Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses

Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study

Looking for Evidence of Public Health's Role for Long-Term Evacuees

Many Canadians have had personal experience of a major emergency or disaster at some point in their lifetime and close to a third of those affected were evacuated from their homes or communities. Most evacuations have lasted less than 2 weeks, but in some instances, people have been displaced for months or years. For example, hundreds of residents evacuated following flooding in Lake St. Martin, Manitoba in 2011, remain displaced today. In order to learn more about the roles and responses of public health for long-term evacuees (LTEs) in Canada, we conducted a narrative review of published English-language documents, beginning with literature specific to Canada and then expanding to include literature on other high-income countries. We found that while researchers have explored public health considerations in emergency preparedness, acute disaster management, and resettlement in these contexts there is a dearth of published evidence regarding the public health implications of prolonged evacuation and the public health responses to long-term evacuation in Canada and in other high-income countries. Because the public health needs of diverse populations of LTEs have not been fully investigated, it is likely that they are neither well-understood nor adequately addressed in public health policy and practice

Introduction of short course treatment for latent tuberculosis infection at a primary care facility for refugees in Winnipeg, Canada: A mixed methods evaluation

BackgroundThe World Health Organization (WHO) End TB strategy document ‘Toward tuberculosis elimination: an action framework for low incidence countries'—like Canada— identifies screening and treatment of latent tuberculosis infection (LTBI) for groups at increased risk for TB disease as a priority, including newcomers from endemic countries. In 2015, the clients-centered model offered at a primary care facility for refugees, BridgeCare Clinic, Winnipeg, Canada was evaluated. The model included LTBI screening, assessment, and treatment, and originally offered 9-months of isoniazid as treatment. This mixed methods evaluation investigates LTBI program outcomes since the introduction of two short-course treatment regimens: 4-months of rifampin, and 3-months of isoniazid and rifapentine.MethodsThis study combined a retrospective analysis of program administrative data with structured interviews of clinic staff. We included LTBI treatment eligibility, the treatment regimen offered, treatment initiation, and completed treatment from January 1, 2015 to August 6, 2020.ResultsSeven hundred and one people were screened, and infection rates varied from 34.1% in 2015 to 53.3% in 2020. Most people living with LTBI came from high TB burden countries in Africa and South-East Asia WHO regions and were younger than 45 years old. Treatment eligibility increased 9% (75% in 2015 to 86% in 2016–2020) and most people diagnosed with LTBI took the short course treatments offered. There was an increase of 14.5% in treatment initiation (75.6 vs. 90.1%), and an increase of 8% in treatment completion (82.4 vs. 90.4%) after short-course regimens were introduced. The final model showed that the treatment regimen tends to affect the frequency of treatment completion, but there are other factors that influence this outcome, in this population. With the new treatments, BridgeCare Clinic achieved the 90% of treatment coverage, and the 90% treatment completion rate targets recommended in the End TB Strategy. Qualitative interviews with clinic staff further affirm the higher acceptability of the new treatments.ConclusionWhile these results are limited to government-sponsored refugees in Winnipeg, they highlight the acceptability and value of short-course LTBI treatment as a possibility for reaching End TB targets in primary care settings

Changing trends in β-hemolytic streptococcal bacteremia in Manitoba, Canada:2007-2012

OBJECTIVES: European surveillance studies have reported an increasing incidence of β-hemolytic group G streptococcal bacteremia, but no studies have evaluated trends in β-hemolytic streptococcal bacteremia in North America. METHODS: We reviewed bacteremic episodes and positive throat swab cultures from two tertiary care centers in Manitoba, Canada, from January 2007 to December 2012. RESULTS: During the study period, 19 864 bacteremic episodes, and 9948 positive throat swabs were identified. There were 1025 (5.16%) bacteremic episodes attributable to β-hemolytic streptococci: 425 (2.03%), 339 (1.71%), 62 (0.31%), and 199 (0.95%) to β-hemolytic groups A, B, C, and G streptococci, respectively. From 2007 to 2012, there were significant increases in the proportion of bacteremia attributable to β-hemolytic streptococci in general (6.32% vs. 4.02%; p<0.0001; linear trend test, p<0.0001), and to groups G (1.49% vs. 0.43%; p<0.0001; linear trend test, p<0.0001) and C (0.58% vs. 0.13%; p=0.0068; linear trend test, p=0.0105) β-hemolytic streptococci in particular. Bacteremia attributable to groups A and B β-hemolytic streptococci and Streptococcus pneumoniae were unchanged. There were no changes in the distribution of β-hemolytic streptococcal groups among throat swabs. CONCLUSIONS: Bacteremia attributable to β-hemolytic groups G and C streptococci increased in Manitoba, Canada. Further study of the factors underlying these changes is required

