The Medicine Wheel: informing the management of tuberculosis outbreaks in Indigenous communities.

Many Indigenous communities in Canada experience endemic tuberculosis with superimposed periodic epidemic outbreaks. Failures in outbreak management have resulted in the "seeding" of future infection and disease. In this paper we present a model that may be used in planning, implementation and review of tuberculosis outbreak management in Cree Indigenous communities in Canada, based on the Medicine Wheel, a paradigm for holistic living. In the context of tuberculosis management, the Medicine Wheel provides a path for the establishment of respectful cross-cultural relationships, the expression of values through action, true community engagement and partnership, and the establishment of culture-based processes of transparency, accountability and change.

"Because of COVID ": The impacts of COVID-19 on First Nation people accessing the HIV cascade of care in Manitoba, Canada.

BACKGROUND: The COVID-19 pandemic (March 2020-May 2023) had a profound effect around the world with vulnerable people being particularly affected, including worsening existing health inequalities. This article explores the impact of the pandemic on health services for First Nations people living with HIV (FN-PWLE) in Manitoba, Canada. This study investigated perceptions of both health care providers and FN-PWLE through qualitative interviews occurring between July 2020 and February 2022 to understand their experience and identify lessons learned that could be translated into health system changes. METHODS: Using a qualitative, participatory-action, intentional decolonizing approach for this study we included an Indigenous knowledge keeper and Indigenous research associates with lived experience as part of the study team. A total of twenty-five [25] in-depth semi-structured interviews were conducted with eleven healthcare providers (HCPs) and fourteen First Nation people with lived HIV experience (FN-PWLE). In total, 18/25 or 72% of the study participants self-identified as First Nation people. RESULTS: The COVID-19 pandemic negatively impacted health services access for FN-PWLE, a) disrupted relationships between FN-PWLE and healthcare providers, b) disrupted access to testing, in-person appointments, and medications, and c) intersectional stigma was compounded. Though, the COVID-19 pandemic also led to positive effects, including the creation of innovative solutions for the health system overall. CONCLUSIONS: The COVID-19 pandemic exaggerated pre-existing barriers and facilitators for Manitoba FN-PWLE accessing and using the healthcare system. COVID-19 impacted health system facilitators such as relationships and supports, particularly for First Nation people who are structurally disadvantaged and needing more wrap-around care to address social determinants of health. Innovations during times of crisis, included novel ways to improve access to care and medications, illustrated how the health system can quickly provide solutions to long-standing barriers, especially for geographical barriers. Lessons learned from the COVID-19 pandemic should be considered for improvements to the health system's HIV cascade of care for FN-PWLE and other health system improvements for First Nations people with other chronic diseases and conditions. Finally, this study illustrates the value of qualitative and First Nation decolonizing research methods. Further studies are needed, working together with First Nations organizations and communities, to apply these recommendations and innovations to change health care and people's lives.

Early Lyme neuroborreliosis manifesting as brachial plexopathy and meningitis in Northwestern Ontario, Canada: A case report.

RATIONALE: Lyme disease is a tick-borne disease caused by the spirochete B. burgdorferi, and patients often present with symptoms comparable to a viral-like illness. The diagnosis can be challenging given its wide range of manifestations and diagnostic testing can take days or longer. Here, we present a case of Lyme disease presenting as brachial plexopathy and meningitis. PATIENT CONCERNS: A 76-years-old male presented to a tertiary-care hospital with left arm weakness and neck pain. DIAGNOSIS: Our patient was diagnosed with Lyme neuroborreliosis and had positive serology, including enzyme immunoassay and Western blot. INTERVENTIONS: Our patient received 17 days of ceftriaxone (2g IV daily) followed by oral doxycycline (100mg bid). OUTCOMES: Over the subsequent year, our patient had eventual complete recovery in muscle strength and sensation, with slower improvement to the cervical neck and left arm pain. LESSONS: Incidence of Lyme disease is increasing in North America, and the disease has a wide range of symptoms. Lyme neuroborreliosis (LNB) is 1 presentation and can present with early or late manifestations; clinicians should maintain a high index of suspicion and begin empiric treatment in individuals with a clinical syndrome consistent with LNB. Early LNB manifestations have onset within 6 months of infection and include cranial and peripheral neuropathy, radiculitis, and aseptic meningitis; late LNB encompasses a chronic encephalomyelitis.

