This Phase 1 clinical trial evaluated the safety and immunogenicity of COVAC-2, a recombinant protein subunit vaccine as a heterologous booster in adults previously immunized with authorized COVID-19 vaccines (NCT05226702). COVAC-2 contains the SARS-CoV-2 S1 spike protein subunit adjuvanted with Sepivac SWE™, an open-access oil-in-water adjuvant. Sixty participants were randomized to receive a single intramuscular dose of COVAC-2 (10 µg or 25 µg) or placebo, with follow-up through Day 180. The vaccine was well tolerated, with most adverse events being mild or moderate; no serious adverse events were attributed to vaccination. Immunogenicity assessments included spike-binding antibody ELISA, pseudovirus neutralization assays (PNA), ELISpot, and flow cytometry. The 25 µg dose elicited the strongest humoral and cellular responses, with peak antibody titers observed 14 d after COVAC-2 vaccination. While titers waned, they were sustained above baseline through Day 180. ELISpot and flow cytometry revealed elevated IFN-γ and IL-2 responses indicating antigen-specific T-cell activation. Minimal IL-4 and IL-13 responses were demonstrated by flow cytometry. These findings support the safety and immunogenicity of COVAC-2 as a heterologous booster, particularly at the 25 µg dose level. The favorable safety profile, induction of immune responses, and thermal stability of the vaccine formulation suggest its potential utility in global vaccination strategies, especially in low- and middle-income countries. COVAC-2 may offer a scalable and accessible platform for enhancing protection against COVID-19.Clinicaltrials.gov: NCT05226702 - Registered 22 Jul 2022.

Background:The rates of HIV and syphilis in Saskatchewan (SK) have been rising rapidly in recent years. The syndemic has raised concern for neurosyphilis, a complication that can occur at any stage of syphilis and is more common in people living with HIV (PLWH). Criteria published by the Public Health Agency of Canada recommends considering a lumbar puncture (LP) in patients with concomitant HIV and syphilis infection whose rapid plasma reagin (RPR) titre is ≥1:32 or whose CD4+ count is ≤350. We assessed whether this recommendation was met at 2 comparable clinical sites. Methods:In this retrospective analysis, we compare rates of LP and corresponding syphilis treatment success at two clinics in Saskatoon, SK: a community-based primary care clinic and a tertiary care hospital-based infectious disease clinic. Results:Of 193 syphilis cases across both sites, 128 cases met laboratory criteria for lumbar puncture. Rates of LP (9% primary care clinic and 19% infectious disease clinic) and syphilis treatment success (87% primary care clinic and 89% infectious disease clinic) were comparable between groups. When RPR titre was controlled for, clinic type did not statistically significantly affect the rates of lumbar puncture (p = 0.104) or syphilis treatment success (p = 0.068). A RPR titre ≥1:32 was positively associated with both treatment success (OR 2.596) and lumbar puncture (OR 4.495). Conclusion:Results suggest that there is no difference in either the community or hospital-based clinic type for syphilis treatment success and that rates of lumbar puncture of patients meeting serologic criteria are low across diverse HIV patient groups and clinical settings.

OBJECTIVE:To compare antiretroviral therapy (ART) utilization and adherence before and after expansion of a drug coverage program. METHODS:A retrospective study was conducted using administrative databases in Saskatchewan, Canada. Beneficiaries with at least one diagnostic claim for HIV infection or AIDS between 1999 and 2021 were eligible. An interrupted time series analysis described trends for three indicators of ART utilization before and after drug coverage expansion in 2018: number of active users (defined by at least one ART claim), number of ART claims, and ART spending. A random-effects logistic regression model, controlling for confounders, was used to evaluate the likelihood of achieving at least 95% adherence measured by the proportion of days covered (PDC) before vs. after coverage expansion. RESULTS:A total of 519 individuals received at least one ART claim during the study period and met all other inclusion criteria. Time series models detected statistically significant increases in the number of active ART users and ART claims within 4 months following coverage expansion. Corresponding increases in ART spending were offset by decreases over prior years. No statistically significant changes were detected in the likelihood of achieving at least 95% PDC between the pre vs. postcoverage periods (adjusted odds ratio 1.26, 95% confidence interval: 0.71-2.25, P  = 0.423). CONCLUSION:ART coverage expansion was associated with a higher number of claims, more active users, and a change in spending pattern; however, we did not detect a difference in the likelihood of achieving optimal adherence. Addressing additional gaps in HIV management remains a priority.

