Dataset Information

Tuberculosis drug resistance in Canada: 2017.

ABSTRACT: Background:Drug-resistant tuberculosis (TB) is a global public health issue. To monitor this in Canada, surveillance systems have been in place for the last 20 years. Objective:To describe drug resistance patterns among TB isolates in Canada in 2017 by type of resistance as well as geographic location, demographic data and origin and to compare current data to those of the previous 10 years. Methods:Data were derived and analyzed from two sources. The Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) is an isolate-based laboratory surveillance system and was used to obtain information on the results of drug susceptibility testing (DST) as well as province or territory, sex and age of the individual from which the sample originated. The Canadian Tuberculosis Reporting System (CTBRS) is a case-based surveillance system with information on active and retreatment TB cases in Canada and was used to derive origin data, which is defined as either foreign-born, Canadian-born Indigenous or Canadian-born non-Indigenous. Analysis was descriptive and compared with data from these two sources for 2007-2016. Results:In 2017, 1,515 TB isolates were tested for resistance to anti-TB drugs, with 123 (8.1%) demonstrating resistance to any first-line anti-TB drug. Of these, 103 were monoresistant, six were polyresistant and 14 were multidrug-resistant tuberculosis (MDR-TB). No extensively drug-resistant tuberculosis (XDR-TB) isolates were reported. Drug resistance was reported in seven provinces/territories (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and New Brunswick). There were 63 isolates from females with drug resistance (9.5%) and 60 isolates from males with drug resistance (7.0%). Drug resistance was found in a greater percentage of isolates among those aged 25-34 (n=29, 23.6%). By origin, 1,072 (11%) foreign-born TB cases reported between 2005 and 2015 were drug-resistant. Among the Canadian-born non-Indigenous and Canadian-born Indigenous TB cases, 143 (9%) and 54 (2%) were drug-resistant, respectively. Compared with previous years, the number of isolates tested increased slightly (from 1,267 to 1,515); however, there was a decrease in the percentage of isolates with reported drug resistance (from 10.5% in 2007 to 8.1% in 2017). Conclusion:In 2017, TB drug resistance rates remained low in Canada.

SUBMITTER: LaFreniere M

PROVIDER: S-EPMC6449088 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Tuberculosis drug resistance in Canada: 2017.

LaFreniere M M Hussain H H Vachon J J

Canada communicable disease report = Releve des maladies transmissibles au Canada 20181101 11

<h4>Background</h4>Drug-resistant tuberculosis (TB) is a global public health issue. To monitor this in Canada, surveillance systems have been in place for the last 20 years.<h4>Objective</h4>To describe drug resistance patterns among TB isolates in Canada in 2017 by type of resistance as well as geographic location, demographic data and origin and to compare current data to those of the previous 10 years.<h4>Methods</h4>Data were derived and analyzed from two sources. The Canadian Tuberculosis ...[more]

PMID: 30996691

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Project description:Background:Drug-resistant tuberculosis (TB) is a public health issue of global importance that poses a threat to TB control efforts. Canada conducts nationwide surveillance to monitor emerging drug resistance trends and document progress towards reaching the goal of TB elimination. Objective:To describe TB drug resistance trends across Canada from 2008-2018, with a focus on 2018, by drug resistance, geographic and demographic patterns. Methods:TB drug resistance data are captured through two independent surveillance systems managed by the Public Health Agency of Canada: Canadian Tuberculosis Laboratory Surveillance System (CTBLSS) and the Canadian Tuberculosis Reporting System (CTBRS). Data from these systems were analyzed and descriptive statistics were reported by resistance profile, place of residence (province), age groups, sex and country of birth. Results:In 2018, 1,459 TB isolates underwent drug susceptibility testing, a 4.3% decrease from 2017. Resistance to any first-line drug was reported in 148 isolates (10.1%), compared to 123 (8.1%) in 2017. Of these, 121 were monoresistant, five were polyresistant, 21 were multidrug-resistant tuberculosis (MDR-TB) and one was extensively drug-resistant TB (XDR-TB). Drug resistance was reported in all provinces and territories except Prince Edward Island, Northwest Territories and Yukon. Among individuals younger than 15 years, very little TB drug resistance was detected. Among individuals aged 15 years and older, the distribution of TB drug resistance varied with no discernable trends. The proportion of drug resistance was slightly higher in females than in males. By origin, 10.7% of foreign-born TB cases reported between 2006 and 2016 were drug-resistant. Among the Canadian-born non-Indigenous cases, 9.3% were drug resistant; among Canadian-born Indigenous, 2.4% were drug resistant. Conclusion:In 2018, the proportion of isolates with TB drug resistance in Canada remained low and below global averages, with stable drug resistance, both geographically and demographically.