Protective effects of prior third dose mRNA vaccination in rural nursing home residents during SARS-CoV-2 outbreaks.

BACKGROUND: In Canada, mortality due to SARS-CoV-2 disproportionately impacted residents of nursing homes (NH). In November 2021, NH residents in the Canadian province of Manitoba became eligible to receive three doses of mRNA vaccine but coverage with three doses has not been universal. The objective of this study was to compare the protection from infection conferred by one, two, and three doses of COVID-19 mRNA vaccine compared to no vaccination among residents of nursing homes experiencing SARS-CoV-2 outbreaks. METHODS: Infection Prevention and Control reports from 8 rural nursing homes experiencing outbreaks of SARS-CoV-2 between January 6, 2022, and March 5, 2022, were analyzed. Attack rates and the number needed to vaccinate (NNV) were calculated. RESULTS: SARS-CoV-2 attack rate was 65% among NH residents not vaccinated, 58% among residents who received 1-2 doses of mRNA COVID-19 vaccine, and 28% among residents who had received 3 vaccine doses. The NNV to prevent one nursing home resident from SARS-CoV-2 infection during an outbreak was 3 for a vaccination with 3 doses and 14 for 1-2 doses of COVID-19 mRNA vaccine. The superiority of receiving the third dose was statistically significant compared to 1-2 doses (Chi-Squared, p < 0.00001). CONCLUSIONS: Nursing home residents who received three doses of COVID-19 mRNA vaccine were at lower risk of SARS-CoV-2 infection compared to those who received 1-2 doses. Our analyses lend support to the protective effects of the third dose of mRNA vaccine for NH residents in the event of a SARS-CoV-2 outbreak.

Sekuwe (My House): building health equity through Dene First Nations housing designs.

The Truth and Reconciliation Commission of Canada determined that the Dene people, among other Indigenous groups, experienced cultural genocide through policies that separated them from their lands and resources, and from their families, languages, cultures, and by forcibly sending children to Indian Residential Schools. The resultant social inequity is manifested in conditions of social injustice including inadequate housing. The Dene healthy housing research was a continuing partnership between the two Dene First Nation communities, the university and a provincial First Nation non-government organisation. This project engaged the creative energies of university students and Dene senior-high students to create and articulate Dene healthy housing so that concepts/plans/designs are ready for future funding interventions. We co-developed methods and networks to reframe housing as a social determinant of health and an important factor in social justice. This project reflects the fundamental requirement for a respectful understanding of Dene perspectives on housing and health and the need for Dene control over their built environment.

Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group.

Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding for def-A1 and def-B1 were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population.

Tuberculosis among northern Manitoba First Nations, 2008-2012: program performance on- and off-reserve.

OBJECTIVES: The objectives of this study were to: (1) report tuberculosis (TB) program performance for northern First Nations in the province of Manitoba; (2) present methods for TB program performance measurement using routinely collected surveillance data; and (3) advance dialogue on performance measurement of Canadian TB programs. METHODS: Data on a retrospective cohort of people diagnosed with TB in Manitoba between January 1, 2008 and December 31, 2010, and their contacts, were extracted from the Manitoba TB Registry. Performance measures based on US-CDC were analyzed. Adjusted probability ratios (aPR) and 95% confidence intervals (CIs) were reported with comparisons between on-/off-reserve First Nations, adjusted for age, sex, and treatment history. RESULTS: A cohort of n = 149 people diagnosed with TB and n = 3560 contacts were identified. Comparisons off-/on-reserve: Treatment completion (aPR = 1.03; 95% CI 0.995-1.07); early detection (aPR = 0.87; 95% CI 0.57-1.33); HIV testing and reporting (aPR = 0.42; 95% CI 0.21-0.83); pediatric TB (age < 15 years) (aPR = 1.20; 95% CI 0.47-3.06); retreatment for TB (aPR = 0.93; 95% CI 0.89-0.97); contact elicitation (aPR = 0.94; 95% CI 0.84-1.05); contact assessment (aPR = 0.69; 95% CI 0.50-0.94). Pediatric (ages < 15 years) TB incidence in northern Manitoba was 37.1 per 100,000/year. CONCLUSION: TB program performance varies depending on residence in a reserve or non-reserve community. Action is urgently needed to address TB program performance in terms of contact investigation and HIV testing/reporting for First Nations off-reserve and to address high rates of pediatric TB in northern Manitoba. First Nations collaboration and models of care should be considered both on- and off-reserve to improve TB program performance.