Chemokine Receptor 5 Δ32 Allele in Patients with Severe Pandemic (H1N1) 2009

Because chemokine receptor 5 (CCR5) may have a role in pulmonary immune response, we explored whether patients with severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population. We found a large proportion of heterozygosity for the CCR5Δ32 allele among white patients with severe disease

The Potential for DPPIV/CD26 usage as a surrogate marker for Antiretroviral Therapy Efficacy in HIV Infected populations

Background: Human Immunodeficiency Virus (HIV) viral load and CD4+ cell counts are the most commonly used markers for monitoring efficacy of anti-retroviral therapy (ART) in HIV infected individuals. The high cost of viral load monitoring limits its usage in resource limited countries, often leaving the use of CD4+ T cell counts as the only alternative. Though cheaper and more readily available, CD4+ cell counts as a measure of detecting treatment failure, is an unreliable predictor of disease progression. Hence, there is a need for more sensitive alternative, but less costly techniques for detecting treatment failure which can be used in resource limited settings. Objective: To evaluate the feasibility of using plasma CD26/Dipeptidyl peptidase IV (DPPIV) as a novel marker for clinical evaluation of treatment efficacy in HIV infected children. Method: Blood samples collected from HIV+ children (n=76) before and after initiation on ART, were assessed for HIV RNA (viral load), CD4+ T-cell count and DPPIV/CD26 levels. Viral load levels were analyzed using Roche Amplicor HIV-1 Monitor Test kit; CD4+ T-Cell Counts were analyzed using BD FACS Calibur flow cytometer while DPPIV/CD 26 levels were analyzed using Human DPPIV/CD26 Quantikine ELISA kit (R&amp;D Systems, Minneapolis MN). Results: The plasma DPPIV/CD26 levels increased significantly in children after ART initiation (p = 0.017), while the viral load levels declined after ART initiation with subsequent CD4+ cell counts increase. The DPPIV/CD 26 increase positively correlated with viral load decrease while negatively correlating to the CD4+ cell count increase. Conclusion: These findings demonstrate an inverse relationship between DPPIV/CD26 levels and HIV viral load and the direct proportionality of CD4+ Cell counts and DPPIV/CD26 levels, suggesting potential for use of DPPIV/CD26 as a surrogate marker for evaluating HIV disease progression in children receiving anti-retroviral therapy. Key words: CD26/Dipeptidyl peptidase IV (DPPIV), ELISA, Surrogate marker, Viral Load, CD4 Count, antiretroviral

Volitional limbic neuromodulation has a multifaceted clinical benefit in Fibromyalgia patients

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplification effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation should improve chronic pain in patients suffering from Fibromyalgia, by balancing disturbed indices for sleep and affect. We further expected that improved clinical status would correspond to successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions and placebo of sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the Real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep Indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the Real-neurofeedback group (both time × group p < 0.05) and to a greater extent among good modulators (both time*sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the treatment. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the Real-neurofeedback group (both time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP- neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation training in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the necessary link between somatic and affective dysregulation that can be successfully targeted using neurofeedback

Integrated Care for Latent Tuberculosis Infection (LTBI) at a Primary Health Care Facility for Refugees in Winnipeg, Canada: A Mixed-Methods Evaluation

