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Background In British Columbia, Canada, most adults 50–69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage. Methods Among adults 50–69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021. Results Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15–52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21–55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%–76%) and 59% (53%–65%) against any infection and 86% (80%–90%) and 94% (85%–97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%–84%] and 80% [75%–84%], respectively) and ChAdOx1 (69% [60%–76%] and 66% [56%–73%], respectively). mRNA VE was lower at 63% (95% CI, 56%–69%) against Delta but 85% (95% CI, 71%–92%) against Delta-associated hospitalization (nonestimable for ChAdOx1). Conclusions A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals. [ABSTRACT FROM AUTHOR]

Background: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.Methods: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.Results: Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.Conclusions: RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.Clinical Trials Registration: NCT04071158. [ABSTRACT FROM AUTHOR]

Background Randomized-controlled trials of messenger RNA (mRNA) vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included relatively few elderly participants. We assess single-dose mRNA vaccine effectiveness (VE) in adults ≥ 70 years old in British Columbia, Canada, where second doses were deferred by up to 16 weeks and where a spring 2021 wave uniquely included codominant circulation of Alpha (B.1.1.7) and Gamma (P.1) variants of concern (VOC). Methods Analyses included community-dwelling adults ≥ 70 years old with specimen collection between 4 April (epidemiological week 14) and 1 May (week 17) 2021. Adjusted VE was estimated by test-negative design. Cases were reverse-transcription polymerase chain reaction (RT-PCR) test-positive for SARS-CoV-2, and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥ 21 days before specimen collection, but a range of intervals was assessed. Variant-specific VE was estimated against viruses genetically characterized as Alpha, Gamma or non-VOC lineages. Results VE analyses included 16 993 specimens: 1226 (7%) test-positive cases and 15 767 test-negative controls. Of 1131 (92%) genetically characterized viruses, 509 (45%), 314 (28%), and 276 (24%) were Alpha, Gamma, and non-VOC lineages, respectively. At 0–13 days postvaccination, VE was negligible at 14% (95% confidence interval [CI], 0–26) but increased from 43% (95% CI, 30–53) at 14–20 days to 75% (95% CI, 63–83) at 35–41 days postvaccination. VE at ≥ 21 days postvaccination was 65% (95% CI, 58–71) overall: 72% (95% CI, 58–81), 67% (95% CI, 57–75), and 61% (95% CI, 45–72) for non-VOC, Alpha, and Gamma variants, respectively. Conclusions A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 by about two-thirds in adults ≥ 70 years old, with protection only minimally reduced against Alpha and Gamma variants. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have characterized the 13-valent pneumococcal conjugate vaccine (PCV13) programme's beneficial effects on acute otitis media (AOM) and acute sinusitis (AS) rates in children; however, few studies have examined the impact on adults.Objectives: This retrospective cohort study evaluates the overall effect of the PCV13 immunization programme on the incidence of AOM and AS at the population level.Methods: Health administrative databases were linked to assess outpatient visits, hospitalizations and antibiotic utilization from 2000 to 2018. Multivariable Poisson regression was used to evaluate the impact of the PCV13 vaccine programme (2011-18) compared with the pre-PCV13 era (2000-10), overall and by age.Results: From 2000 to 2018, the incidence of AOM decreased by 50% (62 to 31 per 1000 population) while sinusitis decreased by 18% (33 to 27 per 1000 population). In the PCV13 era, the incidence of AOM declined [incidence rate ratio (IRR): 0.70; 95% CI: 0.70-0.70], in parallel with decreased incidence of antibiotic utilization (IRR: 0.65; 95% CI: 0.64-0.65). A reduction was also observed in the incidence of AS during the PCV13 era compared with the pre-PCV13 era (IRR: 0.88; 95% CI: 0.88-0.88), mainly driven by declines among those younger than 65 years of age. In contrast, an increase in AS incidence was noted in individuals aged ≥65 years (IRR: 1.03; 95% CI: 1.02-1.03). A decrease in antibiotic prescription rates for sinusitis was observed for those under 65 years of age.Conclusions: The PCV13 immunization programme is associated with a reduction in the incidence of AOM and AS. Moreover, the associated use of antibiotics for these diagnoses has comparably decreased across paediatric, as well as adult populations. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to examine the aggregate rates of antibiotic use at the population level and compare these rates over time against historical averages to identify the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting control measures on community prescribing. Methods We collected antibiotic prescriptions and physician office visits from January 1, 2016, to July 21, 2020. We calculated monthly prescription rates stratified by sex, age group, profession, diagnosis type, and antibiotic class. We looked at monthly prescription rate as a moving average over time. Using the interrupted time series analysis method, we estimated the changes in prescription rates after March 2020. Results The moving average of overall monthly prescription rates during January–June 2020 was below the minimum of the historical years' moving averages (2016–2019). We observed a >30% reduction in overall monthly prescription rates in April, May, and July of 2020 compared with the same months of 2019. We observed that overall monthly prescription rates experienced a significant level change of –12.79 (P  < .001) during the coronavirus disease 2019 pandemic after March 2020, with the greatest level change being –18.02 among children 1–4 years of age (P  < .001). We estimated an average –5.94 (P  < .001) change in respiratory tract infection (RTI)–associated monthly prescription rates after March 2020. Overall prescription rates comparing January–July 2019 and their 2020 counterparts showed a decrease in monthly prescribing ranging from –1 to –5 for amoxicillin, amoxicillin and enzyme inhibitors, azithromycin, clarithromycin, and sulfamethoxazole. Conclusions In British Columbia, Canada, overall and RTI-specific monthly antibiotic prescription rates declined significantly during April–July 2020 compared with the same months in prepandemic years. [ABSTRACT FROM AUTHOR]