An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value remains poorly characterized for influenza A virus (IAV), commonly known as the flu. In this study, we screened tens of thousands of cells using a microfluidic method called droplet quantitative PCR (dqPCR). The high-throughput capability of dqPCR enabled the measurement of a large population of infected cells producing progeny virus. By measuring the fully assembled and successfully released viruses from these infected cells, we discover that the viral burst sizes for both the seasonal H3N2 and the 2009 pandemic H1N1 strains vary significantly, with H3N2 ranging from 101 to 104 viruses per cell, and H1N1 ranging from 101 to 103 viruses per cell. Some infected cells produce average numbers of new viruses, while others generate extensive number of viruses. In fact, we find that only 10% of the single-cell infections are responsible for creating a significant portion of all the viruses. This small fraction produced approximately 60% of new viruses for H3N2 and 40% for H1N1. On average, each infected cell of the H3N2 flu strain produced 709 new viruses, whereas for H1N1, each infected cell produced 358 viruses. This novel method reveals insights into the flu virus and can lead to improved strategies for managing and preventing the spread of viruses.

Future MicrobiologyVol. 18, No. 6 CommentaryZoonotic Staphylococcus pseudintermedius: an underestimated human pathogen?Leah D Blondeau, Harry Deneer, Joseph E Rubin, Rani Kanthan, Stephen E Sanche, Camille L Hamula & Joseph M BlondeauLeah D BlondeauUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada, Harry DeneerDepartment of Pathology & Laboratory Medicine, Saskatoon, SK, S7N 0W8, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada, Joseph E RubinDepartment of Veterinary Microbiology, Saskatoon, SK, S7N 5A2, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada, Rani KanthanDepartment of Pathology & Laboratory Medicine, Saskatoon, SK, S7N 0W8, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada, Stephen E Sanche https://orcid.org/0000-0003-3643-5973Division of Clinical Microbiology, Royal University Hospital & Saskatchewan Health Authority, Saskatoon, SK, S7N 0W8, CanadaDepartment of Medicine, Saskatoon, SK, S7N 0W8, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada, Camille L HamulaDivision of Clinical Microbiology, Royal University Hospital & Saskatchewan Health Authority, Saskatoon, SK, S7N 0W8, CanadaDepartment of Pathology & Laboratory Medicine, Saskatoon, SK, S7N 0W8, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, Canada & Joseph M Blondeau *Author for correspondence: Tel.: +1 306 655 6943; E-mail Address: joseph.blondeau@saskhealthauthority.cahttps://orcid.org/0000-0003-3396-0334Division of Clinical Microbiology, Royal University Hospital & Saskatchewan Health Authority, Saskatoon, SK, S7N 0W8, CanadaDepartment of Biochemistry, Microbiology & Immunology, Saskatoon, SK, S7N 0W8, CanadaDepartment of Pathology & Laboratory Medicine, Saskatoon, SK, S7N 0W8, CanadaDepartment of Ophthalmology, Saskatoon, SK, S7N 0W8, CanadaUniversity of Saskatchewan, Saskatoon, SK, S7N 5A2, CanadaPublished Online:9 May 2023https://doi.org/10.2217/fmb-2023-0069AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: animal transmissionhuman pathogenStaphylococcus pseudintermediuszoonoticPapers of special note have been highlighted as: • of interestReferences1. Messenger AM, Barnes AN, Gray GC. Reverse zoonotic disease transmission (zooanthroponosis): a systematic review of seldom-documented human biological threats to animals. PLOS ONE 9(2), e89055 (2014). • Great review on human-to-animal transmission of pathogens.Crossref, Medline, Google Scholar2. Mallapaty S. Where did COVID come from? Five mysteries that remain. Nature 591(7849), 188–189 (2021). • Good discussion on the origin of COVID.Crossref, Medline, CAS, Google Scholar3. Seimenis A. Zoonoses and poverty – a long road to the alleviation of suffering. Vet. Ital. 48(1), 5–13 (2012).Medline, Google Scholar4. WHO Africa. In Africa, 63% jump in diseases spread from animals to people seen in last decade. African Region: World Health Organization. 14 July 2022 https://www.afro.who.int/news/africa-63-jump-diseases-spread-animals-people-seen-last-decade (Accessed 11 April 2023).Google Scholar5. Overgaauw PaM, Vinke CM, Hagen M, Lipman LJA. 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Uelze L, Grützke J, Borowiak M et al. Typing methods based on whole genome sequencing data. One Health Outlook 2, 3 (2020).Crossref, Medline, Google Scholar18. Eyre DW. Infection prevention and control insights from a decade of pathogen whole-genome sequencing. J. Hosp. Infect. 122, 180–186 (2022).Crossref, Medline, CAS, Google Scholar19. Blondeau LD, Rubin JE, Deneer H, Sanche S, Blondeau JM. Isolation of Staphylococcus kloosii from an ankle wound of an elderly female patient in rural Saskatchewan, Canada: a case report. Ann. Clin. Case Rep. 6, 2073 (2021).Google Scholar20. Danger B, Ripplinger C, Blondeau J, Blondeau L, Peermohamed S. Bacteremia and polyarticular septic arthritis secondary to Moraxella bovis in a pregnant patient with HIV who injects drugs. J. Assoc. Med. Microbiol. Infect. Dis. Can. 7(2), 146–149 (2022).Medline, Google Scholar21. Vitrat V, Hautefeuille S, Janssen C, Bougon D, Sirodot M, Pagani L. Optimizing antimicrobial therapy in critically ill patients. Infect. Drug Resist. 7, 261–271 (2014).Medline, Google ScholarFiguresReferencesRelatedDetails Vol. 18, No. 6 STAY CONNECTED Metrics Downloaded 40 times History Received 21 March 2023 Accepted 30 March 2023 Published online 9 May 2023 Published in print April 2023 Information© 2023 Future Medicine LtdKeywordsanimal transmissionhuman pathogenStaphylococcus pseudintermediuszoonoticAcknowledgmentsThe authors thank D Hills for her excellent clerical support.Financial & competing interests disclosureThe Staphylococcus pseudintermedius investigations are part of the PhD thesis work for L Blondeau, which is funded in part by the Royal University Hospital Foundation grant no. 220207. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Editorial Board Author DisclosureJ.M. Blondeau is a member of the Future Microbiology Editorial Board. They were not involved in any editorial decisions related to the publication of this article, and all author details were blinded to the article's peer reviewers as per the journal's double-blind peer review policyPDF download

