Browsing by Author "Tyrrell, Gregory J"

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    Epidemiological and genomic determinants of tuberculosis outbreaks in First Nations communities in Canada
    (2018-08-08) Doroshenko, Alexander; Pepperell, Caitlin S; Heffernan, Courtney; Egedahl, Mary L; Mortimer, Tatum D; Smith, Tracy M; Bussan, Hailey E; Tyrrell, Gregory J; Long, Richard
    Abstract Background In Canada, tuberculosis disproportionately affects foreign-born and First Nations populations. Within First Nations’ peoples, a high proportion of cases occur in association with outbreaks. Tuberculosis transmission in the context of outbreaks is thought to result from the convergence of several factors including characteristics of the cases, contacts, the environment, and the pathogen. Methods We examined the epidemiological and genomic determinants of two well-characterized tuberculosis outbreaks attributed to two super-spreaders among First Nations in the province of Alberta. These outbreaks were associated with two distinct DNA fingerprints (restriction fragment-length polymorphisms or RFLPs 0.0142 and 0.0728). We compared outbreak isolates with endemic isolates not spatio-temporarily linked to outbreak cases. We extracted epidemiological variables pertaining to tuberculosis cases and contacts from individual public health records and the provincial tuberculosis registry. We conducted group analyses using parametric and non-parametric statistical tests. We carried out whole-genome sequencing and bioinformatic analysis using validated protocols. Results We observed differences between outbreak and endemic groups in the mean number of total and child-aged contacts and the number of contacts with new positive and converted tuberculin skin tests in all group comparisons (p < 0.05). Differences were also detected in the proportion of cases with cavitation on a chest radiograph and the mean number of close contacts in selected group comparisons (p < 0.02). A phylogenetic network analysis of whole-genome sequencing data indicated that most outbreak and endemic strains were closely related to the source case for the 0.0142 fingerprint. For the 0.0728 fingerprint, the source case haplotype was circulating among endemic cases prior to the outbreak. Genetic and temporal distances were not correlated for either RFLP 0.0142 (r2 = − 0.05) or RFLP 0.0728 (r2 = 0.09) when all isolates were analyzed. Conclusions We found no evidence that endemic strains acquired mutations resulting in their emergence in outbreak form. We conclude that the propagation of these outbreaks was likely driven by the combination of characteristics of the source cases, contacts, and the environment. The role of whole-genome sequencing in understanding mycobacterial evolution and in assisting public health authorities in conducting contact investigations and managing outbreaks is important and expected to grow in the future.
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    Evaluation of Potential Factors Contributing to Microbiological Treatment Failure in Streptococcus Pyogenes Pharyngitis
    (2001-01-01) Kuhn, Susan M; Preiksaitis, Jutta; Tyrrell, Gregory J; Jadavji, Taj; Church, Deirdre; Davies, H Dele
    BACKGROUND: A cohort study of children with pharyngitis aged two to 16 years was conducted to assess the role of microbial and host factors in group A beta-hemolytic streptococcus (GABHS) microbiological treatment failure. METHODS: GABHS-infected children had pharyngeal swabs repeated two to five days after completing a 10-day course of penicillin V. M and T typing, and pulsed field gel electrophoresis were performed on the isolates, and the isolates were evaluated for tolerance. Patient characteristics and clinical features were noted and nasopharyngeal swabs for respiratory viruses were taken at enrolment. RESULTS AND CONCLUSIONS: Of 286 patients enrolled, 248 (87%) could be evaluated. GABHS was cultured from 104 patients (41.9%), of whom 33 (33.7%) had microbiological treatment failures on follow-up. Although there was a trend toward failure for younger children (mean 6.5±2.4 years versus 7.3±2.4 years, P=0.07) and M type 12 (24% versus 10%, P=0.08), no factors were associated with treatment failure.
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    Invasive Streptococcus pneumoniae Infection Causing Hemolytic Uremic Syndrome in Children: Two Recent Cases
    (2003-01-01) Vanderkooi, Otto G; Kellner, James D; Wade, Andrew W; Jadavji, Tajdin; Midgley, Julian P; Louie, Thomas; Tyrrell, Gregory J
    INTRODUCTION: Streptococcus pneumoniae is an uncommon cause of hemolytic uremic syndrome (HUS) with a unique pathophysiology that differs from Shiga toxin-related HUS.METHODS: Case descriptions for each patient are provided. Each strain of S pneumoniae was subjected to a pulsed-field gel electrophoresis (PFGE) analysis, Shiga toxin assay and polymerase chain reaction to detect Shiga toxin genes. A review of the current literature was conducted.CASE PRESENTATIONS: Two patients with S pneumoniae-related HUS that presented to the Alberta Children's Hospital, Calgary, Alberta, within four weeks of each other in 2001 are described. Both presented with pneumonia and empyema with associated HUS. Both patients required dialysis, one patient for 10 days and the other for 18 days. Neither patient demonstrated evidence of Shiga toxin-related disease. S pneumoniae isolated from blood or pleural fluid was penicillin susceptible. One isolate was serotype 3 and the other was serotype 14. The two strains had different PFGE patterns. Both patients recovered well with no persistent renal dysfunction.CONCLUSIONS: S pneumoniae continues to be an uncommon but important cause of HUS. Most cases can be confirmed or at least considered probable without performing a renal biopsy.
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    Pneumococcal Peritonitis: Still with Us and Likely to Increase in Importance
    (2010-01-01) Waisman, Darcy C; Tyrrell, Gregory J; Kellner, James D; Garg, Sipi; Marrie, Thomas J
    BACKGROUND: Pneumococcal peritonitis is uncommon and poorly understood.METHODS: As part of a five-year study (2000 to 2004) of invasive pneumococcal disease (IPD) in Alberta, all cases of peritonitis due to Streptococcus pneumoniae were reviewed and compared with all other cases of IPD.RESULTS: Twenty-three of 1768 (1.3%) IPD patients were found to have peritonitis. Patients with peritonitis were more likely to have cirrhosis, hepatitis C, alcoholism and HIV/AIDS, than the remainder of the patients with IPD. The all-cause mortality did not differ between the two groups. Peritonitis was classified as primary in nine (39%) patients, secondary in 12 (52%) patients, and genitourinary in females, specifically, in two (9%) patients. Pneumococcal serotypes causing peritonitis were under-represented in current vaccines – 17% among peritonitis patients versus 53% for the remainder of IPD patients for the 7-valent pneumococcal conjugate vaccine, and 56% versus 86% for the 23-valent pneumococcal polysaccharide vaccine.CONCLUSIONS: Peritonitis represents a small subset of patients with IPD, but one that is likely to grow in importance given the increase in the number of patients with hepatitis C and HIV, and the reduced coverage of peritonitis serotypes in currently available vaccines.