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ABSTRACT The objective of the study was to ascertain an optimal Helicobacter pylori diagnostic strategy using population-level laboratory data comparing the performance of serology against urea breath test (UBT). H. pylori diagnostic test results for serology and UBT from two laboratories over a 12-year period (2006–20017) were extracted, linked, and analyzed. A subset of this population underwent both methods of testing within days of each other, enabling a direct comparison of the two methods. The average prevalence of H. pylori positivity was 21.3% by serology and 17.5% by UBT. There were 2,612 individuals who had serology performed first, followed by UBT within 14 days. For this subset, the sensitivity of serology compared with UBT was 96.5% with a specificity of 79.2%. The negative predictive value for serology was 98.4%. Contrary to various recent clinical guidelines, the data show that serology still has utility as a sensitive enough test to be used as an initial H. pylori screening test in a lower prevalence population. Negative serology can be used with confidence to rule out active infection, whereas a positive serology could be followed up with a UBT or a similar performing test such as stool antigen to differentiate active from past infection. For population-based diagnostic recommendations, such a strategy may be ideal since serology generally costs less than UBT and may be combined with a blood draw being done for other diagnostic tests. Continuing to offer serology increases options for patients and may provide economic benefits for single-payer health care systems or health maintenance organizations.IMPORTANCEThis study compares the performance of serology with urea breath test in the diagnosis of Helicobacter pylori in a population-level data set and mimics a head-to-head direct comparison as the study population had both tests performed within 2 weeks of each other. This provides new information supporting the use of serology in a diagnostic algorithm. There are several instances where serology could be preferable to patients to rule out disease, despite some guidelines suggesting serology should not be used.

Abstract To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Abstract Background Hepatitis C virus (HCV) is a major health threat in Canada. In British Columbia (BC) province, 1.6% of the population had been exposed to HCV by 2012. Prevalence and incidence of HCV are very high in populations of people who use drugs (PWUD) and sex workers (SW), who may experience unique barriers to healthcare. Consequently, they are less likely to be treated for HCV. Overcoming these barriers is critical for HCV elimination. This research sought to explore the healthcare experiences of PWUD and SW and how these experiences impact their willingness to engage in healthcare in the future, including HCV care. Methods Interpretive Description guided this qualitative study of healthcare experiences in BC, underpinned by the Health Stigma and Discrimination framework. The study team included people with living/lived experience of drug use, sex work, and HCV. Twenty-five participants completed in-depth semi-structured interviews on their previous healthcare and HCV-related experiences. Thematic analysis was used to identify common themes. Results Three major themes were identified in our analysis. First, participants reported common experiences of delay and refusal of care by healthcare providers, with many negative healthcare encounters perceived as rooted in institutional culture reflecting societal stigma. Second, participants discussed their choice to engage in or avoid healthcare. Many avoided all but emergency care following negative experiences in any kind of healthcare. Third, participants described the roles of respect, stigma, dignity, fear, and trust in communication in healthcare relationships. Conclusions Healthcare experiences shared by participants pointed to ways that better understanding and communication by healthcare providers could support positive change in healthcare encounters of PWUD and SW, who are at high risk of HCV infection. More positive healthcare encounters could lead to increased healthcare engagement which is essential for HCV elimination.

Summary: Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Abstract Background and objectives Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). Methods We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults

Abstract We sought to evaluate the rates and predictors of SARS-CoV-2 vaccination among members of a structurally-marginalized population of people who use drugs (PWUD) during a targeted, community-wide, vaccination campaign in Vancouver, Canada. Interviewer-administered data were collected from study participants between June 2021 and March 2022. Generalized estimating equation analysis was used to identify factors associated with SARS-CoV-2 vaccine uptake, ascertained through a province-wide vaccine registry. Among 223 PWUD, 107 (48.0%) reported receipt of at least two SARS-CoV-2 vaccine doses at baseline and this increased to 151 (67.7%) by the end of the study period. Using social media as a source of vaccine information was negatively associated with SARS-CoV-2 vaccine uptake (Adjusted odds ratio [AOR] 0.27, 95% confidence interval [CI] 0.09–0.81) and HIV seropositivity (AOR 2.68, 95% CI 1.12–6.39) and older age (AOR 1.27, 95% CI 1.07–1.51) were positively associated with SARS-CoV-2 vaccine uptake. These findings suggest that the targeted vaccination campaign in Vancouver may be an effective model to promote SARS-CoV-2 vaccination in other jurisdictions. However, using social media as a source of vaccine information likely reduced SARS-CoV-2 vaccine uptake in PWUD arguing for further efforts to promote accessible and evidence-based vaccine information among marginalized populations.

