Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial.

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.

Search and Contain: Impact of an Integrated Genomic and Epidemiological Surveillance and Response Program for Control of Carbapenemase-producing Enterobacterales.

BACKGROUND: Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). METHODS: A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program's first 3 years (2016-2018). RESULTS: CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45-0.60 infections/100 000 population, P = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9-14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1-19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4-13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. CONCLUSIONS: We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally.

Incursions of Candida auris into Australia, 2018.

Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization. Phylogenetic analysis revealed putative transmission between 2 patients and suspected overseas acquisition in the others. Vigilant screening of at-risk patients is required.

Randomized Trial of 2 Schedules of Meningococcal B Vaccine in Adolescents and Young Adults, Canada1.

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks.

Performance of a Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease in Nova Scotia.

Compared to the standard two-tiered testing (STTT) algorithm for Lyme disease serology using an enzyme immunoassay (EIA) followed by Western blotting, data from the United States suggest that a modified two-tiered testing (MTTT) algorithm employing two EIAs has improved sensitivity to detect early localized Borrelia burgdorferi infections without compromising specificity. From 2011 to 2014, in the Canadian province of Nova Scotia, where Lyme disease is hyperendemic, sera submitted for Lyme disease testing were subjected to a whole-cell EIA, followed by C6 EIA and subsequently IgM and/or IgG immunoblots on sera with EIA-positive or equivocal results. Here, we evaluate the effectiveness of the MTTT algorithm compared to the STTT approach in a Nova Scotian population. Retrospective chart reviews were performed on patients testing positive with the whole-cell and C6 EIAs (i.e., the MTTT algorithm). Patients were classified as having Lyme disease if they had a positive STTT result, a negative STTT result but symptoms consistent with Lyme disease, or evidence of seroconversion on paired specimens. Of the 10,253 specimens tested for Lyme disease serology, 9,806 (95.6%) were negative. Of 447 patients who tested positive, 271 charts were available for review, and 227 were classified as patients with Lyme disease. The MTTT algorithm detected 25% more early infections with a specificity of 99.56% (99.41 to 99.68%) compared to the STTT. These are the first Canadian data to show that serology using a whole-cell sonicate EIA followed by a C6 EIA (MTTT) had improved sensitivity for detecting early B. burgdorferi infection with specificity similar to that of two-tiered testing using Western blots.

Executive/life coaching for first year medical students: a prospective study.

BACKGROUND: Student physicians are particularly prone to high rates of poor mental and physical quality of life, including depression, anxiety, and fatigue. We prospectively tested whether a structured, theory-based executive/life coaching program tailored to first year medical students in the United States was feasible, tolerable, and would be recommended by participants. Secondary goals included impact on coaching goals, resilience, and perceived stress. METHODS: This single-arm intervention study evaluated a program of two group and two private coaching sessions during the first year, second semester of the Georgetown University School of Medicine Class of 2019. Survey data (global and tailored questions, Connor-Davidson resilience scale, Friedricksson-Larsson stress question) were collected from participants at baseline and post-intervention. RESULTS: 37/40 students completed the intervention; 32 completed the pre-post surveys. Most (32/37) were willing to recommend the program (16/37 were very willing) and 29/37 recommended inclusion in the curriculum. Responses to tailored questions showed significant increases in self-efficacy regarding stress management (p < 0.001); increased awareness of thoughts about stress and management of those thoughts (p = 0.05). Reported improvements in time management (p = 0.10) and energy for relationships and school (p = 0.089) did not achieve significance. Global resilience rating was not different (p = 0.186), but significant changes were seen in control (p = 0.029) and spiritual influence (p = 0.005) factors. Although the Friedricksson-Larsson item was not significantly different (p = 0.242), 40.6% of participants reported decreased stress and 40.6% reported unchanged stress during this most challenging preclinical semester. Substantial ceiling effects were seen in study measures. CONCLUSIONS: We showed that a tailored executive/life coaching program for first year medical students in the United States is feasible, tolerable, and safe; adherence was excellent. Global utility ratings and willingness to recommend coaching provide substantial support for efficacy. Better measures and larger-scale clinical trial designs are needed for formal proof.

A Respiratory Syncytial Virus Vaccine Based on the Small Hydrophobic Protein Ectodomain Presented With a Novel Lipid-Based Formulation Is Highly Immunogenic and Safe in Adults: A First-in-Humans Study.

Background: Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available. Methods: This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 µg) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56. Results: There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-µg and 25-µg groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-µg group at day 421. Responses to the RSV(A)-Alum vaccines were very low. Conclusions: A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile.

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.

The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial.