Rats evoke public health and economic concern in cities globally. Rapid urbanization exacerbates pre-existing rat problems, requiring the development and adoption of more effective methods of prevention, monitoring and mitigation. While previous studies have indicated that city-wide municipal management approaches often fail, such outcomes are often left without specific explanation. To determine how municipalities could more effectively develop and implement large-scale approaches, we interviewed stakeholders in municipal rat management programs to document their opinions, recommendations and the challenges they face. Using a thematic framework method, this study collates and analyzes in-depth interviews with 39 stakeholders from seven cities across the United States. Overall, stakeholders' recommendations for municipal rat management aligned with many conceptual attributes of effective management reported in the literature. Specifically, stakeholders highlighted the need to prioritize the reduction of resources available to sustain rat infestations (e.g. food, water and harborage), to focus on proactive (vs. reactive) measures, and to implement large-scale data collection to increase the efficiency of cross-city rat control. Stakeholders also suggested novel approaches to management, such as mitigating rat-associated risks for vulnerable populations specifically and developing tailored initiatives based on the specific needs and desires of residents. We synthesize these recommendations in light of reported barriers, such as resource limitations, and consider several opportunities that may help municipalities reconceptualize their approaches to city-wide rat management. [ABSTRACT FROM AUTHOR]

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan). Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.5mg; study 2: 2.5-15mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed. Results: Most patients in study 1 (n=171) were white (74.9%); all patients were Japanese in study 2 (n=204). Least squares means (±SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 ± 2.9 for placebo, and -17.5 ± 2.8, -29.1 ± 2.8, -34.4 ± 2.9 for verinurad 5, 10, 12.5mg, respectively. In study 2, results were -2.4 ± 2.5 and -31.7 ± 2.5, -51.7 ± 2.6,-55.8 ± 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo. Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study. [ABSTRACT FROM AUTHOR]

Background. Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients-individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis. Methods. Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections. Results. No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories. Conclusions. Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares. [ABSTRACT FROM AUTHOR]

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Background. A subset of patients reporting a diagnosis of Lyme disease can be described as having alternatively diagnosed chronic Lyme syndrome (ADCLS), in which diagnosis is based on laboratory results from a nonreference Lyme specialty laboratory using in-house criteria. Patients with ADCLS report symptoms similar to those reported by patients with chronic fatigue syndrome (CFS). Methods. We performed a case-control study comparing patients with ADCLS and CFS to each other and to both healthy controls and controls with systemic lupus erythematosus (SLE). Subjects completed a history, physical exam, screening laboratory tests, 7 functional scales, reference serology for Lyme disease using Centers for Disease Control and Prevention criteria, reference serology for other tick-associated pathogens, and cytokine expression studies. Results. The study enrolled 13 patients with ADCLS (12 of whom were diagnosed by 1 alternative US laboratory), 25 patients with CFS, 25 matched healthy controls, and 11 SLE controls. Baseline clinical data and functional scales indicate significant disability among ADCLS and CFS patients and many important differences between these groups and controls, but no significant differences between each other. No ADCLS patient was confirmed as having positive Lyme serology by reference laboratory testing, and there was no difference in distribution of positive serology for other tick-transmitted pathogens or cytokine expression across the groups. Conclusions. In British Columbia, a setting with low Lyme disease incidence, ADCLS patients have a similar phenotype to that of CFS patients. Disagreement between alternative and reference laboratory Lyme testing results in this setting is most likely explained by false-positive results from the alternative laboratory. [ABSTRACT FROM AUTHOR]

