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  • 1
    In: Canadian Journal of Infectious Diseases and Medical Microbiology, Wiley, Vol. 2016 ( 2016), p. 1-8
    Abstract: Background . Clostridium difficile is a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressor tcdC , and a binary toxin. Objectives . To determine the molecular epidemiology of C. difficile in British Columbia and compare between two time points in one region. Methods . C. difficile isolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession, tcdC genotype, and antimicrobial susceptibility. Results . In 2008, 42.7% of isolates had NAP1 designation. Hospital-collected isolates were associated with older patients and more NAP1 types. Unlike other isolates, most NAP1 isolates possessed binary toxin and a 19 bp loss in tcdC . All isolates were susceptible to metronidazole and vancomycin. A 2013 follow-up revealed a 28.9% decrease in NAP1 isolates and 20.0% increase in isolates without NAP designation in one region. Then, community-associated cases were seen in younger patients, while NAP types were evenly distributed. Isolates without NAP designation did not cluster with a PFGE pattern or ribotype. Conclusions . Evaluation of C. difficile infections within British Columbia revealed demographic associations, epidemiological shifts, and characteristics of strain types. Continuous surveillance of C. difficile will enable detection of emerging strains.
    Type of Medium: Online Resource
    ISSN: 1712-9532 , 1918-1493
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 2018
    In:  Pediatric and Developmental Pathology Vol. 21, No. 5 ( 2018-09), p. 497-501
    In: Pediatric and Developmental Pathology, SAGE Publications, Vol. 21, No. 5 ( 2018-09), p. 497-501
    Abstract: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a common cause of periodic fever in children. The pathogenesis of PFAPA is unknown but likely involves immune system dysregulation and may be initiated by an environmental trigger. Tonsillectomy resolves or improves symptoms in some patients, but the reason for this is unknown; moreover, specific abnormalities in tonsillectomy specimens from PFAPA patients have not been described. Here, we report measles virus in tonsil from a child with PFAPA. Measles-type viral cytopathic effect was discovered on histological examination of tonsillar tissue after therapeutic tonsillectomy for PFAPA. Molecular testing showed the left tonsil was positive for measles RNA by reverse transcription polymerase chain reaction (RT-PCR) while the right tonsil was inconclusive (weakly positive). Real-time RT-PCR specific for measles vaccine strain RNA (genotype A) was weakly reactive in the left tonsil tissue when tested in 3 independent replicates, but this result could not be confirmed with conventional genotyping by sequencing. The relationship and clinical significance between measles virus and PFAPA in this case is unclear but may be related to PFAPA-associated immune dysregulation. Additional investigation of measles virus in PFAPA patients would be helpful in further exploring this potential association.
    Type of Medium: Online Resource
    ISSN: 1093-5266 , 1615-5742
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. Supplement_2 ( 2023-11-27)
    Abstract: Multiple combinations of COVID-19 vaccine regimens have been used in Canada throughout the SARS-CoV-2 immunization campaign. Studies evaluating the humoral immune response following COVID-19 vaccination in community dwelling older adults remain limited. This study assessed COVID-19 vaccine elicited antibody responses in older adult populations, alongside factors that influence antibody responses. Methods Community dwelling adults aged 50 to 87 years (mean=65) were enrolled (n=612). Detection of index SARS-CoV-2 anti-spike IgG (anti-S-IgG) concentration and surrogate neutralization were performed on dried blood spot samples via two multiplex assays (Meso Scale Diagnostics). Anti-S-IgG concentration and surrogate neutralization were quantified following mRNA (mRNA-1273 [m-1273], BNT162b2 [BNT] ) or viral vector (ChAdOx1-S [ChAd]) vaccination. Vaccine groups were compared using one-way ANOVA and Tukey-Kramer multiple comparisons tests. Multivariable regression analyses evaluated influences of demographic and clinical factors on humoral immune responses. Results Three doses of m-1273 resulted in significantly higher anti-S-IgG compared with three BNT doses at four months (geometric mean concentration; 10167 AU/mL vs. 5412 AU/mL, P=0.009) post dose three. Three dose mixed vaccination with ChAd, m-1273 and BNT resulted in comparable anti-S-IgG concentration to three dose m-1273 at four months post dose three. Three doses of either m-1273 or mixed mRNA containing vaccines was associated with significantly higher surrogate neutralization compared with three BNT doses at four months (46% & 43% vs. 34%, P=0.002) post dose three. No significant difference in anti-S-IgG concentration was observed in four dose vaccination regimens. SARS-CoV-2 infection, health status of excellent or very good, and m-1273 containing vaccine regimens positively influenced the antibody response. Conclusion Immunization schedules including a minimum of one m-1273 dose elicited the strongest and most durable antibody responses compared with BNT only containing regimens. There is no established correlate of protection for COVID-19, and as such this data should be interpreted alongside vaccine effectiveness studies. Omicron and XBB specific antibody responses will be compared. Disclosures Sofia R. Bartlett, PhD, Abbvie: Advisor/Consultant|Abbvie: Grant/Research Support|Cepheid: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support Theodore Steiner, MD, FRCPC, Edesa: Grant/Research Support|Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Qu Biologics: Advisor/Consultant|Qu Biologics: Stocks/Bonds|Seres: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 75, No. 11 ( 2022-11-30), p. 1980-1992
