229 results on '"Yoav, Keynan"'
Search Results
2. Powassan Virus Encephalitis after Tick Bite, Manitoba, Canada
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Nathan Smith, Yoav Keynan, Terry Wuerz, and Aditya Sharma
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ticks ,Ixodes ,meningitis/encephalitis ,virus ,Powassan virus ,tickborne ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.
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- 2024
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3. Sex differences in houselessness, injection drug use, and mental health conditions among people newly diagnosed with HIV in Manitoba, Canada from 2018 to 2021: a retrospective cohort studyResearch in context
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Alexander Sharp, Megan Sorokopud-Jones, Margaret Haworth-Brockman, Ken Kasper, Lauren MacKenzie, Laurie Ireland, Kathy Gawlik, Lucelly Lopez, Johanna Marcela Vanegas, Jared Bullard, Carl Boodman, Julianne Sanguins, Mike Payne, Kimberly Templeton, Yoav Keynan, and Zulma Vanessa Rueda
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HIV ,Syndemics ,Houselessness ,Methamphetamine ,Mental health condition ,Sex and gender ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90 targets. Our goal was to describe sex differences and syndemic conditions within an incident HIV cohort in Manitoba, and the HIV treatment initiation and undetectable viral load outcomes. Methods: This was a retrospective cohort study of all people 18 years and older newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021. Data was collected as follows: before HIV diagnosis: chlamydia, gonorrhoea, syphilis, and/or hepatitis C antibodies. At the time of HIV diagnosis: age, sex, gender, race/ethnicity, sexual orientation. During follow-up: CD4 counts, viral load, HIV treatment, hospitalizations, and number of visits to HIV care. Main exposures evaluated: methamphetamine use, injection drug use, houselessness, and mental health conditions. Outcomes: started antiretroviral treatment and achieved an undetectable viral load. A descriptive statistical analysis was used. Findings: There were 404 new HIV diagnoses in Manitoba from 2018 to 2021; 44.8% were female, 55.2% male; 76.% self-identified as Indigenous, 13.4% white/European, 4.7% African/black; 86.6% cis-gender; 60.9% heterosexual, 13.4% gay, bisexual and men who have sex with men, and 1.7% lesbian. Injection drug use was reported by 71.8% and 43.5% of females and males respectively. Methamphetamine was the most frequently injected drug (62.4%). Amongst females, 81.8% experienced at least one of the following: houselessness (43.1%), mental health comorbidities (46.4%), and injection drug use (71.8%). Only 64.9% of all individuals had an undetectable viral load (61.1% females and 67.9% males), 56.5% among people experiencing houselessness, 59% among young people (≤29 years), and 60.1% among people who inject drugs. Interpretation: People newly diagnosed with HIV in Manitoba are disproportionately experiencing houselessness, mental illness, and injection drug use (mostly methamphetamine). This pattern is more pronounced for female individuals. These findings highlight the need for syndemic and gender-specific approaches, simultaneously addressing social and health conditions, to treat HIV. Funding: This work was supported by the Canadian Institutes of Health Research, The Manitoba Medical Service Foundation, The James Farley Memorial Fund and the Canada Research Chairs Program.
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- 2024
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4. The association of antiplatelet agents with mortality among patients with non–COVID-19 community-acquired pneumonia: a systematic review and meta-analysis
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Sylvain A. Lother, Lana Tennenhouse, Rasheda Rabbani, Ahmed M. Abou-Setta, Nicole Askin, Alexis F. Turgeon, Srinivas Murthy, Brett L. Houston, Donald S. Houston, Asher A. Mendelson, Jonathan D. Paul, Michael E. Farkouh, Jovan Hasmatali, Barret Rush, Joel Nkosi, Ewan C. Goligher, Emily Rimmer, John C. Marshall, Souradet Y. Shaw, Patrick R. Lawler, Yoav Keynan, and Ryan Zarychanski
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aspirin ,clopidogrel ,infection ,mortality ,pneumonia ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background: Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non–COVID-19 CAP remains uncertain. Objectives: To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non–COVID-19 CAP. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non–COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates. Results: We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I2 = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I2 = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I2 = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias. Conclusion: In hospitalized patients with non–COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.
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- 2024
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5. Does the Recovery of Respiratory Viruses Impact Pulmonary Function at Baseline and 1-, 6-, and 12-Month Follow-Up in People Living with HIV and Pneumonia?
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Iván Arturo Rodríguez-Sabogal, Ruth Cabrera, Diana Marin, Lucelly Lopez, Yudy Aguilar, Gustavo Gomez, Katherine Peña-Valencia, Will Riaño, Lázaro Vélez, Yoav Keynan, and Zulma Vanessa Rueda
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HIV ,pneumonia ,respiratory viruses ,lung function ,cohort study ,Microbiology ,QR1-502 - Abstract
The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of respiratory viruses in bronchoalveolar lavage and induced sputum samples in PLHIV and correlate their presence with lung function. A prospective cohort of adults hospitalized in Medellín between September 2016 and December 2018 included three groups: group 1 = people diagnosed with HIV and a diagnosis of community-acquired pneumonia (CAP), group 2 = HIV, and group 3 = CAP. People were followed up with at months 1, 6, and 12. Clinical, microbiological, and spirometric data were collected. Respiratory viruses were detected by multiplex RT-PCR. Sixty-five patients were included. At least 1 respiratory virus was identified in 51.9%, 45.1%, and 57.1% of groups 1, 2 and 3, respectively. Among these, 89% of respiratory viruses were detected with another pathogen, mainly Mycobacterium tuberculosis (40.7%) and Pneumocystis jirovecii (22.2%). The most frequent respiratory virus was rhinovirus (24/65, 37%). On admission, 30.4% of group 1, 16.6% of group 2, and 50% of group 3 had airflow limitation, with alteration in forced expiratory volume at first second in both groups with pneumonia compared to HIV. Respiratory viruses are frequent in people diagnosed with HIV, generally coexisting with other pathogens. Pulmonary function on admission was affected in patients with pneumonia, improving significantly in the 1st, 6th, and 12th months after CAP onset.
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- 2024
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6. Inflammatory Patterns Associated with Legionella in HIV and Pneumonia Coinfections
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Breanne M. Head, Adriana Trajtman, Ruochen Mao, Kathryn Bernard, Lázaro Vélez, Diana Marin, Lucelly López, Zulma Vanessa Rueda, and Yoav Keynan
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bronchoalveolar lavage ,cytokines ,HIV ,Legionella ,pneumonia ,Medicine - Abstract
Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027–1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity.