Project description:BACKGROUND:The prevalence of drug-resistant tuberculosis (DR-TB) has brought severe challenges to the prevention and control of tuberculosis. Studies have explored the status of antituberculosis drug (ATD) resistance in different regions of China. However, few studies have focused on DR-TB in Sichuan to date. Due to the large population in Sichuan, detailed investigations of the DR-TB burden in Sichuan are needed. The objective of this study was to investigate the drug resistance characteristics of TB isolates from tuberculosis patients with and without HIV (TB-HIV patients and TBw/oHIV patients) in Chengdu, Sichuan, China. METHODS:Isolates from respiratory samples of TBw/oHIV patients and TB-HIV patients hospitalized between January 2014 and December 2017 were collected. Nontuberculosis mycobacteria (NTM) were excluded. Drug sensitivity testing (DST) was performed according to the dilution method in microplates with 4 first-line ATDs and 8 second-line ATDs. TB strains were separated according to patient treatment history, patient age, calendar year and GeneXpert MTB/RIF (GeneXpert) assay results for further analysis. RESULTS:For the 7470 patients recruited, the multidrug-resistant tuberculosis (MDR-TB) rate was 2.1-fold (14.6% vs. 6.8%) higher than the national baseline level. The repeatedly admitted patients were more likely to have a resistance profile than the first-time-admitted cases in both the TB-only group (P<0.05) and the TB-HIV corresponding group (P<0.05). Among the 7273 TBw/oHIV cases and 197 TB-HIV cases, the positivity rates of acid-fast bacilli (AFB) in the TB-HIV group were significantly lower than those in the TBw/oHIV group (P<0.05). The repeatedly admitted TB-HIV patients had lower resistance rates to INH than the repeatedly admitted TBw/oHIV patients (24.4% vs. 41.5%, P<0.05). The Rifampicin-resistant TB strains in the TBw/oHIV group were more likely to be resistant to INH in the repeatedly admitted group than those in the first-time admitted patients (P<0.05). The proportions of XDR (3.6% vs. 1.3%, P<0.05) and XDR-TB/MDR-TB (7.3% vs. 2.2%, P<0.05) in all TB-HIV patients were significantly higher than those in all TBw/oHIV patients. The ratio of XDR-TB was significantly higher in the TB-HIV group than in the TBw/oHIV group (30.4% vs. 9.0%, P<0.05) and the all TB group (9.0% vs. 10.1%, P<0.05). Regarding age, the <25-year-old TB-HIV patients (9.1% vs. 0.7%, P<0.05) and 25~44-year-old TB-HIV patients (5.2% vs. 2.4%, P<0.05) were more likely to have a higher XDR proportion than their TBw/oHIV counterparts. The ATD-resistance profile in terms of different years from high to low was 2014>2015>2016?2017 for TBw/oHIV patients. The same trend was also observed for TB-HIV patients: 2014>2015>2016?2017. The GeneXpert TB-positive rate in the TBw/oHIV group was higher than that in the TB-HIV group [81%(639/792) vs. 65% (13/20), P<0.05]. In TBw/oHIV cases, the agreement was 92.3% and the Kappa value was 0.75. In TB-HIV cases, the agreement was 85.0% and the Kappa value was 0.32. CONCLUSION:In Sichuan, ATD resistance has improved since 2014, but to date, it remains severe. The different resistance profiles of TBw/oHIV patients and TB-HIV patients indicates the need for personalized treatment plans. Specifically, the GeneXpert assay might be more suitable for TBw/oHIV patients than for TB-HIV patients.

