Browsing by Author "Tipples, Graham"

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    Changes in norovirus genotype diversity in gastroenteritis outbreaks in Alberta, Canada: 2012–2018
    (2019-02-19) Hasing, Maria E; Lee, Bonita E; Qiu, Yuanyuan; Xia, Ming; Pabbaraju, Kanti; Wong, Anita; Tipples, Graham; Jiang, Xi; Pang, Xiaoli L
    Abstract Background The emergence of norovirus genotype GII.4 variants has been associated with gastroenteritis pandemics worldwide, prompting molecular surveillance for early detection of novel strains. In this study, we aimed to analyze the outbreak activity of norovirus and characterize the norovirus strains circulating in Alberta between July 2012 and February 2018. Methods Stool samples from gastroenteritis outbreaks in Alberta were tested for norovirus at the Provincial Laboratory for Public Health using a multiplex real time-RT PCR assay. The ORF1 and ORF2-genotypes of norovirus positive samples were assigned based on phylogenetic analyses of partial polymerase and capsid sequences, respectively. Results A total of 530 norovirus outbreaks were identified. During July 2012 and June 2017 there was a gradual decrease in the annual number of GII.4 outbreaks, however, outbreak numbers increased from June 2017–February 2018. Four novel strains emerged: GII.17 Kawasaki in July 2014–June 2015, GII.P16/GII.4 Sydney in July 2015–June 2016, GII.P16/GII.2 and GII.P4 New Orleans/GII.4 Sydney in July 2016–June 2017. GII.Pe/GII.4 Sydney was the single predominant strain responsible for the majority (over 50%) of all norovirus outbreaks up to June 2015. Between June 2017 and February 2018, GII.P16/GII.4 Sydney was the leading strain causing 63% of all norovirus outbreaks. Conclusions GII.4 stands as the predominant capsid genotype causing a large majority of the norovirus outbreaks in early 2018. An increase in genotype diversity was observed in the last years, characterized by a high circulation of non-GII.4 strains and GII.4 recombinants.
  • Thumbnail Image
    ItemOpen Access
    Diagnostic Interpretation Guidance for Pediatric Enteric Pathogens: A Modified Delphi Consensus Process
    (2018-09-27) Stang, Antonia S.; Trudeau, Melanie; Vanderkooi, Otto G.; Lee, Bonita E.; Chui, Linda; Pang, Xiao-Li; Allen, Vanessa; Burnham, Carey-Ann D.; Goldfarb, David M.; MacDonald, Judy; Parsons, Brendon; Petrich, Astrid; Pollari, Frank; Tarr, Phillip I.; Tipples, Graham; Zhuo, Ran; Freedman, Stephen B.
    Background. We sought to develop diagnostic test guidance definitions for pediatric enteric infections to facilitate the interpretation of positive test results in the era of multianalyte molecular diagnostic test platforms. Methods. We employed a systematic, two-phase, modified Delphi consensus process consisting of three web-based surveys and an expert panel face-to-face meeting. In phase 1, we surveyed an advisory panel of North American experts to select pathogens requiring diagnostic test guidance definition development. In phase 2, we convened a 14-member expert panel to develop, refine, and select the final definitions through two web-based questionnaires interspersed with a face-to-face meeting. Both questionnaires asked panelists to rate the degree to which they agreed that if the definition is met the pathogen is likely to be causative of clinical illness. Results. The advisory panel survey identified 19 pathogens requiring definitions. In the expert panel premeeting survey, 13 of the 19 definitions evaluated were rated as being highly likely (“agree” or “strongly agree”) to be responsible for acute gastroenteritis symptoms by ≥67% of respondent panel members. The definitions for the remaining six pathogens (Aeromonas, Clostridium difficile, Edwardsiella, nonenteric adenovirus, astrovirus, and Entamoeba histolytica) were indeterminate. After the expert panel meeting, only two of the modified definitions, C. difficile and E. histolytica/dispar, failed to achieve the a priori specified threshold of ≥67% agreement. Conclusions. We developed diagnostic test guidance definitions to assist healthcare providers for 17 enteric pathogens. We identified two pathogens that require further research and definition development.