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- 2024
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7. Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study
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Katherine Peña-Valencia, Will Riaño, Mariana Herrera-Diaz, Lucelly López, Diana Marín, Sandra Gonzalez, Olga Agudelo-García, Iván Arturo Rodríguez-Sabogal, Lázaro Vélez, Zulma Vanessa Rueda, and Yoav Keynan
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inflammation ,cytokines ,pulmonary dysfunction ,HIV ,pneumonia ,Medicine - Abstract
Previous studies have noted that persons living with human immunodeficiency virus (HIV) experience persistent lung dysfunction after an episode of community-acquired pneumonia (CAP), although the underlying mechanisms remain unclear. We hypothesized that inflammation during pneumonia triggers increased tissue damage and accelerated pulmonary fibrosis, resulting in a gradual loss of lung function. We carried out a prospective cohort study of people diagnosed with CAP and/or HIV between 2016 and 2018 in three clinical institutions in Medellín, Colombia. Clinical data, blood samples, and pulmonary function tests (PFTs) were collected at baseline. Forty-one patients were included, divided into two groups: HIV and CAP (n = 17) and HIV alone (n = 24). We compared the concentrations of 17 molecules and PFT values between the groups. Patients with HIV and pneumonia presented elevated levels of cytokines and chemokines (IL-6, IL-8, IL-18, IL-1RA, IL-10, IP-10, MCP-1, and MIP-1β) compared to those with only HIV. A marked pulmonary dysfunction was evidenced by significant reductions in FEF25, FEF25-75, and FEV1. The correlation between these immune mediators and lung function parameters supports the connection between pneumonia-associated inflammation and end organ lung dysfunction. A low CD4 cell count (
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- 2024
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8. Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol
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Linda Larcombe, Laurie Ireland, Ken Kasper, Yoav Keynan, Neora Pick, Michael Payne, Jared Bullard, Kathleen Deering, Julianne Sanguins, Katharina Maier, Andrea Krüsi, Zulma Vanessa Rueda, Margaret Haworth-Brockman, Cheryl Sobie, Enrique Villacis, Kimberly Templeton, Lauren MacKenzie, Tara Myran, and Adrienne Meyers
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Medicine - Abstract
Introduction In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba.Methods and analysis Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba.Ethics and dissemination We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).
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- 2023
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9. Evaluation of TB elimination strategies in Canadian Inuit populations: Nunavut as a case study
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Elaheh Abdollahi, Yoav Keynan, Patrick Foucault, Jason Brophy, Holden Sheffield, and Seyed M. Moghadas
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Tuberculosis ,Inuit populations ,Treatment ,Agent-based simulation 2000 MSC ,92B05 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Tuberculosis (TB) continues to disproportionately affect Inuit populations in Canada with some communities having over 300 times higher rate of active TB than Canadian-born, non-Indigenous people. Inuit Tuberculosis Elimination Framework has set the goal of reducing active TB incidence by at least 50% by 2025, aiming to eliminate it by 2030. Whether these goals are achievable with available resources and treatment regimens currently in practice has not been evaluated. We developed an agent-based model of TB transmission to evaluate timelines and milestones attainable in Nunavut, Canada by including case findings, contact-tracing and testing, treatment of latent TB infection (LTBI), and the government investment on housing infrastructure to reduce the average household size. The model was calibrated to ten years of TB incidence data, and simulated for 20 years to project program outcomes. We found that, under a range of plausible scenarios with tracing and testing of 25%–100% of frequent contacts of detected active cases, the goal of 50% reduction in annual incidence by 2025 is not achievable. If active TB cases are identified rapidly within one week of becoming symptomatic, then the annual incidence would reduce below 100 per 100,000 population, with 50% reduction being met between 2025 and 2030. Eliminating TB from Inuit populations would require high rates of contact-tracing and would extend beyond 2030. The findings indicate that time-to-identification of active TB is a critical factor determining program effectiveness, suggesting that investment in resources for rapid case detection is fundamental to controlling TB.
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- 2022
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10. Saying it out loud: explicit equity prompts for public health organization resilience
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Margaret Haworth-Brockman, Claire Betker, and Yoav Keynan
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health equity ,emergency preparedness ,public health ,resilience ,intervention ,Public aspects of medicine ,RA1-1270 - Abstract
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.
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- 2023
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11. Cytokine/chemokine profiles in people with recent infection by Mycobacterium tuberculosis
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Mariana Herrera, Yoav Keynan, Lucelly Lopez, Diana Marín, Lázaro Vélez, Paul J. McLaren, and Zulma Vanessa Rueda
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tuberculosis infection ,TST conversion ,Mycobacterium tuberculosis ,cytokines ,chemokines ,tuberculosis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionThe risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker.MethodsWe evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups.ResultsThe concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease.ConclusionsThere were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.
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- 2023
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12. Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination
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Aloysious Ssemaganda, Huong Mai Nguyen, Faisal Nuhu, Naima Jahan, Catherine M. Card, Sandra Kiazyk, Giulia Severini, Yoav Keynan, Ruey-Chyi Su, Hezhao Ji, Bernard Abrenica, Paul J. McLaren, T. Blake Ball, Jared Bullard, Paul Van Caeseele, Derek Stein, and Lyle R. McKinnon
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Science - Abstract
Whether mRNA SARS-CoV-2 vaccines promote T cells within the nasal mucosa of vaccine recipients is not known. Here the authors show that after mRNA SARS-CoV-2 vaccination, antigen specific T cells can be measured in the nasal mucosa and that these T cells may be localised to respond to a subsequent virus infection. Clinical trial registration NCT04713163
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- 2022
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13. Impact of non-pharmaceutical interventions and vaccination on COVID-19 outbreaks in Nunavut, Canada: a Canadian Immunization Research Network (CIRN) study
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Thomas N. Vilches, Elaheh Abdollahi, Lauren E. Cipriano, Margaret Haworth-Brockman, Yoav Keynan, Holden Sheffield, Joanne M. Langley, and Seyed M. Moghadas
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SARS-CoV-2 ,COVID-19 ,Non-pharmaceutical interventions ,Vaccination ,Agent-based simulations ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Nunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks. Methods We used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals. Results We found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015—5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880—4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593—2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798—15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222—265) even in the absence of NPIs. Conclusions NPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.
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- 2022
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14. Introduction of short course treatment for latent tuberculosis infection at a primary care facility for refugees in Winnipeg, Canada: A mixed methods evaluation
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Claudyne Chevrier, Mariana Herrera Diaz, Zulma Vanessa Rueda, Shivoan Balakumar, Margaret Haworth-Brockman, Diana Marcela Marin, Afsaneh Oliver, Pierre Plourde, and Yoav Keynan
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tuberculosis ,tuberculosis infection ,short term treatment ,low incidence countries ,refugee health ,Public aspects of medicine ,RA1-1270 - Abstract
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.