Although Canada has one of the lowest tuberculosis incidence rates in the world, certain groups are disproportionately affected, including foreign born people from high incidence countries. The Winnipeg Regional Health Authority has initiated a process to decentralize latent tuberculosis infection (LTBI) management at primary care clinics in Winnipeg. One of these clinics is BridgeCare Clinic which provides services to government-assisted refugees. The present study describes the BridgeCare Clinic LTBI program and reviews program outcomes from January 2015 to October 2016. Refugees at BridgeCare Clinic receive comprehensive care, including LTBI screening and treatment. The LTBI program is managed by physicians, nurse practitioners, and primary care nurses under a patient-centered model of care. An accessible interpretation service, education to clients, and laboratory sampling at the clinic with free IGRA testing are important components of the program. Anonymized data on client outcomes were statistically analyzed and qualitative interviews were conducted with senior staff. During the study period, 274 IGRA tests were ordered with 158 negative results (57.7%) and 101 positive results (36.9%). Of 45 clients eligible (from January to December 2015) for LTBI treatment, 11 (24.4%) declined to receive treatment and 34 (75.6%) started treatment. Twenty-seven (79.4%) clients completed treatment, 3 (8.8%) clients moved out of province, and 4 (11.8%) did not complete treatment. The most recent World Health Organization strategy for tuberculosis control calls for integrated, patient-centered care and prevention. Aligned with these WHO recommendations, our experience suggests that LTBI care and treatment can be delivered effectively in a primary care setting using an integrated patient-centered approach

Genetic Polymorphisms and Drug Susceptibility in Four Isolates of Leishmania tropica Obtained from Canadian Soldiers Returning from Afghanistan

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease transmitted by the bite of sandflies, resulting in sores on the skin. No vaccines are available, and treatment relies on chemotherapy. CL has been frequently diagnosed in military personnel deployed to Afghanistan and returning from duty. The parasites isolated from Canadian soldiers were characterized by pulsed field gels and by sequencing conserved genes and were identified as Leishmania tropica. In contrast to other Leishmania species, high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. In vitro susceptibility testing in macrophages showed that all isolates, despite their genetic heterogeneity, were sensitive to most antileishmanial drugs (antimonials, miltefosine, amphotericin B, paromomycin) but were insensitive to fluconazole. This study suggests a number of therapeutic regimens for treating cutaneous leishmaniasis caused by L. tropica among patients and soldiers returning from Afghanistan. Canadian soldiers from this study were successfully treated with miltefosine

Saying it out loud: explicit equity prompts for public health organization resilience

IntroductionIn the early days of the COVID-19 pandemic there were numerous stories of health equity work being put “on hold” as public health staff were deployed to the many urgent tasks of responding to the emergency. Losing track of health equity work is not new and relates in part to the need to transfer tacit knowledge to explicit articulation of an organization’s commitment to health equity, by encoding the commitment and making it visible and sustainable in policy documents, protocols and processes.MethodsWe adopted a Theory of Change framework to develop training for public health personnel to articulate where and how health equity is or can be embedded in their emergency preparedness processes and documents.ResultsOver four sessions, participants reviewed how well their understanding of disadvantaged populations were represented in emergency preparedness, response and mitigation protocols. Using equity prompts, participants developed a heat map depicting where more work was needed to explicitly involve community partners in a sustained manner. Participants were challenged at times by questions of scope and authority, but it became clear that the explicit health equity prompts facilitated conversations that moved beyond the idea of health equity to something that could be codified and later measured. Over four sessions, participants reviewed how well their understanding of disadvantaged populations were represented in emergency preparedness, response and mitigation protocols. Using equity prompts, participants developed a heat map depicting where more work was needed to explicitly involve community partners in a sustained manner. Participants were challenged at times by questions of scope and authority, but it became clear that the explicit health equity prompts facilitated conversations that moved beyond the idea of health equity to something that could be codified and later measured.DiscussionUsing the indicators and prompts enabled the leadership and staff to articulate what they do and do not know about their community partners, including how to sustain their involvement, and where there was need for action. Saying out loud where there is – and is not – sustained commitment to achieving health equity can help public health organizations move from theory to true preparedness and resilience