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Background: Essential non-healthcare workers experienced higher rates of SARS-CoV-2 infection compared to non-essential workers., Objective: Identify characteristics associated with SARS-CoV-2 testing, infection and vaccine uptake among essential non-healthcare workers in Montréal, Québec., Methods: Secondary, cross-sectional analysis of data collected from participants prospectively recruited in two observational studies (first study, Onsite Testing Study, January-March 2021; second study, Self-Testing Study, July-October 2021) of essential non-healthcare workers in 2021. Logistic regression with generalized linear mixed models was used to explore characteristics associated with our outcomes (previous SARS-CoV-2 testing, exposure and vaccination)., Results: Overall, 2,755 participants were included (first study, Onsite Testing Study, n=2,128; and second study, Self-Testing Study, n=627). A higher proportion of participants identified as male (n=1,601; 58%), non-White (n=1,527; 55%) and worked in the manufacturing/supplier sector (n=1,706; 62%). Relative to the first study, Onsite Testing Study, participants in the second study, Self-Testing Study, had higher odds (78% vs. 46%; aOR 4.1, 95% CI: 3.2-5.2) of previous SARS-CoV-2 testing and of testing positive prior to study enrolment (6.2% vs. 4.3%; aOR 1.7, 95% CI: 1.1-2.6). Individuals reporting recent SARS-CoV-2 exposure had higher odds of previous SARS-CoV-2 testing (aOR 4.0, 95% CI: 3.0-5.4), while older age (aOR 0.98, 95% CI: 0.98-0.99 per one-year increase) and being male (aOR 0.6, 95% CI: 0.5-0.7) were associated with lower odds of previous testing. Results were similar in stratified analyses. Participants from businesses with more than 50 employees had higher odds of having received a SARS-CoV-2 vaccine (91% vs. 80%; aOR 2.6, 95% CI: 1.4-4.8)., Conclusion: Consideration of individual and business characteristics associated with testing and vaccination programs for SARS-CoV-2 could improve equity, uptake and impact., Competing Interests: Competing interests JP has received grants from AbbVie and MedImmune; personal fees from AstraZeneca and grants and personal fees from Merck; and has served as an advisor to the Canadian Federal COVID-19 Immunity Task Force, unrelated to and outside of the submitted work. CPY has provided consulting services to and sat on independent data monitoring committees for Medicago; and has served as scientific advisor for the Canadian Federal COVID-19 Immunity Task Force, unrelated to and outside the submitted work. JRC has provided SARS-CoV-2 consulting services to the Canadian Federal COVID-19 Immunity Task Force and the World Bank, unrelated to and outside the submitted work. The other authors (CC and DM) report no competing interests.

