2023/24 mid-season influenza and Omicron XBB.1.5 vaccine effectiveness estimates from the Canadian Sentinel Practitioner Surveillance Network (SPSN).

The Canadian Sentinel Practitioner Surveillance Network reports mid-season 2023/24 influenza vaccine effectiveness (VE) of 63% (95% CI: 51-72) against influenza A(H1N1)pdm09, lower for clade 5a.2a.1 (56%; 95% CI: 33-71) than clade 5a.2a (67%; 95% CI: 48-80), and lowest against influenza A(H3N2) (40%; 95% CI: 5-61). The Omicron XBB.1.5 vaccine protected comparably well, with VE of 47% (95% CI: 21-65) against medically attended COVID-19, higher among people reporting a prior confirmed SARS-CoV-2 infection at 67% (95% CI: 28-85).

COVID-19 in correctional facilities in Ontario, Canada: a retrospective epidemiological analysis from 15 January 2020 to 31 December 2022.

PURPOSE: The physical environment of correctional facilities promote infectious disease transmission and outbreaks. The purpose of this study is to compare the COVID-19 burden between the correctional facility (incarcerated individuals and staff members) and non-correctional facility population in Ontario during the COVID-19 pandemic. DESIGN/METHODOLOGY/APPROACH: All individuals in Ontario with a laboratory confirmation of SARS-CoV-2 between 15 January 2020 and 31 December 2022 and entered into the provincial COVID-19 data were included. Cases were classified as a correctional facility case (living or working in a correctional facility) or a non-correctional facility case. COVID-19 vaccination status was obtained from the provincial COVID-19 vaccine registry. Statistics Canada census data were used to calculate COVID-19 incidence and hospitalization rates for incarcerated cases and the non-correctional facility population. FINDINGS: Between 15 January 2020 and 31 December 2022, there were 1,550,045 COVID-19 cases in Ontario of which 8,292 (0.53%) cases were reported in correctional (63.8% amongst incarcerated individuals, 18.6% amongst staff and 17.7% amongst an unknown classification) and 1,541,753 (99.47%) were non-correctional facility cases. Most cases in correctional facilities were men (83.8%) and aged 20-59 years (93.1%). COVID-19 incidence and hospitalization rates were generally higher among incarcerated individuals compared to the non-correctional facility population throughout the study period. COVID-19 incidence peaked in January 2022 for both the correctional facility population (21,543.8 per 100,000 population) and the non-correctional facility population (1915.1 per 100,000 population). The rate of COVID-19 hospitalizations peaked for the correctional facility population aged 20-59 in March 2021 (70.7 per 100,000 population) and in April 2021 for the non-correctional facility population aged 20-59 (19.8 per 100,000 population). A greater percentage of incarcerated individuals (73.0%) were unvaccinated at time of their COVID-19 diagnosis compared to the non-correctional facility population (49.3%). Deaths amongst correctional facility cases were rare (0.1%, 6 / 8,292) compared to 1.0% of non-correctional facility cases (n = 15,787 / 1,541,753). ORIGINALITY/VALUE: During the COVID-19 pandemic, individuals incarcerated in correctional facilities in Ontario had higher COVID-19 incidence and hospitalization rates compared to the non-correctional facility population. These results support prioritizing incarcerated individuals for public health interventions to mitigate COVID-19 impacts in correctional facilities.

Differential interactions between statins and P-glycoprotein: implications for exploiting statins as anticancer agents.

Statins, prescribed for decades to control cholesterol, have more recently been shown to have promising anticancer activity. Statins induce tumor-selective apoptosis by inhibiting the mevalonate (MVA) pathway. In addition, we have recently demonstrated that lovastatin modulates drug accumulation in a MVA-independent manner in multidrug-resistant (MDR) tumor cells overexpressing the P-glycoprotein (P-gp) multidrug transporter. P-gp-mediated drug efflux can contribute to chemotherapy failure. However, direct statin-mediated inhibition of P-gp in human MDR tumor cells at clinically achievable concentrations remains unexplored. An understanding of these interactions is crucial, both to appreciate differences in the anticancer potential of different statins and to safely and effectively integrate statins into traditional chemotherapy regimens that include P-gp substrates. Here we evaluate interactions between 4 statins (lovastatin, atorvastatin, fluvastatin and rosuvastatin) and P-gp, at both the molecular level using purified P-gp and at the cellular level using human MDR tumor cells. Lovastatin bound directly to purified P-gp with high affinity and increased doxorubicin accumulation in MDR tumor cells, potentiating DNA damage, growth arrest and apoptosis. By contrast, while atorvastatin inhibited substrate transport by purified P-gp in proteoliposomes, it had no effect on doxorubicin transport in MDR tumor cells. Finally, fluvastatin and rosuvastatin only interacted with P-gp in vitro at high concentrations and did not inhibit doxorubicin transport in MDR cells. These differential interactions should be considered when combining statins with traditional chemotherapeutic drugs.

Redefining typhoid diagnosis: what would an improved test need to look like?

INTRODUCTION: Typhoid fever is one of the most common bacterial causes of acute febrile illness in the developing world, with an estimated 10.9 million new cases and 116.8 thousand deaths in 2017. Typhoid point-of-care (POC) diagnostic tests are widely used but have poor sensitivity and specificity, resulting in antibiotic overuse that has led to the emergence and spread of multidrug-resistant strains. With recent advances in typhoid surveillance and detection, this is the ideal time to produce a target product profile (TPP) that guides product development and ensure that a next-generation test meets the needs of users in the resource-limited settings where typhoid is endemic. METHODS: A structured literature review was conducted to develop a draft TPP for a next-generation typhoid diagnostic test with minimal and optimal desired characteristics for 36 test parameters. The TPP was refined using feedback collected from a Delphi survey of key stakeholders in clinical medicine, microbiology, diagnostics and public and global health. RESULTS: A next-generation typhoid diagnostic test should improve patient management through the diagnosis and treatment of infection with acute Salmonella enterica serovars Typhi or Paratyphi with a sensitivity ≥90% and specificity ≥95%. The test would ideally be used at the lowest level of the healthcare system in settings without a reliable power or water supply and provide results in <15 min at a cost of