Objectives: In British Columbia (BC), Canada, neuraminidase inhibitors (NIs) were publicly funded during the 2009 A(H1N1)pdm09 pandemic for treatment of high-risk patients and/or anyone with moderate-to-severe illness. We assessed antiviral effectiveness (AVE) against hospitalization in that context.Methods: A population-based cohort study was conducted using linked administrative data. The cohort included all individuals living in BC during the study period (1 September to 31 December 2009) with a diagnostic code consistent with influenza or pandemic H1N1. The main study period pertained to the second-wave A(H1N1)pdm09 circulation (1 October to 31 December 2009), with sensitivity analyses around the more specific pandemic peak (18 October to 7 November). Exposure was defined by same-day NI prescription. The main outcome was all-cause hospitalization within 14 days of the outpatient influenza diagnosis. Cox proportional hazards models assessed AVE with 1 : 1 propensity-score matching and covariate adjustment.Results: After matching, there were 304/58,061 NI-exposed and 345/58,061 unexposed patients hospitalized during the main study period. The very young [<6 months (35.0; 95% CI 16.7-73.4)], the old [65-79 years (13.7; 95% CI 10.1-18.6)] and the very old [≥80 years (38.7; 95% CI 26.6-56.5)] had the highest hospitalization rate per 1000 patients overall. Fully adjusted AVE against all-cause hospitalization during the main study period was 16% (95% CI 2%-28%), similar to the pandemic peak (15%; 95% CI -4%-30%).Conclusions: The use of NIs was associated with modest protection against hospitalization during the 2009 pandemic, but appeared underutilized in affected age groups with the highest hospitalization risk. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate if debonding microspheres (DM) could enhance electrothermal orthodontic debonding, and specifically to evaluate if the addition of DM, in varying concentrations to the orthodontic adhesive process, will affect bond strength.Bovine teeth (n = 8) were mounted in acrylic using a silicone mould. Four test groups of three preparations of primer (Rely-a-Bond) with DM and a control were examined. Five incisor brackets were bonded to each tooth using the assigned primer and cold cure composite (Rely-a-Bond). Bracket tensile bond strength was measured in vitro in an Instron machine and recorded as debonding force (N). Differences between the groups were statistically analysed using analysis of variance, and repeatability was assessed.The mean debonding force of the control group was statistically significantly greater than all the other groups to which DM had been added (P < 0.001). Comparison of the mean debonding forces of 1, 2.5, and 5 per cent concentrations of DM revealed no statistically significant difference between the groups.The addition of DM to orthodontic adhesive produced a highly statistically significant reduction in debonding force. There was no statistical difference in debonding force between varying concentrations of DM. [ABSTRACT FROM PUBLISHER]

Background. Pandemic H1N1 (pH1N1) surveillance data showed lower attack rates but higher risk of severe outcomes with advanced age. We explored immuno-epidemiologic correlates of surveillance findings including humoral and cell-mediated immunity (CMI). Methods. In an age-based design, ∼100 banked/residual sera per 10-year age stratum were assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays for preexisting antibody to pH1N1 and recent seasonal H1N1 and H3N2 strains. In a separate birth cohort design defined by childhood influenza A/subtype priming (1919-1929: H1N1; 1945-1949: H1N1; 1958-1960: H2N2; 1969-1970: H3N2; 1978-1989: H3N2/H1N1), whole blood was collected from up to 50 volunteers per birth cohort. The ratio of Th1(IFN-γ):Th2(IL-10) cytokine responses was evaluated in vitro. Results. Antibody to seasonal viruses was highest in school-age children. Cross-reactive HI/MN antibody to pH1N1 was low among participants ,70 years of age (yoa; 6%/4% ⩾ 40), but seroprevalence increased at 70-79 yoa (27%/6%), increased even more at 80-89 yoa (65%/47%), and was highest at ⩾90 yoa (88%/76%). CMI to pH1N1 was evident in all 5 birth cohorts but was lower compared with seasonal strains. There was little differentiation by subtype priming, but the Th1:Th2 ratio for all viruses dropped significantly in the 2 oldest cohorts. Conclusions. Preexisting antibody may have protected the very old from pH1N1 infection, while diminished CMI may have contributed to greater severity once infected. In the young, cross-reactive pH1N1 antibody was mostly absent, while more intact CMI may have protected against severe outcomes. [ABSTRACT FROM AUTHOR]