Background: 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., Methods: 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., Results: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir ( n = 634) or standard of care ( n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care ( p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups., Interpretation: 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. Trial registration : ClinicalTrials.gov, no. NCT04330690., Competing Interests: Competing interests: Alexandra Binnie reports receiving research grants from the Canadian Institutes of Health Research (CIHR) and the Physicians Services Incorporated Foundation. Sergio Borgia reports receiving honoraria from Gilead Sciences and GSK. Yiorgos Alexandros Cavayas reports receiving a grant from CIHR. Matthew Cheng reports receiving grants from the McGill Interdisciplinary Initiative in Infection and Immunity and from CIHR, during the conduct of the study (payments made to the institution). Dr. Cheng also reports receiving personal fees from AstraZeneca, outside the submitted work; and from Nplex Biosciences and GEn1E lifesciences (in the form of stock options for being a member of the scientific advisory board) outside the submitted work. Dr. Cheng co-founded Kanvas Biosicences and owns equity in the company, and reports 3 patents pending. John Conly reports receiving grants from CIHR, Pfizer, the World Health Organization (WHO), Sunnybrook Research Institute, University of Calgary, and the Calgary Health Foundation. Dr. Conly also reports receiving support to attend the Think Tank Meeting 2019. Dr. Conly is a member and Chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19, a member of the WHO Health Emergencies Programme (WHE) Ad-hoc COVID-19 IPC Guidance Development Group, and a member of the Cochrane Acute Respiratory Infections Group. Madeleine Durand reports receiving grants from CIHR and the Fonds Recherche du Québec–Santé (FRQS). Rob Fowler reports receiving a grant from CIHR for the CATCO trial and is the H. Barrie Fairley Professor of Critical Care at the University Health Network. Michael Fralick reports receiving multiple grants from CIHR and support from grants from the Canadian military for clinical trials to identify treatments for COVID-19 (payments made to institution). Dr. Fralick is a paid consultant for a start-up company called Proof DiagnosticsDx, which has created a point-of-care testing device using CRISPR for COVID-19. Holly Hoang reports receiving payment from CATCO Sunnybrook to fund research assistant (payment made to institution) and a research grant from Covenant Health Research Centre. Marina Klein reports receiving grants from Gilead, ViiV Healthcare, Merck and AbbVie for investigator-initiated studies, and consulting fees from Gilead, ViiV Healthcare, Merck and AbbVie, all outside the submitted work. Todd Lee reports receiving operating grants from CIHR and McGill Interdisciplinary Initiative in Infection and Immunity (MI4), and research salary support from FRQS. Alexandra Lostun reports receiving per-case funding to cover the costs of enrolling patients (paid to institution, North York General Hospital). François Carrier reports receiving grants from the Instituts de recherche en santé du Canada and the Canadian Donation and Transplantation Research Program, and a grant and salary support from FRQS. Marlee McGuinty reports receiving speaking fees from Merck. Srinivas Murthy reports receiving a grant from CIHR, during the conduct of the study, and is the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research. Conar O’Neil reports receiving conference sponsorship from Gilead Sciences, and is a member of a Gilead Sciences advisory board. Jesse Papenburg reports receiving a grant from CIHR, during the conduct of the study, as well as research grants and contracts from AbbVie and research contracts (site investigator for clinical trial) from MedImmune, Merck and Sanofi Pasteur. Dr. Papenburg has received consulting fees from Merck for an ad hoc advisory board meeting, and honoraria for presentations from Seegene, AbbVie and AstraZeneca. Dr. Papenburg is also a voting member of the National Advisory Committee on Immunization. Ken Kuljit S. Parhar reports receiving a CIHR project grant, Alberta Innovates grant and Alberta Health Innovation Implementation and Spread grant (all paid to institution). Seema Nair Parvathy reports receiving funding from St. Joseph’s Health Care Foundation and London Health Sciences Foundation. Moira Rushton-Marovac reports receiving advisory board honoraria from Gilead. Marina Salvadori reports being an employee of the Public Health Agency of Canada. Makeda Semret reports receiving support from the McGill MI4 for the clinical research platform through which CATCO was supported at the McGill University Health Centre. Ameeta Singh reports receiving consulting fees from Gilead for membership of an advisory board. Ranjani Somayaji reports receiving contract research funding from Sunnybrook Research Institute, University of Calgary and Calgary Health Foundation, and clinical research funding from CIHR and the Cystic Fibrosis Foundation. Dr. Somayaji also reports participation on an oncovir data monitoring safety board. Darrell Tan reports receiving grants from AbbVie (in-kind drug only) and Gilead (in-kind drug and grants to institution), and a contract between GSK and the institution for clinical trials. Alain Tremblay reports receiving contract research funding from the Sunnybrook Research Institute, and grants for COVID-19 clinical trials from the University of Calgary and Calgary Health Foundation. Alexis Turgeon reports receiving a grant from CIHR. Jason Weatherald reports receiving grants (paid to institution) and consulting fees (paid to Dr. Weatherald) from Janssen and Actelion, as well as honoraria and travel support from Janssen. Dr. Weatherald has served on advisory boards for Janssen and Acceleron (paid) and on a Data Safety Monitoring Board for Université Laval (unpaid). Dr. Weatherald also reports membership of the Medical Advisory Committee of the Pulmonary Hypertension Association of Canada, and is a shareholder of Precision Lung Consultants and Diagnostics. Cedric Yansouni reports receiving grants from FRQS and consulting fees from Medicago Inc. Dr. Yansouni also reports participation in a Medicago Inc. Independent Data Monitoring Committee and held the role of scientific advisor for the COVID-19 Immunity Task Force. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

This review provides an update on the factors fuelling antimicrobial resistance and shows the impact of these factors in low-resource settings. We detail the challenges and barriers to integrating clinical bacteriology in hospitals in low-resource settings, as well as the opportunities provided by the recent capacity building efforts of national laboratory networks focused on vertical single-disease programmes. The programmes for HIV, tuberculosis and malaria have considerably improved laboratory medicine in Sub-Saharan Africa, paving the way for clinical bacteriology. Furthermore, special attention is paid to topics that are less familiar to the general medical community, such as the crucial role of regulatory frameworks for diagnostics and the educational profile required for a productive laboratory workforce in low-resource settings. Traditionally, clinical bacteriology laboratories have been a part of higher levels of care, and, as a result, they were poorly linked to clinical practices and thus underused. By establishing and consolidating clinical bacteriology laboratories at the hospital referral level in low-resource settings, routine patient care data can be collected for surveillance, antibiotic stewardship and infection prevention and control. Together, these activities form a synergistic tripartite effort at the frontline of the emergence and spread of multi-drug resistant bacteria. If challenges related to staff, funding, scale, and the specific nature of clinical bacteriology are prioritized, a major leap forward in the containment of antimicrobial resistance can be achieved. The mobilization of resources coordinated by national laboratory plans and interventions tailored by a good understanding of the hospital microcosm will be crucial to success, and further contributions will be made by market interventions and business models for diagnostic laboratories. The future clinical bacteriology laboratory in a low-resource setting will not be an "entry-level version" of its counterparts in high-resource settings, but a purpose-built, well-conceived, cost-effective and efficient diagnostic facility at the forefront of antimicrobial resistance containment., (Copyright © 2019 Jacobs, Hardy, Semret, Lunguya, Phe, Affolabi, Yansouni and Vandenberg.)

Background: There is an urgent need for integrated diagnosis of febrile syndromes able to account for multiple pathogens and to inform decisions for clinical care and public health., Aims: To reflect on the evolving roles of laboratory-based testing for non-malarial febrile illnesses (NMFIs) in low-resource settings, and to consider how advances in diagnostics, in connectivity and transport, and in implementation of quality systems may substantially enhance the capacity of reference laboratories to bridge the current gap between remote passive surveillance and clinically meaningful integrated fever diagnosis., Sources: Iterative search of PubMed databases, organizational reports, and expert consultation., Content: Implementation of new technologies-such as very broad molecular panels for surveillance and mass spectrometry-may considerably diminish capability gaps in reference laboratories in low-resource settings. Although the need for clinical bacteriology diagnostics is now recognized, the lack of new simple and rapid phenotypic tests for antimicrobial resistance remains a key deficiency. Several initiatives to strengthen diagnostic preparedness for infectious disease outbreaks have highlighted the need for functional tiered laboratory networks. Recently, dramatic headway in connectivity-such as combining automated readers with the image processing and data transmission capabilities of smartphones-now allows for more complex testing and interfacing with distant laboratory information systems while reducing workload and errors. Together with connectivity to transmit and receive results, new approaches to specimen collection and transport-such as the validation of rectal swabs and the use of aerial drones to transport specimens to distant laboratories-now make remote testing feasible. The above innovations also open up the possibility of implementing quality systems through community-level diagnostic stewardship. Finally, strengthened laboratory networks actively support the feasibility of implementing quality-assured point-of-care testing where it is needed., Implications: Recent advances offer the present-day possibility of innovations to re-invent the relationship between distant reference laboratories and end-users for integrated diagnosis of NMFIs., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The declining trend of malaria and the recent prioritization of containment of antimicrobial resistance have created a momentum to implement clinical bacteriology in low-resource settings. Successful implementation relies on guidance by a quality management system (QMS). Over the past decade international initiatives were launched towards implementation of QMS in HIV/AIDS, tuberculosis and malaria., Aims: To describe the progress towards accreditation of medical laboratories and to identify the challenges and best practices for implementation of QMS in clinical bacteriology in low-resource settings., Sources: Published literature, online reports and websites related to the implementation of laboratory QMS, accreditation of medical laboratories and initiatives for containment of antimicrobial resistance., Content: Apart from the limitations of infrastructure, equipment, consumables and staff, QMS are challenged with the complexity of clinical bacteriology and the healthcare context in low-resource settings (small-scale laboratories, attitudes and perception of staff, absence of laboratory information systems). Likewise, most international initiatives addressing laboratory health strengthening have focused on public health and outbreak management rather than on hospital based patient care. Best practices to implement quality-assured clinical bacteriology in low-resource settings include alignment with national regulations and public health reference laboratories, participating in external quality assurance programmes, support from the hospital's management, starting with attainable projects, conducting error review and daily bench-side supervision, looking for locally adapted solutions, stimulating ownership and extending existing training programmes to clinical bacteriology., Implications: The implementation of QMS in clinical bacteriology in hospital settings will ultimately boost a culture of quality to all sectors of healthcare in low-resource settings., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ten Belgian travelers returned from Mali with a Schistosoma haematobium-Schistosoma bovis hybrid infection, confirmed by DNA sequencing from eggs. Clinical symptoms and laboratory findings resembled those of classic acute schistosomiasis, but the detected eggs were morphologically unusual., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Competing Interests: The authors have declared that no competing interests exist.

Background: In light of the 2016 summer Olympic games it is anticipated that Canadian practitioners will require information about common illnesses that may affect travellers returning from Brazil., Objective: To identify the demographic and travel correlates of illness among recent Canadian travellers and migrants from Brazil attending a network of travel health clinics across Canada., Methods: Data was analyzed on returned Canadian travellers and migrants presenting to a CanTravNet site for care of an illness between June 2013 and June 2016., Results: During the study period, 7,707 ill travellers and migrants presented to a CanTravNet site and 89 (0.01%) acquired their illness in Brazil. Tourists were most well represented (n=45, 50.6%), followed by those travelling to "visit friends and relatives" (n=14, 15.7%). The median age was 37 years (range <1-78 years), 49 travellers were men (55.1%) and 40 were women (44.9%). Of the 40 women, 26 (65%) were of childbearing age. Nine percent (n=8) of travellers were diagnosed with arboviruses including dengue (n=6), chikungunya (n=1) and Zika virus (n=1), while another 14.6% (n=13) presented for care of non-specific viral syndrome (n=7), non-specific febrile illness (n=1), peripheral neuropathy (n=1) and non-specific rash (n=4), which are four syndromes that may be indicative of Zika virus infection. Ill returned travellers to Brazil were more likely to present for care of arboviral or Zika-like illness than other ill returned travellers to South America (23.6 per 100 travellers versus 10.5 per 100 travellers, respectively [ p =0.0024])., Interpretation: An epidemiologic approach to illness among returned Canadian travellers to Brazil can inform Canadian practitioners encountering both prospective and returned travellers to the Olympic games. Analysis showed that vector-borne illnesses such as dengue are common and even in this small group of travellers, both chikungunya and Zika virus were represented. It is extremely important to educate travellers about mosquito-avoidance measures in advance of travel to Brazil., Competing Interests: Conflict of interest: None.

Bacteremia due to Cloacibacillus species is poorly described. We present three cases involving either Cloacibacillus evryensis or Cloacibacillus porcorum. The isolates were identified by 16S rRNA gene sequencing and were susceptible to antibiotics commonly used for anaerobic infections. The clinical significance of these organisms as potential emerging pathogens is discussed., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

The detection of schistosomiasis cases among Belgian military personnel returning from a mission in the Democratic Republic of Congo (DRC) prompted a nested case-control study of all military personnel deployed in the DRC between 2005 and 2008 to identify all infections and to start appropriate treatment. Of 197 patients exposed at Lake Tanganyika in the Kalemie area of DRC, 49 (24.9%) were diagnosed with schistosomiasis. Swimming was significantly more frequent than wading in the seropositive group than in the seronegative group (88.9% vs. 73.6%; odds ratio [OR], 2.86; 95% confidence interval [CI], 0.97-9.01). Thirty-one of 49 patients (63.3%) were symptomatic; including skin problems in 34.7%, respiratory symptoms in 12.2%, fever in 14.3%, and 51.0% with gastrointestinal problems. Median eosinophil counts were significantly higher in seropositive patients (375 vs. 138 per tL; Wilcoxon rank sum test [Ws] = 10,559.00; p < 0.01; r = -0.49). In total, 20 (40.8%) of the 49 patients were treated for symptomatic infections and the remainder for asymptomatic schistosomiasis. Our study emphasizes the need for active systematic post-tropical screening in military personnel after deployment to Schistosoma-endemic regions of the world.

Tuberculosis (TB) infection is relatively frequent among travellers to high incidence-countries, especially in long-term travellers and those involved in health work. It is important to diagnose recent infection, both for the affected individual and to prevent further transmission. Based on published literature, we assess the value of interferon-γ release assays (IGRAs) as a complement to or replacement of the tuberculin skin test (TST) for the diagnosis of latent TB infection in the setting of a travel clinic. A comparison of available IGRAs with the TST in terms of operating characteristics and practical considerations is presented. We conclude that IGRAs offer some practical advantages that may benefit certain well-defined patient groups of a travel clinic, but that current evidence is incomplete. We identify research questions to better define the role of IGRAs in these populations.

Many human epithelial carcinomas are characterized by the overexpression and constitutive activation of the epidermal growth factor receptor (EGF-R) via an autocrine signaling loop. We have investigated the effects of a ligand-blocking monoclonal antibody (mAb) against the EGF-R LA1 on selected parameters of human lung cancer cell lines (H322 and H661) and normal human bronchial epithelial (NHBE) cells. Using Western blot analysis, we show that H322 and NHBE cell lines express comparable levels of EGF-R/p170erbB-1. The LA1 mAb against EGF-R inhibits growth, induces differentiation to a more epithelial phenotype, reduces the constitutive activation of EGF-R, and upregulates epithelial cadherin glycoprotein expression in H322 and NHBE cells. In contrast, LA1 had no effect on either growth, differentiation, receptor tyrosine phosphorylation, or the expression of adhesion molecules in H661 cells, which is consistent with our finding that this cell line does not express detectable levels of EGF-R. These studies demonstrate that a blocking anti-EGF-R mAb can regulate proliferation, differentiation, and the expression of cell adhesion molecules in human bronchial epithelial cells. Our findings suggest possible therapeutic avenues for the treatment of invasive carcinomas via the blockade of EGF-R with antibodies.

The investigation of a N-terminally truncated human transforming growth factor-alpha (TGF-alpha; residues 8-50) has been completed to determine the contribution of the N terminus to receptor binding and activation. The deletion protein was proposed and designed through study of NMR relaxation and nuclear Overhauser enhancement data obtained from the TGF-alpha-epidermal growth factor (EGF) receptor complex, which indicated that the residues N-terminal to the A loop remain flexible in receptor-bound TGF-alpha and thus suggested their lack of involvement in receptor binding (Hoyt, D. W., Harkins, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283-15292; McInnes, C., Hoyt, D. W., Harkins, R. N., Pagila, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1996) J. Biol. Chem. 271, 32204-32211). TGF-alpha 8-50 was shown to have approximately 10-fold lower affinity for the receptor than the native molecule in an assay quantifying the ability to compete with EGF for binding and to have a similar reduction in activity as indicated by a cell proliferation assay. NMR solution structural calculations on this molecule demonstrate correct formation of the three disulfide bonds of TGF-alpha 8-50 and have established the presence of native secondary structure in the B and C loops of the protein. However, some perturbation of the global fold with respect to the orientation of the subdomains was observed. These results suggest that although the N-terminal residues do not contribute directly to binding, they make a significant contribution in defining the conformation of the growth factor, which is required for complete binding and activity and is therefore significant in terms of producing native folding of TGF-alpha. They also show that information obtained from the receptor-bound ligand can be used to guide the design and minimization of TGF-alpha analogues. The implications of the study of TGF-alpha 8-50 for the design and synthesis of reductants of this growth factor are therefore discussed.