Project description:Sociodemographic correlates of engagement in human immunodeficiency virus (HIV) care are well studied, however the association with accessing drug resistance testing (DRT) and the development of drug resistance have not been characterized. Between 1996-2014, 11 801 HIV patients accessing therapy in British Columbia were observed longitudinally. A subset of 9456 patients had testable viral load; of these 8398 were linked to census data. Sociodemographic (census tract-level) and clinical (individual-level) correlates of DRT were assessed using multivariable General Estimating Equation logistic regression adjusted odds ratios (aOR). The mean number of tests per patient was 2.1 (Q1-Q3; 0-3). Separately, any drug resistance was determined using IAS-USA (2013) list for 5703 initially treatment naïve patients without baseline resistance; 5175 were census-linked (mean of 1.5 protease-reverse transcriptase sequences/patient, Q1-Q3; 0-2). Correlates of detecting drug resistance in this subset were analyzed using Cox PH regression adjusted hazard ratios (aHR). Our results indicate baseline CD4 <200 cells/?L (aOR: 1.5, 1.3-1.6), nRTI-only baseline regimens (aOR: 1.4, 1.3-1.6), and unknown (therapy initiation before routine pVL in BC) baseline pVL (aOR: 1.8, 1.5-2.1) were among individual-level clinical covariates strongly associated with having accessed DRT; while imperfect adherence (aHR: 2.2, 1.9-2.5), low baseline CD4 count (aHR: 1.9, 1.6-2.3), and high baseline pVL (aHR: 2.0, 1.6-2.6) were associated with a higher likelihood of developing drug resistance. A higher median income (aOR: 0.83, 0.77-0.89) and higher percentage of those with aboriginal ancestry (aOR: 0.85, 0.76-0.95) were census tract-level sociodemographic covariates associated with decreased access to DRT. Similarly, aboriginal ancestry (aHR: 1.2, 1.1-1.5) was associated with development of drug resistance. In conclusion, clinical covariates continue to be the strongest correlates of development of drug resistance and access to DRT for individuals. Regions of high median income and high aboriginal ancestry were weak census-level sociodemographic indicators of reduced DRT uptake, however high aboriginal ancestry was the only sociodemographic indicator for development of drug resistance.

Project description:"Drug resistance is an unavoidable consequence of the use of drugs; however, the emergence of multi-drug resistance can be managed by accurate diagnosis and tailor-made regimens."Antimicrobial resistance (AMR), is one of the most paramount health perils that has emerged in the 21st century. The global increase in drug-resistant strains of various bacterial pathogens prompted the World Health Organization (WHO) to develop a priority list of AMR pathogens. Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes tuberculosis (TB), merits being one of the highest priority pathogens on this list since drug-resistant TB (DR-TB) accounts for ∼29% of deaths attributable to AMR. In recent years, funded collaborative efforts of researchers from academia, not-for-profit virtual R&D organizations and industry have resulted in the continuous growth of the TB drug discovery and development pipeline. This has so far led to the accelerated regulatory approval of bedaquiline and delamanid for the treatment of DR-TB. However, despite the availability of drug regimes, the current cure rate for multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) treatment regimens is 50% and 30%, respectively. It is to be noted that these regimens are administered over a long duration and have a serious side effect profile. Coupled with poor patient adherence, this has led to further acquisition of drug resistance and treatment failure. There is therefore an urgent need to develop new TB drugs with novel mechanism of actions (MoAs) and associated regimens.This Account recapitulates drug resistance in TB, existing challenges in addressing DR-TB, new drugs and regimens in development, and potential ways to treat DR-TB. We highlight our research aimed at identifying novel small molecule leads and associated targets against TB toward contributing to the global TB drug discovery and development pipeline. Our work mainly involves screening of various small molecule chemical libraries in phenotypic whole-cell based assays to identify hits for medicinal chemistry optimization, with attendant deconvolution of the MoA. We discuss the identification of small molecule chemotypes active against Mtb and subsequent structure-activity relationships (SAR) and MoA deconvolution studies. This is followed by a discussion on a chemical series identified by whole-cell cross-screening against Mtb, for which MoA deconvolution studies revealed a pathway that explained the lack of in vivo efficacy in a mouse model of TB and reiterated the importance of selecting an appropriate growth medium during phenotypic screening. We also discuss our efforts on drug repositioning toward addressing DR-TB. In the concluding section, we preview some promising future directions and the challenges inherent in advancing the drug pipeline to address DR-TB.

Dataset Information

Tuberculosis drug resistance in Canada: 2017.

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Tuberculosis drug resistance in Canada: 2017.

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