BACKGROUND: The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. METHODS: In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding. RESULTS: Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180. INTERPRETATION: In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385.

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

BACKGROUND: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. METHODS: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. RESULTS: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). CONCLUSIONS: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

The changing epidemiology of antimicrobial resistance in Fiji: a descriptive analysis of antimicrobial susceptibility and trends of endemic and emerging pathogens, 2019-2022.

Background: There is a paucity of data on antimicrobial resistance in Fiji. The aim of this study was to determine the antimicrobial susceptibility profile of bacterial isolates from clinical samples at Colonial War Memorial Hospital in Fiji. Methods: This retrospective study reviewed four-year of data from January 1, 2019, through December 31, 2022. Laboratory testing was carried out using locally approved protocols. Selective antimicrobial susceptibility testing was performed whereby only isolates resistant to first line antimicrobials were tested against second line antimicrobials. Only the first isolate of a given species per patient in a single year were included in the analysis. WHONET software and Microsoft Excel were used for analysis. Findings: A total of 29,222 bacterial isolates were included, 62% (n = 18,084) were Gram-negative bacteria. K. pneumoniae was the most common (n = 5363), followed by E. coli (n = 4321). Extended spectrum beta lactamase (ESBL) production increased from 30% in 2019 to 43% in 2022 amongst K. pneumoniae, and 10%-23% in E coli. There were 733 carbapenem-resistant isolates identified from clinical samples, 61% (n = 445) were A. baumannii, 15% (n = 110) E. coli and 14% (n = 101) P. aeruginosa. Amongst the E. coli isolates tested, susceptibility to meropenem declined from 99% (272/274) in 2019 to 79% (255/325) in 2022. The rate of methicillin resistance amongst Staphylococcus aureus was steady, remaining between 11% and 13%. Interpretation: This study demonstrated a high rate of MDR amongst Gram-negative bacteria, especially ESBL producing K. pneumoniae and E. coli and carbapenem-resistant A. baumannii. The emergence and rapid spread of carbapenemase producing E. coli in Fiji's largest hospital is of particular concern. There is an urgent need to allocate resources to improve existing capacity and to develop effective multimodal strategies to detect, manage and control the spread of MDR organisms. Funding: This study was supported by the Medical Research Future Fund through the Australian government (grant number APP 1200970).

Knowledge, attitudes, and readiness about critical antimicrobial resistant organisms among healthcare workers at colonial war memorial hospital in Fiji: a pre and post intervention study.

BACKGROUND: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms. METHODS: A questionnaire was designed using a Likert scale to assess knowledge, attitudes, and readiness. Two cross-sectional studies were conducted, before and after the implementation of targeted educational activities which were informed by the pre-intervention study findings. RESULTS: A total of 393 and 420 HCW participated in the pre- and post-intervention studies, respectively. The majority of respondents were female (77.3%) and 18-34 years of age (67%). HCW professional roles included nurses (56.3%), doctors (31.6%), and laboratory personnel (12.2%). In the post-intervention study, significantly more HCW reported having received infection prevention and control (IPC) and antimicrobial resistance education and training (26.8% in pre to 45.5% in post intervention, p < 0.001). The majority of nurses and doctors (> 85% to ≥ 95%) were aware of how AMR organisms spread in healthcare settings and knew the IPC measures to prevent transmission of AMR infections including hand hygiene, standard and transmission-based precautions. Attitudes towards AMR were positive, with 84.2% pre intervention and 84.8% of HCW post intervention expressing their willingness to change their work environment to assist with AMR prevention. Perceived readiness to address the problem showed mixed results. Improvements in laboratory AMR surveillance data availability were noted (29.4-52.4%, p < 0001). Modest improvement in the hospital's capacity for outbreak response (44-51.9%, p = 0.01), and treatment of AMR infections (38.9-44.4%, p = 0.01) was reported. CONCLUSIONS: Our data revealed high levels of staff awareness and knowledge about AMR and IPC. However, readiness for outbreak response and treatment of critical AMR infections requires more attention. Improving AMR prevention and containment in CWMH will likely require sustained and multisectoral interventions with strong administrative commitment.

The epidemiology of enterococci in a tertiary hospital and primary healthcare facilities in Fiji (2019-2022).