A Dene First Nation's community readiness assessment to take action against HIV/AIDS: a pilot project.

BACKGROUND: Among Indigenous people in Canada the incidence of HIV is 3.5 times higher than other ethnicities. In Manitoba First Nations, Metis and Inuit people are disproportionately represented (40%) among people who are new to HIV care. Northlands Denesuline First Nation (NDFN) identified the need to revisit their level of knowledge and preparedness for responding to the increasing rates of HIV. NDFN piloted a community readiness assessment (CRA) tool to assess its appropriateness for use in northern Manitoba. METHODS: A First Nation and non-First Nation research team trained to administer the CRA tool at NDFN in Manitoba. Five informants were interviewed using the CRA tool and the responses were scored, analysed and reviewed at community workshops and with stakeholders to develop a 1-year action plan. RESULTS: CRA training was best conducted in the community. Using the readiness score of 2.4 along with feedback from two workshops, community members, the research team and stakeholders, we identified priorities for adult education and youth involvement in programmes and planning. CONCLUSIONS: In response to the increasing incidence of HIV, a northern First Nation community successfully modified and implemented a CRA tool to develop an action plan for culturally appropriate interventions and programmes.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood, and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients.

Tuberculosis transmission in the Indigenous peoples of the Canadian prairies.

SETTING: The prairie provinces of Canada. OBJECTIVE: To characterize tuberculosis (TB) transmission among the Indigenous and non-Indigenous Canadian-born peoples of the prairie provinces of Canada. DESIGN: A prospective epidemiologic study of consecutively diagnosed adult (age ≥ 14 years) Canadian-born culture-positive pulmonary TB cases on the prairies, hereafter termed "potential transmitters," and the transmission events generated by them. "Transmission events" included new positive tuberculin skin tests (TSTs), TST conversions, and secondary cases among contacts. RESULTS: In the years 2007 and 2008, 222 potential transmitters were diagnosed on the prairies. Of these, the vast majority (198; 89.2%) were Indigenous peoples who resided in either an Indigenous community (135; 68.2%) or a major metropolitan area (44; 22.2%). Over the 4.5-year period between July 1st, 2006 and December 31st 2010, 1085 transmission events occurred in connection with these potential transmitters. Most of these transmission events were attributable to potential transmitters who identified as Indigenous (94.5%). With a few notable exceptions most transmitters and their infected contacts resided in the same community type. In multivariate models positive smear status and a higher number of close contacts were associated with increased transmission; adjusted odds ratios (ORs) and 95% confidence intervals (CIs), 4.30 [1.88, 9.84] and 2.88 [1.31, 6.34], respectively. Among infected contacts, being Indigenous was associated with disease progression; OR and 95% CI, 3.59 [1.27, 10.14] and 6.89 [2.04, 23.25] depending upon Indigenous group, while being an infected casual contact was less likely than being a close contact to be associated with disease progression, 0.66 [0.44, 1.00]. CONCLUSION: In the prairie provinces of Canada and among Canadian-born persons, Indigenous peoples account for the vast majority of cases with the potential to transmit as well as the vast majority of infected contacts. Active case finding and preventative therapy measures need to focus on high-incidence Indigenous communities.

HLA-A, B, DRB1, DQA1, DQB1 alleles and haplotype frequencies in Dene and Cree cohorts in Manitoba, Canada.