  • Thumbnail Image
    ItemOpen Access
    False negative rate of COVID-19 PCR testing: a discordant testing analysis
    (2021-01-09) Kanji, Jamil N; Zelyas, Nathan; MacDonald, Clayton; Pabbaraju, Kanti; Khan, Muhammad N; Prasad, Abhaya; Hu, Jia; Diggle, Mathew; Berenger, Byron M; Tipples, Graham
    Abstract Background COVID-19 is diagnosed via detection of SARS-CoV-2 RNA using real time reverse-transcriptase polymerase chain reaction (rtRT-PCR). Performance of many SARS-CoV-2 rtRT-PCR assays is not entirely known due to the lack of a gold standard. We sought to evaluate the false negative rate (FNR) and sensitivity of our laboratory-developed SARS-CoV-2 rtRT-PCR targeting the envelope (E) and RNA-dependent RNA-polymerase (RdRp) genes. Methods SARS-CoV-2 rtRT-PCR results at the Public Health Laboratory (Alberta, Canada) from January 21 to April 18, 2020 were reviewed to identify patients with an initial negative rtRT-PCR followed by a positive result on repeat testing within 14 days (defined as discordant results). Negative samples from these discordant specimens were re-tested using three alternate rtRT-PCR assays (targeting the E gene and N1/N2 regions of the nucleocapsid genes) to assess for false negative (FN) results. Results During the time period specified, 95,919 patients (100,001 samples) were tested for SARS-CoV-2. Of these, 49 patients were found to have discordant results including 49 positive and 52 negative swabs. Repeat testing of 52 negative swabs found five FNs (from five separate patients). Assuming 100% specificity of the diagnostic assay, the FNR and sensitivity in this group of patients with discordant testing was 9.3% (95% CI 1.5–17.0%) and 90.7% (95% CI 82.6–98.9%) respectively. Conclusions Studies to understand the FNR of routinely used assays are important to confirm adequate clinical performance. In this study, most FN results were due to low amounts of SARS-CoV-2 virus concentrations in patients with multiple specimens collected during different stages of infection. Post-test clinical evaluation of each patient is advised to ensure that rtRT-PCR results are not the only factor in excluding COVID-19.
  • Thumbnail Image
    ItemOpen Access
    Pediatric antibody responses to SARS-CoV-2 after infection and vaccination in Calgary, Canada
    (2024-07-18) Ricketson, Leah J.; Doucette, Emily J.; Alatorre, Isabella; Tarannum, Tarannum; Gray, Joslyn; Booth, William; Tipples, Graham; Charlton, Carmen; Kanji, Jamil N.; Fonseca, Kevin; Kellner, James D.
    Abstract Background There are few reports of longitudinal serologic responses in children following Sars-CoV-2 infection and vaccination. This study describes longitudinal SARS-CoV-2 antibody responses following infection, vaccination, or both (hybrid immunity) in a cohort of Canadian children. The objectives of our study were to compare antibody levels following SARS-CoV-2 infection, vaccination, and hybrid immunity and to examine antibody decline after final antigen exposure. Methods The Alberta Childhood COVID-19 Cohort (AB3C) study was a prospective longitudinal cohort study conducted from July 2020 to September 2022 with repeat sampling across 5 visits. Children under 18 years of age were enrolled for serial measurement of antibody responses to SARS-CoV-2 virus vaccine and infection. Results The final sample size was 919; participants were 50.5% female, 48.2% were > 12 years and 88.5% were white ethnicity. The median peak spike IgG level of those with only infection was not different from those with no vaccination or infection (233 AU/mL (IQR: 99–944 AU/mL) vs. 3 AU/mL (IQR: 1–5 AU/mL; P = 0.1765). Participants with infections after vaccination had higher IgG levels than those where infection preceded vaccination (median: 36,660 (IQR: 22,084 − 40,000 AU/mL) vs. 17,461 AU/mL (IQR: 10,617 − 33,212 AU/mL); P < 0.0001). In a linear mixed methods model, children with infection-only had low levels of antibody that stayed stable over the study duration without further antigen exposures. Those with infection after vaccination had the slowest rate of antibody decline over time at 4% (95%CI: 2-5%) per week, compared with children where infection preceded vaccine 7% (95%CI: 6-8%) per week. Conclusions Children with hybrid immunity conferred through vaccination (2 + doses) followed by a SARS-CoV-2 infection had the highest and longest lasting antibody levels, compared to children who had an infection followed by vaccination, vaccination-only, or infection-only. The longer-term clinical importance of these findings, related to prevention of repeated infections and severe outcomes and need for further vaccine doses, is not yet known.