OBJECTIVES: We analysed 4 y of laboratory data to characterise the species and determine the antimicrobial susceptibility profiles of enterococci as human pathogens in Fiji. The study also investigated the molecular epidemiology amongst the subset of vancomycin-resistant enterococci (VRE). METHODS: This retrospective study reviewed bacteriological data from Colonial War Memorial Hospital (CWMH) and other healthcare facilities in the Central and Eastern divisions of Fiji. Phenotypic, antimicrobial susceptibility and vanA and vanB PCR testing were performed using locally approved protocols. The first clinical isolates per patient with antimicrobial susceptibility testing results in a single year were included in the analysis. Data was analysed using WHONET software and Microsoft Excel. RESULTS: A total of 1817 enterococcal isolates were reported, 1415 from CWMH and 402 from other healthcare facilities. The majority of isolates, 75% (n = 1362) were reported as undifferentiated Enterococcus spp., 17.8% (n = 324) were specifically identified as Enterococcus faecalis and 6.7% (n = 122) as E. faecium. Overall, 10% of the enterococci isolates were from blood cultures. Among isolates from CWMH, <15% of E. faecium were susceptible to ampicillin, and 17.2% were vancomycin resistant. Overall, 874 enterococcal isolates (including the undifferentiated species) were tested against vancomycin, of which 4.8% (n = 42) were resistance. All of the VRE isolates tested (n = 15) expressed vanA genes. CONCLUSIONS: This study demonstrates the clinical importance of VRE, particularly van A E. faecium in the national referral hospital in Fiji. Enhanced phenotypic and molecular surveillance data are needed to better understand enterococci epidemiology and help guide specific infection prevention and control measures and antibiotic prescribing guidelines.

Development of a cross-sectoral antimicrobial resistance capability assessment framework.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR.

Healthcare-associated infections and antimicrobial use at a major referral hospital in Papua New Guinea: a point prevalence survey.

Background: Healthcare-associated infections (HAI) and antimicrobial use (AMU) are drivers for antimicrobial resistance, and robust data are required to inform interventions and track changes. We aimed to estimate the prevalence of HAI and AMU at Port Moresby General Hospital (PMGH), the largest hospital in Papua New Guinea. Methods: We did a point prevalence survey (PPS) on HAI and AMU at PMGH in May 2023 using the European Centre for Disease Prevention and Control (ECDC) PPS protocol. We included all critical care patients and randomly sampled half of the patients in other acute-care wards. We calculated weighted HAI and AMU prevalence estimates to account for this sampling strategy. Weighted HAI estimates were also calculated for an expanded definition that included physician diagnosis. Findings: Of 361 patients surveyed in 18 wards, the ECDC protocol identified 28 HAIs in 26 patients, resulting in a weighted HAI prevalence of 6.7% (95% CI: 4.6, 9.8). Surgical site infections (9/28, 32%) were the most common HAI. When adding physician diagnosis to the ECDC definitions, more skin and soft tissue, respiratory, and bloodstream HAIs were detected, and the weighted HAI prevalence was 12.4% (95% CI: 9.4, 16.3). The prevalence of AMU was 66.5% (95%CI: 61.3, 71.2), and 73.2% (263/359) of antibiotics were from the World Health Organization Access group. Interpretation: This is the first reported hospital PPS of HAI and AMU in Papua New Guinea. These results can be used to prioritise interventions, and as a baseline against which future point prevalence surveys can be compared. Funding: Australian Government Department of Foreign Affairs and Trade and Therapeutic Guidelines Limited Australia.

Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services.

OBJECTIVES: To determine the incidence, risk factors for and outcomes of Staphylococcus aureus bacteraemia (SAB) associated with peripheral intravenous catheters (PIVCs). DESIGN, SETTING AND PATIENTS: A review of prospectively collected data from two tertiary health services on all health care-associated SAB episodes occurring in adults aged > 17 2013s from January 2007 to July 2012. MAIN OUTCOME MEASURES: Numbers of health care-associated SAB episodes; device type, location of insertion, device dwell time and outcome at 7 and 30 days for all SAB episodes associated with use of a PIVC; rates of SAB per 10 000 occupied bed-days (OBDs). RESULTS: Overall, 137 of 583 health care-associated-SAB episodes (23.5%) were deemed to be PIVC associated, with an incidence of 0.26/10 000 OBD. The mean dwell time for PIVCs was 3.5 days (range, 0.25-9 days) and 45.2% of SABs occurred in PIVCs with a dwell time ≥ 4 days. Of the PIVC-associated SAB episodes, 39.6% involved PIVCs inserted in the ED, 39.6% involved PIVCs inserted on wards and 20.8% involved PIVCs inserted by the ambulance service. Of the PIVC-associated SABs occurring within 4 days of insertion, 61% were inserted by ED staff or the ambulance service. PIVC-associated SAB were associated with a 30-day all-cause mortality rate of 26.5%. CONCLUSION: PIVC-associated SAB is an under-recognised complication. The high incidences of SAB associated with PIVCs inserted in emergency locations and with prolonged dwell times support recommendations in clinical guidelines for routine removal of PIVCs.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

High-level immunogenicity is achieved vaccine with adjuvanted pandemic H1N1(2009) and improved with booster dosing in a randomized trial of HIV-infected adults.

