB patients in Japan may be infected with internationally disseminated clones of M. tuberculosis and disseminate these in Japan (2,3). MDR-TB in European countries with a low incidence of TB is more prevalent among migrants than among the native population (6). ...
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.
Currently, tuberculosis (TB) in Japan is highly prevalent among elderly patients who were born during a time when TB was highly prevalent. Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is the predominant strain in the country. Moreover, the proportion of foreign-born patients with TB has been increasing. This epidemiological situation in Japan motivated us to explore the heterogeneity in transmission dynamics among the sublineages of Mtb L2 within this aging population. For this purpose, we conducted a population-based whole genome sequencing analysis of 550 Mtb strains in Kobe, Japan, and employed pairwise single nucleotide polymorphism (SNP) distance clustering and terminal branch length (TBL) distribution analysis to assess Mtb transmission. The genomic clustering rate with a threshold of ≤5 SNPs was significantly lower in elderly patients aged 70 years or higher than in non-elderly patients. The elderly patient group showed significantly longer TBL than the non-elderly group. These results supported the notion that reactivation of distant infection is a major driving force for the high incidence of TB in elderly individuals. The age group distribution and frequency of lineages/sublineages were found to significantly differ between foreign-born and Japan-born patients. The increased proportion of foreign-born patients might have resulted in more strain diversity in Japan. The L2.2.A sublineage demonstrated a significant association with elderly patients and exhibited lower transmission rates, which indicate to be prone to reactivate from long-term latency. In contrast, L2.2.Modern, showed a strong association with younger and foreign-born patients. This sublineage showed a high genomic cluster rate, suggesting its high transmissibility. The other three major sublineages, namely L2.2.AA2, L2.2.AA3.1, and L2.2.AA3.2, exhibited a consistent increase in cluster rates across varying SNP thresholds, indicating their relatively recent emergence as endemic sublineages in Japan. In conclusion, this study highlights distinct differences in the transmission dynamics of L2 sublineages within an aging society.
Background
Pathogen genomics have become increasingly important in infectious disease epidemiology and public health. The Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) guidelines were developed to outline a minimum set of criteria that should be reported in genomic epidemiology studies to facilitate assessment of study quality. We evaluate such reporting practices, using tuberculosis as an example.
Methods
For this systematic review, we initially searched MEDLINE, Embase Classic, and Embase on May 3, 2017, using the search terms “tuberculosis” and “genom* sequencing”. We updated this initial search on April 23, 2019, and also included a search of bioRxiv at this time. We included studies in English, French, or Spanish that recruited patients with microbiologically confirmed tuberculosis and used whole genome sequencing for typing of strains. Non-human studies, conference abstracts, and literature reviews were excluded. For each included study, the number and proportion of fulfilled STROME-ID criteria were recorded by two reviewers. A comparison of the mean proportion of fulfilled STROME-ID criteria before and after publication of the STROME-ID guidelines (in 2014) was done using a two-tailed t test. Quasi-Poisson regression and tobit regression were used to examine associations between study characteristics and the number and proportion of fulfilled STROME-ID criteria. This study was registered with PROSPERO, CRD42017064395.
Findings
976 titles and abstracts were identified by our primary search, with an additional 16 studies identified in bioRxiv. 114 full texts (published between 2009 and 2019) were eligible for inclusion. The mean proportion of STROME-ID criteria fulfilled was 50% (SD 12; range 16–75). The proportion of criteria fulfilled was similar before and after STROME-ID publication (51% [SD 11] vs 46% [14], p=0·26). The number of criteria reported (among those applicable to all studies) was not associated with impact factor, h-index, country of affiliation of senior author, or sample size of isolates. Similarly, the proportion of criteria fulfilled was not associated with these characteristics, with the exception of a sample size of isolates of 277 or more (the highest quartile). In terms of reproducibility, 100 (88%) studies reported which bioinformatic tools were used, but only 33 (33%) reported corresponding version numbers. Sequencing data were available for 86 (75%) studies.
Interpretation
The reporting of STROME-ID criteria in genomic epidemiology studies of tuberculosis between 2009 and 2019 was low, with implications for assessment of study quality. The considerable proportion of studies without bioinformatics version numbers or sequencing data available highlights a key concern for reproducibility.
Funding
None.
