The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014.

During the 2013/14 influenza season in Canada, 631 of 654 hospitalisations for laboratory-confirmed influenza enrolled in sentinel hospitals were due to Influenza A. Of the 375 with known subtype, influenza A(H1N1) accounted for 357. Interim unmatched vaccine effectiveness adjusted for age and presence of one or more medical comorbidities was determined by test-negative case-control design to be 58.5% (90% confidence interval (CI): 43.9-69.3%) overall and 57.9% (90% CI: 37.7-71.5) for confirmed influenza A(H1N1).

Factors associated with HCV antiviral treatment uptake among participants of a community-based HCV programme for marginalized patients.

While the majority of cases of hepatitis C virus (HCV) in developed countries occur among illicit drug users, HCV antiviral treatment uptake is poor in this population. Several studies have shown that patients can successfully be treated for HCV in the context of methadone maintenance programmes, but little evidence exists evaluating HCV treatment models for substance users where methadone maintenance is not indicated. This retrospective cohort study involved 129 persons participating in psycho-educational support groups and integrated, interprofessional, community-based health services focused on the treatment for HCV among marginalized populations with high rates of crack cocaine use and mental health comorbidities. We sought to identify the factors associated with antiviral treatment uptake. Group participation improved access to health care. While 19% had previously seen an HCV specialist prior to group initiation, 59% saw an HCV specialist during the group. Half of the participants were nonimmune to hepatitis A or B at baseline, and 80% of these patients received immunization through the programme. The programme treated 24 patients with pegylated interferon and ribavirin and achieved a sustained virologic response (SVR) rate of 91% for genotype 2 or 3 and 54% for genotype 1. Stable housing was independently associated with initiation of treatment, and there was a nonsignificant trend towards lower rates of treatment initiation among women. SVR rates for those who had used crack or injection drugs in the month prior to joining the programme did not differ significantly from those who had abstained.

Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8.

The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature >or=38.0 degrees C, 80% had respiratory symptoms in the emergency department, and 76% were >or=65 years old. Multivariable analysis revealed a triage temperature >or=38.0 degrees C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3-4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2-2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3-2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6-3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1-5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was >or=38.0 degrees C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is >or=38.0 degrees C or admission is during the weeks of peak influenza activity.

Sources of viral respiratory infections in Canadian acute care hospital healthcare personnel.

BACKGROUND: Viral respiratory illnesses are common causes of outbreaks and can be fatal to some patients. AIM: To investigate the association between laboratory-confirmed viral respiratory infections and potential sources of exposure during the previous 7 days. METHODS: In this nested case-control analysis, healthcare personnel from nine Canadian hospitals who developed acute respiratory illnesses during the winters of 2010/11-2013/14 submitted swabs that were tested for viral pathogens. Associated illness diaries and the weekly diaries of non-ill participants provided information on contact with people displaying symptoms of acute respiratory illness in the previous week. Conditional logistic regression assessed the association between cases, who were matched by study week and site with controls with no respiratory symptoms. FINDINGS: There were 814 laboratory-confirmed viral respiratory illnesses. The adjusted odds ratio (aOR) of a viral illness was higher for healthcare personnel reporting exposures to ill household members [7.0, 95% confidence interval (CI) 5.4-9.1], co-workers (3.4, 95% CI 2.4-4.7) or other social contacts (5.1, 95% CI 3.6-7.1). Exposures to patients with respiratory illness were not associated with infection (aOR 0.9, 95% CI 0.7-1.2); however, healthcare personnel with direct patient contact did have higher odds (aOR 1.3, 95% CI 1.1-1.6). The aORs for exposure and for direct patient contact were similar for illnesses caused by influenza. CONCLUSION: Community and co-worker contacts are important sources of viral respiratory illness in healthcare personnel, while exposure to patients with recognized respiratory infections is not associated. The comparatively low risk associated with direct patient contact may reflect transmission related to asymptomatic patients or unrecognized infections.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Immunogenicity and reactogenicity of high- vs. standard-dose trivalent inactivated influenza vaccine in healthcare workers: a pilot randomized controlled trial.

OBJECTIVES: To compare immunogenicity, reactogenicity and acceptability of high- and standard-dose trivalent inactivated influenza vaccine (HDTIV, SDTIV) in 18- to 64-year-olds. METHODS: We randomized 18- to 64-year-olds to HDTIV or SDTIV in two consecutive years. We collected serum on days 0 and 21, measured haemagglutination inhibition geometric mean titres (GMT) and compared seroconversion, day 21 titres, seroprotection, reactogenicity and acceptability. RESULTS: Immunogenicity was evaluable in 42 of 47 2014 participants, all 33 both-year participants and 87 of 90 2015-only participants. First-dose HDTIV recipients experienced seroconversion more frequently than SDTIV recipients to A(H3N2) in 2014 (13/21, 62% vs. 4/21, 19%, p 0.01) and to all vaccine strains in 2015: (A(H1N1): 24/42, 57% vs. 15/59, 25%; A(H3N2): 42/42, 100% vs. 47/59, 80%; B: 25/42, 60% vs. 13/59, 22%; all p <0.01). Day 21 haemagglutination inhibition GMT were higher in first and two sequential-year HDTIV vs. SDTIV recipients: A(H1N1): GMT 749 and 768 vs. 384 (p <0.0001, p 0.002); A(H3N2): 1238 and 956 vs. 633 (p 0.0003, p 0.1); and B: 1113 and 1086 vs. 556 (p 0.0005, p 0.02). HDTIV was more reactogenic (local pain score 3 vs. 1 of 10 on day 0/1, p 0.0003), but recipients were equally willing to be revaccinated (HDTIV: 76/83 (92%); SDTIV: 76/80 (95%), p 0.54). The ratios of day 21 GMT in SDTIV recipients vaccinated in 0 to 4 prior years to those in SDTIV and HDTIV recipients vaccinated in 15 or more prior years were A(H1N1): 3.73 and 1.38; A(H3N2) 3.07 and 1.16; and B: 2.01 and 1.21. CONCLUSIONS: HDTIV is more immunogenic and reactogenic and as acceptable as SDTIV in 18- to 64-year-olds.

Improving healthcare worker adherence to the use of transmission-based precautions through application of human factors design: a prospective multi-centre study.

A key component of transmission-based precautions (TBPs) is the use of personal protective equipment (PPE) but healthcare worker (HCW) adherence remains suboptimal. A human factors-based intervention was implemented to improve adherence to TBPs including (i) improved signage, (ii) standardized placement of signage, (iii) introduction of a mask with integrated face shield, and (iv) improvement in PPE availability. Donning of the correct PPE by HCWs improved significantly (79.7 vs 56.4%; P < 0.001). This approach may be more effective than education alone, but further study is required to determine sustainability and subsequent impact on transmission of healthcare-associated infections.

Exploring differences in response to treatment with peginterferon alpha 2a (40kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3.

Chronic hepatitis C virus (HCV) infections with genotype 2 or 3 are associated with favourable sustained virologic response (SVR) rates. However, genotype 3 may respond less well. We reassessed all treatment-naive patients with genotype 2 and 3 participating in a large expanded-access, non-randomized, open-label trial, evaluating 180microg pegylated interferon (peg-IFN) alpha-2a (40kD) once weekly and 800 mg/day ribavirin for 24-48 weeks. Factors measured prior to initiation of antiviral therapy were considered in the multiple logistic regression model for predicting SVR. In total, 180 patients were analysed of which 72 (40%) were infected by genotype 2 and 108 (60%) genotype 3. The baseline characteristics between patients infected by genotype 2 or 3 were no different including the distribution of hepatic fibrosis stages by METAVIR score. Overall SVR was lower in those patients infected with genotype 3. The significant multivariate predictors of lack of SVR were hepatic fibrosis (P = 0.014) and genotype 3 (P = 0.030). The negative impact of cirrhosis (METAVIR score F4) on treatment response was more evident among subjects with genotype 3 than those with genotype 2 (P = 0.027). There is significant interaction between cirrhosis and genotype 3 leading to a poor antiviral response in such patients requiring an alternate management strategy. This finding should be confirmed in a larger population.

Leptin depolarizes rat hypothalamic paraventricular nucleus neurons.

Leptin, the protein product of the ob/ob gene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. THe paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the type I cells tested (n = 17) and 67% of the type II cells tested (n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no discernible effect on membrane potential (n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near -30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.

Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation.

The overall prevalence of human papillomavirus (HPV) cervical infection in 131 women attending a family planning clinic was 7% (HPV 6/11, 16, 18, 31) by dot blot hybridisation, 53% (HPV 11, 16, 31) by polymerase chain reaction (PCR), and 56% by the two methods combined. HPV 16 and 18 were the commonest types (4% each) by dot blot, HPV 16 (39%) by PCR. Fifteen percent of subjects had mildly abnormal cervical cytology (grades 1A, 2A, or 3). There was no significant correlation between cytological abnormality and HPV positivity, or between cytological or HPV status and other postulated risk factors for cervical neoplasia. It is concluded that PCR is considerably more sensitive than dot blot DNA hybridisation in detecting HPV cervical infection in such a "low risk" setting, where HPV copy number may be low. Firm conclusions cannot be drawn from our results regarding a causal role for HPV or other factors in the development of cervical neoplasia.

PIP: In 1989, health practitioners scraped the cervixes of 131 women who came to the St. Giles Clinic for family planning services in Northampton, England to compare the sensitivity of dot blot DNA hybridization and polymerase chain reaction (PCR). They also wanted to determine the prevalence of human papilloma virus (HPV) infection in a sexually active but not a high risk population. PCR detected HPV infection in 53% of the women while dot blot hybridization only detected it in 7%. Therefore PCR was more sensitive than dot blot hybridization. Together the 2 techniques indicated a 56% prevalence. Mildly abnormal cytology existed in 15% of the women. HPV positivity did not necessarily correlate with abnormal cytology. This lack of association did not necessarily indicate that HPV does not play a role in development of cervical neoplasia, however. This study found a significant relationship between cytological abnormality and being parous and between cytological abnormality and a history of genital warts (p.01). Further women with abnormal cytology tended to be younger (median, 21 years) than women with normal cytology or the group as a whole (24 years). In addition, the median number of sexual partners was higher in HPV positive women (3-4 partners) than HPV negative women or the entire group (=or- 2 partners). Nevertheless the correlation between abnormal cytology and age and sex partners was not significant. The researchers proposed that these cofactors may be more important in development of cervical neoplasia than HPV. Since HPV appeared frequently in women of median age of 24 years and a median of 2 lifetime sexual partners indicated that they may have been infected early with HPV by nonsexual routes. Researchers should investigate this possibility further by conducting age related serological studies in children.

Longitudinal profiles of semantic impairment for living and nonliving concepts in dementia of Alzheimer's type.

Two types of theoretical account have been proposed to explain the phenomenon of category-specific impairment in tests of semantic memory: One stresses the importance of different cortical regions to the representation of living and nonliving categories, while the other emphasize the importance of statistical relationships among features of concepts belonging to these two broad semantic domains. Theories of the latter kind predict that the direction of a domain advantage will be determined in large part by the overall damage to the semantic system, and that the profiles of patients with progressive impairments of semantic memory are likely to include a point at which an advantage for one domain changes to an advantage for the other. The present series of three studies employed semantic test data from two separate cohorts of patients with probable dementia of Alzheimer's type (DAT) to look for evidence of such a crossover. In the first study, longitudinal test scores from a cohort of 58 patients were examined to confirm the presence of progressive semantic deterioration in this group. In the second study, Kaplan-Meier survival curves based on serial naming responses and plotted separately for items belonging to living and nonliving domains indicated that the representations of living concepts (as measured by naming) deteriorated at a consistently and significantly faster rate than those of nonliving concepts. A third study, carried out to look in detail at the performance of mildly affected patients, employed an additional cross-sectional cohort of 20 patients with mild DAT and utilized a graded naming assessment. This study also revealed no evidence for a crossover in the advantage of one domain over the other as a function of disease severity. Taken together with the model of anatomical progression in DAT based on the work of Braak and Braak (1991), these findings are interpreted as evidence for the importance of regional cerebral anatomy to the genesis of semantic domain effects in DAT.

What constitutes an effective and efficient package of services for the prevention, diagnosis, treatment and care of tuberculosis among refugees and migrants in the WHO European Region? Themed issues on migration and health, VIII

The WHO European Region has faced high rates of external and internal migration in recent years, with concerns that this is contributing to the burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and TB/HIV coinfection in some countries. This report examines evidence of effective and efficient service packages for the prevention, diagnosis and treatment of TB to inform strategies to address the TB burden in refugee and migrant populations. Significant regional variations were identified in both migration levels and TB burden in refugees and migrants, as well as in approaches to TB control, with low quality of evidence in many cases. While it is unlikely that a single strategy/package will be effective for all situations, the evidence highlights some common approaches that could guide policy-making and service development. TB elimination targets for the Region will not be met unless inequalities in access to screening and treatment for migrants are addressed, alongside efforts to tackle TB globally.