BACKGROUND: First Nations in the Canadian province of Manitoba have disproportionately high rates of epidemic and endemic TB. Gene polymorphisms that modulate HLA Class I and II antigens are among the risk markers for TB, along with other biologic, and social determinants of health. HLA-A, B, DRB1, DQA1, DQB1 were typed in two Manitoba First Nation indigenous groups to identify and compare the frequency of gene polymorphisms that may influence susceptibility or resistance to TB. METHODS: Participants who self-identified as either Dene or Cree enrolled into the study from two First Nation communities in Manitoba, Canada. Genomic DNA was extracted from blood samples collected with informed consent from Dene (N=63) and Cree (N=42) First Nation study participants. Participants self-reported having treated active TB, treated latent TB or no TB. HLA Class I and II molecules were typed using sequence-specific oligonucleotide (SSO) probes from commercially available kits. RESULTS: The rates of treated active and latent TB were marginally higher among the Dene than the Cree participants (p=0.112). Class I and II HLA loci were in Hardy-Weinberg equilibrium in both the Dene and Cree groups. In this exploratory analysis of TB and HLA allele frequencies in Dene and Cree cohorts HLA-A*03 and HLA-DQB1*05:03 were significantly associated with TB. CONCLUSIONS: The high incidence of TB in both Dene and Cree populations in Canada requires both biomedical and socioeconomic prevention and control measures. Among the former, an understanding of HLA diversity among First Nations groups may aid the development of new effective vaccine and therapeutic modalities that depend on the interaction between small molecules and specific HLA epitopes.

Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis.

BACKGROUND: Canadian First Nation populations have experienced endemic and epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host defence peptide LL-37 is known to enhance control of pathogens such as Mycobacterium tuberculosis. OBJECTIVE: Evaluate associations between serum levels of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation participants (N = 34) and assess correlations with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). DESIGN: Venous blood was collected from all participants at baseline (winter and summer) and in conjunction with taking vitamin D supplements (1,000 IU/day) (winter and summer). Samples were analysed using ELISA for concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were genotyped. RESULTS: Circulating levels of 25(OH)D were not altered by vitamin D supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs did not correlate with serum concentrations of 25(OH)D, but LL-37 levels significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR SNP Bsm1 T/T genotypes. CONCLUSIONS: Our findings suggest that vitamin D supplementation may not be beneficial as an intervention to boost innate immune resistance to M. tuberculosis in the Dene population.

Hypermucoviscous Klebsiella syndrome without liver abscess in a patient with immunoglobulin g2 immune deficiency.

BACKGROUND: Hypermucoviscous Klebsiella pneumoniae (HMVKP) emerged as a cause of invasive infections in South-East (SE) Asia. It has become the most common cause of liver abscess in that region, and it is a significant causative organism in endogenous endophthalmitis and meningitis. During the past decade, cases of this uniquely virulent organism have been reported outside of SE Asia, with a propensity to affect individuals of SE Asian descent. Cases have been reported from North America including Canada. METHODS: We report a case of a patient of Filipino descent living in Canada who presented with recurrent HMVKP bacteremia in the absence of pyogenic liver abscess or other localized metastatic Klebsiella infection. RESULTS: Investigations identified an immunoglobulin (Ig)G2 deficiency and low IgM indicating potential common variable immunodeficiency, and administration of intravenous immunoglobulins was associated with prevention of further recurrences. CONCLUSIONS: To our knowledge, this is the first report of HMVKP associated with predisposing antibody deficiency.

Dietary intake of vitamin D in a northern Canadian Dené First Nation community.

BACKGROUND: Increased awareness of the wide spectrum of activity of vitamin D has focused interest on its role in the health of Canada's Aboriginal peoples, who bear a high burden of both infectious and chronic disease. Cutaneous vitamin D synthesis is limited at northern latitudes, and the transition from nutrient-dense traditional to nutrient-poor market foods has left many Canadian Aboriginal populations food insecure and nutritionally vulnerable. OBJECTIVE: The study was undertaken to determine the level of dietary vitamin D in a northern Canadian Aboriginal (Dené) community and to determine the primary food sources of vitamin D. DESIGN: Cross-sectional study. METHODS: Dietary vitamin D intakes of 46 adult Dené men and women were assessed using a food frequency questionnaire and compared across age, gender, season and body mass index. The adequacy of dietary vitamin D intake was assessed using the 2007 Adequate Intake (AI) and the 2011 Recommended Dietary Allowance (RDA) values for Dietary Reference Intake (DRI). RESULTS: Mean daily vitamin D intake was 271.4 IU in winter and 298.3 IU in summer. Forty percent and 47.8% of participants met the vitamin D 1997 AI values in winter and summer, respectively; this dropped to 11.1 and 13.0% in winter and summer using 2011 RDA values. Supplements, milk, and local fish were positively associated with adequate vitamin D intake. Milk and local fish were the major dietary sources of vitamin D. CONCLUSIONS: Dietary intake of vitamin D in the study population was low. Only 2 food sources, fluid milk and fish, provided the majority of dietary vitamin D. Addressing low vitamin D intake in this population requires action aimed at food insecurity present in northern Aboriginal populations.

