Ingrid Smith

An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers

Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 μg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic.

High case-fatality rates of meningococcal disease in Western Norway caused by serogroup C strains belonging to both sequence type (ST)-32 and ST-11 complexes, 1985-2002.

A total of 293 meningococcal disease (McD) patients from Western Norway hospitalized during 1985-2002 were examined for risk factors related to death. The case-fatality rate (CFR) increased from 4% during 1985-1993 to 17% during 1994-2002. We analysed the phenotypic and genotypic characteristics of the meningococcal patient isolates, with the aim of identifying whether highly virulent meningococcal strains contributed to the increased CFR. The Norwegian epidemic strain B:15:P1.7,16/ST-32 complex was overall the most common phenotype/genotype (n=75) and caused most deaths (n=9; CFR 12.0%). However, fatality was significantly associated with disease caused by serogroup C meningococcal strains; C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains, which had the highest CFRs of 21.1% and 18.2% respectively. Serogroup B strains of the ST-32 complex differing by serotype and/or serosubtype from the epidemic strain had a CFR of 5.1%, while the CFR of disease caused by other strains (all phenotypes and genotypes pooled) was 2.2%. The distribution of phenotypes/clonal complexes varied significantly between 1985-1993 and 1994-2002 (P<0.001); B:15/ST-32 complex strains decreased whereas both C:15:P1.7,16/ST-32 complex strains and strains with other phenotypes/clonal complexes increased. Our results indicate that C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains were highly virulent strains and contributed to the high CFR of McD in patients from Western Norway. To reduce fatality, rapid identification of such virulent strains is necessary. In addition, early and specific measures should include public information, vaccination of populations at risk of disease and carriage eradication, when clustering of patients occurs.

FcγRIIa and FcγRIIIb polymorphisms were not associated with meningococcal disease in Western Norway

Fcgamma-receptor (FcyR) polymorphisms have been associated with acquisition and severity of invasive meningococcal disease. We studied FcgammaR polymorphisms in a population with a high incidence of meningococcal disease. Fifty meningococcal disease patients aged 14-60 years, with bacteriologically confirmed disease and without detected complement deficiency, together with 100 healthy adult controls were included in the study. Clinical and bacteriological data were collected prior to FcgammaRIIa and FcgammaRIIb genotyping, which was performed by polymerase chain reaction. The distribution of the FcgammaRIIa and FcgammaRIIIb allotypes and their allele frequencies were not significantly different amongst the patients and the controls. The combination FcgammaRIIa-R/R and FcgammaRIIb-Na2/Na2 was less common among patients than controls (OR = 0.11, Fishers exact P = 0.05). No significant association was found between the two FcgammaRs and severity of disease, meningococcal serogroup, age groups or gender. In contrast to previous findings, our study indicates that in Norwegian teenagers and adults, the FcgammaRIIa and FcgammaRIIIb allotypes are not decisive for the acquisition or for the severity of meningococcal disease.

Outbreak of meningococcal disease in western Norway due to a new serogroup C variant of the ET-5 clone: effect of vaccination and selective carriage eradication.

A new sulphonamide resistant (SR) C: 15:P1.7,16 meningococcal strain, a variant of the ET-5 clone, dominated in an outbreak of 22 cases in western Norway commencing in 1995. The first eight patients were 15-21 years old from the Nordhordland area, initiating a carrier study in the local high schools. Carriage of SR serogroup C meningococci was detected by routine methods and treated with a single dose of ofloxacin 400 mg. Of 20 treated carriers, 14 harboured the outbreak strain C: 15:P1.7,16. Vaccination of 4000 children, adolescents and close contacts of patients was also performed. After the intervention, 14 additional cases of meningococcal disease occurred, 8 due to the outbreak strain. However, incidence rates dropped from 180 to 30 per 100000 per year in the student population, but increased from 0 to 13 in the rest of the population in Nordhordland. Carriage eradication is not generally recommended in Norway. However, tracing and treating meningococcal carriage may have reduced transmission and disease in this outbreak situation.

An antimicrobial stewardship program initiative: a qualitative study on prescribing practices among hospital doctors

BackgroundNorway has a low, but increasing prevalence of resistance and few antimicrobial stewardship initiatives. When developing stewardship interventions, an understanding of the determinants of antimicrobial prescribing is needed. We report on the first qualitative study investigating factors influencing doctors’ antimicrobial prescribing practices in Norwegian hospitals.MethodsQualitative semi-structured interviews were conducted with 15 Norwegian hospital doctors prescribing antimicrobials to adult patients. Interviews were transcribed verbatim and thematic analysis was applied to analyse the data.ResultsColleagues, in particular infectious disease specialists, microbiology test results and the newly published national guideline on antimicrobials were identified as key factors influencing antimicrobial prescribing practices. Delayed availability was a barrier for the utilization of microbiology test results and increasing clinical experience overrides the influence of the national guideline.Patient assessment, informal training by experienced colleagues, and infectious disease specialists replacing managers in promoting prudent prescribing policies, also influenced prescribing practices.ConclusionThis study identified the following contextual factors that need to be addressed when developing antimicrobial stewardship programs in Norway: a common work practice for seeking collegial advice, logistics of microbiology test results, and formal leadership and systematic training on prudence. Other countries initiating stewardship programmes may benefit from performing a similar mapping of facilitators and barriers, to identify important stakeholders and organisational obstacles, before developing sustainable and tailored antimicrobial stewardship interventions.

Variations in case fatality and fatality risk factors of meningococcal disease in Western Norway, 1985–2002

In a retrospective epidemiological study, 293 meningococcal disease patients hospitalized during 1985-2002, were examined for fatality and risk factors related to death. The overall case fatality rate (CFR) was 8.2%, but increased from 4% during 1985-1993 to 17% during 1994-2002. The latter 9-year period was characterized by more serogroup C infections and more patients with thrombocytopenia on admission to hospital. All patients categorized as meningitis on admission survived. Of the 24 patients who died, 21 had meningococcal skin rash on admission, 23 had an onset to admission time of < or =24 h, and 16 had severe septicaemia with hypotension and/or ecchymoses without meningitis on admission. By multivariate analyses, a short onset to admission time, >50 petechiae, thrombocytopenia and severe septicaemia on admission were associated with fatality. More lives could be saved through earlier admission to hospital. This can be achieved through more information to the public about the early signs of meningococcal septicaemia, with the recommendation to look for skin rash in patients with acute fever during the first day and night.

Immune responses after live attenuated influenza vaccination

ABSTRACT Since 2003 (US) and 2012 (Europe) the live attenuated influenza vaccine (LAIV) has been used as an alternative to the traditional inactivated influenza vaccines (IIV). The immune responses elicted by LAIV mimic natural infection and have been found to provide broader clinical protection in children compared to the IIVs. However, our knowledge of the detailed immunological mechanisims induced by LAIV remain to be fully elucidated, and despite 14 years on the global market, there exists no correlate of protection. Recently, matters are further complicated by differing efficacy data from the US and Europe which are not understood. Better understanding of the immune responses after LAIV may aid in achieving the ultimate goal of a future “universal influenza vaccine”. In this review we aim to cover the current understanding of the immune responses induced after LAIV.

Causal Analysis of World Health Organization's Surgical Safety Checklist Implementation Quality and Impact on Care Processes and Patient Outcomes: Secondary Analysis From a Large Stepped Wedge Cluster Randomized Controlled Trial in Norway

