Dataset Information

Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland.

ABSTRACT: In East Greenland, a dramatic increase of tuberculosis (TB) incidence has been observed in recent years. Classical genotyping suggests a genetically similar Mycobacterium tuberculosis (Mtb) strain population as cause, however, precise transmission patterns are unclear. We performed whole genome sequencing (WGS) of Mtb isolates from 98% of culture-positive TB cases through 21?years (n?=?182) which revealed four genomic clusters of the Euro-American lineage (mainly sub-lineage 4.8 (n?=?134)). The time to the most recent common ancestor of lineage 4.8 strains was found to be 100?years. This sub-lineage further diversified in the 1970s, and massively expanded in the 1990s, a period of lowered TB awareness in Greenland. Despite the low genetic strain diversity, WGS data revealed several recent short-term transmission events in line with the increasing incidence in the region. Thus, the isolated setting and the uniformity of circulating Mtb strains indicated that the majority of East Greenlandic TB cases originated from one or few strains introduced within the last century. Thereby, the study shows the consequences of even short interruptions in TB control efforts in previously TB high incidence areas and demonstrates the potential role of WGS in detecting ongoing micro epidemics, thus guiding public health efforts in the future.

SUBMITTER: Bjorn-Mortensen K

PROVIDER: S-EPMC5018808 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland.

Bjorn-Mortensen K K Soborg B B Koch A A Ladefoged K K Merker M M Lillebaek T T Andersen A B AB Niemann S S Kohl T A TA

Scientific reports 20160912

In East Greenland, a dramatic increase of tuberculosis (TB) incidence has been observed in recent years. Classical genotyping suggests a genetically similar Mycobacterium tuberculosis (Mtb) strain population as cause, however, precise transmission patterns are unclear. We performed whole genome sequencing (WGS) of Mtb isolates from 98% of culture-positive TB cases through 21 years (n = 182) which revealed four genomic clusters of the Euro-American lineage (mainly sub-lineage 4.8 (n = 134)). The ...[more]

PMID: 27615360

Similar Datasets

Project description:BACKGROUND:The recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of Mycobacterium tuberculosis due to non-compliance or inadequate therapy or exogenous reinfection with a new strain. Genotyping or whole genome sequencing (WGS) of M. tuberculosis isolates from initial and recurrent cases can differentiate between reinfection and reactivation. This study examined cases of recurrent TB in New South Wales, Australia, using genotyping and WGS. METHODS:Culture-confirmed TB cases diagnosed at least 12 months apart between January 2011 and December 2016 were included. Isolates of M. tuberculosis from patients were compared using 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-24) typing and WGS. RESULTS:Eighteen cases of recurrent disease were identified but isolates from only 15 (83%) were available for study. MIRU-24 findings classified 13 (13/15; 87%) as reactivation and two (13%), as reinfection. Sequencing 13 cultivable paired isolates demonstrated 11 reactivations and two reinfections. There was genomic similarity in 10 out of 13 pairs while one case (1/13; 8%) had 12 SNPS differences. Two other cases (2/13;15%) had >?200 SNPs differences and were classified as reinfection. No phenotypic or genomic evidence of drug resistance was observed. CONCLUSION:TB control programs can achieve consistently low rates of recurrent disease in low incidence settings. WGS of implicated isolates augments the differentiation between reactivation and reinfection and indicates that the majority of recurrences are due to reactivation rather than reinfection. Predominance of reactivation over reinfection indicates high-quality public health practices and a low risk of local transmission. TRIAL REGISTRATION:This study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (HREC Ref: AU RED LNR/17/WMEAD/190; SSA Ref: LNR SSA/17/WMEAD/191).

Project description:BackgroundIn current epidemiology of tuberculosis (TB), heterogeneity in infectiousness among TB patients is a challenge, which is not well studied. We aimed to quantify this heterogeneity and the presence of "super-spreading" events that can assist in designing optimal public health interventions.MethodsTB epidemiologic investigation data notified between 1 January 2005 and 31 December 2015 from Victoria, Australia were used to quantify TB patients' heterogeneity in infectiousness and super-spreading events. We fitted a negative binomial offspring distribution (NBD) for the number of secondary infections and secondary active TB disease each TB patient produced. The dispersion parameter, k, of the NBD measures the level of heterogeneity, where low values of k (e.g. k?<?1) indicate over-dispersion. Super-spreading was defined as patients causing as many or more secondary infections as the 99th centile of an equivalent homogeneous distribution. Contact infection was determined based on a tuberculin skin test (TST) result of ?10?mm. A NBD model was fitted to identify index characteristics that were associated with the number of contacts infected and risk ratios (RRs) were used to quantify the strength of this association.ResultsThere were 4190 (2312 pulmonary and 1878 extrapulmonary) index TB patients and 18,030 contacts. A total of 15,522 contacts were tested with TST, of whom 3213 had a result of ?10?mm. The dispersion parameter, k for secondary infections was estimated at 0.16 (95%CI 0.14-0.17) and there were 414 (9.9%) super-spreading events. From the 3213 secondary infections, 2415 (75.2%) were due to super-spreading events. There were 226 contacts who developed active TB disease and a higher level of heterogeneity was found for this outcome than for secondary infection, with k estimated at 0.036 (95%CI 0.025-0.046). In regression analyses, we found that infectiousness was greater among index patients found by clinical presentation and those with bacteriological confirmation.ConclusionTB transmission is highly over dispersed and super-spreading events are responsible for a substantial majority of secondary infections. Heterogeneity of transmission and super-spreading are critical issues to consider in the design of interventions and models of TB transmission dynamics.

Project description:BackgroundMultidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission.MethodsWe did a population-based, retrospective study of patients who tested positive for tuberculosis between Jan 1, 2009, and Dec 31, 2012, in Shanghai, China. We did variable-number-of-tandem-repeat genotyping and whole-genome sequencing of isolates. We measured strain diversity within and between genomically clustered isolates. Genomic and epidemiological data were combined to construct transmission networks.Findings367 (5%) of 7982 patients with tuberculosis had MDR tuberculosis and 324 (88%) of these had isolates available for genomic analysis. 103 (32%) of the 324 MDR strains were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission of MDR strains. Patients who had delayed diagnosis or were older than 45 years had high risk of recent transmission. 235 (73%) patients with MDR tuberculosis probably had transmission of MDR strains. Transmission network analysis showed that 33 (87%) of the 38 clusters accumulated additional drug-resistance mutations through emergence or fixation of mutations during transmission. 68 (66%) of 103 clustered MDR strains had compensatory mutations of rifampicin resistance.InterpretationRecent transmission of MDR tuberculosis strains, with increasing drug-resistance, drives the MDR tuberculosis epidemic in Shanghai, China. Whole-genome sequencing can measure of the heterogeneity of drug-resistant mutations within and between hosts and help to determine the transmission patterns of MDR tuberculosis.FundingNational Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health.

Project description:BackgroundTuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks.MethodsIn a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit-variable-number tandem-repeat data.FindingsWe sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis. The estimated rate of change in DNA sequences was 0.5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0.3-0.7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p<0.0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters.InterpretationWhole-genome sequencing can delineate outbreaks of tuberculosis and allows inference about direction of transmission between cases. The technique could identify super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatment of infectious patients and their contacts.FundingMedical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.

Dataset Information

Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland.

Publications

Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets