The frequency of interleukin-1ß-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents.

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

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.

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.

A new species of Anchoviella (Clupeiformes: Engraulidae) from the western Amazon River in Peru, with comments on congeners in the Peruvian Amazon River.

Anchoviella hernanni sp. nov. is described from the upper Amazon River basin, in tributaries of the Marañon, Ucayali and Madre de Dios river drainages that drain the Peruvian Andes. The new taxon can be distinguished from all congeners except Anchoviella jamesi, Anchoviella manamensis and Anchoviella perezi, by having 12-15 gill rakers in the lower branch of the first gill arch (v·16-35) and from those species by the distance between verticals through the posterior margin of the orbit to the posterior margin of the upper jaw 9·5-14·8% head length; LH (v. up to 6·0% LH ). An updated identification key of all freshwater species of Anchoviella and morphological comparisons between all species of the genus occurring in Peru are provided.

Role of pharmaceutical care for self-administered pulmonary tuberculosis treatment in Thailand.

WHAT IS KNOWN AND OBJECTIVE: With resource constraints in Thailand, directly observed therapy (DOT) for treating tuberculosis (TB) may not be feasible to implement. To improve patients' adherence, hospitals either modify DOT or adopt different approaches: pharmaceutical care or home visit. Our objective was to assess pulmonary TB treatment success rate of pharmaceutical care compared to home visit and modified DOT in Thailand. METHODS: We conducted a retrospective cohort study using data collected in adult pulmonary TB patients starting treatment between October 2010 and September 2013 in three hospitals in Thailand. This study was approved by the Research Ethics Board at each of the participating hospitals. We built a propensity score matching to account for differences in patient baseline characteristics. RESULTS: Analysis included 1398 patients. Before matching, the treatment success rate for patients receiving pharmaceutical care was 94.9%, home visit 93.6% and modified DOT 90.1%. The propensity score-matched cohorts indicated that differences in the treatment success rate were not statistically significant when comparing pharmaceutical care with either home visit (success rate: 92.76% vs 94.74%, risk difference: 1.97%, 95% CI -3.64 to 7.59) or modified DOT (success rate 93.37% for both, risk difference: 0%, 95% CI -5.30 to 5.30). WHAT IS NEW AND CONCLUSION: Pharmaceutical care, home visit and modified DOT are all associated with high success rate for pulmonary TB treatment and exceeded the WHO target, in this retrospective analysis.

Identification of genetic variants associated with susceptibility to West Nile virus neuroinvasive disease.

West Nile virus (WNV) infection results in a diverse spectrum of outcomes, and host genetics are likely to influence susceptibility to neuroinvasive disease (West Nile neuroinvasive disease (WNND)). We performed whole-exome sequencing of 44 individuals with WNND and identified alleles associated with severe disease by variant filtration in cases, kernel association testing in cases and controls and single-nucleotide polymorphism (SNP) imputation into a larger cohort of WNND cases and seropositive controls followed by genome-wide association analysis. Variant filtration prioritized genes based on the enrichment of otherwise rare variants, but did not unambiguously implicate variants shared by a majority of cases. Kernel association demonstrated enrichment for risk and protective alleles in the human leukocyte antigen (HLA)-A and HLA-DQB1 loci that have well understood roles in antiviral immunity. Two loci, HERC5 and an intergenic region between CD83 and JARID2, were implicated by multiple imputed SNPs and exceeded genome-wide significance in a discovery cohort (n=862). SNPs at two additional loci, TFCP2L1 and CACNA1H, achieved genome-wide significance after association testing of directly genotyped and imputed SNPs in a discovery cohort (n=862) and a separate replication cohort (n=1387). The context of these loci suggests that immunoregulatory, ion channel and endothelial barrier functions may be important elements of the host response to WNV.

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).

Genetic susceptibility to West Nile virus and dengue.

This article focuses on the host genetic predisposition to 2 viruses, West Nile virus and dengue virus, which belong to the genus Flavivirus. Although by definition these viruses have shared characteristics (e.g. similar size, single stranded, RNA viruses, both transmitted by the bite from an infected mosquito), they differ greatly in epidemiology and clinical manifestations. The text below not only summarizes the genetic factors that predispose to complications of these 2 important flaviviruses, but also illustrates the challenges in determining the genomic basis for complications to these viruses.

Aging, frailty and age-related diseases.

The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.

Meta-analysis: proton pump inhibitor use and the risk of community-acquired pneumonia.

BACKGROUND: Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community-acquired pneumonia are conflicting. AIM: To assess systematically the association between risk of community-acquired pneumonia and PPI use in adults. METHODS: We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (> or =18 years) who took PPIs as an out-patient. The primary outcome was community-acquired pneumonia. Only observational studies with a comparison arm were included. RESULTS: Over 2600 citations were reviewed. Six studies were included. All were nested case-control studies. Meta-analysis found an increased risk of community-acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12-1.65)]; significant heterogeneity remained (I(2) 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community-acquired pneumonia [OR 1.92 (95% CI 1.40-2.63), I(2) 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90-1.38), I(2) 91%, P < 0.001], a significant interaction (P < 0.005). CONCLUSIONS: Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community-acquired pneumonia, a finding that should be explored in future studies.

Variation in mortality rates among long-term care facilities for residents with lower respiratory tract infection.

OBJECTIVE: To identify variables contributing to interfacility differences in mortality among residents of long-term care facilities who have lower respiratory tract infection. DESIGN: Multicenter, prospective, 1-year observational study. SETTING: Twenty-one long-term care facilities in 4 geographic areas of Canada. PARTICIPANTS: Residents of long-term care facilities prescribed antimicrobials for treatment of lower respiratory tract infection. METHODS: Mortality rates were calculated for 3 definitions of lower respiratory tract infection: episodes with a clinical or radiographic diagnosis and treated with antimicrobials (definition 1); episodes with a physician diagnosis of pneumonia (definition 2); and episodes with chest radiography findings consistent with pneumonia (definition 3). Multilevel modeling was used to evaluate variables describing premorbid resident status, clinical presentation, management, and facility characteristics. Multivariable models were developed to identify independent predictors of mortality and determine whether facility-level variables remained independently associated with mortality rate after incorporation of individual-level variables. RESULTS: Facility mortality rates varied from 0% to 17.8% for definition 1, from 0% to 47.1% for definition 2, and from 0% to 37.5% for definition 3. There were significant differences in mortality rate depending on which definition was used; for definitions 1 and 2, there were significant differences in mortality rate across facilities. Poorer premorbid resident status and a more severe presentation remained independent predictors of mortality in the multivariable analysis. There were also significantly increased mortality rates for episodes in which a fluoroquinolone was prescribed for initial treatment. For definitions 1 and 3, facility-level variables remained independently associated with mortality rate in the final multivariable model. CONCLUSIONS: Rates of mortality due to lower respiratory tract infection varied among long-term care facilities and differed within a facility, depending on the definition applied. Variables describing premorbid resident status, severity of presentation, and management did not fully explain the variation in mortality rate. Some facility-level variables remained independent predictors of mortality.

Factors associated with critical-care healthcare workers' adherence to recommended barrier precautions during the Toronto severe acute respiratory syndrome outbreak.

OBJECTIVE: To assess factors associated with adherence to recommended barrier precautions among healthcare workers (HCWs) providing care to critically ill patients with severe acute respiratory syndrome (SARS). SETTING: Fifteen acute care hospitals in Ontario, Canada. DESIGN: Retrospective cohort study. PATIENTS: All patients with SARS who required intubation during the Toronto SARS outbreak in 2003. PARTICIPANTS: HCWs who provided care to or entered the room of a SARS patient during the period from 24 hours before intubation until 4 hours after intubation. METHODS: Standardized interviews were conducted with eligible HCWs to assess their interactions with the SARS patient, their use of barrier precautions, their practices for removing personal protective equipment, and the infection control training they received. RESULTS: Of 879 eligible HCWs, 795 (90%) participated. In multivariate analysis, the following predictors of consistent adherence to recommended barrier precautions were identified: recognition of the patient as a SARS case (odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.5-4.5); recent infection control training (OR for interactive training, 2.7 [95% CI, 1.7-4.4]; OR for passive training, 1.7 [95% CI, 1.0-3.0]), and working in a SARS unit (OR, 4.0 [95% CI, 1.8-8.9]) or intensive care unit (OR, 4.3 [95% CI, 2.0-9.0]). Two factors were associated with significantly lower rates of consistent adherence: the provision of care for patients with higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR for score APACHE II of 20 or greater, 0.4 [95% CI, 0.28-0.68]) and work on shifts that required more frequent room entry (OR for 6 or more entries per shift, 0.5 [95% CI, 0.32-0.86]). CONCLUSIONS: There were significant deficits in knowledge about self-protection that were partially corrected by education programs during the SARS outbreak. HCWs' adherence to self-protection guidelines was most closely associated with whether they provided care to patients who had received a definite diagnosis of SARS.

