BackgroundThe host, microbial, and environmental factors that contribute to variation in tuberculosis (TB) disease are incompletely understood. Accumulating evidence suggests that one driver of geographic variation in TB disease is the local ecology of mycobacterial genotypes or strains, and there is a need for a comprehensive and systematic synthesis of these data. The objectives of this study were to (1) map the global distribution of genotypes that cause TB disease and (2) examine whether any epidemiologically relevant clinical characteristics were associated with those genotypes.MethodsWe performed a systematic review of PubMed and Scopus to create a comprehensive dataset of human TB molecular epidemiology studies that used representative sampling techniques. The methods were developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We extracted and synthesized data from studies that reported prevalence of bacterial genotypes and from studies that reported clinical characteristics associated with those genotypes.ResultsThe results of this study are twofold. First, we identified 206 studies for inclusion in the study, representing over 200,000 bacterial isolates collected over 27 years in 85 countries. We mapped the genotypes and found that, consistent with previously published maps, Euro-American lineage 4 and East Asian lineage 2 strains are widespread, and West African lineages 5 and 6 strains are geographically restricted. Second, 30 studies also reported transmission chains and 4 reported treatment failure associated with genotypes. We performed a meta-analysis and found substantial heterogeneity across studies. However, based on the data available, we found that lineage 2 strains may be associated with increased risk of transmission chains, while lineages 5 and 6 strains may be associated with reduced risk, compared with lineage 4 strains.ConclusionsThis study provides the most comprehensive systematic analysis of the evidence for diversity in bacterial strains that cause TB disease. The results show both geographic and epidemiological differences between strains, which could inform our understanding of the global burden of TB. Our findings also highlight the challenges of collecting the clinical data required to inform TB diagnosis and treatment. We urge future national TB programs and research efforts to prioritize and reinforce clinical data collection in study designs and results dissemination.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1180-x) contains supplementary material, which is available to authorized users.

2 AbstractObjective: To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR). Methods:A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d. Results:Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR= [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI 2.01, 7.9), rifampicin (OR 3.4, 95%CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI 2.8, 25.6), and their effect sizes were ≥ 0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI 1.7, 5.8; p <0.001), treatment failure (HR 2.04; 95% CI 1.07, 3.8; p 0.02) and relapse (HR 2.1; 95% CI 1.2, 3.8; p 0.002), with effect sizes ≥0.39. Conclusion:T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes.Keywords: Tuberculosis, type 2 diabetes mellitus, effect, size 3 IntroductionThe overall prevalence of diabetes mellitus (DM) has increased rapidly as a result of an aging population, urbanization and associated changes lifestyle during the last decades. The International Diabetes Federation (IDF) estimated in 2015 the worldwide prevalence of type 2 diabetes mellitus (T2DM) was 8.8% (415 million people) (IDF). In Mexico, the prevalence of T2DM increased by 4.7% from 1998 to 2012, with a morbidity rate of 358.2 per 100 000 in 2012 (Sistema.Nacional. de.Vigilancia.Epidemiológica, 2013). Meanwhile, the World Health Organization (WHO) reported 9.5 million new cases of TB in 2014 and 1.5 million deaths.( WHO, 2015) In Mexico, the tuberculosis (TB) incidence was 23 per 100,000, reflecting a serious public health problem (Delgado-Sanchez et al., 2015).The increase in prevalence of T2DM has had a significant impact on tuberculosis comorbidity, with prevalence rates ranging from 10% to 30%, mainly affecting developing countries, including Some studies report that T2DM increased two to three times the risk of TB (Dooley & Chaisson, 2009;Jeon & Murray, 2008;Perez-Navarro et al., 2015), and diminishes the success of treatment cure (Baker et al., 2011...

All isolates from humans had spoligotype patterns that matched those observed in the cattle isolates, and all human isolates shared common ancestors with cattle in Baja California based on SNP analysis. This suggests that most human tuberculosis caused by M. bovis in Baja California is derived from M. bovis circulating in Baja California cattle. These results reinforce the importance of bovine tuberculosis surveillance and control in this region.

MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish.

The variety and presence or absence of the mutations found suggest the circulation of an important diversity of strains and the existence of additional mechanisms contributing to streptomycin resistance in the region.