Browsing by Author "Pabbaraju, Kanti"

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    Adamantane Resistance in Seasonal Human Influenza A Viruses from Calgary, Alberta (January 2007 to August 2008)
    (2010-01-01) Pabbaraju, Kanti; Wong, Sallene; Kits, Dmitri K; Fox, Julie D
    The available antivirals for the treatment and prophylaxis of influenza A infections include the adamantanes (amantadine and rimantadine), which are matrix (M2) protein inhibitors, and the neuraminidase inhibitors (oseltamivir and zanamivir). Resistance to the adamantanes is conferred by mutations at amino acid positions 26, 27, 30, 31 or 34 within the M2 protein of influenza A viruses. A significant increase in adamantane resistance has been reported worldwide since 2003, reflected by a similar increase in Canada. The present study reports on the frequency of adamantane resistance in seasonal influenza A viruses in Calgary, Alberta, for the period between January 2007 and August 2008, as an update to the previous report. Positive influenza A samples (221 original patient specimens and 34 isolates obtained by viral culture) were analyzed for changes in the critical amino acid residues of the M2 gene. The amplification and sequencing of regions that confer adamantane resistance directly from RNA extracts of clinical samples (without previous culture) makes this approach a fast and efficient process for monitoring resistance. The results showed that the frequency of resistance varied from 37.5% to 49.2% in circulating influenza A H3N2 virus strains (n=213) between January 2007 and April 2007. The frequency of resistance increased to 100% in May 2007, after which all H3N2 viruses were resistant until the end of the monitoring period. All resistant H3N2 viruses contained the serine to asparagine substitution at amino acid position 31. Resistance was not observed in the H1N1 viruses tested (n=39) within this monitoring period. The level of adamantane resistance in H3N2 viruses continues to remain high since resistant viruses became the prevalent circulating strains in 2005. Recent reports have indicated that the currently circulating swine-origin influenza A H1N1 subtype viruses are adamantane resistant. It is, thus, important to continue to monitor seasonal influenza A viruses for antiviral resistance markers to ensure optimal prophylaxis and treatment.
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    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.
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    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.
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    Genetic characterization of a Coxsackie A9 virus associated with aseptic meningitis in Alberta, Canada in 2010
    (BioMed Central, 2013-03-22) Pabbaraju, Kanti; Wong, Sallene; Chan, Eve N Y; Tellier, Raymond
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    Identification and Epidemiology of Severe Respiratory Disease due to Novel Swine-Origin Influenza A (H1N1) Virus Infection in Alberta
    (2010-01-01) Zahariadis, George; Joffe, Ari R; Talbot, James; deVilliers, Albert; Campbell, Patricia; Pabbaraju, Kanti; Wong, Sallene; Bastien, Nathalie; Li, Yan; Mitchell, Robyn L; Pang, Xiao-Li; Yanow, Stephanie; Chui, Linda; Predy, Gerald; Willans, David; Lee, Bonita E; Preiksaitis, Jutta K; Clement, Bev; Jacobs, Angela; Jaipaul, Joy; Fonseca, Kevin
    BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada.METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods.RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain.CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.
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    Patient and ward related risk factors in a multi-ward nosocomial outbreak of COVID-19: Outbreak investigation and matched case–control study
    (2023-03-22) Leal, Jenine; O’Grady, Heidi M.; Armstrong, Logan; Dixit, Devika; Khawaja, Zoha; Snedeker, Kate; Ellison, Jennifer; Erebor, Joyce; Jamieson, Peter; Weiss, Amanda; Salcedo, Daniel; Roberts, Kimberley; Wiens, Karen; Croxen, Matthew A.; Berenger, Byron M.; Pabbaraju, Kanti; Lin, Yi-Chan; Evans, David; Conly, John M.
    Abstract Background Risk factors for nosocomial COVID-19 outbreaks continue to evolve. The aim of this study was to investigate a multi-ward nosocomial outbreak of COVID-19 between 1st September and 15th November 2020, occurring in a setting without vaccination for any healthcare workers or patients. Methods Outbreak report and retrospective, matched case–control study using incidence density sampling in three cardiac wards in an 1100-bed tertiary teaching hospital in Calgary, Alberta, Canada. Patients were confirmed/probable COVID-19 cases and contemporaneous control patients without COVID-19. COVID-19 outbreak definitions were based on Public Health guidelines. Clinical and environmental specimens were tested by RT-PCR and as applicable quantitative viral cultures and whole genome sequencing were conducted. Controls were inpatients on the cardiac wards during the study period confirmed to be without COVID-19, matched to outbreak cases by time of symptom onset dates, age within ± 15 years and were admitted in hospital for at least 2 days. Demographics, Braden Score, baseline medications, laboratory measures, co-morbidities, and hospitalization characteristics were collected on cases and controls. Univariate and multivariate conditional logistical regression was used to identify independent risk factors for nosocomial COVID-19. Results The outbreak involved 42 healthcare workers and 39 patients. The strongest independent risk factor for nosocomial COVID-19 (IRR 3.21, 95% CI 1.47–7.02) was exposure in a multi-bedded room. Of 45 strains successfully sequenced, 44 (97.8%) were B.1.128 and differed from the most common circulating community lineages. SARS-CoV-2 positive cultures were detected in 56.7% (34/60) of clinical and environmental specimens. The multidisciplinary outbreak team observed eleven contributing events to transmission during the outbreak. Conclusions Transmission routes of SARS-CoV-2 in hospital outbreaks are complex; however multi-bedded rooms play a significant role in the transmission of SARS-CoV-2.