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- 2023
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15. Tuberculosis among people living with HIV/AIDS in Jazan Region, Southwestern Saudi Arabia
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Majid A. Darraj, Ahmed A. Abdulhaq, Abuobaida Yassin, Sultan Mubarki, Heba M. Shalaby, Yoav Keynan, Khalid Y. Ghailan, and Hesham M. Al-Mekhlafi
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TB-HIV co-infection ,Risk factors ,Infectious diseases ,PLWHA ,Saudi Arabia ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Background: Tuberculosis (TB) and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) infections are leading causes of morbidity and mortality worldwide. People living with HIV/AIDS (PLWHA) are highly susceptible to TB infection and progression to active TB disease. This study aims to determine the proportion and risk factors of TB among PLWHA in Jazan Region, southwestern Saudi Arabia. Methods: A cross-sectional study was conducted among HIV-infected individuals attending the main referral hospital in Jazan Region during the period 2017–2019. The participants’ TB status, CD4+ lymphocyte count, and viral load were assessed. In addition, their demographic and clinical information was collected using a structured questionnaire. Results: A total of 316 HIV-positive individuals aged between 13 and 81 years (75% male and 25% female) were enrolled in this study. Of them, 30 (9.5%; 95% confidence interval [CI]: 5.2, 10.6%) were diagnosed with TB: 46.7% (14/30) had pulmonary TB and 53.3% (16/30) had extrapulmonary TB. The highest proportion of TB-positive PLWHA was found among participants aged 18–30 years (11.6%) and among non-Saudis (14.0%) when compared to other age groups and Saudi participants (7.4%). Multivariate analysis showed that male gender (adjusted odds ratio [AOR] = 4.79; 95% CI = 1.22, 18.74), past medical history (PMH) of TB (AOR = 29.67; 95% CI = 5.31, 164.32), PMH of other RTIs (AOR = 5.86; 95 % CI = 2.14, 16.06), CD4+ lymphocyte count of
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- 2021
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16. Slipping through: mobility’s influence on infectious disease risks for justice-involved women in Canada
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Susie Taylor, Margaret Haworth-Brockman, and Yoav Keynan
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Migration ,Incarceration ,Sexually transmitted and blood-borne infections ,Women ,Canada ,Public aspects of medicine ,RA1-1270 ,Social pathology. Social and public welfare. Criminology ,HV1-9960 - Abstract
Abstract Background The relationship between incarceration and women’s vulnerability to sexually transmitted and blood-borne infections (STBBI) is understudied in Canada, despite numerous studies showing that justice-involved women experience very high rates of infection. Justice-involved women in Canada are highly mobile, as a result of high rates of incarceration and extremely short sentences. From a public health perspective, it is productive to understand how the mobility of justice-involved women shapes their vulnerability to STBBI. Results This narrative review demonstrates that mobility between incarceration facilities and communities drives sexually transmitted and blood-borne disease risk for justice-involved women in Canada. Associations and interactions between epidemics of gender-based and intimate partner violence, substance use, and STBBIs shape the experiences of justice-involved women in Canada. In correctional facilities, the pre-existing vulnerability of justice-involved women is compounded by a lack of comprehensive STBBI care and limited harm reduction services. On release, unstable housing, disruptions to social support networks, interruptions in medical care, and relapse to or continuation of substance use, significantly increase individual disease risk and the likelihood of community transmission. High rates of incarceration for short periods perpetuate this cycle and complicate the delivery of healthcare. Conclusions The review provides evidence of the need for stronger gender-transformative public health planning and responses for incarcerated women, in both federal and provincial corrections settings in Canada. A supportive, evidence-based approach to STBBI identification and treatment for incarcerated women - one that that removes stigma, maintains privacy and improves access, combined with structural policies to prevent incarceration - could decrease STBBI incidence and interrupt the cycle of incarceration and poor health outcomes. A coordinated and accountable program of reintegration that facilitates continuity of public health interventions for STBBI, as well as safe housing, harm reduction and other supports, can improve outcomes as well. Lastly, metrics to measure performance of STBBI management during incarceration and upon release would help to identify gaps and improve outcomes for justice-involved women in the Canadian context.
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- 2021
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17. An urgent call to include men who have sex with men in the HPV immunisation programme in Kenya
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Sharmistha Mishra, Marissa L Becker, Souradet Shaw, Yoav Keynan, Parinita Bhattacharjee, Stephen Moses, Joshua Kimani, Lyle R McKinnon, Robert R Lorway, Pascal Macharia, John Maina, John Mathenge, Samuel Anyula Gorigo, Peter Arimi, Lisa Lazarus, and Matthew Thomann
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Published
- 2022
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18. Increased susceptibility to pneumonia due to tumour necrosis factor inhibition and prospective immune system rescue via immunotherapy
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Ryan Ha, Yoav Keynan, and Zulma Vanessa Rueda
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Tumour necrosis factor (TNF) inhibitors ,immunotherapy ,pneumonia ,infection ,opportunistic pathogens ,cytokines ,Microbiology ,QR1-502 - Abstract
Immunomodulators such as tumour necrosis factor (TNF) inhibitors are used to treat autoimmune conditions by reducing the magnitude of the innate immune response. Dampened innate responses pose an increased risk of new infections by opportunistic pathogens and reactivation of pre-existing latent infections. The alteration in immune response predisposes to increased severity of infections. TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, transplant recipients, and inflammatory bowel disease. The efficacies of immunomodulators are shown to be varied, even among those that target the same pathways. Monoclonal antibody-based TNF inhibitors have been shown to induce stronger immunosuppression when compared to their receptor-based counterparts. The variability in activity also translates to differences in risk for infection, moreover, parallel, or sequential use of immunosuppressive drugs and corticosteroids makes it difficult to accurately attribute the risk of infection to a single immunomodulatory drug. Among recipients of TNF inhibitors, Mycobacterium tuberculosis has been shown to be responsible for 12.5-59% of all infections; Pneumocystis jirovecii has been responsible for 20% of all non-viral infections; and Legionella pneumophila infections occur at 13-21 times the rate of the general population. This review will outline the mechanism of immune modulation caused by TNF inhibitors and how they predispose to infection with a focus on Mycobacterium tuberculosis, Legionella pneumophila, and Pneumocystis jirovecii. This review will then explore and evaluate how other immunomodulators and host-directed treatments influence these infections and the severity of the resulting infection to mitigate or treat TNF inhibitor-associated infections alongside antibiotics.
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- 2022
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19. A population data-driven approach to identifying ‘Long COVID’ cases in support of diagnosis and treatment.
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Jennifer Enns, Alan Katz, Marina Yogendran, Marcelo Urquia, Saman Muthukumarana, Surani Matharaarachchi, Alexander Singer, Nathan Nickel, Leona Star, Teresa Cavett, Yoav Keynan, Lisa Lix, and Diana Sanchez-Ramirez
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COVID-19 ,administrative data ,electronic medical records ,long COVID ,symptoms ,clinical diagnosis ,Demography. Population. Vital events ,HB848-3697 - Abstract
Objective Post-acute COVID-19 (or ‘long COVID’) manifests as a wide range of long-lasting symptoms affecting multiple organ systems. We are developing criteria for identifying long COVID cases using administrative, clinical, survey and other data from Manitoba, Canada, with the ultimate goal of examining long COVID prevalence, risk factors, prognosis and recovery. Approach Given the lack of an accepted clinical definition and resulting lack of diagnostic codes, we are adopting several different creative and complementary strategies to identify long COVID cases. We are examining administrative and clinical data sources (laboratory data, physician claims, drug prescriptions, and electronic medical records) for information on positive COVID tests, common symptoms and complaints, and treatment provided. To identify people with long COVID who may not have sought healthcare, we are collecting survey data from a convenience community sample (members of a medical health fitness facility) and mining data on long COVID symptoms from Twitter. Results The combination of approaches we have adopted and the expanding scientific literature on long COVID are contributing to a more comprehensive understanding of the impacts of long COVID in Manitoba. Through preliminary work on the laboratory data (positive COVID tests March 2020-June 2021), we have developed and characterized a COVID-positive cohort (n=47,515). Work is now underway to develop an algorithm for long COVID using symptoms from free text in electronic medical records, ICD-9 codes, and changes in health-seeking behaviour (compared to the pre-positive COVID test period and a matched sample). This population data-driven approach will then allow us to examine how multiple underlying health conditions, COVID illness severity, COVID vaccination status, and various socio-demographic factors are related to risk of long COVID. Conclusion This research is generating actionable information by identifying risk factors to support clinical diagnosis of long COVID, making it easier for clinicians to recognize this new illness and develop plans to manage it, and will inform healthcare system planning by quantifying the burden of long COVID at the population level.
