Drug-resistance profiling and transmission dynamics of multidrug-resistant &lt;em&gt;Mycobacterium tuberculosis&lt;/em&gt; in Saudi Arabia revealed by whole genome sequencing

Al-Ghafli, Hawra; Kohl, Thomas A.; Merker, Matthias; Varghese, Bright; Halees, Anason; Niemann, Stefan; Al‐Hajoj, Sahal

doi:10.2147/idr.s181124

Cited by 19 publications

(22 citation statements)

References 27 publications

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“…The authors concluded that the healthcare worker had contacted the infection from a patient that displayed nearly identical mutation and MIRU-VNTR patterns. More elaborate sequence comparisons derived from WGS or cgMLST have also identified transmission of infection in low-TB-incidence settings [59–61].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

2019

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BackgroundIncreasing incidence of multidrug-resistant Mycobacterium tuberculosis infections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% of M. tuberculosis strains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait.MethodsNinety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplus assay and/or PCR sequencing of three rpoB regions, katG codon 315 (katG315) + inhA regulatory region, pncA, three embB regions and rpsL + rrs-500–900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing of gidB and rpsA was performed for cluster isolates.ResultsPansusceptible isolates contained wild-type sequences. Mutations in rpoB and katG and/or inhA were detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates in pncA, embB and rpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additional gidB and rpsA sequence data.ConclusionsOur study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2–6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

2019

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“…Older studies have used blunt genotyping tools (e.g., IS 6110 restriction fragment length polymorphism, spoligotyping, and mycobacterial interspersed repetitive unit–variable-number tandem-repeat) with limited or convenient sample sizes. DR TB studies using WGS in Saudi Arabia and Portugal have revealed transmission clusters of MDR TB; however, they had small samples and provided limited data on epidemiologic links ( 36 , 37 ). Extrapolating from our findings, primary-resistant TB strains may be the main contributors to the current global problem of high MDR TB and XDR TB prevalence.…”

Section: Discussionmentioning

confidence: 99%

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample, Thailand, 2014–2017

Nonghanphithak¹,

Chaiprasert²,

Smithtikarn³

et al. 2021

Emerg. Infect. Dis.

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Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis (pre-XDR TB), and extensively drug-resistant tuberculosis (XDR TB) complicate disease control. We analyzed whole-genome sequence data for 579 phenotypically drug-resistant M. tuberculosis isolates (28% of available MDR/pre-XDR and all culturable XDR TB isolates collected in Thailand during 2014–2017). Most isolates were from lineage 2 (n = 482; 83.2%). Cluster analysis revealed that 281/579 isolates (48.5%) formed 89 clusters, including 205 MDR TB, 46 pre-XDR TB, 19 XDR TB, and 11 poly–drug-resistant TB isolates based on genotypic drug resistance. Members of most clusters had the same subset of drug resistance-associated mutations, supporting potential primary resistance in MDR TB (n = 176/205; 85.9%), pre-XDR TB (n = 29/46; 63.0%), and XDR TB (n = 14/19; 73.7%). Thirteen major clades were significantly associated with geography (p<0.001). Clusters of clonal origin contribute greatly to the high prevalence of drug-resistant TB in Thailand.

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“…A summary of key characteristics of included studies is shown in table 1 (further detail in appendix 2 ). 1 , 19 – 130 Studies were classified into four themes based on their overall aims (these themes were not mutually exclusive): transmission (n=82), evolution (n=36), strain identification (n=11), and clinical outcomes (n=2; appendix 1 p 5). The number of patients was missing for 21 (18%) articles.…”

Section: Resultsmentioning

confidence: 99%

Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark

et al. 2021

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Summary 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.

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Drug-resistance profiling and transmission dynamics of multidrug-resistant <em>Mycobacterium tuberculosis</em> in Saudi Arabia revealed by whole genome sequencing

Cited by 19 publications

References 27 publications

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample, Thailand, 2014–2017

Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark

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