The detection of SARS-CoV-2 biomarkers by real time PCR (rRT-PCR) has shown that the sensitivity of the test is negatively affected by low viral loads and the severity of the disease. This limitation can be overcome by the use of more sensitive approaches such as mass spectrometry (MS), which has not been explored for the detection of SARS-CoV-2 proteins in saliva. Thus, this study aimed at assessing the translational applicability of mass spectrometry-based proteomics approaches to identify viral proteins in saliva from people diagnosed with COVID-19 within fourteen days after the initial diagnosis, and to compare its performance with rRT-PCR. After ethics approval, saliva samples were self-collected by 42 COVID-19 positive and 16 healthy individuals. Samples from people positive for COVID-19 were collected on average on the sixth day (± 4 days) after initial diagnosis. Viable viral particles in saliva were heat-inactivated followed by the extraction of total proteins and viral RNA. Proteins were digested and then subjected to tandem MS analysis (LC-QTOF-MS/MS) using a data-dependent MS/MS acquisition qualitative shotgun proteomics approach. The acquired spectra were queried against a combined SARS-CoV-2 and human database. The qualitative detection of SARS-CoV-2 specific RNA was done by rRT-PCR. SARS-CoV-2 proteins were identified in all COVID-19 samples (100%), while viral RNA was detected in only 24 out of 42 COVID-19 samples (57.1%). Seven out of 18 SARS-CoV-2 proteins were identified in saliva from COVID-19 positive individuals, from which the most frequent were replicase polyproteins 1ab (100%) and 1a (91.3%), and nucleocapsid (45.2%). Neither viral proteins nor RNA were detected in healthy individuals. Our mass spectrometry approach appears to be more sensitive than rRT-PCR for the detection of SARS-CoV-2 biomarkers in saliva collected from COVID-19 positive individuals up to 14 days after the initial diagnostic test. Based on the novel data presented here, our MS technology can be used as an effective diagnostic test of COVID-19 for initial diagnosis or follow-up of symptomatic cases, especially in patients with reduced viral load.

BACKGROUND:Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis.OBSERVATIONS:A 3-year-old male who had recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes, which were aborted with levetiracetam and midazolam. Head computed tomography revealed a multilobulated left supratentorial mass with solid and cystic components and measuring 8.0 × 4.8 × 6.5 cm. The patient had successful resection of the mass, which was positive for M. tuberculosis. He was started on rifampin, isoniazid, pyrazinamide, ethambutol, and fluoroquinolone and was discharged home in stable condition.LESSONS:A literature review on pediatric intracranial tuberculoma was performed, which included 48 studies (n = 49). The mean age was 8.8 ± 5.4 years with a slight female predilection (59%). Predominant solitary tuberculomas (63%) were preferentially managed with both resection and antituberculosis therapy (ATT), whereas multifocal tuberculomas were preferentially managed with ATT. Intracranial tuberculoma is a rare but treatable cause of space-occupying lesions in children. Clinicians should maintain a high level of suspicion in patients from endemic regions and involve the infectious disease service early.

Background: Influenza has been shown to exacerbate heart failure (HF). Importantly, no study to date has examined the relationship between HF hospitalizations (HFH) with laboratory confirmed influenza infections. This study evaluated the association between laboratory confirmed influenza infection and HFH in the two largest hospitals in Saskatchewan, Canada. Methods: We used a retrospective self-controlled case series design to evaluate the association between laboratory-confirmed influenza infection and HFH. We compared the incidence ratio for HFH during the influenza risk interval with the control interval. We defined the influenza risk interval as the seven days after a laboratory confirmed influenza result and the control interval as one year before and after the risk interval. Results: We identified 114 HFH that occurred within one year before and after a positive test result for influenza between April 1, 2010, and April 30, 2018. Of these, 28 (28 admissions per week) occurred during the risk interval and 86 (0.853 admissions per week) occurred during the control interval. The incidence ratio of a HFH during the risk interval as compared with the control interval was 33.53 (95% confidence interval [CI], 21.89 to 51.36). A decline in incidence was observed after day seven; between days 8 to 14 and 14 to 28 incidence ratios was 0.91 (95% CI, 0.13 to 6.52) and 0.91 (95% CI, 0.22 to 3.68) respectively. Conclusion: We have observed a significant association between acute influenza infection and HFH. However, further research with a larger sample size and involving a multicenter setting is warranted. Highlights Influenza may contribute and exacerbate heart failure events especially during annual influenza season. Early identification of influenza among patients with heart failure, could lead to earlier treatment with antiviral medication, reduce unnecessary antibiotic use, and tail off the morbidity and mortality. In this study, despite our efficient study design, our sample size was limited to only the two largest hospitals in the province, possibly excluding a significant population in remote areas.

Background The burden of mucormycosis has increased with the expansion of risk groups and improved diagnosis. Although diabetes mellitus has been the leading risk factor for mucormycosis globally, the emergence of risk groups such as hemato-oncology patients, allogeneic bone marrow transplantation and solid organ transplantation have shifted the epidemiology of mucormycosis. There is a paucity of literature describing the burden, clinical presentation, treatment and outcomes of mucormycosis in Canada. CANMUS (Canadian Mucormycosis Study)is a national registry with broad geographical representation ,that will assess the epidemiology and clinical outcomes of Canadian patients affected by mucormycosis. Here we assess the outcomes at 6 and 12 weeks of therapy and last clinical assessment. Methods This retrospective registry involving 15 centers across Canada, from 1/1/2009 to 1/31/2020 using pathology/microbiology records to identify proven cases of mucormycosis in patients ≥18 years of age. Patient medical record data were collected and reported in a web-based data management program (REDCap). Descriptive statistics analyzed both categorical and continuous data. Cox proportional hazards models were used to explore risk factors for 6 and 12-week survival. Logistical regression was employed to investigate factors associated with positive clinical outcomes (defined as partial or complete response versus stable disease or progression). Results Interim data was available on 108 patients. The mean age was 53 (range 20-91) and 55.6% were male patients. The leading diagnostic risk factor for mucormycosis was hematological malignancy (50.9%, of which AML comprised 54.5%) followed by diabetes mellitus (25%). The most common sites of infection were: pulmonary (42.6%) rhino-sinus and/or orbital and/or cerebral (22.2%) and cutaneous (18%). The distribution of pathogens was: Mucor spp. (45.2%), Rhizopus spp. (34.5%) and Lichtheimia spp. (10.7%). Clinical response (composite of complete and partial responses) at 6 and 12 weeks was 31% and 29%, respectively. Survival analyses will be presented using hazard ratios and confidence intervals (CI). Logistic regression of factors associated with a positive clinical response will also be presented. Conclusions The epidemiology of mucormycosis in Canada is evolving. Hematological malignancies rather than diabetes are the major predisposing risk factor for mucormycosis with Mucor spp. being the predominant pathogen. Despite modest advances in therapies, outcomes remain poor.

Discovery of reliable signatures for the empirical diagnosis of neurological diseases—both infectious and non-infectious—remains unrealized. One of the primary challenges encountered in such studies is the lack of a comprehensive database representative of a signature background that exists in healthy individuals, and against which an aberrant event can be assessed. For neurological insults and injuries, it is important to understand the normal profile in the neuronal (cerebrospinal fluid) and systemic fluids (e.g., blood). Here, we present the first comparative multi-omic human database of signatures derived from a population of 30 individuals (15 males, 15 females, 23–74 years) of serum and cerebrospinal fluid. In addition to empirical signatures, we also assigned common pathways between serum and CSF. Together, our findings provide a cohort against which aberrant signature profiles in individuals with neurological injuries/disease can be assessed—providing a pathway for comprehensive diagnostics and therapeutics discovery.

BackgroundAdvances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART).ObjectiveTo examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada.MethodsData were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly.ResultsAll CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016.ConclusionsConcordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

Considerable effort has been made to better understand why some people suffer from severe COVID-19 while others remain asymptomatic. This has led to important clinical findings; people with severe COVID-19 generally experience persistently high levels of inflammation, slower viral load decay, display a dysregulated type-I interferon response, have less active natural killer cells and increased levels of neutrophil extracellular traps. How these findings are connected to the pathogenesis of COVID-19 remains unclear. We propose a mathematical model that sheds light on this issue by focusing on cells that trigger inflammation through molecular patterns: infected cells carrying pathogen-associated molecular patterns (PAMPs) and damaged cells producing damage-associated molecular patterns (DAMPs). The former signals the presence of pathogens while the latter signals danger such as hypoxia or lack of nutrients. Analyses show that SARS-CoV-2 infections can lead to a self-perpetuating feedback loop between DAMP expressing cells and inflammation, identifying the inability to quickly clear PAMPs and DAMPs as the main contributor to hyperinflammation. The model explains clinical findings and reveal conditions that can increase the likelihood of desired clinical outcome from treatment administration. In particular, the analysis suggest that antivirals need to be administered early during infection to have an impact on disease severity. The simplicity of the model and its high level of consistency with clinical findings motivate its use for the formulation of new treatment strategies.

SARS-CoV-2 rapidly spread from a regional outbreak to a global pandemic in just a few months. Global research efforts have focused on developing effective vaccines against COVID-19. However, some of the basic epidemiological parameters, such as the exponential epidemic growth rate and the basic reproductive number, R-0, across geographic areas are still not well quantified. Here, we developed and fit a mathematical model to case and death count data collected from the United States and eight European countries during the early epidemic period before broad control measures were implemented. Results show that the early epidemic grew exponentially at rates between 0.18 and 0.29/day (epidemic doubling times between 2.4 and 3.9 days). We found that for such rapid epidemic growth, high levels of intervention efforts are necessary, no matter the goal is mitigation or containment. We discuss the current estimates of the mean serial interval, and argue that existing evidence suggests that the interval is between 6 and 8 days in the absence of active isolation efforts. Using parameters consistent with this range, we estimated the median R-0 value to be 5.8 (confidence interval: 4.7-7.3) in the United States and between 3.6 and 6.1 in the eight European countries. We further analyze how vaccination schedules depend on R-0, the duration of protective immunity to SARS-CoV-2, and show that individual-level heterogeneity in vaccine induced immunity can significantly affect vaccination schedules. (C) 2021 The Author(s). Published by Elsevier Ltd.

We report a case of borderline oxacillin-resistant S. pseudintermedius (BORSP) in a rheumatoid arthritis patient with severe osteoporosis. The organism is also resistant to erythromycin and clindamycin. We also present clear evidence on transmission from the family dog.

Background:The clinical and demographic characteristics that predict antiretroviral efficacy among patients co-infected with HIV and hepatitis B virus (HBV) remain poorly defined. We evaluated HIV virological suppression and rebound in a cohort of HIV-HBV co-infected patients initiated on antiretroviral therapy.Methods:A retrospective cohort analysis was performed with Canadian Observation Cohort Collaboration data. Cox proportional hazards models were used to determine the factors associated with time to virological suppression and time to virological rebound.Results:HBV status was available for 2,419 participants. A total of 8% were HBV co-infected, of whom 95% achieved virological suppression. After virological suppression, 29% of HIV-HBV co-infected participants experienced HIV virological rebound. HBV co-infection itself did not predict virological suppression or rebound risk. The rate of virological suppression was lower among patients with a history of injection drug use or baseline CD4 cell counts of <199 cells per cubic millimetre. Low baseline HIV RNA and men-who-have-sex-with-men status were significantly associated with a higher rate of virological suppression. Injection drug use and non-White race predicted viral rebound.Conclusions:HBV co-infected HIV patients achieve similar antiretroviral outcomes as those living with HIV mono-infection. Equitable treatment outcomes may be approached by targeting resources to key subpopulations living with HIV-HBV co-infection.

AbstratThe COVID-19 pandemic caused more than 800,000 infections and 40,000 deaths by the end of March 2020. However, some of the basic epidemiological parameters, such as the exponential epidemic growth rate and R0 are debated. We developed an inference approach to control for confounding factors in data collection, such as underreporting and changes in surveillance intensities, and fitted a mathematical model to infection and death count data collected from eight European countries and the US. In all countries, the early epidemic grew exponentially at rates between 0.19-0.29/day (epidemic doubling times between 2.4-3.7 days). This suggests a highly infectious virus with an R0 likely between 4.0 and 7.1. We show that similar levels of intervention efforts are needed, no matter the goal is mitigation or containment. Early, strong and comprehensive intervention efforts to achieve greater than 74-86% reduction in transmission are necessary. One-sentence SummaryWe estimated that COVID-19 spreads rapidly in 8 European countries and the US, suggesting that early, strong and comprehensive interventions are necessary.

Methicillin-resistant Staphylococcus aureus (MRSA) has unfortunately become a common pathogen in many healthcare facilities. In many institutions, vancomycin remains the preferred agent for treating serious MRSA infections including bacteraemia with or without endocarditis. The mutant prevention concentration (MPC) testing >= 10(9) colony forming units of bacteria, describes the antimicrobial drug concentration blocking the growth of the least susceptible cell from high density bacterial populations. With blood culture isolates of MRSA, we discovered strains with MPC values >= 32 mu g/ml and viable cells could be readily recovered from agar plates containing 32 mu g/ml of vancomycin. To investigate MRSA strains surviving in high concentrations of vancomycin on drug containing agar plates, we utilized electron microscopy to measure cell wall thickness as this has been previously reported as a potential mechanism of resistance(1) along with septum thickening. Our data shows MRSA replication from high density bacterial populations in the presence of >= 32 mu g/ml of vancomycin. Such observations may explain vancomycin failure in some patients and/or persistent bacteraemia and could potentially question the use of this drug in some critically ill patients in favour of an alternative agent.

Background: cART has significantly improved the life expectancy of people living with HIV (PLWH). However, it fails to eliminate the long-lived reservoir of latent HIV-infected cells. Radioimmunotherapy (RIT) relies on antigen-specific monoclonal antibodies (mAbs) for targeted delivery of lethal doses of ionizing radiation to cells. Previously, we have demonstrated that human mAb 2556 against HIV gp41 conjugated with (213)Bismuth radioisotope (t(1/2) = 46 min, alpha-emitter) selectively killed HIV-infected cells. (225)Actinium (t(1/2 )= 9.92 d, alphaemitter) and (177)Lutetium (t(1/2) = 6.7 d, beta-emitter) are two long-lived clinically proven radioisotopes for cancer treatment which might be more effective in killing infected cells systemically and in CNS. Methods: In this study we have conjugated 2556 mAb with Bi-213, Ac-225 and Lu-177, and compared their ability to kill HIV-infected human peripheral blood mononuclear cells (PBMCs) and monocytes. PBMCs and monocytes from healthy donors were infected with HIVp49.5 and treated in vitro with increasing concentrations of Bi-213 (4-20 mu Ci )-, Ac-225 (20-100 nCi)- and 177 Lu (4-50 mu Ci)-2556 mAb. Results: After three days post-treatment of infected PBMCs and monocytes, Bi-213- and Lu-177-conjugated 2556 mAb reduced virus production measured by p24 level in a dose-dependent manner, whereas, Ac-225-2556 showed minimal effect However, seven days post-treatment all three radioisotopes showed significantly more pronounced reduction of virus replication as compared to control labeled mAb with Ac-225-2556 showing the least non-specific killing. Conclusion: These results indicate that RTT holds promise as a novel treatment option for the eradication of HIV-infected cells that merits further study in combination with cART and reactivation drugs. (C) 2020 Elsevier Inc. All rights reserved.

Abstrat The COVID-19 pandemic caused more than 800,000 infections and 40,000 deaths by the end of March 2020. However, some of the basic epidemiological parameters, such as the exponential epidemic growth rate and R 0 are debated. We developed an inference approach to control for confounding factors in data collection, such as underreporting and changes in surveillance intensities, and fitted a mathematical model to infection and death count data collected from eight European countries and the US. In all countries, the early epidemic grew exponentially at rates between 0.19-0.29/day (epidemic doubling times between 2.4-3.7 days). This suggests a highly infectious virus with an R 0 likely between 4.0 and 7.1. We show that similar levels of intervention efforts are needed, no matter the goal is mitigation or containment. Early, strong and comprehensive intervention efforts to achieve greater than 74-86% reduction in transmission are necessary. One-sentence Summary We estimated that COVID-19 spreads rapidly in 8 European countries and the US, suggesting that early, strong and comprehensive interventions are necessary.