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- 2022
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20. Courtage de connaissances sur les maladies infectieuses pour la santé publique
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Margaret Haworth-Brockman and Yoav Keynan
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santé publique ,maladies infectieuses ,courtage de connaissances ,canada ,covid-19 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Les Centres de collaboration nationale (CCN) en santé publique (CCNSP) ont été établis en 2005 dans le cadre de l'engagement du gouvernement fédéral à renouveler et à renforcer la santé publique à la suite de l'épidémie du syndrome respiratoire aigu sévère (SRAS). Ils ont été mis sur pied pour appuyer l'application des connaissances en vue d'une utilisation plus opportune de la recherche scientifique et d'autres connaissances dans les pratiques, les programmes et les politiques de santé publique au Canada. Six centres composent les CCNSP, dont le Centre de collaboration nationale des maladies infectieuses (CCNMI). Le CCNMI collabore avec des professionnels de la santé publique pour trouver, comprendre et utiliser des recherches et des données probantes sur les maladies infectieuses et les déterminants de la santé associés. Le CCNMI a pour mandat de forger des liens entre ceux qui génèrent et ceux qui utilisent les connaissances sur les maladies infectieuses. À titre de premier article d'une série sur le CCNSP, nous décrivons notre rôle dans le courtage de connaissances et les nombreuses méthodes et produits que nous avons élaborés. De plus, nous illustrons comment le CCNMI a été en mesure de travailler avec la santé publique pour générer et échanger des connaissances pendant la pandémie du coronavirus de 2019 (COVID-19).
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- 2021
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21. Real-life experience with ceftobiprole in Canada: Results from the CLEAR (CanadianLEadership onAntimicrobialReal-life usage) registry
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George G. Zhanel, Justin Kosar, Melanie Baxter, Rita Dhami, Sergio Borgia, Neal Irfan, Kelly S. MacDonald, Gordon Dow, Philippe Lagacé-Wiens, Maxime Dube, Marco Bergevin, Carlo Tascini, Yoav Keynan, Andrew Walkty, and James Karlowsky
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Ceftobiprole ,CLEAR registry ,Efficacy ,Adverse effects ,Pneumonia ,Endocarditis ,Microbiology ,QR1-502 - Abstract
Objectives: Ceftobiprole is an advanced-generation cephalosporin with a favourable safety profile. Published data on the clinical use of ceftobiprole are limited. We report use of ceftobiprole in Canadian patients using data captured by the CLEAR registry. Methods: The CLEAR registry uses the web-based research data management program REDCap™ (online survey) to facilitate clinicians entering details associated with their clinical experiences using ceftobiprole. Results: Data were available for 38 patients treated with ceftobiprole. The most common infections treated were endocarditis (42.1% of patients), bone and joint infection (23.7%) and hospital-associated bacterial pneumonia (15.8%). 92.1% of patients had bacteraemia and 21.1% were in intensive care. Ceftobiprole was used because of failure of (71.1%), resistance to (18.4%) or adverse effects from (10.5%) previously prescribed antimicrobial agents. Ceftobiprole was primarily used as directed therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections (94.7% of patients). Ceftobiprole susceptibility testing was performed on isolates from 47.4% of patients. It was used concomitantly with daptomycin in 55.3% of patients and with vancomycin in 18.4% of patients. Treatment duration was primarily >10 days (65.8% of patients) with microbiological success in 97.0% and clinical success in 84.8% of patients. 2.6% of patients had gastrointestinal adverse effects. Conclusion: In Canada to date, ceftobiprole is used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to, and thus used in combination with daptomycin or vancomycin with high microbiological and clinical cure rates and an excellent safety profile.
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- 2021
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22. Knowledge brokering on infectious diseases for public health
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Margaret Haworth-Brockman and Yoav Keynan
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public health ,infectious diseases ,knowledge brokering ,canada ,covid-19 ,Infectious and parasitic diseases ,RC109-216 - Abstract
The National Collaborating Centres (NCCs) for Public Health (NCCPH) were established in 2005 as part of the federal government’s commitment to renew and strengthen public health following the severe acute respiratory syndrome (SARS) epidemic. They were set up to support knowledge translation for more timely use of scientific research and other knowledges in public health practice, programs and policies in Canada. Six centres comprise the NCCPH, including the National Collaborating Centre for Infectious Diseases (NCCID). The NCCID works with public health practitioners to find, understand and use research and evidence on infectious diseases and related determinants of health. The NCCID has a mandate to forge connections between those who generate and those who use infectious diseases knowledge. As the first article in a series on the NCCPH, we describe our role in knowledge brokering and the numerous methods and products that we have developed. In addition, we illustrate how NCCID has been able to work with public health to generate and share knowledge during the coronavirus disease 2019 (COVID-19) pandemic.
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- 2021
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23. Gene expression profiling identifies candidate biomarkers for new latent tuberculosis infections. A cohort study.
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Mariana Herrera, Yoav Keynan, Paul J McLaren, Juan Pablo Isaza, Bernard Abrenica, Lucelly López, Diana Marin, and Zulma Vanessa Rueda
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Medicine ,Science - Abstract
ObjectiveTo determine the gene expression profile in individuals with new latent tuberculosis infection (LTBI), and to compare them with people with active tuberculosis (TB) and those exposed to TB but not infected.DesignA prospective cohort study. Recruitment and follow-up were conducted between September 2016 to December 2018. Gene expression and data processing and analysis from April 2019 to April 2021.SettingTwo male Colombian prisons.Participants15 new tuberculin skin test (TST) converters (negative TST at baseline that became positive during follow-up), 11 people that continued with a negative TST after two years of follow-up, and 10 people with pulmonary ATB.Main outcome measuresGene expression profile using RNA sequencing from PBMC samples. The differential expression was assessed using the DESeq2 package in Bioconductor. Genes with |logFC| >1.0 and an adjusted p-value < 0.1 were differentially expressed. We analyzed the differences in the enrichment of KEGG pathways in each group using InterMiner.ResultsThe gene expression was affected by the time of incarceration. We identified group-specific differentially expressed genes between the groups: 289 genes in people with a new LTBI and short incarceration (less than three months of incarceration), 117 in those with LTBI and long incarceration (one or more years of incarceration), 26 in ATB, and 276 in the exposed but non-infected individuals. Four pathways encompassed the largest number of down and up-regulated genes among individuals with LTBI and short incarceration: cytokine signaling, signal transduction, neutrophil degranulation, and innate immune system. In individuals with LTBI and long incarceration, the only enriched pathway within up-regulated genes was Emi1 phosphorylation.ConclusionsRecent infection with MTB is associated with an identifiable RNA pattern related to innate immune system pathways that can be used to prioritize LTBI treatment for those at greatest risk for developing active TB.
