Search

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.

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.

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.

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.

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.

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.

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

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.

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 tuberculosishas been shown to be responsible for 12.5-59% of all infections;Pneumocystis jiroveciihas been responsible for 20% of all non-viral infections; andLegionella pneumophilainfections 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 onMycobacterium tuberculosis,Legionella pneumophila, andPneumocystis 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.

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.

ObjectivePost-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. ApproachGiven 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. ResultsThe 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. ConclusionThis 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.

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

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decrease post-vaccination. Similar increases in nasal CD8+CD69+CD103− T cells are observed, particularly following the second dose. CD4+ cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8+ T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

Seasonal influenza is an acute respiratory infection that presents a significant annual burden to Canadians and the Canadian healthcare system. Social distancing measures that were implemented to control the 2019-2020 novel coronavirus outbreak were investigated for their ability to lessen the incident cases of seasonal influenza.We conducted an ecological study using data from Canada's national influenza surveillance system to investigate whether social distancing measures to control COVID-19 reduced the incident cases of seasonal influenza. Data taken from three separate time frames facilitated analysis of the 2019-2020 influenza season prior to, during, and following the implementation of COVID-19-related measures and enabled comparisons with the same time periods during three preceding flu seasons. The incidence, which referred to the number of laboratory-confirmed cases of specific influenza strains, was of primary focus. Further analysis determined the number of new laboratory-confirmed influenza or influenza-like illness outbreaks.Our results indicate a premature end to the 2019-2020 influenza season, with significantly fewer cases and outbreaks being recorded following the enactment of many COVID-19 social distancing policies. The incidence of influenza strains A (H3N2), A (unsubtyped), and B were all significantly lower at the tail end of the 2019-2020 influenza season as compared with preceding seasons (p = 0.0003, p = 0.0007, p = 0.0019).Specific social distancing measures and behaviours may serve as effective tools to limit the spread of influenza transmission moving forward, as they become more familiar.RéSUMé: OBJECTIFS: La grippe saisonnière est une infection aiguë des voies respiratoires qui représente un important fardeau annuel pour la population et pour le système de soins de santé du Canada. Nous avons cherché à déterminer si les mesures de distanciation sociale appliquées pour contrôler l’éclosion du nouveau coronavirus en 2019–2020 ont pu atténuer les cas incidents de grippe saisonnière. MéTHODES: Nous avons mené une étude écologique à l’aide des données du système national de surveillance de l’activité grippale au Canada pour déterminer si les mesures de distanciation sociale appliquées pour contrôler la COVID-19 ont réduit les cas incidents de grippe saisonnière. Des données provenant de trois périodes distinctes ont facilité l’analyse de la saison grippale 2019–2020 avant, pendant et après l’application des mesures liées à la COVID-19 et permis des comparaisons avec les mêmes intervalles durant trois saisons grippales antérieures. L’incidence, c’est-à-dire le nombre de cas confirmés en laboratoire de souches grippales particulières, était notre principal objectif. Des analyses plus poussées ont permis de déterminer le nombre de nouvelles éclosions de syndrome grippal ou de grippe confirmée en laboratoire. RéSULTATS: Selon nos résultats, la saison grippale 2019–2020 a connu une fin prématurée; un nombre sensiblement moins élevé de cas et d’éclosions ont été enregistrés après la mise en place des nombreuses politiques de distanciation sociale liées à la COVID-19. L’incidence des souches grippales A (H3N2), A (non sous-typée) et B a été sensiblement moins élevée vers la fin de la saison grippale 2019–2020 comparativement aux saisons précédentes (p = 0,0003, p = 0,0007, p = 0,0019). CONCLUSION: Des mesures et des comportements de distanciation sociale particuliers peuvent être des outils efficaces pour limiter la propagation de la grippe maintenant qu’ils sont plus familiers.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

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).

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.

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.

The level of clustering and the adjustment by cluster-robust standard errors have yet to be widely considered and reported in cross-sectional studies of tuberculosis (TB) in prisons. In two cross-sectional studies of people deprived of liberty (PDL) in Medellin, we evaluated the impact of adjustment versus failure to adjust by clustering on prevalence ratio (PR) and 95% confidence interval (CI). We used log-binomial regression, Poisson regression, generalized estimating equations (GEE), and mixed-effects regression models. We used cluster-robust standard errors and bias-corrected standard errors. The odds ratio (OR) was 20% higher than the PR when the TB prevalence was >10% in at least one of the exposure factors. When there are three levels of clusters (city, prison, and courtyard), the cluster that had the strongest effect was the courtyard, and the 95% CI estimated with GEE and mixed-effect models were narrower than those estimated with Poisson and binomial models. Exposure factors lost their significance when we used bias-corrected standard errors due to the smaller number of clusters. Tuberculosis transmission dynamics in prisons dictate a strong cluster effect that needs to be considered and adjusted for. The omission of cluster structure and bias-corrected by the small number of clusters can lead to wrong inferences.

