SARS-CoV-2 Outbreak Investigation Using Contact Tracing and Whole-Genome Sequencing in an Ontario Tertiary Care Hospital.

Genomic epidemiology can facilitate an understanding of evolutionary history and transmission dynamics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. We used next-generation sequencing techniques to study SARS-CoV-2 genomes isolated from patients and health care workers (HCWs) across five wards of a Canadian hospital with an ongoing SARS-CoV-2 outbreak. Using traditional contact tracing methods, we show transmission events between patients and HCWs, which were also supported by the SARS-CoV-2 lineage assignments.

Genomic epidemiology of Mycobacterium abscessus in a Canadian cystic fibrosis centre.

The Mycobacterium abscessus complex causes significant morbidity and mortality among patients with Cystic Fibrosis (CF). It has been hypothesized that these organisms are transmitted from patient to patient based on genomics. However, few studies incorporate epidemiologic data to confirm this hypothesis.

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis.

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control.

Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with VRE, MRSA, ESBL (ESBL-Ec), or ESBL (ESBL-Kp).

What Can Genetic Relatedness Tell Us About Risk Factors for Tuberculosis Transmission?

Background: To stop tuberculosis (TB), the leading infectious cause of death globally, we need to better understand transmission risk factors. Although many studies have identified associations between individual-level covariates and pathogen genetic relatedness, few have identified characteristics of transmission pairs or explored how closely covariates associated with genetic relatedness mirror those associated with transmission.

Methods: We simulated a TB-like outbreak with pathogen genetic data and estimated odds ratios (ORs) to correlate each covariate and genetic relatedness.

Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia.

Objectives: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.

Design: Pilot prospective multicenter surveillance study.

Setting: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.

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

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.

Estimation of the generation interval using pairwise relative transmission probabilities.

The generation interval (the time between infection of primary and secondary cases) and its often used proxy, the serial interval (the time between symptom onset of primary and secondary cases) are critical parameters in understanding infectious disease dynamics. Because it is difficult to determine who infected whom, these important outbreak characteristics are not well understood for many diseases. We present a novel method for estimating transmission intervals using surveillance or outbreak investigation data that, unlike existing methods, does not require a contact tracing data or pathogen whole genome sequence data on all cases.

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

Background: In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing.

Methods: Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS).

Estimating the relative probability of direct transmission between infectious disease patients.

Background: Estimating infectious disease parameters such as the serial interval (time between symptom onset in primary and secondary cases) and reproductive number (average number of secondary cases produced by a primary case) are important in understanding infectious disease dynamics. Many estimation methods require linking cases by direct transmission, a difficult task for most diseases.

Methods: Using a subset of cases with detailed genetic and/or contact investigation data to develop a training set of probable transmission events, we build a model to estimate the relative transmission probability for all case-pairs from demographic, spatial and clinical data.

Using Genetic Distance from Archived Samples for the Prediction of Antibiotic Resistance in .

The rising rates of antibiotic resistance increasingly compromise empirical treatment. Knowing the antibiotic susceptibility of a pathogen's close genetic relative(s) may improve empirical antibiotic selection. Using genomic and phenotypic data for isolates from three separate clinically derived databases, we evaluated multiple genomic methods and statistical models for predicting antibiotic susceptibility, focusing on potentially rapidly available information, such as lineage or genetic distance from archived isolates.

Rapid inference of antibiotic resistance and susceptibility by genomic neighbour typing.

Surveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empirical antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could affect patient treatment and outcomes. Here, we present a method called 'genomic neighbour typing' for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata.

Previously undetected super-spreading of revealed by deep sequencing.

Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether 'deep' sequencing can provide additional resolution compared to standard sequencing, using a well-characterized outbreak from the Arctic (2011-2012, 50 cases).

Beta-Lactam/Beta-Lactamase Inhibitor Therapy for Potential AmpC-Producing Organisms: A Systematic Review and Meta-Analysis.

The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.

Multiple exposures, reinfection and risk of progression to active tuberculosis.

A recent study reported on a tuberculosis (TB) outbreak in a largely Inuit village. Among newly infected individuals, exposure to additional active cases was associated with an increasing probability of developing active disease within a year. Using binomial risk models, we evaluated two potential mechanisms by which multiple infections during the first year following initial infection could account for increasing disease risk with increasing exposures.

Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission.

Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited - making it difficult to determine precisely who transmitted to whom.

The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: a population-level genomic study.

Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm.

Methods: A population-level study of VREfm (10 November-9 December 2015) was conducted.

Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand.

Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high.

Methods: A population-level study of N.

Real-Time Sequencing of Mycobacterium tuberculosis: Are We There Yet?

Whole-genome sequencing has taken a leading role in epidemiologic studies of tuberculosis, but thus far, its real-time clinical utility has been low, in part because of the requirement for culture. In their report in this issue, Votintseva et al. (A.

Progression to tuberculosis disease increases with multiple exposures.

During a single year, a Canadian village had 34 individuals with microbiologically confirmed tuberculosis (TB) among 169 people with a new infection (20%). A contact investigation revealed multiple exposures for each person. We investigated whether the intensity of exposure might contribute to this extraordinary risk of disease.

Housing and tuberculosis in an Inuit village in northern Quebec: a case-control study.

Background: Between November 2011 and November 2012, an Inuit village in Nunavik, Quebec experienced a surge in the occurrence of active TB; contact investigations showed that TB infection was highly prevalent (62.6%), particularly among those over age 14 years (78.8%).

Does Choice Matter? Reference-Based Alignment for Molecular Epidemiology of Tuberculosis.

When using genome sequencing for molecular epidemiology, short sequence reads are aligned to an arbitrary reference strain to detect single nucleotide polymorphisms. We investigated whether reference genome selection influences epidemiological inferences of Mycobacterium tuberculosis transmission by aligning sequence reads from 162 closely related lineage 4 (Euro-American) isolates to 7 different genomes. Phylogenetic trees were consistent with use of all but the most divergent genomes, suggesting that reference choice can be based on considerations other than M.

The implications of whole-genome sequencing in the control of tuberculosis.

The availability of whole-genome sequencing (WGS) as a tool for the diagnosis and clinical management of tuberculosis (TB) offers considerable promise in the fight against this stubborn epidemic. However, like other new technologies, the best application of WGS remains to be determined, for both conceptual and technical reasons. In this review, we consider the potential value of WGS in the clinical laboratory for the detection of Mycobacterium tuberculosis and the prediction of antibiotic resistance.