The value of the continuous genotyping of multi-drug resistant tuberculosis over 20 years in Spain

Abstract

Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson’s chi-squared or Fisher’s exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann–Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples.

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005–2020

“…After cluster analysis, six clusters containing a total of 19 strains were identified (clustering rate 29.23%), most of which were formed by Beijing lineage isolates. In general, the clustering rate in our study was lower compared to the continuous 20 years genotyping study of MDR-TB in Spain (clustering rate 48.4%), 4-years drug-resistant TB WGS study in Thailand (48.5%) and the 3-years study involving MDR isolates from European Union countries (clustering rate 51.6%) 41 – 43 . These findings confirm the discriminatory power of WGS in terms of the definition of clonal complexes and the diversity of genotypes circulating in the country and highlight the need for a public health service to control and diagnose resistant TB.…”

The MtZ Strain: Molecular Characteristics and Outbreak Investigation of the Most Successful Mycobacterium tuberculosis Strain in Aragon Using Whole-Genome Sequencing

“…Traditionally, restriction fragment length polymorphism (RFLP), spoligotyping, and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) have been used to investigate outbreaks due to its value in interpreting transmission dynamics ( Borgdorff et al., 2000 ; Gonzalo-Asensio et al., 2018 ; Iglesias et al., 2020 ). The development of whole-genome sequencing (WGS) technologies marked a milestone in outbreak investigation, as it offers unsurpassed resolution power ( Nikolayevskyy et al., 2019 ).…”