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- 2022
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24. Simulating the effect of school closure during COVID-19 outbreaks in Ontario, Canada
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Elaheh Abdollahi, Margaret Haworth-Brockman, Yoav Keynan, Joanne M. Langley, and Seyed M. Moghadas
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COVID-19 ,School closure ,Self-isolation ,Social distancing ,Pandemic ,Simulation ,Medicine - Abstract
Abstract Background The province of Ontario, Canada, has instituted indefinite school closures (SC) as well as other social distancing measures to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) pandemic. We sought to evaluate the effect of SC on reducing attack rate and the need for critical care during COVID-19 outbreaks, while considering scenarios with concurrent implementation of self-isolation (SI) of symptomatic cases. Methods We developed an age-structured agent-based simulation model and parameterized it with the demographics of Ontario stratified by age and the latest estimates of COVID-19 epidemiologic characteristics. Disease transmission was simulated within and between different age groups by considering inter- and intra-group contact patterns. The effect of SC of varying durations on the overall attack rate, magnitude and peak time of the outbreak, and requirement for intensive care unit (ICU) admission in the population was estimated. Secondly, the effect of concurrent community-based voluntary SI of symptomatic COVID-19 cases was assessed. Results SC reduced attack rates in the range of 7.2–12.7% when the duration of SC increased from 3 to 16 weeks, when contacts among school children were restricted by 60–80%, and in the absence of SI by mildly symptomatic persons. Depending on the scenario, the overall reduction in ICU admissions attributed to SC throughout the outbreak ranged from 3.3 to 6.7%. When SI of mildly symptomatic persons was included and practiced by 20%, the reduction of attack rate and ICU admissions exceeded 6.3% and 9.1% (on average), respectively, in the corresponding scenarios. Conclusion Our results indicate that SC may have limited impact on reducing the burden of COVID-19 without measures to interrupt the chain of transmission during both pre-symptomatic and symptomatic stages. While highlighting the importance of SI, our findings indicate the need for better understanding of the epidemiologic characteristics of emerging diseases on the effectiveness of social distancing measures.
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- 2020
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25. Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection
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Yoann Zerbib, Emily K. Jenkins, Maryam Shojaei, Adrienne F. A. Meyers, John Ho, T. Blake Ball, Yoav Keynan, Amarnath Pisipati, Aseem Kumar, Anand Kumar, Marek Nalos, Benjamin M. Tang, Klaus Schughart, Anthony McLean, and on behalf of the Nepean Genomic Research Group
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Influenza ,Transcriptome ,Neutrophils ,Neutrophil extracellular trap ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. Methods To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. Results 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. Conclusions These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.
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- 2020
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26. Tick-Borne-Agents Detection in Patients with Acute Febrile Syndrome and Ticks from Magdalena Medio, Colombia
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Ruth Cabrera, Willington Mendoza, Loreth López-Mosquera, Miguel Angel Cano, Nicolas Ortiz, Valentina Campo, Yoav Keynan, Lucelly López, Zulma Vanessa Rueda, and Lina Andrea Gutiérrez
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bacterial zoonoses ,molecular diagnostic techniques ,serologic tests ,Coxiella ,Medicine - Abstract
Acute febrile illness (AFI) is a morbid condition with a sudden onset of fever with at least seven days of evolution, where no signs or symptoms related to an apparent infection have been identified. In Latin America, a high proportion of disease is typically due to malaria and arboviruses. However, among the infectious etiologies, tick-borne diseases (TBDs) should also be considered, especially in areas where people come into direct contact with these arthropods. This study aims to describe the etiology and epidemiology related to tick-borne agents in patients with AFI and the tick’s natural infection by agents of TBD in the rural tropical Magdalena Medio region in Colombia, and explore the factors associated with the presence of Coxiella burnetii infection. We conduct a cohort study enrolling 271 patients with AFI to detect the bacteria of the genera Anaplasma, Ehrlichia, Coxiella, Rickettsia, Borrelia, and Francisella through molecular techniques, and additionally evaluate the presence of IgG antibodies with commercially available kits. We also conduct tick collection in the patient’s households or workplaces for the molecular screening of the same bacterial genera. Seropositivity to IgG antibodies was obtained for all the bacteria analyzed, with Francisella being the most common at 39.5% (107/271), followed by R. rickettsii at 31.4% (85/271), Ehrlichia at 26.9% (73/271), R. typhi at 15.5% (42/271), Anaplasma at 14.4% (39/271), and Borrelia at 6.6% (18/271). However, these bacteria were not detected by the molecular techniques used. Coxiella burnetii infection was detected in 39.5% of the patients: 49.5% only by phase I and II IgG antibodies, 33.6% only by real-time PCR, and 16.8% had a concordant positive result for both techniques. A total of 191 adult ticks, 111 females and 80 males, were collected and identified as Rhipicephalus sanguineus s.l. and Rhipicephalus microplus. In the 169 adult ticks in which natural infection was evaluated, Ehrlichia spp. was detected in 21.3% (36/169), Coxiella spp. in 11.8% (20/169), and Anaplasma spp. in 4.7% (8/169). In conclusion, we identified the prior exposition to Francisella, Anaplasma, Ehrlichia, Rickettsia, Borrelia, and Coxiella in patients through serological tests. We also detected the infection of C. burnetii using molecular techniques. In the ticks, we identified bacteria of the genera Coxiella, Anaplasma, and Ehrlichia. These results suggest the importance of these zoonotic agents as possible causes of AFI in this region.
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- 2022
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27. Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection
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Benjamin M. Tang, Maryam Shojaei, Sally Teoh, Adrienne Meyers, John Ho, T. Blake Ball, Yoav Keynan, Amarnath Pisipati, Aseem Kumar, Damon P. Eisen, Kevin Lai, Mark Gillett, Rahul Santram, Robert Geffers, Jens Schreiber, Khyobeni Mozhui, Stephen Huang, Grant P. Parnell, Marek Nalos, Monika Holubova, Tracy Chew, David Booth, Anand Kumar, Anthony McLean, and Klaus Schughart
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Science - Abstract
Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.
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- 2019
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28. Inguinal Ulceroglandular Tularemia Caused by Francisella tularensis Subspecies holarctica, Canada
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Carl Boodman, Quinlan Richert, Sylvain Lother, Ken Kasper, Sergio Fanella, Philippe Lagacé-Wiens, and Yoav Keynan
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tularemia ,vector-borne infections ,genital ulcer disease ,Francisella tularensis ,laboratory-acquired infection ,bacteria ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis, a Biosafety Level 3 pathogen and potential agent of bioterrorism. We describe 2 cases of perigenital ulcer disease caused by Francisella tularensis subspecies holarctica in Manitoba, Canada. These cases caused inadvertent exposure among laboratory personnel.
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- 2021
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29. Cohort profile: the LHIV-Manitoba clinical cohort of people living with HIV in Manitoba, Canada
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James Blanchard, Laurie Ireland, Marissa Becker, Eve Cheuk, Claire Kendall, Christine Bibeau, Ken Kasper, Yoav Keynan, Carla Loeppky, and Leigh M McClarty
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Medicine - Abstract
Purpose The LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province.Participants In total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants’ clinical records are linked to provincial administrative health datasets.Findings to date The average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort’s median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019.Future plans The LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.
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- 2020
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30. Review of Evidence for Using Chest X-Rays for Active Tuberculosis Screening in Long-Term Care in Canada
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Mariana Herrera Diaz, Margaret Haworth-Brockman, and Yoav Keynan
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tuberculosis ,mandatory testing ,nursing homes ,cost effectiveness ,mass chest X-ray ,aged ,Public aspects of medicine ,RA1-1270 - Abstract
Background: People living in long-term care facilities (LTCF) are at high risk to develop active tuberculosis primarily as a result of reactivation of a latent TB infection, or endemic transmission between residents. Current national guidelines in Canada are to use a posterior-anterior and lateral chest X-ray to screen for TB for those over 65 years old, upon admission to a LTCF.Objective: To assess the available evidence for cost benefits of universal chest X-ray screening for new LTCF residents.Methodology: We conducted a search for all articles published until September 2018, in PubMed and WorlCat databases, in English, using a combination of key words: chest X-ray, chest radiography or CXR, long-term care, elderly, screening, and tuberculosis. We also reviewed publicly available guidelines for screening new residents to LTCF from across Canada. We report on a qualitative synthesis of the evidence in the documents retrieved.Results: The final review yielded four cost-effectiveness studies (2 of 4 conducted in countries with low incidence), one systematic review, one recommendation/editorial, and one cohort study. We found that in a tuberculosis low-incidence country the CXR cost per identified case was $672,298 CAD. Enacting a more targeted screening program, perhaps one that tests only those who previously had TB, or other high-risk medical conditions may enhance the cost-effectiveness.Recommendations: We suggest reviewing the screening policy for active TB in people entering LTCF, which is based on a CXR. The results indicate that a targeted search for active TB in people with symptoms or other high-risk medical conditions may be more cost-effective.