Summary: Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality. Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders. Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2–32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9–30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1–8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18–0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78–84%). Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors (C2–C5a). Our lead direct-acting antiviral (DAA), C5a, is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro. The compounds C2–C5a exhibit broad-spectrum activity against Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) and seasonal human coronavirus-229E infection in human cells. Notably, C5a has median effective concentrations of 30–50 nM against BQ.1.1 and XBB.1.5 in two different human cell lines. X-ray crystallography has confirmed the unique binding modes of C2–C5a to the 3CLpro, which can limit virus cross-resistance to emerging Paxlovid-resistant variants. We tested the effect of C5a with two of our newly discovered host-directed antivirals (HDAs): N-0385, a TMPRSS2 inhibitor, and bafilomycin D (BafD), a human vacuolar H+-ATPase [V-ATPase] inhibitor. We demonstrated a synergistic action of C5a in combination with N-0385 and BafD against Omicron BA.5 infection in human Calu-3 lung cells. Our findings underscore that a SARS-CoV-2 multi-targeted treatment for circulating Omicron subvariants based on DAAs (C5a) and HDAs (N-0385 or BafD) can lead to therapeutic benefits by enhancing treatment efficacy. Furthermore, the high-resolution structures of SARS-CoV-2 3CLpro in complex with C2–C5a will facilitate future rational optimization of our novel broad-spectrum active-site-directed 3C-like protease inhibitors.

Background: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). Methods: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. Results: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3–4 viruses (vs. 0–2) was associated with a shorter LTL. Conclusions: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.

Summary: Background: Shifting from cytology to human papillomavirus (HPV)-based cervical cancer screening will initially increase colposcopy referrals. The anticipated impact on health systems has been raised as a concern for implementation. It is unclear if the higher rate of colposcopy referrals is sustained after initial HPV-based screens or reverts to new lower baselines due to earlier detection and treatment of precancer. This study aimed to investigate long-term rates of colposcopy referrals after participation in HPV-based screening. Methods: Participants of HPV for Cervical Cancer Screening trial (HPV FOCAL) received one (HPV1, N = 6204) or two (HPV2, N = 9540) HPV-based screens. After exit, they returned to British Columbia's (BC) cytology screening program. A comparison cohort from the BC screening population (BCS, N = 1,140,745) was identified, mirroring trial inclusion criteria. All participants were followed for 10–14 years through the provincial screening registry. Colposcopy referral rates per 1000 screens were calculated for each group. Trial colposcopy referrals for HPV1 and HPV2 were calculated under two referral scenarios: (1) all HPV positive referred to colposcopy; (2) cytology triage with ASCUS or greater referred to colposcopy. Colposcopy referrals from post-trial screens in HPV1 an HPV2 and all screens in BCS were based on actual recommendations from the screening program. A multivariable flexible survival regression model compared hazard ratios (HR) throughout follow-up. Findings: Scenario 2 referral rates were higher during initial HPV screen(s) vs cytology screen (HPV1: 28 per 1000 screens (95% CI: 24, 33), HPV2: 32 per 1000 screens (95% CI: 29, 36), BCS: 8 per 1000 screens (95% CI: 8.9)). However, post-trial rates in HPV1 and HPV2 were significantly lower than in BCS. Cumulative rates in HPV1 and HPV2 approached the cumulative rate in BCS 11–12 years after HPV-based screening (HPV1: 11 per 1000 screens (95% CI: 10, 12), HPV2: 16 per 1000 screens (95% CI: 15–17), BCS: 11 per 1000 screens (95% CI: 10, 11)). Adjusted models demonstrated reductions in referral rates in HPV1 (HR = 0.6, 95% CI: 0.5, 0.7) and HPV2 (HR = 0.7, 95% CI: 0.6, 0.8) relative to BCS by 54 and 72 months post-final HPV screen respectively. Interpretation: Reduced colposcopy referral rates were observed after initial rounds of HPV-based screening. After initial HPV screening, referral rates to colposcopy after cytology triage were below the current rates seen in a centralized cytology program after approximately four years. Any expected increase in referrals at initiation of HPV-based screening could be countered by staged program implementation. Funding: This work was supported by the National Institutes of Health (R01 CA221918), Michael Smith Health Research BC (RT-2021-1595), and the Canadian Institutes of Health Research (MCT82072).

