The present study determined whether a pattern of functional single-nucleotide polymorphisms (SNPs) was present that could predispose a Dené cohort to a suboptimal response to Mycobacterium tuberculosis. Compared with a Caucasian cohort, the Dené and Cree were found to maintain a significantly higher frequency of SNPs associated with low expression of vitamin D receptor (VDR), interferon (IFN)-gamma (+874), and tumor necrosis factor-alpha (-308) and high production of monocyte chemoattractant protein (MCP)-1 (-2518) and interleukin (IL)-6 (-174). Given the roles played by IFN-gamma and VDR in facilitating macrophage containment of M. tuberculosis and the opposing role of MCP-1 and IL-6, the observed allelic variation by ethnicity may in part contribute to the high rates of tuberculosis among the Dené.

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Setting Substance use remains a pervasive public health issue throughout Canada, exerting substantial economic, social, and political pressure on health care systems, while impacting lives of affected individuals. The advent of COVID-19 has been doubly perilous; it restricts existing programming, while exacting a worsening toll on mental health and substance use fronts across the demographic landscape. Intervention In response to the crisis, the Mobile Withdrawal Management Service (MWMS) was established in 2019 through a Winnipeg-based community health centre. MWMS is a community-based outreach withdrawal service that supports individuals for up to 30 days. Clients may choose where services are accessed in the community, including their own home. For those without safe housing, short-term accommodation is offered. Additionally, Indigenous cultural support, peer support, trauma counselling, and linkage to primary care are available. Outcomes The MWMS approach is resolutely patient-centred. The program meets people where they are at, both figuratively and literally. Agility and adaptability—particularly in the context of substance use treatment—is uniquely advantageous in maintaining service delivery to the broad demographic cross-section revealed in the data. Moreover, relative to inpatient detoxification services, MWMS holds significant potential for system-wide cost savings. Implications The presented approach addresses a significant gap in addiction services. There is substantial capacity for both increased access and system savings with implementation of this approach. Furthermore, the principles behind the program are readily transferable to different contexts and easily modifiable to local conditions. There is particular potential for servicing hard-to-reach populations, with respect to both physical and social geography.

Objectives: The natural resistance-associated macrophage protein 1 (NRAMP1) regulates susceptibility to infectious and autoimmune diseases. NRAMP1 gene polymorphisms have been implicated in susceptibility to tuberculosis. The frequency of NRAMP1 gene polymorphisms was therefore evaluated in three Manitoba First Nations subgroups (Dene, Cree, and Saulteaux) with differential but high rates of tuberculosis (636/100,000, 496/100,000, and 0/100,000 respectively). Methods: Venous blood samples were collected from 281 study participants from three First Nations subgroups (Dene (N=108), Cree (N=41), Saulteaux (N=49)), and a non-indigenous Canadian-born (European-descent) group (N=83). Genomic DNA was extracted and four single nucleotide polymorphisms in the NRAMP1 gene (5′ (GT)n,-274 (C/T), Intron 4 (469+14 G/C), D543N (G/A)) were genotyped using restriction fragment length polymorphism. NRAMP1 SNP allele frequencies were counted and compared between studied subgroups. Results: The Dene subgroup had significantly different allele frequencies of NRAMP1 (5′(GT)n,-274 (C/T), Intron 4(G/C), D543N (G/A)) compared to the European-descent group. The NRAMP1 allele frequencies at D543N (G/A) and Intron 4(G/C) differed significantly between the Cree and the European-descent group while the allele frequencies of the Saulteaux were not significantly different from the European-descent group. Two subgroups (Dene and Cree) had higher frequency of NRAMP1 D543N (A) allele, which is associated with tuberculosis in other populations. Conclusion: High, but differential rates of tuberculosis among the First Nation subgroups in Manitoba are related to social determinants of health (i.e. poverty, racism, inadequate housing) but other potential risk factors such as gene polymorphisms associated with tuberculosis have only recently come under investigation. NRAMP1 allele frequencies were found to be different comparing the Dene, Cree and Saulteaux and their role in tuberculosis susceptibility/resistance needs further investigation.