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- 2020
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31. Molecular detection of Coxiella burnetii in livestock farmers and cattle from Magdalena Medio in Antioquia, Colombia.
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Ruth Cabrera Orrego, Leonardo Alberto Ríos-Osorio, Yoav Keynan, Zulma Vanessa Rueda, and Lina Andrea Gutiérrez
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Medicine ,Science - Abstract
Coxiella burnetii causes Q fever in humans and coxiellosis in animals. In humans, it causes acute febrile illnesses like influenza, pneumonia, hepatitis, and chronic illnesses such as endocarditis, vascular infection, and post-infectious fatigue syndrome. It is widely distributed worldwide, and its main reservoirs are sheep, goats, and cattle. This study aimed to determine the frequency of C. burnetii infection using molecular detection and to identify the associated factors in livestock farmers and cattle from the Magdalena Medio region of Antioquia, Colombia. Using real-time polymerase chain reaction (PCR), molecular detection was performed for the IS1111 insertion sequence of C. burnetii using genomic DNA collected from the peripheral blood of 143 livestock farmers and 192 cattle from 24 farms located in Puerto Berrío, Puerto Nare, and Puerto Triunfo. To confirm the results, bidirectional amplicon sequencing of 16S rRNA was performed in four of the positive samples. Additionally, factors associated with C. burnetii were identified using a Poisson regression with cluster effect adjustment. Real-time PCR showed positive results in 25.9% and 19.5% of livestock farmer samples and cattle samples, respectively. For livestock farmers, factors associated with C. burnetii were the area where the farm was located [Puerto Berrío, adjusted prevalence ratio (aPR): 2.13, 95% confidence interval (CI): 1.10-4.11], presence of hens (aPR: 1.47, 95% CI: 1.21-1.79), horses (aPR: 1.61, 95% CI: 1.54-1.67), and ticks (aPR: 2.36, 95% CI: 1.03-5.42) in the residence, and consumption of raw milk (aPR: 1.47, 95% CI: 1.26-1.72). For cattle, the factors associated with Coxiella genus were municipality (Puerto Nare; aPR: 0.39, 95% CI: 0.37-0.41) and time of residence on the farm (≥49 months; aPR: 2.28, 95% CI: 1.03-5.20). By analyzing sequences of the 16S rRNA molecular marker, C. burnetii infection was confirmed in livestock farmers. However, in cattle, only the presence of Coxiella-type bacteria was identified. Further research is necessary to determine the potential role that these types of bacteria have as etiological agents for disease in livestock farmers and cattle from the study area.
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- 2020
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32. Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review
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Mariana Herrera, Cristian Vera, Yoav Keynan, and Zulma Vanessa Rueda
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Background. Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective. To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods. We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants’ information, diagnostic criteria, IP, detection methods, and biases were collected. Results. We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions. It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.
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- 2020
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33. The value of program science to optimize knowledge brokering on infectious diseases for public health
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Marissa Becker, Margaret Haworth-Brockman, and Yoav Keynan
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Program science ,Knowledge broker ,Public health ,Knowledge translation ,Infectious diseases ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Knowledge translation (KT) and related terms have variously been defined as process and as products. In this paper we contribute to debates on effective KT, specifically knowledge brokering, by describing an adaptation of Program Science that aligns with the real-world of public health activities. Main abstract We describe an adaptation of the Program Science framework to our knowledge translation and brokering planning and projects at the National Collaborating Centre for Infectious Diseases. The systematic approach allows for layering of knowledge year to year and translating knowledge from one infectious disease content area to another. Using a recent forum on syphilis outbreaks as an example, we also demonstrate the value of using Program Science to shape the design and delivery of the knowledge brokering event. Conclusion The use of scientific knowledge to improve public health program design, implementation and evaluation forms the basis for the program science framework. Providing the right public health information to the right audience at the right time can foster long-term outcomes of networks and new partnerships which can potentially improve delivery of public health services.
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- 2018
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34. Rapid CD4 decline prior to antiretroviral therapy predicts subsequent failure to reconstitute despite HIV viral suppression
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Majid Darraj, Leigh A. Shafer, Shanna Chan, Ken Kasper, and Yoav Keynan
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Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
HIV-1 infection is characterized by loss of CD4 T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15–30% of individuals having suboptimal increase of CD4 T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes. We sought to characterize the factors associated with decreased immunological response among Manitoba’s HIV patient population.This retrospective case-control study included HIV patients with immune reconstitution failure despite suppression of HIV replication by ART. The immune reconstitution failure was defined by CD4 cell count increase from baseline of less than 100 CD4 cells/mm3 or lack of increase to above 200 CD4 cells/mm3 within one year of viral load suppression. Age and nadir CD4 cell counts are known risk factors associated with immune reconstitution failure. We chose controls (Patients with immune reconstitution success) of similar age and CD4 nadir cell with cases (Patients with immune reconstitution failure). We explored the potential effects of gender, HLA type, presence of co-infection, ethnicity, ART type, and rate of pre-treatment CD4 decline among cases and controls. Of more than 550 patients followed by our HIV clinic, 42 individuals met our definition of immune reconstitution failure and they were assigned to the cases group. 31 patients, comprising a range of ages and CD4 nadirs similar to those of the cases, were assigned to the control group. Our primary analysis was a regression model, predicting post-ART change in CD4 over time.After controlling for age and nadir CD4 cell counts, the only potential predictor that appears consistently associated with the rate of post-ART rise in CD4 over time in our cohort, regardless of the other variables that we have controlled for, is the rate of decline in CD4 pre-ART initiation.Several factors have been variably correlated with immune reconstitution failure of CD4 T cell count. Age and low CD4 nadir are factors previously shown to correlate with immune reconstitution failure; and we have controlled for them in our study. Another possible predictor is the rate of decline in CD4 pre-ART, which can serve as an additional marker of reconstitution failure and necessitate prioritizing individuals to ART initiation or identification of a subset of individuals that may be targeted for future adjunct strategies to improve immune recovery. Keywords: HIV, CD4, Immune reconstitution, Virologic suppression
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- 2018
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35. Emerging group C and group G streptococcal endocarditis: A Canadian perspective
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Sylvain A. Lother, Davinder S. Jassal, Philippe Lagacé-Wiens, and Yoav Keynan