Narrowband UVB therapy for vitiligo: does the repigmentation last?

BACKGROUND: Since 1997, a number of trials have shown promising results in treating generalized vitiligo with narrowband ultraviolet B (UVB) both in adults and children. However, there is little knowledge concerning the duration and permanency of the treatment-induced repigmentation. OBJECTIVE: Our main objective was to perform a follow-up trial of successfully treated patients receiving narrowband UVB for generalized vitiligo. METHODS: We have investigated to what degree the treatment-induced repigmentation remains stable for up to 2 years post-treatment. We performed an initial open trial including 31 patients with generalized vitiligo. They received narrowband UVB thrice weekly for up to 12 months. Patients experiencing > 75% repigmentation were defined responders and were included in the follow-up trial. Responders were followed every 6 months for up to 2 years after cessation of treatment. We observed the pigmentation status and registered any changes indicating loss of pigmentation and relapse. RESULTS: Eleven of the 31 treated patients were included in the follow-up trial. Six patients had relapse and five patients had stable response 24 months after cessation of treatment. Four out of six relapses were within 6 months post-treatment. CONCLUSION: In our study population of 31 patients with generalized vitiligo, five patients (16%) experienced > 75% stable repigmentation 2 years after cessation of a treatment programme of up to 1 years narrowband UVB therapy.

Point prevalence survey for healthcare-associated infections within Canadian adult acute-care hospitals.

A survey of adult patients 19 years of age and older was conducted in February 2002 in hospitals across Canada to estimate the prevalence of healthcare-associated infections (HAIs). A total of 5750 adults were surveyed; 601 of these had 667 HAIs, giving a prevalence of 10.5% infected patients and 11.6% HAIs. Urinary tract infections (UTI) were the most frequent HAI, shown by 194 (3.4%) of the patients surveyed. Pneumonia was found in 175 (3.0%) of the patients, surgical site infections (SSI) in 146 (2.5%), bloodstream infections (BSI) in 93 (1.6%) and Clostridium difficile-associated diarrhoea (CDAD) in 59 (1%). In this first national point prevalence study in Canada, the prevalence of HAI was found to be similar to that reported by other industrialized countries.

Growth and mitogenic effects of arylphorin in vivo and in vitro.

In insects, developmental responses are organ- and tissue-specific. In previous studies of insect midgut cells in primary tissue cultures, growth-promoting and differentiation factors were identified from the growth media, hemolymph, and fat body. Recently, it was determined that the mitogenic effect of a Manduca sexta fat body extract on midgut stem cells of Heliothis virescens was due to the presence of monomeric alpha-arylphorin. Here we report that in primary midgut cell cultures, this same arylphorin stimulates stem cell proliferation in the lepidopterans M. sexta and Spodoptera littoralis, and in the beetle Leptinotarsa decemlineata. Studies using S. littoralis cells confirm that the mitogenic effect is due to free alpha-arylphorin subunits. In addition, feeding artificial diets containing arylphorin increased the growth rates of several insect species. When tested against continuous cell lines, including some with midgut and fat body origins, arylphorin had no effect; however, a cell line derived from Lymantria dispar fat body grew more rapidly in medium containing a chymotryptic digest of arylphorin.

Risk of hospitalization during influenza season among a cohort of patients with congestive heart failure.

It is uncertain whether hospitalization among patients with congestive heart failure (CHF) increases during the influenza season. This retrospective cohort study used influenza surveillance data from the United States (1986-1987 to 1990-1991), clinical information from the Studies of Left Ventricular Dysfunction (SOLVD) database, and daily temperature data from the National Climatic Data Center to assess the effect of influenza season on hospitalizations in this cohort of patients. The overall hospitalization rate was higher during influenza seasons compared to non-influenza seasons [relative risk (RR) 1.08, 95% confidence interval (CI) 1.01-1.16]. Multivariable Cox modelling revealed an adjusted hazard ratio (HR) of 1.11 for hospitalization during the influenza season (95% CI 1.03-1.20, P=0.005). Overall death rates were also higher during influenza seasons than non-influenza seasons (RR 1.09, 95% CI 0.97-1.21), but the corresponding adjusted HR for death was not significant (HR 1.01, 95% CI 0.98-1.24, P=0.11). Patients with CHF have a greater risk of hospitalization during the influenza season than in the non-influenza season, supporting the current belief that patients with CHF should be regarded as a high-risk group.