Background. The incidence of invasive group A Streptococcus (GAS) disease can vary over time and geographic region, possibly reflecting the population's susceptibility to particular strains but also variation in the predominant M/emm types. Canadian surveillance documented an epidemic of an uncommon M/emm59 type from 2006 to 2009. Methods. Invasive GAS isolates are submitted by Public Health Laboratories in Canada to the National Centre for Streptococcus for M/emm typing. Patient age, sex, geographic location, and the anatomical source of isolate are provided with the isolate. When it was recognized that M/emm59 strains were increasing in prevalence, clinical information was collected on M/emm59 cases captured in Alberta and compared with cases of other M/emm types occurring in this province. Results. From January 2006 through December 2009, 539 (13.0%) of 4150 invasive GAS cases were identified as M/emm59: 164 from British Columbia, 146 from Alberta, 62 from Saskatchewan, 82 from Manitoba, 68 from Ontario, 14 from Quebec, 1 from New Brunswick, 1 from Newfoundland, 1 from Yukon, and 1 from Nunavut. The predominant clinical presentation was bacteremia (45.0%) followed by cellulitis (41.4%). Compared with concurrent cases of invasive GAS disease caused by all other M/emm types, identified risk factors for M/emm59 disease were alcohol abuse (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-3.8), homelessness (OR, 2.0; 95% CI, 1.2-3.4), hepatitis C virus infection (OR, 2.0; 95% CI, 1.1-3.5), and illicit drug use (OR, 1.7; 95% CI, 1.0-3.0). Conclusions. Western Canada has witnessed the rapid emergence of a rare GAS strain causing invasive disease predominately in a select population of disadvantaged persons. [ABSTRACT FROM AUTHOR]

Background. In April 2009, an elementary school outbreak of pandemic H1N1 (pH1N1) influenza was reported in a community in northern British Columbia, Canada—an area that includes both non-Aboriginal and Aboriginal residents living on or off a reserve. During the outbreak investigation, we explored the relationship between prior receipt of trivalent inactivated influenza vaccine (TIV) and pH1N1-related illness. Methods. A telephone survey was conducted from 15 May through 5 June 2009 among households of children attending any school in the affected community. Members of participating households where influenza-like illness (ILI) was described were then invited to submit blood samples for confirmation of pH1N1 infection by hemagglutination inhibition and microneutralization assays. Circulation of pH1N1 was concentrated among households of the elementary school and elsewhere on-reserve to which analyses of TIV effect were thus restricted. Odds ratios (ORs) for the TIV effect on ILI were computed through logistic regression, with adjustment for age, comorbidity, household density, and Aboriginal status. The influence of within-household clustering was assessed through generalized-linear-mixed models. Results. Of 408 participants, 92 (23%) met ILI criteria: 29 (32%) of 92 persons with ILI, compared with 61 (19%) 316 persons without ILI, had received the 2008-2009 formulation of TIV. Fully adjusted ORs for 2008- 2009 TIV effect on ILI were 2.45 (95% confidence interval, 1.34-4.48) by logistic regression and 2.68 [95% confidence interval, 1.37-5.25) by generalized-linear-mixed model. Conclusions. An outbreak investigation in British Columbia during the late spring of 2009 provided the first indication of an unexpected association between receipt of TIV and pH1N1 illness. This led to 5 additional studies through the summer 2009 in Canada, each of which corroborated these initial findings. [ABSTRACT FROM AUTHOR]

