Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden

Abstract

Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.

Probable long-term prevalence for a predominant Mycobacterium tuberculosis clone of a Beijing genotype in Colon, Panama

“…Our findings confirm the homoplasy described before in MIRU-VNTR typing, particularly for the Beijing lineage (Alaridah et al, 2019;Gurjav et al, 2016;Nikolayevskyy, Kranzer, Niemann, & Drobniewski, 2016), revealed by the high discriminatory power of WGS, as described for other settings (Gardy et al, 2011;Stucki et al, 2016). Moreover, our data allows to suggest that the Beijing A strain has probably been present for a long time, with only a minority of cases due to recent transmission.…”

Pulmonary Tuberculosis Outbreak in a High School, China

“…Another study from Hawaii reported 24-loci MIRU-VNTR typing has specificity of 28.6% for identifying actual transmission clusters, and this traditional typing has poor performance especially when identifying transmission in Beijing and Manila family clusters [21]. Contrary to traditional genotyping methods, WGS Provides detailed insights into transmission dynamics [22,23]. Study in low TB incidence setting showed that WGS provides better correlation with epidemiologic data than MIRU-VNTR typing [23].…”

“…Contrary to traditional genotyping methods, WGS Provides detailed insights into transmission dynamics [22,23]. Study in low TB incidence setting showed that WGS provides better correlation with epidemiologic data than MIRU-VNTR typing [23]. Previous studies have indicated that MIRU-VNTR typing may overestimate recent TB transmission, particularly in regions with high TB incidence settings [24,25].…”

PathOGiST: A Novel Method for Clustering Pathogen Isolates by Combining Multiple Genotyping Signals

“…Notice the connection with the minimum correlation clustering problem: solving the minimum consensus problem for a given set of clusterings π (1) , . .…”

“…the alleles at a small number of pre-specified housekeeping genes) [23] have been the predominant mode of genotyping bacterial pathogens. These low-resolution signals, which we may refer to as "fingerprints", could lead to incorrectly clustered strains [1] since unrelated bacterial isolates may happen to share identical fingerprints. With the advent of next-generation sequencing (NGS) [22], new genotypic signals have become available.…”