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Zahid A Butt,1 Nabin Shrestha,1 Dionne Gesink,2 Michelle Murti,2,3 Jane A Buxton,1,4 Mark Gilbert,4 Robert F Balshaw,4 Stanley Wong,4 Margot Kuo,4 Jason Wong,1,4 Amanda Yu,4 Maria Alvarez,4 Hasina Samji,4 David Roth,4 Theodora Consolacion,4 Mark W Hull,5,6 Gina Ogilvie,1,4 Mark W Tyndall,1,4 Mel Krajden,1,4,7 Naveed Z Janjua1,4 1School of Population and Public Health, University of British Columbia, Vancouver, BC, 2Dalla Lana School of Public Health, University of Toronto, 3Public Health Ontario, Toronto, ON, 4Clinical Prevention Services, British Columbia Centre for Disease Control, 5Division of AIDS, Faculty of Medicine, University of British Columbia, 6AIDS Research Program, British Columbia Centre for Excellence in HIV/AIDS, 7BCCDC Public Health Laboratory, Vancouver, BC, Canada Background: Understanding differences in HIV incidence among people living with hepatitis C virus (HCV) can help inform strategies to prevent HIV infection. We estimated the time to HIV diagnosis among HCV-positive individuals and evaluated factors that could affect HIV-infection risk in this population.Patients and methods: The British Columbia Hepatitis Testers Cohort includes all BC residents (~1.5 million: about a third of all residents) tested for HCV and HIV from 1990 to 2013 and is linked to administrative health care and mortality data. All HCV-positive and HIV-negative individuals were followed to measure time to HIV acquisition (positive test) and identify factors associated with HIV acquisition. Adjusted HRs (aHRs) were estimated using Cox proportional-hazard regression.Results: Of 36,077 HCV-positive individuals, 2,169 (6%) acquired HIV over 266,883 years of follow-up (overall incidence of 8.1 per 1,000 person years). Overall median (IQR) time to HIV infection was 3.87 (6.06) years. In Cox regression, injection-drug use (aHR 1.47, 95% CI 1.33–1.63), HBV infection (aHR 1.34, 95% CI 1.16–1.55), and being a man who has sex with men (aHR 2.78, 95% CI 2.14–3.61) were associated with higher risk of HIV infection. Opioid-substitution therapy (OST) (aHR 0.59, 95% CI 0.52–0.67) and mental health counseling (aHR 0.48, 95% CI 0.43–0.53) were associated with lower risk of HIV infection.Conclusion: Injection-drug use, HBV coinfection, and being a man who has sex with men were associated with increased HIV risk and engagement in OST and mental health counseling were associated with reduced HIV risk among HCV-positive individuals. Improving access to OST and mental health services could prevent transmission of HIV and other blood-borne infections, especially in settings where access is limited. Keywords: opioid-substitution therapy, mental health counseling, HIV, risk, hepatitis

Summary: This study evaluates trends in hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct‐acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995‐2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001‐2012/2013/2014, respectively) and mortality (1995‐2013/2014/2015, respectively). Age‐standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid‐2000s, HCC diagnosis numbers increased in all jurisdictions. Age‐standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001‐2006 and 2007‐2011) and NSW (0.9 years in 2001‐2006 and 2007‐2013) and improved in Scotland (0.7 years in 2001‐2006 to 1.5 years in 2007‐2014). Across the settings, HCC burden increased, individual‐level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon‐based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years. [ABSTRACT FROM AUTHOR]

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus ( HCV) treatments and those who received recently introduced direct-acting antivirals ( DAAs) in British Columbia ( BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (Peg IFN/ RBV) with/without boceprevir or telaprevir, DAAs with RBV or Peg IFN/ RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or Peg IFN/ RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [ aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis ( aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis ( aOR: 1.72, 95% CI: 1.31-2.28), diabetes ( aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use ( aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy ( aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations. [ABSTRACT FROM AUTHOR]

T-cell host immune response against hepatitis C virus ( HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46 783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [ aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females ( aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV ( aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance. [ABSTRACT FROM AUTHOR]

