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). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. RESULTS: During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97-1.0). CONCLUSIONS: Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

The latent tuberculosis infection cascade of care in Iqaluit, Nunavut, 2012-2016.

BACKGROUND: A remote arctic region of Canada predominantly populated by Inuit with the country's highest incidence of tuberculosis. METHODS: The study was undertaken to describe the latent tuberculosis infection (LTBI) cascade of care and identify factors associated with non-initiation and non-completion of LTBI treatment. Data were extracted retrospectively from medical records for all patients with a tuberculin skin test (TST) implanted in Iqaluit, Nunavut between January 2012 and March 2016. Associations between demographic and clinical factors and both treatment non-initiation among and treatment non-completion were identified using log binomial regression models where convergence could be obtained and Poisson models with robust error variance where convergence was not obtained. RESULTS: Of 2303 patients tested, 439 (19.1%) were diagnosed with LTBI. Treatment was offered to 328 patients, was initiated by 246 (75.0% of those offered) and was completed by 186 (75.6% of initiators). In multivariable analysis, older age (adjust risk ratio [aRR] 1.17 per 5-year increase, 95%CI:1.09-1.26) and undergoing TST due to employment screening (aRR 1.63, 95%CI:1.00-2.65, compared to following tuberculosis exposure) were associated with increased non-initiation of treatment. Older age (aRR 1.13, 95%CI: 1.03-1.17, per 5-year increase) was associated with increased non-completion of treatment. CONCLUSIONS: A similar rate of treatment initiation and higher rate of treatment completion were found compared to previous North American studies. Interventions targeting older individuals and those identified via employment screening may be considered to help to address the largest losses in the cascade of care.

Effect of implementation of a 12-dose once-weekly treatment (3HP) in addition to standard regimens to prevent TB on completion rates: Interrupted time series design.

OBJECTIVES: We aimed to determine if offering a 12-dose once-weekly treatment (3HP) as an additional treatment option would result in an increase in the overall proportion of patients completing TB preventive treatment (TPT) above the baseline rate. METHODS: We analyzed outcomes in consecutive adults referred to a TB clinic from January 2010 to May 2019. Starting December 2016, 3HP was offered as an alternative to standard clinic regimens which included 9 months of daily isoniazid or 4 months of daily rifampin. The primary outcome was the proportion of patients who completed TPT among all patients who started treatment. Using segmented autoregression analysis, we compared completion at the end of the study with projected completion had the intervention not been introduced. RESULTS: A total of 2803 adults were referred for assessment over the study period. There was an absolute increase in completions among those who started a treatment of 19.0% at the end of the study between the observed intervention completion rate and the projected completion rate from the baseline study period (the completion rate had the 3HP intervention not been introduced) (76% observed vs 57% projected; 95% CI 6.6 to 31.4%; p = 0.004) and an absolute increase among those who were offered treatment (17.3%; 95% CI, 2.3 to 32.3%; p = 0.025). CONCLUSIONS: The introduction of 3HP for TPT as an alternative to the regular regimens offered resulted in a significant increase in the proportion of patients completing treatment. Our study provides evidence to support accelerated use of 3HP in Canada.

Knowledge, Attitudes, and Perceptions Associated With Antimicrobial Stewardship Among Veterinary Students: A Multi-Country Survey From Nigeria, South Africa, and Sudan.