    Abstract: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada’s larger provinces. Methods Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22–47) 2021. Results In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of & gt;90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7–8-week versus manufacturer-specified 3–4-week intervals between mRNA doses. Conclusions Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7–8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 74, No. 7 ( 2022-04-09), p. 1158-1165
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 226, No. 3 ( 2022-08-26), p. 485-496
    Abstract: 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 & gt;85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
    In: International Journal of Infectious Diseases, Elsevier BV, Vol. 114 ( 2022-01), p. 178-182
    Type of Medium: Online Resource
    ISSN: 1201-9712
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. Supplement_2 ( 2023-11-27)
    Abstract: Adults aged & gt; 50 years are at increased risk for severe coronavirus disease 2019 (COVID-19). This study evaluated immunogenicity of COVID-19 vaccines in healthy adults aged & gt; 50 years through quantification of antigen specific antibody concentration and function post-vaccination with two, three and four COVID-19 vaccine doses. Methods Eighty-four immunocompetent, community-dwelling adults 50 to 83 years old (median age 61 years) were enrolled. We measured index virus spike protein (S) specific antibody responses to mRNA (mRNA-1273 or BNT162b2) and/or ChAdOx1-S COVID-19 vaccines. Participants were separated into three groups: (1) mRNA/mRNA/mRNA/mRNA; (2) ChAdOx1-S/mRNA/mRNA; (3) ChAdOx1-S/ChAdOx1-S/mRNA. Responses were quantified via: anti-S IgG geometric mean concentrations (GMCs) (binding antibody units [BAU]/mL), total relative IgG avidity index (TRAI) (avidity units, AU) collected up to one, four, and seven-months after each dose. One-way ANOVA, Tukey-Kramer post-hoc compared groups and Welch’s t-test compared timepoints. Results At one month post-dose two, mRNA/mRNA (1137 BAU/mL, p = 0.0003) and ChAdOx1-S/mRNA (1388, p & lt; 0.0001) had higher anti-S IgG GMCs compared with ChAdOx1-S/ChadOx1-S (195 BAU/mL). However, TRAI was similar amongst the three groups (all p & gt; 0.05); mRNA/mRNA (70 AU), ChAdOx1-S/mRNA (66 AU) and ChAdOx1-S/ChAdOx1-S (58 AU). S-IgG GMCs at one month post-dose three were higher for mRNA/mRNA/mRNA than ChAdOx1-S/ChAdOx1-S/mRNA (1316 vs. 569 BAU/mL p = 0.0162). Similar to post-dose two, post-dose three there were no significant differences in TRAI between groups (all p & gt; 0.05); mRNA/mRNA/mRNA (95 AU), ChAdOx1-S/mRNA/mRNA (98 AU), ChAdOx1-S/ChAdOx1-S/mRNA (101 AU). For mRNA/mRNA/mRNA participants, a fourth mRNA vaccine dose increased S-IgG GMCs at one-month post-dose four compared with one month post-dose two (2825 vs. 1137 BAU/mL, p = 0.0126) and maintained TRAI between timepoints (71 vs. 70 AU, p = 0.9877). Conclusion mRNA vaccines are more immunogenic compared to ChAdOx1-S with regards to S-specific antibody concentration. mRNA boosters maintained antibody avidity. Together, TRAI and anti-S IgG GMCs should be further evaluated when recommending additional booster doses and considered when determining protection against COVID-19.     Disclosures Sofia R. Bartlett, PhD, Abbvie: Advisor/Consultant|Abbvie: Grant/Research Support|Cepheid: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. Supplement_2 ( 2023-11-27)
    Abstract: A vaccine series consisting of two doses of coronavirus disease 2019 (COVID-19) mRNA vaccines plus one booster dose is currently recommended for healthy children aged 5-11 years in Canada. Additional studies are needed to understand the longitudinal immunity to COVID-19 vaccination in the pediatric population. The Severe acute respiratory syndrome-related coronavirus 2 PRevalence In children and youNG adults in British Columbia (SPRING) sub-study aimed to specifically investigate antibody responses to COVID-19 vaccination in children aged 5-11 years. Methods Fifty-four children without immunocompromising conditions or taking immunosuppressive medications were enrolled prior to dose one or dose two of their COVID-19 vaccine. Responses were quantified via: anti-index virus spike protein specific IgG (S-IgG) geometric mean concentrations (GMCs) (binding antibody units, BAU/mL) and S-IgG avidity reported as total relative IgG avidity index (TRAI) (avidity units, AU) at pre-dose two, as well as one and six months post-dose two. A Welch’s t-test compared responses between timepoints. Results The cohort consisted of 55% male and 45% female with a median age of 8 years. The interval between first and second doses ranged from 7 – 18 (median 11) weeks. Concentrations of S-IgG increased from pre-dose two to one month post-dose two (222 vs. 1152 BAU/mL, p & lt; 0.0001). GMCs then decreased by six months post-dose two (1152 vs. 343 BAU/mL, p & lt; 0.0001) to levels similar to pre-dose two (p = 0.0696). TRAI increased between time points. By six months post-dose two, S-IgG TRAI (68 AU) remained higher than pre-dose two (46 AU, p & lt; 0.0001) and one month post-dose two (65 AU, p = 0.0495). This increase in avidity was due to higher concentrations of medium high, high and very high avidity S-IgG as well as a decrease in very low avidity S-IgG at six months post-dose two. Conclusion Concentrations of S-IgG waned significantly by six months post-dose two. The results suggest that due to repeated exposure to the S-protein, affinity maturation has resulted in the production of higher avidity antibodies post-dose two. This suggests that both S-IgG concentrations and avidity should be considered when determining protection against COVID-19 and need to be further explored to support future booster recommendations. Disclosures Sofia R. Bartlett, PhD, Abbvie: Advisor/Consultant|Abbvie: Grant/Research Support|Cepheid: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 10
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 5 ( 2022-10-26)
    Abstract: SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long ( 〉 158 days) first vaccination-to-blood collection and long ( 〉 71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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