Killer immunoglobulin-like receptor (KIR) centromeric-AA haplotype is associated with ethnicity and tuberculosis disease in a Canadian First Nations cohort.

Killer immunoglobulin-like receptors (KIR) on natural killer (NK) cells interact with other immune cells to monitor the immune system and combat infectious diseases, such as tuberculosis (TB). The balance of activating and inhibiting KIR interactions helps determine the NK cell response. In order to examine the enrichment or depletion of KIRs as well as to explore the association between TB status and inhibitory/stimulatory KIR haplotypes, we performed KIR genotyping on samples from 93 Canadian First Nations (Dene, Cree, and Ojibwa) individuals from Manitoba with active, latent, or no TB infection, and 75 uninfected Caucasian controls. There were significant differences in KIR genes between Caucasians and First Nations samples and also between the First Nations ethnocultural groups (Dene, Cree, and Ojibwa). When analyzing ethnicity and tuberculosis status in the study population, it appears that the KIR profile and centromeric haplotype are more predictive than the presence or absence of individual genes. Specifically, the decreased presence of haplotype B centromeric genes and increased presence of centromeric-AA haplotypes in First Nations may contribute to an inhibitory immune profile, explaining the high rates of TB in this population.

Marked disparity in the epidemiology of tuberculosis among Aboriginal peoples on the Canadian prairies: the challenges and opportunities.

BACKGROUND: While it is established that Aboriginal peoples in the prairie provinces of Canada are disproportionately affected by tuberculosis (TB), little is known about the epidemiology of TB either within or across provincial borders. METHODS: Provincial reporting systems for TB, Statistics Canada censuses and population estimates of Registered Indians provided by Aboriginal Affairs and Northern Development Canada were used to estimate the overall (2004 to 2008) and pulmonary (2007 to 2008) TB rates in the prairie provinces. The place of residence at diagnosis of pulmonary TB cases in 2007 to 2008 was also documented. RESULTS: The age- and sex-adjusted incidence of TB in Registered Indians was 52.6 per 100,000 person-years, 38 times higher than in Canadian-born 'others'. Incidence rates in Registered Indians were highest in Manitoba and lowest in Alberta. In Alberta and Saskatchewan, on-reserve rates were more than twice that of off-reserve rates. Rates in the Métis and Registered Indians were similar in Saskatchewan (50.0 and 52.2 per 100,000 person-years, respectively). In 2007 to 2008, approximately 90% of Canadian-born pulmonary TB cases in the prairie provinces were Aboriginal. Outside of one metropolitan area (Winnipeg, Manitoba), most Registered Indian and Métis pulmonary TB cases were concentrated in a relatively small number of communities north of the 53rd parallel. Rates of pulmonary TB in 11 of these communities were >300 per 100,000 person-years. In Manitoba, 49% of off-reserve Registered Indian pulmonary cases were linked to high-incidence reserve communities. INTERPRETATION: The epidemiology of TB among Aboriginal peoples on the Canadian prairies is markedly disparate. Pulmonary TB is highly focal, which is both a concern and an opportunity.

Vitamin D in a northern Canadian first nation population: dietary intake, serum concentrations and functional gene polymorphisms.

The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D(3) (25-OHD(3)) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD(3) and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD(3) and VDBP concentrations (N = 46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD(3) serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD(3). The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD(3). The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD(3) serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.