Harvesting timber is a common form of land use that has the potential to cause declines in amphibian populations. It is essential to understand the behavior and fate of individuals and the resulting consequences for vital rates (birth, death, immigration, emigration) under different forest management conditions. We report on experimental studies conducted in three regions of the United States to identify mechanisms of responses by pond-breeding amphibians to timber harvest treatments. Our studies demonstrate that life stages related to oviposition and larval performance in the aquatic stage are sometimes affected positively by clearcutting, whereas effects on juvenile and adult terrestrial stages are mostly negative. Partial harvest treatments produced both positive and weaker negative responses than clearcut treatments. Mitigating the detrimental effects of canopy removal, higher surface temperature, and loss of soil-litter moisture in terrestrial habitats surrounding breeding ponds is critical to maintaining viable amphibian populations in managed forested landscapes. [ABSTRACT FROM AUTHOR]

The Canadian province of Ontario introduced universal influenza immunization in 2000, offering free vaccines to the entire population. We compared changes in rates of influenza-associated respiratory antibiotic prescriptions before and after universal immunization in Ontario with corresponding changes in other provinces. Universal influenza immunization is associated with reduced influenza-associated antibiotic prescriptions. [ABSTRACT FROM AUTHOR]

Background. There is strong evidence that human papillomavirus (HPV) is necessary for the development of cervical cancer. A prophylactic HPV vaccine with high reported efficacy was approved in North America in 2006. Methods. A mathematical model of HPV transmission dynamics was used to simulate different scenarios of natural disease outcomes and intervention strategies. A sensitivity analysis was performed to compensate for uncertainties surrounding key epidemiological parameters. Results. The expected impact that HPV vaccines have on cervical cancer incidence and HPV prevalence in the province of British Columbia in Canada revealed that, for lifelong vaccine-related protection, an immunization routine targeting younger females (grade 6), combined with a 3-year program for adolescent females (grade 9), is the most effective strategy. If vaccine-related protection continues for <10 years, then the targeting of adolescent females would be more beneficial than the targeting of younger females. The incremental benefit if boys, as well as girls, are vaccinated is small. Conclusions. Optimization of the design of immunization strategies for treatment of HPV depends substantially on the duration of vaccine-induced immunity. Given the uncertainty in estimating this duration, it may be prudent to assume a value close to the lower limit reported and adjust the program when more-accurate information for the length of vaccine-induced immunity becomes available. [ABSTRACT FROM AUTHOR]

Antibiotic consumption in populations affects the emergence of resistant organisms. We compared 1996-2000 trends in consumption in British Columbia, Canada, with those in Europe. Prescription data from the British Columbia PharmaNet database were converted into SAS files and classified using the Anatomical Therapeutic Chemical system, and weights of antibiotics were converted into defined daily doses (DDDs) using the 2001 definitions from the World Health Organization Collaborating Center for Drug Statistics Methodology. During 1996-2000, consumption in British Columbia decreased from 19.5 to 17.9 DDDs/1000 inhabitant-days. Although antibiotic consumption in British Columbia was less than the European median in 2000, it exceeded that in northern European countries with established antibiotic surveillance and control programs. The consumption rates for fluoroquinolones, newer macrolides, and cephalosporins in British Columbia exceeded those in Denmark (1.44 vs. 0.15, 1.59 vs. 0.92, and 1.86 vs. 0.02 DDDs/1000 inhabitant-days, respectively). The observed increase in and pattern of consumption associated with newer antimicrobials may increase the risk for emergence of antimicrobial-resistant organisms in British Columbia. [ABSTRACT FROM AUTHOR]

During the 2000-2001 influenza immunization campaign in Canada, a new adverse event, oculo-respiratory syndrome (ORS), was noted in association with administration of vaccine supplied by one manufacturer. The original case definition for ORS specified bilateral conjunctivitis, facial edema, or respiratory symptoms beginning 2-24 h after influenza vaccination and resolving within 48 h after onset. To characterize the spectrum, severity, and impact of ORS, we contacted persons who had reported any influenza vaccine-associated adverse event in British Columbia, Canada, during the 2000-2001 vaccination campaign. With use of a standardized telephone interview, we collected information from 609 (79%) of 769 eligible persons. Thirteen percent of ORS-affected persons reported onset &les;2 h after vaccination, 27% experienced symptoms for >48 h, and 42% considered the symptoms to be severe. The surveillance case definition for ORS for 2001-2002 was revised to include onset &les;24 h after vaccination, with no restriction on duration. ORS should be incorporated into annual influenza vaccine safety monitoring. [ABSTRACT FROM AUTHOR]

Presents letters to the editor about infectious diseases published in the November 15, 2002 issue of the 'Journal of Infectious Diseases.' Identification of indigeneous hepatitis E virus from a Japanese patient who contracted sporadic acute hepatitis in 1982; Changing age and seasonal profile of pertussis in British Columbia.