This retrospective study included allDuring the study period, 1014

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.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).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.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.

A retrospective study of medically treated isolated left-sided infective endocarditis (LSIE) patients identifying predictors of outcomes with nonoperative management was undertaken.Medical records of 135 Manitoban medically managed LSIE patients from January 2004 to December 2016 were reviewed. Five-year survival for 135 patients and hospitalization data till March 2016 for 65 patients were collected from the Manitoba Centre for Health Policy.In-hospital mortality was 44%. Patients with surgical indications were more likely to die in-hospital than those without (53% vs 24%; P = 0.002). Survival at 1 and 5 years was 43% and 23%, respectively. All-cause readmission at 1 and 5 years was 64% and 84%, respectively. At 1 and 5 years, readmission from major adverse events (heart failure, stroke, endocarditis) was 25% and 47%, and from recurrent endocarditis was 17% and 26%, respectively. Severe valvular regurgitation was a risk factor for in-hospital mortality (odds ratio, 3.52; P = 0.022), poor long-term survival (hazard ratio [HR], 2.57; P0.001), and recurrent endocarditis (HR, 5.93; P 0.001). Prosthetic valve endocarditis was a risk factor for poor long-term survival (HR, 2.11; P = 0.002). Streptococcus viridans group was associated with better rates of in-hospital mortality (odds ratio, 0.28; P = 0.018) and long-term survival (HR, 0.34; P0.001).Nonoperative management of LSIE carries a poor prognosis but may have a role in select cases. Surgical management remains the mainstay for patients with clear surgical indications, including severe regurgitation and prosthetic valve endocarditis. Further prospective analyses are required to better delineate appropriate patient selection for nonsurgical management.

Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP). However, the mechanism causing pulmonary dysfunction remains an enigma. HIV patients experience chronic inflammation. We hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. A prospective cohort pilot study enrolled HIV patients hospitalized in Medellin, Colombia, with a diagnosis of CAP. Sixteen patients were eligible for the study; they were split into 2 groups: HIV and HIV+CAP. Plasma, sputum, and pulmonary function test (PFT) measurements were retrieved within 48 h of hospital admission and at 1 month follow-up. The concentrations of 13 molecules and PFT values were compared between the 2 cohorts. The HIV+CAP group had lower lung function compared to the HIV group; forced vital capacity (FVC)% predicted and forced expiratory volume in 1 s (FEV

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.

The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems.We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation.Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation.

BackgroundThe 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.ResultsThis 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.ConclusionsThe 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.

Objective To 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. Design A 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. Setting Two male Colombian prisons. Participants 15 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 measures Gene 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. Results The 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. Conclusions Recent 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.

Due to poor diagnostics and increased co-infections, HIV-associated Legionella infections are underreported. We aimed to retrospectively determine the frequency of Legionella infections in bronchoalveolar lavage (BAL) from HIV-associated pneumonia patients hospitalized in Medellin, Colombia, between February 2007 and April 2014. Although culture was negative, 17 BAL (36%) were positive for Legionella by quantitative polymerase chain reaction, most of which were in the Mycobacterium tuberculosis or Pneumocystis jirovecii co-infected patients, and included L. anisa (n = 6), L. bozemanae (n = 4), L. pneumophila (n = 3), and L. micdadei (n = 2). All L. bozemanae and L. micdadei associated with Pneumocystis, while all L. pneumophila associated with M. tuberculosis. Legionella probable cases had more complications and higher mortality rates (P = 0.02) and were rarely administered empirical anti-Legionella therapy while in hospital. Clinicians should be aware of the possible presence of Legionella in HIV and M. tuberculosis or P. jirovecii co-infected patients.