Background: It was unknown if the effectiveness of COVID-19 vaccines could vary between regions. Objective: To explore key differences in COVID-19 pandemics in British Columbia (BC) and Ontario (ON) and to investigate if the vaccine effectiveness (VE) among maintenance dialysis population could vary between these 2 provinces. Study Design: Retrospective cohort. Setting and Patients: This retrospective cohort study included patients from population-level registry in BC who were on maintenance dialysis from December 14, 2020, to December 31, 2021. The COVID-19 VE among BC patients were compared to the previously published VE among similar patient population in ON. Two-sample t -test for unpaired data were used to investigate if the VE estimates from BC and ON were statistically significantly different. Exposure: Exposure to COVID-19 vaccines (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) was modeled in a time-dependent fashion. Outcome: Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and related severe outcome defined by hospitalization or death. Analytical Approach: Time-dependent Cox regression analysis. Results: This study using BC data included 4284 patients. Median age was 70 years and 61% was male. Median follow-up time was 382 days. 164 patients developed COVID-19 infection. The ON study by Oliver et al included 13 759 patients with a mean age of 68 years. 61% of the study sample was male. Median follow-up time for patients in the ON study was 102 days. A total of 663 patients developed COVID-19 infection. During the overlapped study periods, BC had 1 pandemic wave compared to 2 in Ontario with substantially higher infection rates. Vaccination timing and roll out among the study population were substantially different. Median time between first and second dose was 77 days (interquartile range [IQR] 66-91) in BC compared to 39 days (IQR = 28-56) in Ontario. Distribution of COVID-19 variants during the study period appeared to be similar. In BC, compared to pre-vaccination person-time, risk of developing COVID-19 infection was 64% (aHR [95% CI] 0.36 [0.21, 0.63]), 80% (0.20 [0.12, 0.35]) and 87% (0.13 [0.06, 0.29]) less when exposed to 1 dose, 2 doses, and 3 doses, respectively. In contrast, risk reduction among Ontario patients was 41% (0.59 [0.46, 0.76]) and 69% (0.31 [0.22, 0.42]) for 1 dose and 2 doses, respectively (patients did not receive the third dose by study end date of June 30, 2021). VE against COVID-19 infection in BC and ON was not statistically significantly different, the P values for exposure to 1 dose and 2 doses comparisons were 0.103 and 0.163, respectively. Similarly, in BC, risk of developing COVID-19-related hospitalization or death were 54% (0.46 [0.24, 0.90]), 75% (0.25 [0.13, 0.48]) and 86% (0.14 [0.06, 0.34]) less for 1 dose, 2 doses, and 3 doses, respectively. Interestingly, exposure to second dose appeared to provide better protection against severe outcomes in Ontario versus BC, risk reduction was 83% (aHR = 0.17, 95% CI [0.10, 0.30]) and 75% (aHR = 0.25, 95% CI [0.13, 0.48]), respectively. However, the adjusted hazard ratios were not statistically significantly different between BC and ON, the P values were 0.676 and 0.369 for exposure to 1 dose and 2 doses, respectively. Limitations: Infection rate, variant distribution, and vaccination strategies were compared using publicly available data. VE estimates were compared from 2 independent cohort studies from 2 provinces without patient-level data sharing. Conclusions: Health Canada approved COVID-19 vaccines were highly effective among patients with maintenance dialysis from BC and ON. Although there appeared to be between province differences in pandemic waves and vaccination strategies, the VE against COVID-19 infection as well as related severe outcome appeared to be not statistically significantly different. A nationally representative VE could be estimated using pooled data from multiple regions.

