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Objective Many individuals exposed to SARS-CoV-2 experience long-term symptoms as part of a syndrome called post-COVID condition (PCC). Research on PCC is still emerging but is urgently needed to support diagnosis, clinical treatment guidelines and health system resource allocation. In this study, we developed a method to identify PCC cases using administrative health data and report PCC prevalence and predictive factors in Manitoba, Canada.Design Cohort study.Setting Manitoba, Canada.Participants All Manitobans who tested positive for SARS-CoV-2 during population-wide PCR testing from March 2020 to December 2021 (n=66 365) and were subsequently deemed to have PCC based on International Classification of Disease-9/10 diagnostic codes and prescription drug codes (n=11 316). Additional PCC cases were identified using predictive modelling to assess patterns of health service use, including physician visits, emergency department visits and hospitalisation for any reason (n=4155).Outcomes We measured PCC prevalence as % PCC cases among Manitobans with positive tests and identified predictive factors associated with PCC by calculating odds ratios with 95% confidence intervals, adjusted for sociodemographic and clinical characteristics (aOR).Results Among 66 365 Manitobans with positive tests, we identified 15 471 (23%) as having PCC. Being female (aOR 1.64, 95% CI 1.58 to 1.71), being age 60–79 (aOR 1.33, 95% CI 1.25 to 1.41) or age 80+ (aOR 1.62, 95% CI 1.46 to 1.80), being hospitalised within 14 days of COVID-19 infection (aOR 1.95, 95% CI 1.80 to 2.10) and having a Charlson Comorbidity Index of 1+ (aOR 1.95, 95% CI 1.78 to 2.14) were predictive of PCC. Receiving 1+ doses of the COVID-19 vaccine (one dose, aOR 0.80, 95% CI 0.74 to 0.86; two doses, aOR 0.29, 95% CI 0.22 to 0.31) decreased the odds of PCC.Conclusions This data-driven approach expands our understanding of the prevalence and epidemiology of PCC and may be applied in other jurisdictions with population-based data. The study provides additional insights into risk and protective factors for PCC to inform health system planning and service delivery.

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.

We analyzed body lice collected from persons experiencing homelessness in Winnipeg, Manitoba, Canada, during 2020–2021 to confirm vector species and ecotype and to identify louseborne pathogens. Of 556 lice analyzed from 7 persons, 17 louse pools (218 lice) from 1 person were positive for the louseborne bacterium Bartonella quintana.

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.

Background:Bartonella quintana is a body-louse-borne bacterium. Canadian B. quintana disease has been reported primarily in populations experiencing homelessness and in Indigenous communities with limited access to water. We sought to understand the epidemiology of B. quintana in Canada. Methods: This study combined an analysis of laboratory data from Canada’s National Microbiology Laboratory (NML) with a systematic review of the literature. Laboratory data included quantitative polymerase chain reaction (qPCR) cycle threshold values and indirect immunofluorescent antibody titers with the year and province of the sample acquisition. For the systematic review, we searched PubMed, Scopus, Embase, and Web of Science for articles published before 15 July 2024, with terms related to B. quintana in Canada. Results: Thirty-three individuals with qPCR-positive B. quintana were documented in seven provinces and one territory. The number of cases increased over time (p-value = 0.005), with the greatest number of cases being reported in 2022 and 2023. The percent positivity for the B. quintana qPCR performed at the NML increased over time (p-value = 0.036). The median immunoglobulin G titer demonstrated a sustained increase starting in 2017. The systematic review identified fourteen individuals with qPCR-positive B. quintana (none had a qPCR performed at the NML) and seven probable cases of B. quintana disease. Four of these twenty-one individuals from the systematic review died (19%). All fatalities were attributed to endocarditis. Conclusions: The detection of B. quintana disease in seven provinces and one territory suggests that B. quintana has a national distribution. B. quintana disease is increasingly diagnosed in Canada, indicating ongoing transmission across geographic settings.

Marginalized groups in Manitoba, Canada, especially females and people who inject drugs, are overrepresented in new HIV diagnoses and disproportionately affected by HIV and structural disadvantages. Informed by syndemic theory, our aim was to understand people living with HIV’s (PLHIV) gendered and intersecting barriers and facilitators across the cascade of HIV care before and during the COVID-19 pandemic. This study was co-designed and co-led alongside people with lived experience and a research advisory committee. We employed semi-structured interviews with thirty-two participants and three questionnaires. Interviews were audio-recorded, transcribed, and coded, and descriptive statistics were performed on the first two questionnaires. Qualitative data analysis used thematic analysis and focused on identifying categories (individual, healthcare, and social/structural) related to the barriers and facilitators to HIV care. A total of 32 PLHIV completed this study and over 70% of females and 50% of males reported severe and moderate sexual abuse among other traumatic childhood experiences. Barriers to accessing or continuing in the cascade of HIV care included navigating the initial shock of receiving an HIV diagnosis, mental health challenges and inaccessible supports, substance use, violence (including intimate partner), internalized and enacted compounded stigma related to houselessness and substance use, discrimination by primary care service providers and social networks, lack of preventative and social supports, lack of accessible housing, and programmatic issues. COVID-19 increased mental health problems and disrupted relationships with HIV service providers and peers living with HIV. Facilitators to HIV care included stopping substance use, caring service providers particularly during HIV diagnosis, welcoming healthcare environments, social opportunities and integrated supports, and supportive social networks. Women, men, and non-binary PLHIV experience interconnected factors complicating their experiences with HIV care. Interventions should consider holistic, person-centered, and trauma-informed care options to address the barriers found in this research and appropriately serve PLHIV.

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.

Legionella is an underdiagnosed and underreported etiology of pneumonia. Legionella pneumophila serogroup 1 (LpSG1) is thought to be the most common pathogenic subgroup. This assumption is based on the frequent use of a urinary antigen test (UAT), only capable of diagnosing LpSG1. We aimed to explore the frequency of Legionella infections in individuals diagnosed with pneumonia and the performance of diagnostic methods for detecting Legionella infections. We conducted a scoping review to answer the following questions: (1) “Does nucleic acid testing (NAT) increase the detection of non-pneumophila serogroup 1 Legionella compared to non-NAT?”; and (2) “Does being immunocompromised increase the frequency of pneumonia caused by non-pneumophila serogroup 1 Legionella compared to non-immunocompromised individuals with Legionnaires’ disease (LD)?”. Articles reporting various diagnostic methods (both NAT and non-NAT) for pneumonia were extracted from several databases. Of the 3449 articles obtained, 31 were included in our review. The most common species were found to be L. pneumophila, L. longbeachae, and unidentified Legionella species appearing in 1.4%, 0.9%, and 0.6% of pneumonia cases. Nearly 50% of cases were caused by unspecified species or serogroups not detected by the standard UAT. NAT-based techniques were more likely to detect Legionella than non-NAT-based techniques. The identification and detection of Legionella and serogroups other than serogroup 1 is hampered by a lack of application of broader pan-Legionella or pan-serogroup diagnostics.

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.

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).

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.

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.

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.

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.

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

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.

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 (

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.

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.

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.

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.

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.