Browsing by Author "Long, Richard"
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Item Open Access Antituberculous Drug Resistance in Western Canada (1993 to 1994)(1997-01-01) Long, Richard; Fanning, Anne; Cowie, Robert; Hoeppner, Vernon; Fitzgerald, Mark; The Western Canada Tuberculosis Group,OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify prospectively the risk factors for its development in tuberculosis (TB) patients in western Canada over a one-year period.DESIGN: Comparison of drug-resistant and nondrug-resistant cases of TB.SETTING: Western Canada.PATIENTS: All people with TB reported to the TB registries of Manitoba, British Columbia, Alberta and Saskatchewan between February 1, 1993 and January 31, 1994.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive tuberculosis. Patients at risk for human immunodeficiency virus (HIV) infection were serotested.RESULTS: Of 534 culture positive cases of TB, 37 (6.9%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among those with reactivation than among those with new disease, and among those born outside of Canada than among those born in Canada. Ninety per cent of the foreign-born patients with drug-resistant disease were from Asia. Of the 35 patients with drug resistance whose type of resistance was known, 76% had initial and 24% had acquired drug resistance. The initial resistance rate in Asian-born patients was 14%. Most of the 37 drug-resistant cases were resistant to isoniazid (68%), streptomycin (49%) or both (22%). Twelve (32%) of the 37 cases were resistant to two or more first-line drugs. Of 14 patients who were HIV seropositive only one, a foreign-born patient, was drug resistant.CONCLUSION: Antituberculous drug resistance is low among Canadian-born patients in western Canada, but not uncommon among those born outside Canada. Initial therapy of foreign-born patients should include four first-line drugs.Item Open Access 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, RichardAbstract 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.Item Open Access Multidrug-Resistant Tuberculosis in Alberta and British Columbia, 1989 to 1998(1999-01-01) Hersi, Ahmed; Elwood, Kevin; Cowie, Robert; Kunimoto, Dennis; Long, RichardOBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (Pud_less_than0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.