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%–63%), specificities (99%–96%), and precision (intraclass correlation coefficient 0.55–0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants.

A new computational method, BugSplit, teases out individual species’ genomes from metagenomic samples. The authors show that BugSplit is able to identify the presence of a novel coronavirus in COVID-19 patients using a database from 2019 predating the pandemic and can separate host and pathogen sequences in other clinical samples with much higher specificity and accuracy than competing tools.

Several severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) emerged in late 2020; lineage B.1.1.7 initially dominated globally. However, lineages B.1.351 and P.1 represent potentially greater risk for transmission and immune escape. In British Columbia, Canada, B.1.1.7 and B.1.351 were first identified in December 2020 and P.1 in February 2021. We combined quantitative PCR and whole-genome sequencing to assess relative contribution of VOCs in nearly 67,000 infections during the first 16 weeks of 2021 in British Columbia. B.1.1.7 accounted for 50% by week 8. P.1 accounted for

Abstract Background Women living with hepatitis C virus (HCV) are rarely addressed in research and may be overrepresented within key populations requiring additional support to access HCV care and treatment. We constructed the HCV care cascade among people diagnosed with HCV in British Columbia, Canada, as of 2019 to compare progress in care and treatment and to assess sex/gender gaps in HCV treatment access. Methods The BC Hepatitis Testers Cohort includes 1.7 million people who tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 2000 to 2019. Test results were linked to medical visits, hospitalizations, cancers, prescription drugs, and mortality data. Six HCV care cascade stages were identified: (1) antibody diagnosed; (2) RNA tested; (3) RNA positive; (4) genotyped; (5) initiated treatment; and (6) achieved sustained virologic response (SVR). HCV care cascade results were assessed for women, and an ‘inverse’ cascade was created to assess gaps, including not being RNA tested, genotyped, or treatment initiated, stratified by sex. Results In 2019, 52,638 people with known sex were anti-HCV positive in BC; 37% (19,522) were women. Confirmatory RNA tests were received by 86% (16,797/19,522) of anti-HCV positive women and 83% (27,353/33,116) of men. Among people who had been genotyped, 68% (6756/10,008) of women and 67% (12,640/18,828) of men initiated treatment, with 94% (5023/5364) of women and 92% (9147/9897) of men achieving SVR. Among the 3252 women and 6188 men not yet treated, higher proportions of women compared to men were born after 1975 (30% vs. 21%), had a mental health diagnosis (42% vs. 34%) and had used injection drugs (50% vs. 45%). Among 1619 women and 2780 men who had used injection drugs and were not yet treated, higher proportions of women than men used stimulants (64% vs. 57%), and opiates (67% vs. 60%). Conclusions Women and men appear to be equally engaged into the HCV care cascade; however, women with concurrent social and health conditions are being left behind. Treatment access may be improved with approaches that meet the needs of younger women, those with mental health diagnoses, and women who use drugs.

IntroductionChronic infection with hepatitis C virus (HCV) is an established risk factor for liver cancer. Although several epidemiologic studies have evaluated the risk of extrahepatic malignancies among people living with HCV, due to various study limitations, results have been heterogeneous.MethodsWe used data from the British Columbia Hepatitis Testers Cohort (BC-HTC), which includes all individuals tested for HCV in the Province since 1990. We assessed hepatic and extrahepatic cancer incidence using data from BC Cancer Registry. Standardized incidence ratios (SIR) comparing to the general population of BC were calculated for each cancer site from 1990 to 2016.ResultsIn total, 56,823 and 1,207,357 individuals tested positive and negative for HCV, respectively. Median age at cancer diagnosis among people with and without HCV infection was 59 (interquartile range (IQR): 53-65) and 63 years (IQR: 54-74), respectively. As compared to people living without HCV, a greater proportion of people living with HCV-infection were men (66.7% vs. 44.7%, P-value

Objectives Gathering population-based data on prevalence of SARS-CoV-2 infection is vital to the public health response and planning. Current seroprevalence data in BC are limited with respect to considerations of how socioeconomic and demographic factors, such as age, sex, gender, income, identifying as a visibility minority and occupation, are related to SARS-CoV-2 antibody detection due to infection-acquired immunity. We aimed to estimate the SARS-CoV-2 seropositivity in a cohort of British Columbians, using at-home self-collected dried blood spot (DBS) samples.Design This cross-sectional study included online surveys that collected sociodemographic and COVID-19 vaccine receipt information, and an at-home DBS collection kit.Setting British Columbia (BC), Canada.Participants Eligible participants were aged 25–69 years and residents of BC.Primary outcome measure SARS-CoV-2 anti-spike IgG antibody detection in unvaccinated individuals. Adjusted incidence rate ratios (aIRR) explored factors associated with seropositivity.Results SARS-CoV-2 serology was performed on a total of 4048 unvaccinated participants 25–69 years of age who submitted DBS samples taken from November 2020 to June 2021. A total of 118 seropositive cases were identified, for an estimated overall seropositivity of 2.92% (95% CI 2.42% to 3.48%). Participants identifying as a visible minority had a higher seropositivity, 5.1% vs 2.6% (p=0.003), compared with non-visible minority participants. After adjustment by age and sex, identifying as a visible minority (aIRR=1.85, 95% CI 1.20 to 2.84) remained the only significant factor associated with SARS-CoV-2 antibody detection in this cohort of unvaccinated individuals.Conclusions SARS-CoV-2 seropositivity in the BC population due to infection-acquired immunity was low. Seropositivity indicated that among those unvaccinated, visible minority communities have been most impacted. Continued monitoring of SARS-CoV-2 serology due to both infection-acquired and vaccine-acquired immunity will be vital in public health planning and pandemic response.

Objectives The COVID-19 pandemic has necessitated access to large health system datasets to inform the public health response. To meet this need, the Provincial Health Services Authority and the British Columbia (BC) Ministry of Health collaborated to create a population-based platform that integrates COVID-19 datasets with sociodemographic and administrative health data. Approach A BC COVID Data Library proof-of-concept was created as a cloud-based, dynamic platform composed of de-identified datasets. The BC COVID-19 Cohort (BCC19C) represents a subset composed of people accessing COVID-19 health services (e.g., testing, vaccination) and linked health histories. Provincial COVID-19 datasets are updated daily and include COVID-19 lab tests, case surveillance, vaccinations and hospitalizations/deaths. These can be linked to administrative data holdings for the BC population, which are updated weekly/monthly and include vital statistics, medications, hospital admissions, medical visits, among others. A patient matching algorithm creates unique patient keys that allows the same individual to be linked across datasets. Results The BCC19C has been used provincially to 1) support ongoing surveillance, reporting, and modelling of COVID-19; 2) describe and characterize the epidemiology of COVID-19; and 3) inform acute care planning, public health interventions and health care services in BC. Ongoing and completed BCC19C analyses include assessment of vaccine safety, vaccine effectiveness, and characteristics associated with infection and severe outcomes; use of medical visit data for syndromic surveillance and monitoring of unintended outcomes of the pandemic (e.g., mental health visits); and characterization of long-COVID. Availability of linked administrative data holdings has been crucial for identifying non-COVID control groups, measuring sociodemographics and co-morbidities, and complementing COVID-19 datasets for more complete capture of health outcomes (e.g., deaths, hospitalizations). Conclusions The large scope/breadth and timeliness of the linkable datasets integrated within the COVID Data Library and the BCC19C has supported the public health response in BC. Additional linkage to other data sources will further strengthen this data platform.