BACKGROUND: More severe influenza disease and poor vaccine immunogenicity in HIV-infected patients necessitate improved immunization strategies to maximize vaccine efficacy. METHODS: A phase III, randomized trial was conducted at 4 Canadian sites. Two dosing strategies (standard dose vs standard dose plus booster on day 21) were assessed in HIV patients aged 20 to 59 years during the H1N1(2009) pandemic. A single antigen, inactivated split adjuvanted (AS03(A)) influenza vaccine (Arepanrix) was utilized. Serum hemagglutination inhibition (HAI) titres were assessed at days 21 and 42 and at month 6. RESULTS: 150 participants received at least one injection. Baseline parameters were similar between groups: 83% male, 85% on HAART, median CD4 = 519 cells/mm(3), 84% with HIV RNA < 50 copies/mL. At day 21, seroprotection (HAI ≥1:40) was achieved in 80% (95% CI, 70-89) of participants. Seroconversion occurred in 74% (63-85). Seroprotection and seroconversion were further improved in those randomized to booster dosing: day 42, 94% (85-98) versus 73% (60-83) (P < .01) and 86% (75-93) versus 66% (5-77) (P = .01). Seroprotec-tion was retained in 40% (28-54) of recipients at month 6 with trends toward greater retention of immunity in booster recipients. CONCLUSION: High-level immunogenicity was achieved with a single dose of this adjuvanted vaccine. Immunogenicity was further improved with booster dosing. Use of this adjuvanted vaccine and booster represent an important approach to increasing immunogenicity in this vaccine hypo-responsive population.

Healthcare provider awareness, attitudes, beliefs, and behaviors regarding the role of pharmacists as immunizers.

We explored perceptions of healthcare providers in Nova Scotia and New Brunswick about pharmacists as immunizers. Pharmacists' scopes of practice are increasingly broadening to include immunization, and providers and policymakers may find meaning in the lessons we learned. Invitations to participate in our online survey were circulated by professional associations, health authorities, and in social media posts. A total of 204 healthcare providers completed our survey, of whom 59.3% were pharmacists, 17.6% were nurses, and 23.0% were physicians. Nurses (30.6%) and physicians (34.0%) experienced fewer logistical barriers to immunizing compared to pharmacists, 71.1% of whom identified practice logistics as a determinant in offering vaccines to patients (p < .001). Pharmacists were most supportive of the expansion of their own scope of practice to include the provision of vaccines to adults (95.9%) and children as young as five years (92.6%) compared to nurses (72.2% and 69.4%) and physicians (61.7% and 40.4%) (p < .001). Diversity of opinion was evident even among pharmacists about whether they should be permitted to vaccinate children younger than five years. Nurse and physician respondents had lower odds of thinking pharmacists have enough training to vaccinate (p < .001), that vaccines should be given in a pharmacy (p < .001), and of supporting the expansion of pharmacists' scope of practice (p < .001) than pharmacists did in the multivariable analyses. Pharmacists are well-positioned and willing to vaccinate and generally have support from their nurse and physician peers, but logistical challenges and interprofessional complexities persist as barriers to optimizing immunization by pharmacists.

In most Canadian provinces and territories, pharmacists are trained and able to give vaccines alongside traditional immunizers like doctors and nurses. In this study, we surveyed the views of immunizing professionals (pharmacists, doctors, and nurses) in Nova Scotia and New Brunswick about pharmacists giving vaccines. Healthcare providers were invited to do our online survey by their professional associations, provincial health authorities, and through posts on social media. Healthcare providers generally supported pharmacists giving vaccines, but not without some conditions from nurses, doctors, and some pharmacists themselves. We found all three professions to be very vaccine positive but learned that pharmacists experience barriers to giving vaccines that their nurse and doctor colleagues do not such as working by themselves, volume of work, time, compensation, and record-keeping. We highlight the importance of collaboration between immunizing professionals, acknowledgment of pharmacists' training as immunizers, a uniform funding model for all immunization providers, and a central and accessible vaccine registry. We also suggest that until power dynamics and complexities between professions are addressed in meaningful and structural ways, we might not enjoy the full benefits of pharmacists as immunizers. We hope these findings are useful in places where pharmacists cannot yet vaccinate and where pharmacists' scopes of practice are in the process of widening to include immunization.