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Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: The aim of this study was to determine the incidence of infective endocarditis (IE) in patients with bacteremia caused by group C and group G streptococci (GCGS) and to characterize the burden of disease, clinical characteristics, and outcomes through a case series of patients with GCGS IE. Methods: Individuals with blood cultures growing GCGS in Manitoba, Canada, between January 2012 and December 2015 were included. Clinical and echocardiographic parameters were collected retrospectively. IE was suspected or confirmed according to the modified Duke criteria. Results: Two hundred and nine bacteremic events occurred in 198 patients. Transthoracic echocardiography (TTE) was performed in 33%. Suspected or confirmed IE occurred in 6% of all patients and in 18% of those with TTE. Native valve infection was more common than prosthetic valve and device-related infections (75%, 17%, and 8%, respectively). Metastatic infection was observed in 64%, primarily to the lungs (57%), skin (43%), osteoarticular system (29%), and central nervous system (29%). Sepsis occurred in 58% and streptococcal toxic shock syndrome in 50% of those with IE, with overall mortality of 17%. Conclusions: IE from GCGS bacteremia is common and is frequently associated with severe disease, embolic events, and mortality. In the appropriate clinical context, GCGS bacteremic events should prompt investigation for IE. Keywords: Streptococcus dysgalactiae, Group C streptococci, Group G streptococci, Bacteremia, Infective endocarditis
- Published
- 2017
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36. Tularémie pharyngée acquise en milieu urbain au Canada
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Fiona Vickers, Andrew Walkty, and Yoav Keynan
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General Medicine - Published
- 2022
37. Atypical bacterial pneumonia in the HIV-infected population
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Breanne M. Head, Adriana Trajtman, Zulma V. Rueda, Lázaro Vélez, and Yoav Keynan
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Atypical ,Bacteria ,Pneumonia ,HIV ,Legionella ,Chlamydophila ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Human immunodeficiency virus (HIV)-infected individuals are more susceptible to respiratory tract infections by other infectious agents (viruses, bacteria, parasites, and fungi) as their disease progresses to acquired immunodeficiency syndrome. Despite effective antiretroviral therapy, bacterial pneumonia (the most frequently occurring HIV-associated pulmonary illness) remains a common cause of morbidity and mortality in the HIV-infected population. Over the last few decades, studies have looked at the role of atypical bacterial pneumonia (i.e. pneumonia that causes an atypical clinical presentation or responds differently to typical therapeutics) in association with HIV infection. Due to the lack of available diagnostic strategies, the lack of consideration, and the declining immunity of the patient, HIV co-infections with atypical bacteria are currently believed to be underreported. Thus, following an extensive database search, this review aimed to highlight the current knowledge and gaps regarding atypical bacterial pneumonia in HIV. The authors discuss the prevalence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, Legionella species and others in the HIV-infected population as well as their clinical presentation, methods of detection, and treatment. Further studies looking at the role of these microbes in association with HIV are required. Increased knowledge of these atypical bacteria will lead to a more rapid diagnosis of these infections, resulting in an improved quality of life for the HIV-infected population.
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- 2017
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38. Clonal Clusters and Virulence Factors of Group C and G Streptococcus Causing Severe Infections, Manitoba, Canada, 2012–2014
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Sylvain A. Lother, Walter Demczuk, Irene Martin, Michael R. Mulvey, Brenden Dufault, Philippe Lagacé-Wiens, and Yoav Keynan
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Streptococcus dysgalactiae ,group C streptococci ,group G streptococci ,invasive disease ,bacteremia ,virulence factor ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012–2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.
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- 2017
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39. Immune Reconstitution Syndrome secondary to Rhodococcus equi infection in a patient with HIV and Burkitt's lymphoma
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Majid Darraj, Rachel Fainstein, Ken Kasper, and Yoav Keynan
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Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV.We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy. Keywords: Human immunodeficiency virus, Rhodococcus equi, Burkitt's lymphoma, Cavitating pneumonia
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- 2017
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40. Serologic testing for Bartonella in Manitoba, Canada, 2010–2020: a retrospective case series
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Carl Boodman, Terence Wuerz, Philippe Lagacé-Wiens, Robbin Lindsay, Antonia Dibernardo, Jared Bullard, Derek R. Stein, and Yoav Keynan
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General Medicine - Published
- 2022
41. Integrated Care for Latent Tuberculosis Infection (LTBI) at a Primary Health Care Facility for Refugees in Winnipeg, Canada: A Mixed-Methods Evaluation
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Dione Benjumea-Bedoya, Marissa Becker, Margaret Haworth-Brockman, Shivoan Balakumar, Kimberly Hiebert, Jo-Anne Lutz, Alison Bertram Farough, Yoav Keynan, and Pierre Plourde
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refugee health ,latent TB ,treatment completion ,integrated management ,LTBI evaluation ,Public aspects of medicine ,RA1-1270 - Abstract
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.
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- 2019
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42. Looking for Evidence of Public Health's Role for Long-Term Evacuees
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Barbara Clow, Margaret Haworth-Brockman, Geneviève Boily-Larouche, Zeeshan Qadar, and Yoav Keynan
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public health ,evacuation ,disaster ,long-term evacuees ,Canada ,emergency ,Public aspects of medicine ,RA1-1270 - Abstract
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.
- Published
- 2019
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43. Inflammatory mediators and lung abnormalities in HIV: A systematic review.
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Breanne M Head, Ruochen Mao, Yoav Keynan, and Zulma Vanessa Rueda
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Medicine ,Science - Abstract
HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.
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- 2019
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44. A Dene First Nation’s community readiness assessment to take action against HIV/AIDS: a pilot project
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Linda Larcombe, Albert McLeod, Sarah Samuel, Jennifer Samuel, Michael Payne, Stephanie Van Haute, Matthew Singer, Laurie Ringaert, Adrienne F. A. Meyers, Kathi Kinew, Yoav Keynan, Kelly MacDonald, Joe Antsanen, and Pamela Orr
- Subjects
hiv/aids ,community readiness assessment ,first nation ,community-led research ,pilot study ,culturally appropriate action ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
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.
- Published
- 2019
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45. Development of a Fluorescent Tool for Studying Legionella bozemanae Intracellular Infection
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Breanne M. Head, Christopher I. Graham, Teassa MacMartin, Yoav Keynan, and Ann Karen C. Brassinga
- Subjects
Acanthamoeba castellanii ,GFP ,intracellular infection ,Legionella ,Legionella bozemanae ,non-pneumophila ,Biology (General) ,QH301-705.5 - Abstract
Legionnaires’ disease incidence is on the rise, with the majority of cases attributed to the intracellular pathogen, Legionella pneumophila. Nominally a parasite of protozoa, L. pneumophila can also infect alveolar macrophages when bacteria-laden aerosols enter the lungs of immunocompromised individuals. L. pneumophila pathogenesis has been well characterized; however, little is known about the >25 different Legionella spp. that can cause disease in humans. Here, we report for the first time a study demonstrating the intracellular infection of an L. bozemanae clinical isolate using approaches previously established for L. pneumophila investigations. Specifically, we report on the modification and use of a green fluorescent protein (GFP)-expressing plasmid as a tool to monitor the L. bozemanae presence in the Acanthamoeba castellanii protozoan infection model. As comparative controls, L. pneumophila strains were also transformed with the GFP-expressing plasmid. In vitro and in vivo growth kinetics of the Legionella parental and GFP-expressing strains were conducted followed by confocal microscopy. Results suggest that the metabolic burden imposed by GFP expression did not impact cell viability, as growth kinetics were similar between the GFP-expressing Legionella spp. and their parental strains. This study demonstrates that the use of a GFP-expressing plasmid can serve as a viable approach for investigating Legionella non-pneumophila spp. in real time.