In African countries, antimicrobial resistance (AMR) issue remains pertinent. Despite this, little efforts have been made to assess the future veterinary prescribers on their knowledge, attitudes and practices (KAP) related to antimicrobial usage. This multi-country survey attempts to explore the KAP of future veterinarians on stewardship of antimicrobial and identify knowledge gaps. Eight veterinary schools participated from Nigeria, Sudan and South Africa. Data regarding perceptions and knowledge were analyzed using Chi-square χ2 test, Spearman's (Rho) Rank order correlation and factor analysis using principal component factoring extraction method. Fifty-two percent of the study participants were final year veterinary students, respectively, and majority (77.2%) had no previous knowledge of biomedical sciences. Majority age were 22-27 years (24.7 ± 2.8) 79% and multiple career fields post-graduation were preferred. Overall, poor perceptions and knowledge of antimicrobial stewardship were observed with variations among countries and only 36.3% (n = 123) of the students were confident in their ability to choose the ideal antimicrobial agents for a specific patient/group of animals. The majority of the final year students were confident of their knowledge regarding AMR (68%), making of Gram staining (69.2%) and in choosing the most ideal route for administering a specific antimicrobial (74.7%). The final year students had significantly (p < 0.05) higher confidence level for knowledge compared with the pre-final year students. Tetracyclines, penicillins, and sulphonamides represent the three most abused veterinary antimicrobials with similar ranking across countries. South African (69.7 ± 20.5) and Sudanese (68.1 ± 15.4) had significantly (p < 0.0001) higher mean scores compared to the Nigerian students (44.3 ± 6.8) in the student's ability to correctly match some specific antimicrobials against their classes but Nigerian students performed better in ranking antimicrobials. This survey revealed poor to average knowledge of antimicrobial stewardship among veterinary students with significant knowledge gaps across the countries. It is recommended that the relevant regulatory and standardization authorities should make concerted efforts and interventions to regularly review curricula to ensure the delivery of targeted formative and normative training, and improved lectures on antimicrobial usage and stewardship in order to improve the awareness and behaviors of future prescribers. The identified knowledge gaps of veterinary medical students on antimicrobial stewardship must be bridge to safeguard the future.

Social determinants of health among residential areas with a high tuberculosis incidence in a remote Inuit community.

BACKGROUND: Tuberculosis (TB) remains a significant health burden among Inuit in Canada. Social determinants of health (SDH) play a key role in TB infection, disease and ongoing transmission in this population. The objective of this research was to estimate the prevalence of social determinants of Inuit health as they relate to latent TB infection (LTBI) among people living in residential areas at high risk for TB in Iqaluit, Nunavut. METHODS: Inperson home surveys were conducted among those who lived in predetermined residential areas at high risk for TB identified in a door-to-door TB prevention campaign in Iqaluit, Nunavut in 2011. Risk ratios for SDH and LTBI were estimated, and multiple imputation was used to address missing data. RESULTS: 261 participants completed the questionnaire. Most participants identified as Inuit (82%). Unadjusted risk ratios demonstrated that age, education, smoking tobacco, crowded housing conditions and Inuit ethnicity were associated with LTBI. After adjusting for other SDH, multivariable analysis showed an association between LTBI with increasing age (relative risk, RR 1.07, 95% CI 1.04 to 1.11), crowded housing (RR 1.48, 95% CI 1.10 to 2.00) and ethnicity (RR 2.76, 95% CI 1.33 to 5.73) after imputing missing data. CONCLUSION: Among high-risk residential areas for TB in a remote Arctic region of Canada, crowded housing and Inuit ethnicity were associated with LTBI after adjusting for other SDH. In addition to strong screening and treatment programmes, alleviating the chronic housing shortage will be a key element in the elimination of TB in the Canadian Inuit Nunangat.

Implication of the knowledge and perceptions of veterinary students of antimicrobial resistance for future prescription of antimicrobials in animal health, South Africa.

Understanding the knowledge and perceptions of veterinary students of antimicrobial resistance (AMR) as potential future prescribers of antimicrobials may serve as an opportunity to improve stewardship of AMR. Pre-final (n = 42) and final (n = 29) year veterinary students of the University of Pretoria completed questionnaires to determine their knowledge and perceptions of AMR. Of the 71 respondents, mixed practice (48%) and small animal practice (45%) were the most preferred career choices post-graduation, with the field of gross pathology being the least preferred. Over 80% of the respondents believed that veterinary practitioners' misuse of antimicrobials contributes to AMR and a higher percentage (98.6%) believed that farmers' misuse of antimicrobials encourages the development of AMR, in particular, in food animals (60.6%) compared to companion animals (50.7%). Agreement in the ranking of abuse of antimicrobials between pre-final and final year students was fair (36.4%; kappa 0.3), and the most abused antimicrobials in descending order listed by the students were tetracyclines, penicillins, sulphonamides and aminoglycosides. There was wide disparity between training and potential field application, as well as variations in the correct matching of antimicrobials to their respective antibiotic classes. Responses to the clinical application of antimicrobials also varied widely. Despite the apparent teaching of AMR to veterinary students, gaps may exist in the translation of theoretical concepts to clinical applications, hence the need for focused and targeted antimicrobial prescription and stewardship training to bridge these potential identified gaps.