Objective: We hypothesize that high-quality implementation of the World Health Organizations Surgical Safety Checklist (SSC) will lead to improved care processes and subsequently reduction of peri- and postoperative complications. Background: Implementation of the SSC was associated with robust reduction in morbidity and length of in-hospital stay in a stepped wedge cluster randomized controlled trial conducted in 2 Norwegian hospitals. Further investigation of precisely how the SSC improves care processes and subsequently patient outcomes is needed to understand the causal mechanisms of improvement. Methods: Care process metrics are reported from one of our earlier trial hospitals. Primary outcomes were in-hospital complications and care process metrics, e.g., patient warming and antibiotics. Secondary outcome was quality of SSC implementation. Analyses include Pearsons exact &khgr;2 test and binary logistic regression. Results: A total of 3702 procedures (1398 control vs. 2304 intervention procedures) were analyzed. High-quality SSC implementation (all 3 checklist parts) improved processes and outcomes of care. Use of forced air warming blankets increased from 35.3% to 42.4% (P < 0.001). Antibiotic administration postincision decreased from 12.5% to 9.8%, antibiotic administration preincision increased from 54.5% to 63.1%, and nonadministration of antibiotics decreased from 33.0% to 27.1%. Surgical infections decreased from 7.4% (104/1398) to 3.6% (P < 0.001). Adjusted SSC effect on surgical infections resulted in an odds ratio (OR) of 0.52 (95% confidence interval (CI): 0.38–0.72) for intervention procedures, 0.54 (95% CI: 0.37–0.79) for antibiotics provided before incision, and 0.24 (95% CI: 0.11–0.52) when using forced air warming blankets. Blood transfusion costs were reduced by 40% with the use of the SSC. Conclusions: When implemented well, the SSC improved operating room care processes; subsequently, high-quality SSC implementation and improved care processes led to better patient outcomes.

Reduced Hospital Stay in Influenza Patients after Mass Vaccination during the 2009 Influenza Pandemic in Norway

Background: Norway had a pre-order of vaccine, when the pandemic influenza A (H1N1)pdm09 in 2009 was declared. Mass vaccination occurred 1-3 weeks prior to the peak of the pandemic. Emergency plans were in place, but the predicted severe numbers of hospitalizations did not occur. Objective: To study the epidemiology and clinical presentation of adult patients hospitalized with influenza A (H1N1) pdm09, and to evaluate the impact of vaccination on the course of the pandemic at a tertiary hospital. Methods: The low dose oil-in-water adjuvanated vaccine was used to vaccinate healthcare workers (HCWs) and at risk patients groups, and vaccination rates were recorded for the community and the hospital. Demographic and clinical information was obtained for 129 patients (>15 years), hospitalized with influenza A (H1N1)pdm09 between August 2009-January 2010. A confirmed case of influenza A (H1N1)pdm09 was defined as meeting a clinical case definition and/or laboratory confirmed disease (rt-PCR or serology). Hospital stay of more than 2 days was defined as a sign of severe illness. Results: 1/3 of at risk patients in the community and >90% of frontline HCWs at the hospital were vaccinated. The median length of hospital stay of infected patients was significantly reduced 7 days after the onset of mass vaccination (p=0.029). There was a predominance of female and moderately obese (BMI 25-30) patients. Infiltration on chest X-ray upon admission was significantly associated with a hospital stay of >2 days (p=0.001). Conclusion: Mass vaccination of frontline HCWs at the hospital and at risk patients in the community contributed to the observed significant reduction in hospital stay of patients infected with influenza. Almost no absenteeism enabled staff confidence and the ability for quick and safe patient turnover. This study highlights the importance of early influenza vaccination, to protect the high-risk patients and the integrity of the healthcare system.

Addressing the key communication barriers between microbiology laboratories and clinical units: a qualitative study

Background: Many countries are on the brink of establishing antibiotic stewardship programmes in hospitals nationwide. In a previous study we found that communication between microbiology laboratories and clinical units is a barrier to implementing efficient antibiotic stewardship programmes in Norway. We have now addressed the key communication barriers between microbiology laboratories and clinical units from a laboratory point of view. Methods: Qualitative semi‐structured interviews were conducted with 18 employees (managers, doctors and technicians) from six diverse Norwegian microbiological laboratories, representing all four regional health authorities. Interviews were recorded and transcribed verbatim. Thematic analysis was applied, identifying emergent themes, subthemes and corresponding descriptions. Results: The main barrier to communication is disruption involving specimen logistics, information on request forms, verbal reporting of test results and information transfer between poorly integrated IT systems. Furthermore, communication is challenged by lack of insight into each others area of expertise and limited provision of laboratory services, leading to prolonged turnaround time, limited advisory services and restricted opening hours. Conclusions: Communication between microbiology laboratories and clinical units can be improved by a review of testing processes, educational programmes to increase insights into the others area of expertise, an evaluation of work tasks and expansion of rapid and point‐of‐care test services. Antibiotic stewardship programmes may serve as a valuable framework to establish these measures.