Examines the changing age and seasonal profile of pertussis in British Columbia. Decline in the incidence of pertussis; Reduction of susceptibility; Changes in the childhood immunization program.

An in vitro blood-brain barrier (BBB) model consisting of primary cultures of bovine brain microvascular endothelial cells was used to examine the effect of Haemophilus influenzae type b (Hib) on the BBB. Whole bacteria and purified lipopolysaccharide (LPS; >10 ng/ml) caused marked cytotoxicity on the bovine brain endothelial cells. This effect could be completely blocked by polymyxin B. Similar cytotoxic effects were observed with a cultured bovine pulmonary endothelial cell line. Serum was essential for the LPS-mediated cytotoxic effect, and human, horse, bovine, or fetal calf serum all had similar effects. The serum factor was not a complement component. A monoclonal antibody against CD14, a receptor involved in mediating the effect of LPS in monocytes, completely blocked the cytotoxic effect in both brain and pulmonary endothelial cells. These results suggest that Hib LPS disrupts an in vitro BBB model via a serum- and CD14-dependent pathway and that LPS has cytotoxic effects on bovine endothelial cells without the involvement of monocytic cells, an effect that may be important in gram-negative meningitis and in endotoxic shock. [ABSTRACT FROM PUBLISHER]

Background Many jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015). Methods Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression. Results A total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13. Conclusion Although PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Early-life exposure to antibiotics is associated with childhood asthma. We previously reported that a dramatic drop in infant antibiotic use is correlated with a decline in asthma incidence in children in British Columbia (BC). This study aims to see whether antibiotic exposure predicts asthma at a fine geographic scale after adjustment for known covariates. Methods We used prescribing data from BC PharmaNet, a population-based database capturing all outpatient prescribing for BC population (n = 4.7 million). Prescribing rates for infants <1 year were calculated as prescriptions per 1000 population per year using age and sex-specified denominator estimates. Age-adjusted aggregate asthma incidence data for children 1–4 years were obtained from the BC Ministry of Health Chronic Disease Registry. The disease identification uses a standard case definition making using of diagnostic codes (ICD9-493 and ICD10-J45) in BC's universal hospital and physician billing databases and relevant asthma-specific drug data from BC PharmaNet. We modeled the association between antibiotic prescribing rate and asthma incidence in 91 Local Health Areas using multivariable Poisson regression employing a generalized linear mixed-effects model adjusting for covariates. Results Between 2000 and 2014, the annual asthma incidence (ages 1–4 years) fell 26% from 27.3 (95% CI: 26.5–28.0) to 20.2 (95% CI: 19.5–20.8) per 1000 population. For children aged 1–4 years in 2000, the average proportion of infants exposed to one or more courses of antibiotics fell from 66.9 to 32.1% over the same interval. Antibiotic was a significant predictor of asthma rate (IRR=1.24 per 10% absolute increase in antibiotic prescribing; 95% CI: 1.19–1.27). Other covariates that remained significant in the model included male sex (IRR=1.56; 95% CI: 1.53–1.58), and atmospheric particulate matter PM 2.5 (IRR=1.08 per interquartile increase; 95% CI: 1.06–1.10). Conclusion Our findings suggest that antibiotic exposure in the first year of life increases the risk of being diagnosed with asthma later in childhood. This is congruent with similar findings at the individual level in a prospective cohort of Canadian children that also points to a pathway through altered gut microbiota. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Examines the role of antigen testing in the diagnosis of histoplasmosis in a group of students and teachers who visited a cave in Belize. Risk factors and symptoms of histoplasmosis; Duration of the symptoms; Sensitivity of antigen detection in patients with subacute or chronic pulmonary histoplasmosis.

