Comparison of routine field epidemiology and whole genome sequencing to identify tuberculosis transmission in a remote setting.

Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005-2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

Whole genome sequencing for improved understanding of Mycobacterium tuberculosis transmission in a remote circumpolar region.

Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings - regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005-2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.

A clonal outbreak of tuberculosis in a homeless population in the interior of British Columbia, Canada, 2008-2015.

A tuberculosis (TB) case was reported May 2008 in Kelowna, British Columbia, leading to a multi-year outbreak in homeless persons. The epidemiological characteristics and social networks of cases are described. Outbreak-related cases were identified from epidemiological information in medical records and from genotyping of TB isolates. Social network information from case interviews were used to identify potential locations of TB transmission, where symptom screening and tuberculin skin testing was conducted. Fifty-two cases that were predominantly male (47/52), Canadian-born (44/50), and were homeless or associated with homeless individuals (42/52) were reported from May 2008 to May 2014. Many isolates (40/49) had partial resistance to isoniazid. Transmission primarily occurred at two homeless shelters, with potential further transmission at sites visited by the general population. TB outbreaks in homeless populations can occur in small, low-incidence cities. Social network information helped prioritize sites for TB screening, thereby improving detection of persons with TB disease or latent infection for treatment.

Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010.

In pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross-reactive antibodies to a representative swine H3N2 (swH3N2) and a related ancestral human H3N2 (A/Sydney/5/1997) influenza virus. Few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres ≥40 to either virus. Titres increased with age among children but decreased in adults. Fewer than 20% showed a four-fold rise in antibody titres to either virus following immunisation. Further investigation is warranted to guide ongoing risk assessment and response to emerging swine H3N2 viruses.

Spatio-temporal analysis of tuberculous infection risk among clients of a homeless shelter during an outbreak.

SETTING: British Columbia (BC) has a low incidence of tuberculosis (TB), with the burden of endogenously acquired disease concentrated among vulnerable populations, including the homeless. In May 2008, a TB outbreak began in a BC homeless shelter, with a single index case seeding multiple secondary cases within the shelter. OBJECTIVE: To use nightly shelter records to quantify the risk of latent tuberculous infection (LTBI) among shelter clients as a function of their sleeping distance from and duration of exposure to the index case. DESIGN: Distance and duration of exposure were visualised and assessed using logistic regression with LTBI status as outcome. We used a novel machine learning approach to establish exposure thresholds that optimally separated infected and non-infected individuals. RESULTS: Of 161 exposed shelter clients, 58 had a recorded outcome of infected (n = 39) or non-infected (n = 19). Only duration of exposure to the index was associated with increased odds of infection (OR 1.26); stays of ⩾ 5 nights put shelter clients at higher odds of infection (OR 4.97). CONCLUSION: The unique data set and analytical approach suggested that, in a shelter environment, long-term clients are at highest risk of LTBI and should be prioritised for screening during an outbreak investigation.

PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis.

MOTIVATION: PSORTb v.1.1 is the most precise bacterial localization prediction tool available. However, the program's predictive coverage and recall are low and the method is only applicable to Gram-negative bacteria. The goals of the present work are as follows: increase PSORTb's coverage while maintaining the existing precision level, expand it to include Gram-positive bacteria and then carry out a comparative analysis of localization. RESULTS: An expanded database of proteins of known localization and new modules using frequent subsequence-based support vector machines was introduced into PSORTb v.2.0. The program attains a precision of 96% for Gram-positive and Gram-negative bacteria and predictive coverage comparable to other tools for whole proteome analysis. We show that the proportion of proteins at each localization is remarkably consistent across species, even in species with varying proteome size. AVAILABILITY: Web-based version: http://www.psort.org/psortb. Standalone version: Available through the website under GNU General Public License. CONTACT: psort-mail@sfu.ca, brinkman@sfu.ca SUPPLEMENTARY INFORMATION: http://www.psort.org/psortb/supplementaryinfo.html.