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.

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).

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.

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.

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.

Impact of respiratory viral infections on mortality and critical illness among hospitalized patients with chronic obstructive pulmonary disease.

BACKGROUND: Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients. RESEARCH QUESTION: To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients. STUDY DESIGN AND METHODS: We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use. RESULTS: Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza. INTERPRETATION: Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01517191.

Older Age and Frailty are Associated with Higher Mortality but Lower ICU Admission with COVID-19.

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Patients with laboratory-confirmed COVID-19 admitted to 11 sites in Ontario, Quebec, Alberta, and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Measures included age, sex, demographics, housing, exposures, Clinical Frailty Scale, comorbidities; in addition, length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were assessed. Descriptive analyses and multivariable logistic regressions were conducted. Results: Among 2,011 patients, mean age was 71.0 (range 19-105) years. 29.7% were admitted from assisted living or long-term care facilities. The full spectrum of frailty was represented in both younger and older age groups. 81.8% had at least one underlying comorbidity and 27.2% had obesity. Mortality was 14.3% without ICU admission, and 24.6% for those admitted to ICU. Older age and frailty were independent predictors of lower ICU use and higher mortality; accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened. Conclusions: Frailty is a critical clinical factor in predicting outcomes of COVID-19, which should be considered in research and clinical settings.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay.

OBJECTIVE(S): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. METHODS: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. RESULTS: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. CONCLUSION(S): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

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.

A Randomized Controlled Study to Evaluate the Safety and Reactogenicity of a Novel rVLP-Based Plant Virus Nanoparticle Adjuvant Combined with Seasonal Trivalent Influenza Vaccine Following Single Immunization in Healthy Adults 18-50 Years of Age.

Inactivated influenza vaccines efficacy is variable and often poor. We conducted a phase 1 trial (NCT02188810), to assess the safety and immunogenicity of a novel nanoparticle Toll-like receptor 7/8 agonist adjuvant (Papaya Mosaic Virus) at different dose levels combined with trivalent influenza vaccine in healthy persons 18-50 years of age. Hemagglutination-inhibition assays, antibody to Influenza A virus nucleoprotein and peripheral blood mononuclear cells for measurement of interferon-gamma ELISPOT response to influenza antigens, Granzyme B and IFNγ:IL-10 ratio were measured. The most common adverse events were transient mild to severe injection site pain and no safety signals were observed. A dose-related adjuvant effect was observed. Geometric mean hemagglutination-inhibition titers increased at day 28 in most groups and waned over time, but fold-antibody responses were poor in all groups. Cell mediated immunity results were consistent with humoral responses. The Papaya Mosaic Virus adjuvant in doses of 30 to 240 µg combined with reduced influenza antigen content was safe with no signals up to 3 years after vaccination. A dose-related adjuvant effect was observed and immunogenicity results suggest that efficacy study should be conducted in influenza antigen-naïve participants.

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.

Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015.

BACKGROUND: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age. METHODS: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years). RESULTS: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

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.

Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study.

BACKGROUND: Streptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes. METHODS: We completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood. RESULTS: Twenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides. CONCLUSION: The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237].

Streptococcus pneumoniae serotype 3 is masking PCV13-mediated herd immunity in Canadian adults hospitalized with community acquired pneumonia: A study from the Serious Outcomes Surveillance (SOS) Network of the Canadian immunization research Network (CIRN).

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. METHODS: Active surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. RESULTS: Of 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. CONCLUSION: Herd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

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.

Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD.

BACKGROUND: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal. METHODS: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations. RESULTS: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]). CONCLUSIONS: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population. TRIAL REGISTRY: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.

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.