- Published
- 2021
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46. Incidence and Risk Factors Associated with Latent Tuberculosis Infection and Pulmonary Tuberculosis among People Deprived of Liberty in Colombian Prisons
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Mariana Herrera, Yoav Keynan, Lucelly López, Diana Marín, Luisa Arroyave, María Patricia Arbeláez, Lázaro Vélez, and Zulma Vanessa Rueda
- Subjects
Adult ,Male ,Tuberculin Test ,Incidence ,Prisoners ,Colombia ,Middle Aged ,bacterial infections and mycoses ,Article ,Cohort Studies ,Infectious Diseases ,Latent Tuberculosis ,Risk Factors ,Virology ,Humans ,Female ,Parasitology - Abstract
People deprived of liberty (PDL) are at high risk of acquiring Mycobacterium tuberculosis infection (latent tuberculosis infection [LTBI]) and progressing to active tuberculosis (TB). We sought to determine the incidence rates and factors associated with LTBI and active TB in Colombian prisons. Using information of four cohort studies, we included 240 PDL with two-step tuberculin skin test (TST) negative and followed them to evaluate TST conversion, as well as, 2,134 PDL that were investigated to rule out active TB (1,305 among people with lower respiratory symptoms of any duration, and 829 among people without respiratory symptoms and screened for LTBI). Latent tuberculosis infection incidence rate was 2,402.88 cases per 100,000 person-months (95% CI 1,364.62–4,231.10) in PDL with short incarceration at baseline, and 419.66 cases per 100,000 person-months (95% CI 225.80–779.95) in individuals with long incarceration at baseline (who were enrolled for the follow after at least 1 year of incarceration). The TB incidence rate among PDL with lower respiratory symptoms was 146.53 cases/100,000 person-months, and among PDL without respiratory symptoms screened for LTBI the incidence rate was 19.49 cases/100,000 person-months. History of Bacillus Calmette-Guerin vaccination decreased the risk of acquiring LTBI among PDL who were recently incarcerated. Female sex, smoked drugs, and current cigarette smoking were associated with an increased risk of developing active TB. This study shows that PDL have high risk for LTBI and active TB. It is important to perform LTBI testing at admission to prison, as well as regular follow-up to control TB in prisons.
- Published
- 2022
47. Healthcare utilization among persons living with HIV in Manitoba, Canada, prior to HIV diagnosis: A case-control analysis
- Author
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Souradet Y Shaw, Laurie Ireland, Leigh M McClarty, Carla Loeppky, Jared Bullard, Paul Van Caeseele, Yoav Keynan, Ken Kasper, Stephen Moses, James F Blanchard, and Marissa L Becker
- Subjects
Canada ,Infectious Diseases ,Case-Control Studies ,Public Health, Environmental and Occupational Health ,Humans ,Mass Screening ,HIV Infections ,Manitoba ,Pharmacology (medical) ,Dermatology ,Patient Acceptance of Health Care ,Delivery of Health Care ,Retrospective Studies - Abstract
Background Understanding care patterns of persons living with HIV prior to diagnosis can inform prevention opportunities, earlier diagnosis, and engagement strategies. We examined healthcare utilization among HIV-positive individuals and compared them to HIV-negative controls. Methods Data were from a retrospective cohort from Manitoba, Canada. Participants included individuals living with HIV presenting to care between 2007 and 2011, and HIV-negative controls, matched (1:5) by age, sex, and region. Data from population-based administrative databases included physician visits, hospitalizations, drug dispensation, and chlamydia and gonorrhea testing. Diagnoses associated with physician visits were classified according to International Classification of Diseases chapters. Conditional logistic regression models were used to compare cases/controls, with adjusted odds ratios (AORs) and their 95% confidence intervals (95% CI) reported. Results A total of 193 cases and 965 controls were included. Physician visits and hospitalizations were higher for cases, compared to controls. In the 2 years prior to case date, cases were more likely to be diagnosed with “blood disorders” (AOR: 4.2, 95% CI: 2.0–9.0), be treated for mood disorders (AOR: 2.4, 95% CI: 1.6–3.4), and to have 1+ visits to a hospital (AOR: 2.2, 95% CI: 1.4–3.6). Conclusion Opportunities exist for prevention, screening, and earlier diagnosis. There is a need for better integration of healthcare services with public health.
- Published
- 2021
48. Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial
- Author
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Vincent I. Lau, Robert Fowler, Ruxandra Pinto, Alain Tremblay, Sergio Borgia, François M. Carrier, Matthew P. Cheng, John Conly, Cecilia T. Costiniuk, Peter Daley, Erick Duan, Madeleine Durand, Patricia S. Fontela, George Farjou, Mike Fralick, Anna Geagea, Jennifer Grant, Yoav Keynan, Kosar Khwaja, Nelson Lee, Todd C. Lee, Rachel Lim, Conar R. O’Neil, Jesse Papenburg, Makeda Semret, Michael Silverman, Wendy Sligl, Ranjani Somayaji, Darrell H.S. Tan, Jennifer L.Y. Tsang, Jason Weatherald, Cedric Philippe Yansouni, Ryan Zarychanski, and Srinivas Murthy
- Subjects
Adult ,Canada ,Alanine ,Cost-Benefit Analysis ,Humans ,General Medicine ,Adenosine Monophosphate ,COVID-19 Drug Treatment - Abstract
The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir.Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed.The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737],From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation.ClinicalTrials. gov, no. NCT04330690.
- Published
- 2022
49. Relapse of Visceral Leishmaniasis in an HIV-Infected Patient Successfully Treated with a Combination of Miltefosine and Amphotericin B
- Author
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Shauna McQuarrie, Ken Kasper, Dana C Moffatt, Daniel Marko, and Yoav Keynan
- Subjects
Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.
- Published
- 2015
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50. Effect of flight connectivity on the introduction and evolution of the COVID-19 outbreak in Canadian provinces and territories
- Author
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Roberto Hincapie, Diego A Munoz, Nathalia Ortega, Harpa K Isfeld-Kiely, Souradet Y Shaw, Yoav Keynan, and Zulma Vanessa Rueda
- Subjects
General Medicine - Abstract
Background The COVID-19 pandemic has challenged health services and governments in Canada and around the world. Our research aims to evaluate the effect of domestic and international air travel patterns on the COVID-19 pandemic in Canadian provinces and territories. Methods Air travel data were obtained through licensed access to the ‘BlueDot Intelligence Platform’, BlueDot Inc. Daily provincial and territorial COVID-19 cases for Canada and global figures, including mortality, cases recovered and population data were downloaded from public datasets. The effects of domestic and international air travel and passenger volume on the number of local and non-local infected people in each Canadian province and territory were evaluated with a semi-Markov model. Provinces and territories are grouped into large (>100 000 confirmed COVID-19 cases and >1 000 000 inhabitants) and small jurisdictions (≤100 000 confirmed COVID-19 cases and ≤1 000 000 inhabitants). Results Our results show a clear decline in passenger volumes from March 2020 due to public health policies, interventions and other measures taken to limit or control the spread of COVID-19. As the measures were eased, some provinces and territories saw small increases in passenger volumes, although travel remained below pre-pandemic levels. During the early phase of disease introduction, the burden of illness is determined by the connectivity of jurisdictions. In provinces with a larger population and greater connectivity, the burden of illness is driven by case importation, although local transmission rapidly replaces imported cases as the most important driver of increasing new infections. In smaller jurisdictions, a steep increase in cases is seen after importation, leading to outbreaks within the community. Conclusions Historical travel volumes, combined with data on an emerging infection, are useful to understand the behaviour of an infectious agent in regions of Canada with different connectivity and population size. Historical travel information is important for public health planning and pandemic resource allocation.
- Published
- 2022
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