Antioquia Department is the state with the highest burden of tuberculosis (TB) in Colombia. Our aim was to determine the risk factors associated with unsuccessful TB treatment in HIV-seropositive and homeless persons, compared with non-HIV-infected and non-homeless persons with TB. We conducted a retrospective cohort study using observational, routinely collected health data from all drug-susceptible TB cases in homeless and/or HIV-seropositive individuals in Antioquia from 2014 to 2016. Unsuccessful TB treatment was defined as individuals having been lost to follow-up, having died, or treatment failure occurrence during the study period. Successful treatment was defined as cure of TB or treatment completion according to the WHO definitions. We identified 544 homeless persons with TB (432 HIV- and 112 HIV+), 835 HIV+ persons with TB and non-homeless, and 5,086 HIV-/non-homeless people with TB. Unsuccessful treatment rates were 19.3% in HIV-/non-homeless persons, 37.4% in non-homeless HIV+ patients, 61.5% in homeless HIV- patients, and 70.3% in homeless HIV+ patients; all rates fall below End TB strategy targets. More than 50% of homeless patients were lost to follow-up. Risk factors associated with unsuccessful treatment were HIV seropositivity, homelessness, male gender, age ≥ 25 years, noncontributory-type health insurance, TB diagnosis made during hospitalization, and previous treatment for TB. These results highlight the challenge of treating TB in the homeless population. These findings should put an onus on TB programs, governments, clinicians, and others involved in the collaborative care of TB patients to pursue innovative strategies to improve treatment success in this population.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ∼12 days following the first and second doses, by 0.31 and 0.43 log10cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.191075][2]][2] A 37-year-old man with HIV infection (CD4+ cell count 706 cells/μL, viral load undetectable) presented with a 3-month history of cough, pharyngitis, low-grade fevers and dark black hemoptysis. A rash had also developed

The current scale of public and private testing cannot be expected to meet the emerging need for higher levels of community-level and repeated screening of asymptomatic Canadians for SARS-CoV-2. Rapid point-of-care techniques are increasingly being deployed to fill the gap in screening levels required to identify undiagnosed individuals with high viral loads. However, rapid, point-of-care tests often have lower sensitivity in practice. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) for SARS-CoV-2 has proven sensitive and specific and provides visual results in minutes. Using a commercially available kit for RT-LAMP and primer set targetting nucleocapsid (N) gene, we tested a blinded set of 101 archived nasopharyngeal (NP) swab samples with known RT-PCR results. RT-LAMP reactions were incubated at 65°C for 30 minutes, using heat-inactivated nasopharyngeal swab sample in viral transport medium, diluted tenfold in water, as input. RT-LAMP agreed with all RT-PCR defined negatives (N=51), and all positives with Ct less than 20 (N=24), 65% of positives with Ct between 20-30 (N=17), and no positives with Ct greater than 30 (N=9). RT-LAMP requires fewer and different core components, so may not compete directly with the mainline testing workflow, preserving precious central laboratory resources and gold standard tests for those with the greatest need. Careful messaging must be provided when using less-sensitive tests, so that people are not falsely reassured by negative results – “glass half empty” – in exchange for reliable detection of those with high levels of virus within an hour, using

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.

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.

Objectives The aim of this work was to review current treatment options and propose alternatives for immune reconstitution inflammatory syndrome (IRIS) in HIV-infected individuals with cryptococcal meningitis (CM) (termed 'HIV-CM IRIS'). As a consequence of the immunocompromised state of these individuals, the initial immune response to CM is predominantly type 2 T helper (Th2) /Th17 rather than Th1, leading to inefficient fungal clearance at the time of antiretroviral initiation, and a subsequent overexaggeration of the Th1 response and life-threatening IRIS development. Methods An article-based and clinical trial-based search was conducted to investigate HIV-CM IRIS pathophysiology and current treatment practices. Results Guidelines for CM treatment, based on the Cryptococcal Optimal Antiretroviral Timing (COAT) trial, recommend delayed antiretroviral therapy (ART) following antifungal treatment. The approach aims to decrease fungal burden and allow immune balance restoration prior to ART initiation. If the initial immune balance is not restored, the fungal burden is not sufficiently reduced and there is a risk of developing IRIS post-ART, highlighted by a Th1 immune overcompensation, leading to increased mortality. The mainstay treatment for Th1-biased IRIS is corticosteroids; however, this treatment has been shown to correlate with increased mortality and significant associated adverse events. We emphasize targeting a more specific Th1 mechanism via the tumour necrosis factor (TNF)-α cytokine antagonist thalidomide, as it is the only TNF-α antagonist currently approved for use in infectious disease settings and has been shown to decrease Th1 overreaction, restoring immune balance in HIV-CM IRIS. Conclusions Although the side effects and limitations of thalidomide must be considered, it is currently being successfully used in infectious disease settings and warrants mainstream application as a therapeutic option for treatment of IRIS in HIV-infected patients with CM.