Background Antibiotic prescribing in pediatric care is highly prevalent. Often children are prescribed antibiotics for conditions that are commonly self-limiting and viral in etiology such as upper respiratory tract infections. The purpose of this study was to examine the scope of pediatric antibiotic prescribing in British Columbia from 2013 to 2016 and identify potential new provincial antimicrobial stewardship targets. Methods Antibiotic prescription data for children were extracted from a provincial prescription database, and linked to demographic files in order to obtain patient age, sex and geographic location. Prescription rates were then calculated, and trends were examined by major anatomical therapeutic chemical (ATC) classification. Results Our cohort included an average of 271,134 children per year and 1,767,652 antibiotic prescriptions. Over the 4 years, rates of antibiotic prescribing increased 4.5% (from 453 to 474 prescriptions per 1,000 population per year). The greatest increase, across all classes of antibiotics, was seen in children aged 0–2 years of age. By 2016, the greatest increase in prescribing, by class, was observed in J01X (e.g. nitrofurantoin, fosfomycin) with a 1360% increase for children aged 3–9. Across all ages, quinolones (J01M) increased 98%. Remaining classes, including β lactams (J01C), and macrolides (J01F), experienced modest reductions in the older age groups. Conclusion Past studies have illustrated decreasing or static rates of antibiotic prescribing in British Columbia. However, we have identified a paradoxical (4.5%) increase in pediatric antibiotic prescribing since 2013. Although it appears that provincial efforts have been successful in reducing the use of broad-spectrum penicillins (J01C), marked surges in the use of classes like tetracylines (J01A), quinolones (J01M), and other antibacterials (J01X) identify a new potential target for provincial stewardship. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Antibiotic prescribing in pediatric care is highly prevalent, and quite often children are prescribed for conditions which are commonly self-limiting and viral in etiology. The purpose of this study was to examine the scope of pediatric antibiotic prescribing by indication, from 2013 to 2016, and identify potential new targets for provincial antimicrobial stewardship efforts. Methods Antibiotic prescription data for children were extracted from a provincial prescription database, and linked to physician billing data in order to obtain diagnostic information. Prescription rates were then calculated, and trends were examined by indication. Major categories included: upper respiratory tract infection, acute otitis media, lower respiratory tract, skin and soft tissue, and urinary tract infections. Results Our database included an average of 244,763 children per year, and 5,896,173 total antibiotic prescriptions. Increased indication-specific rates of prescribing were observed in children aged 0–2 years, for every category. Children aged 3–18 years experienced decreased prescribing across all indications, with the exception of urinary tract infections for those aged between 10–18 years. Urinary tract infections increased by 134% for children aged 0–2 years, and 75% for those aged 10–18 years, from 2013 to 2016. Although antibiotic use for upper respiratory tract infections decreased by 11% for all ages, these diagnoses continue to be prescribed for at rates 2 – 5 times higher than other conditions. Conclusion Although this study found a decrease in prescribing over time across all indications, antibiotic use continues to be a concern for upper respiratory tract infections in pediatric care. These diagnoses generally do not require antibiotics, and inappropriate prescribing is a major factor in antimicrobial resistance. The increased prescribing rates in the youngest age group (0–2 years) offers a new target for provincial stewardship efforts. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Pneumococcal conjugate vaccines have substantially reduced the incidence of invasive pneumococcal disease (IPD); however, the impact of the vaccine on non-vaccine serotypes (NVT) remains unclear. We evaluated the effect of PCV13 use in British Columbia, Canada. Methods The annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) was calculated using provincial laboratory surveillance data. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–10) and pre-PCV7 (2002–03) baselines using Poisson regression for non-conjugate vaccine type IPD. Results A total of 4,490 cases were reported over the 14 year period. The overall annual incidence increased from 5.73 cases per 100,000 population in 2002 to 7.90 cases per 100,000 population in 2015. Compared with baseline, PCV7 reduced VT-IPD (IRR: 0.49; 95% CI: 0.42–0.56), but the additional 6 serotypes in the PCV13 vaccine caused 214% increase in IPD (IRR: 2.65; 95% CI: 2.12–3.39). The majority of this increase is related to an increase in NVT disease (IRR: 3.17; 95% CI: 2.62–3.87) such as 23B, 23A, 9N, 20, 33F, 15C, 17F and 6C. IPD from PCV13 vaccine serotypes 19A and 7F which emerged after PCV7 continue to be high. Conclusion The introduction of PCV13 has a modest impact on IPD rates, due to inadequate control of serotypes 19A and 7F, and, of concern, IPD rates continue to escalate due to serotype replacement by non-vaccine serotypes. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background A significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 on IPD in British Columbia, Canada over a 14 year period (2002–2015). Methods Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in children less than 17 years of age. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression. Results A total of 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds. Conclusion While IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]