Background: Although Canada eliminated endemic measles in 1998, outbreaks are expected to occur periodically through import-related transmission in geographically clustered unvaccinated communities. In the spring of 2014, in association with an outbreak in the Netherlands, a large measles outbreak occurred in British Columbia in a community unvaccinated for religious reasons. Methods: Case finding with assistance of the local community, its school and religious leaders and local health care providers was conducted to identify confirmed, probable and suspect cases. Measles control guidelines were implemented with limited uptake of measles-containing vaccine (MCV) but higher adherence with infection control measures and travel restrictions. Results: A total of 433 cases (325 confirmed and 108 probable) were identified. Rash onset ranged from February 22 to June 9, with 98% during March and April. Fifty-seven percent of cases were students of one school. The median age of cases was 11 years and 68% of cases were aged five to 19 years. Ninety-nine percent of cases were unvaccinated. One case had encephalitis and recovered. Only five cases occurred outside of the affected community. Genotyping results were consistent with importation from the Netherlands outbreak. Conclusion: This outbreak in a community with low-vaccination rates affected largely the pediatric-age population, compatible with acquisition of measles immunity by adult members due to prior wild-type measles infection. Although vaccine hesitancy persisted in this population, containment of the outbreak was facilitated by a high degree of community cooperation with infection control measures and restriction of movement. [ABSTRACT FROM AUTHOR]

Background: Enterovirus D68 (EV-D68) has been detected infrequently and has not been associated with severe disease in Canada. In the early fall of 2014, following an unusual case increase in the United States, clusters of EV-D68 among children and some adults manifesting severe symptoms were reported in Canada. Objective: To provide an initial epidemiological summary of pediatric cases hospitalized with EV-D68 in Canada. Methods: A time-limited surveillance pilot was conducted collecting information on pediatric cases (less than 18 years of age) hospitalized with EV-D68 between September 1 and 30, 2014. Results: In total, 268 cases were reported from Ontario (n=210), Alberta (n=45), and British Columbia (n=13). Of the 268 reported cases, 64.9% (n=174) were male; the sex difference was statistically significant (p<0.01). Age was reported for 255 cases, with a mean age for males of 5.4 years and for females of 5.3 years. For cases with data available, 6.8% (18/266) were admitted to an intensive care unit. Of those where clinical illness was recorded, respiratory illness alone was present in 98.3% (227/231), neurologic illness alone was present in 0.4% (n=1), and both illnesses were present in 0.9% of cases (n=2); cases with neither respiratory nor neurologic illness were rare (n=1). Of the 90 cases with additional clinical information available, 43.3% were reported as having asthma. No deaths were reported among the 268 cases. Conclusion: The EV-D68 outbreak in Canada in September 2014 represents the beginning of a novel outbreak associated with severe illness in children. These findings provide the first epidemiological summary of severe cases of EV-D68 as an emergent respiratory pathogen in Canada. The continued investigation of this pathogen is necessary to build on these results and capture the full spectrum of associated illness. [ABSTRACT FROM AUTHOR]

From 1990 to 1993, an outbreak of respiratory Acinetobacter baumannii infection occurred in five intensive care units (ICUs) of a tertiary care center. A. baumannii was subsequently isolated from disinfected temperature probes and ventilator circuits. Pulsed-field gel electrophoresis suggested that a single strain accounted for 93% of patient isolates and 88% of environmental isolates. Univariate risk factors for A. baumannii acquisition were tracheostomy (P < .01), ventilation >3 days (P < .01), dialysis (P = .03), Stenotrophomonas maltophilia respiratory colonization (P = .02), parenteral nutrition (P = .05), and enteric feeding (P < .01). Logistic regression analysis showed duration of ventilation and enteric feeding to be independent risk factors. The outbreak strain was relatively antibiotic-susceptible, but the mortality attributable to respiratory A. baumannii acquisition was 23%. Only the APACHE II score was independently associated with increased mortality. Multifaceted control measures, including gas sterilization of temperature probes, terminated the outbreak. [ABSTRACT FROM AUTHOR]