To determine the prevalence and incidence of LTBI among prison guards and to the risk factors associated with infection. Two male prisons in Medellín and Itaguí, Colombia. A cohort study was conducted in adult prison guards that consented to participate. Exclusion criteria included: previous or current active TB, or conditions that preclude TST administration. We screened 194 guards and completed 155 TST administrations. The prevalence of LTBI was 55.8% in prison one, and 39.1% in prison two. The risk factors associated with LTBI diagnosis included drug use at least once in a lifetime (PR: 1.75; 95% CI 1.42-2.15) and male sex (PR: 2.16; 95% CI 1.01-4.62). The cumulative incidence of TST conversion over 6 months was 3.2%. All conversions occurred in prison 1. Our findings suggest an occupational risk for LTBI prevalence and incidence among guards (different prevalence and incidence according to the prison they work).

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

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

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.

Lung infection in human immunodeficiency virus (HIV)-positive individuals remains an important cause of morbidity and mortality, even in the current antiretroviral therapy era. Pneumonia is the most common cause of admission in HIV-positive individuals in our centre as reported in a previously published study. The objective of this retrospective observational study was to further characterize these admissions, with respect to index of disease severity at presentation, organisms identified, and investigations pursued including bronchoalveolar lavage (BAL). There were 123 unique patients accounting for a total of 209 admissions from 2005 to 2015. An organism was isolated in only 33% of all admissions (68/209). The most common organism was Pneumocystis jirovecii with a frequency of 29% of all admissions. Eighty-seven percent of presentations were mild, and 13% were moderate by CURB-65 criteria. A total of 39 BALs were performed, of which 27 yielded an organism (69%). Considering the burden of disease, low diagnostic yield of the current diagnostic strategy and increased morbidity and mortality caused by pneumonia in HIV-positive individuals, further methods are needed to more accurately target therapy. The preponderance of mild disease in this study suggests that better diagnostic tests may identify individuals that can be candidates for outpatient therapy.

Introduction Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. Methods Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. Results and conclusions APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

This study aims to analyze survival, repeat hospitalization, and risk factors for surgically treated left-sided endocarditis. Retrospective review of all 166 (114 native and 52 prosthetic) patients operated between January 2004 and March 2015 was performed. Long-term survival and repeat hospitalization data for 134 of 166 patients were obtained via linked clinical databases with the Manitoba Centre for Health Policy. Kaplan-Meier estimates of survival and hospital readmission and Cox multivariable regression analysis of factors influencing outcomes were performed. Survival at 1 and 5 years was 91% and 80%, respectively, and major adverse prosthesis-related event repeat hospitalization rates were 12% and 21%, respectively. Repeat hospitalization because of endocarditis was 7% and 11% at 1 and 5 years, respectively. Survival and repeat hospitalization were similar for aortic and mitral valves. Survival after surgically treated endocarditis was similar to survival for age-, sex-, and valve-matched surgical valve replacements for noninfectious indications (P = 0.53). Viridans Streptococci was the most common organism in native valve endocarditis, and culture negative endocarditis was most common in prosthetic valves. Prosthetic valve endocarditis (P 0.01) and preoperative renal dysfunction (P 0.01) were risk factors for in-hospital mortality and major postoperative adverse events. Diabetes and renal dysfunction were associated with poor long-term survival, functional survival, and repeat hospitalization. This analysis suggests that surgery remains a very effective tool in management of these complex patients in terms of survival and major adverse prosthesis-related event repeat hospitalization.

Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history.

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.

Colombia has an underreporting of 30% of the total cases, according to World Health Organization (WHO) estimations. In 2016, successful tuberculosis (TB) treatment rate was 70%, and the mortality rate ranged between 3.5% and 10%. In 2015, Colombia adopted and adapted the End TB strategy and set a target of 50% reduction in incidence and mortality by 2035 compared with 2015. The aims of this study were: To evaluate whether Colombia will be able to achieve the goals of TB incidence and mortality by 2050, using the current strategies; and whether the implementation of new screening, diagnosis and TB treatment strategies will allow to achieve those WHO targets. An ecological study was conducted using TB case-notification, successful treatment and mortality rates from the last 8 years (2009–17). System dynamics analysis was performed using simulated scenarios: (1) continuation with the same trends following the trajectory of the last 8 years (Status quo) and (2) modification of the targets between 2017 through 2050, assuming the implementation of multimodal strategies to increase the screening, to improve the early diagnosis and to improve the treatment adherence. Following the current strategies, it is projected that Colombia will not achieve the End TB strategy targets. Achieving the goal of TB incidence of 10/100 000 by 2050 will only be possible by implementing combined strategies for increasing screening of people with respiratory symptoms, improving access to rapid diagnostic tests and improving treatment adherence. Therefore, it is necessary to design and implement simultaneous strategies according to the population needs and resources, in order to stride towards the End TB targets.