Developing and Field Testing a Community Based Youth Initiative to Increase Tuberculosis Awareness in Remote Arctic Inuit Communities.

BACKGROUND: Inuit in Canada have the highest reported tuberculosis (TB) incidence rate in Canada, even higher than other Canadian Indigenous groups. The aim of this study was to increase TB awareness among Inuit youth and their communities by equipping those who can best reach this population with a community based, youth focused, education initiative built on interventions adapted from a previous TB awareness study. METHODS: The Taima TB Youth Education Initiative was a field test case study of a knowledge translation (KT) strategy aimed at community members who provide health education in these communities. In the first stage of this study, interventions from a larger TB awareness campaign were adapted to focus on youth living in remote Inuit communities. During the second stage of the study, investigators field tested the initiative in two isolated Inuit communities. It was then applied by local implementation teams in two other communities. Evaluation criteria included feasibility, acceptability, knowledge uptake and health behavior change. RESULTS: Implementation of the adapted KT interventions resulted in participation of a total of 41 youth (19 females, 22 males) with an average age of 16 years (range 12-21 years) in four different communities in Nunavut. Community celebration events were attended by 271 community members where TB messaging were presented and discussed. All of the health care workers and community members surveyed reported that the adapted interventions were acceptable and a useful way of learning to some extent. Knowledge uptake measures indicated an average TB knowledge score of 64 out of 100. Local partners in all four communities indicated that they would use the Taima TB Youth Education Initiative again to raise awareness about TB among youth in their communities. CONCLUSIONS: The TB awareness interventions adapted for the Taima TB Youth Education Initiative were acceptable to the Inuit communities involved in the study. They resulted in uptake of knowledge among participants. Implementation by local implementation teams was feasible as evidenced by the participation and attendance of youth and community members in all communities. The ability to implement the interventions by local implementation teams indicates there is potential to scale up in other remote communities in the arctic setting.

The feasibility of the interferon gamma release assay and predictors of discordance with the tuberculin skin test for the diagnosis of latent tuberculosis infection in a remote Aboriginal community.

BACKGROUND: The tuberculin skin test (TST) is the standard test used to screen for latent TB infection (LTBI) in the northern Canadian territory of Nunavut. Interferon gamma release assays (IGRA) are T cell blood-based assays to diagnose LTBI. The Bacillus Calmette-Guerin (BCG) vaccine is part of the routine immunization schedule in Nunavut. The objective of this study was to test the feasibility, and predictors of discordance between the Tuberculin Skin Test (TST) and the IGRA assay in a medically under-serviced remote arctic Aboriginal population. METHODS: Both the TST and QuantiFERON-TB Gold (Qiagen group) IGRA tests were offered to people in their homes as part of a public health campaign aimed at high TB risk residential areas in Iqaluit, Nunavut, Canada. Feasibility was measured by the capacity of the staff to do the test successfully as measured by the proportion of results obtained. RESULTS: In this population of predominantly young Inuit who were mostly BCG vaccinated, the use of IGRA for the diagnosis of LTBI was feasible. IGRA testing resulted in more available test results reaching patients (95.6% vs 90.9% p = 0.02) but took longer (median 8 days (IGRA) vs 2 days (TST), p value < 0.0001). 44/256 participants (17.2%) had discordant results. Multivariable regression analysis suggested that discordant results were most likely to have received multiple BCG vaccinations (RR 20.03, 95% CI, 3.94-101.82)), followed by BCG given post infancy (RR 8.13, 95% CI, 2.54-26.03)) and then to a lesser degree when BCG was given in infancy (RR 6.43, 95% CI, 1.72-24.85). INTERPRETATION: IGRA is feasible in Iqaluit, Nunavut, a remote Arctic community. IGRA testing results in more test results available to patients compared to TST. This test could result in fewer patients requiring latent TB treatment among those previously vaccinated with BCG in a region with limited public health human resources.