ABSTRACT British Columbia (BC) implemented the syphilis reverse screening algorithm and Treponema pallidum PCR testing in 2014. We summarize the performance characteristics of the algorithm, together with PCR direct detection, and report on syphilis cases identified from 2015 to 2020. Prior to 2015, samples for syphilis diagnosis were first screened by rapid plasma reagin (RPR). As of 2015, sera were screened by the Siemens Advia Centaur syphilis assay (enzyme immunoassay [EIA]). Positive and equivocal samples were reflex tested by a T. pallidum passive particle agglutination assay (TPPA) and RPR. We used T. pallidum DNA PCR on clinical samples and restriction fragment length polymorphism analysis to identify azithromycin resistance mutations. Case/epidemiological data were obtained from the BC surveillance system. Of 1,631,519 samples screened by the EIA, 72,492 (4.4%) were positive and 187 (

Abstract The Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population‐based Cervix Screening Program in British Columbia, Canada. We conducted a cost‐effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high‐grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid‐based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co‐testing at the 48‐month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of ‐$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC‐based testing every 2 years for cervical cancer screening at a lower cost.

Objectives: Addressing the needs of ethnic minorities will be key to finding undiagnosed individuals living with hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). To inform screening initiatives in British Columbia (BC), Canada, the factors associated with HBV and/or HCV and/or HIV infection among different ethnic groups within a large population-based cohort were assessed. Methods: Persons diagnosed with HBV, HCV, or HIV in BC between 1990 and 2015 were grouped as East Asian, South Asian, Other Visible Minority (African, Central Asian, Latin American, Pacific Islander, West Asian, unknown ethnicity), and Not a Visible Minority, using a validated name-recognition software. Factors associated with infection within each ethnic group were assessed with multivariable multinomial logistic regression models. Results: Participants included 202 521 East Asians, 126 070 South Asians, 65 210 Other Visible Minorities, and 1 291 561 people who were Not a Visible Minority, 14.4%, 3.3%, 4.5%, and 6.3% of whom had HBV and/or HCV and/or HIV infections, respectively. Injection drug use was most prevalent among infection-positive people who were Not a Visible Minority (22.1%), and was strongly associated with HCV monoinfection, HBV/HCV coinfection, and HCV/HIV coinfection, but not with HBV monoinfection among visible ethnic minorities. Extreme material deprivation and social deprivation were more prevalent than injection drug use or problematic alcohol use among visible ethnic minorities. Conclusions: Risk factor distributions varied among persons diagnosed with HBV and/or HCV and/or HIV of differing ethnic backgrounds, with lower substance use prevalence among visible minority populations. This highlights the need for tailored approaches to infection screening among different ethnic groups.

ABSTRACT We investigate the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) samples tested by a quantitative multiplex anti-immunoglobulin G (IgG) assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after infection or vaccination. This cross-sectional study involved participants (n = 6,841) from several serological surveys conducted in nonhospitalized children and adults throughout 2020 and 2021 in British Columbia (BC), Canada. Analysis used paired DBS and serum samples from a subset of participants (n = 642) prior to vaccination to establish signal thresholds and calculate diagnostic accuracy by logistic regression. Discrimination of the logistic regression model was assessed by receiver operator curve (ROC) analysis in an n = 2,000 bootstrap of the paired sample (n = 642). The model was cross-validated in a subset of vaccinated persons (n = 90). Unpaired DBS samples (n = 6,723) were used to evaluate anti-IgG signal distributions. In comparison to paired serum, DBS samples from an unvaccinated population possessed a sensitivity of 79% (95% confidence interval [95% CI]: 58 to 91%) and specificity of 97% (95% CI: 95 to 98%). ROC analysis found that DBS samples accurately classify SARS-CoV-2 seroconversion at an 88% percent rate (area under the curve [AUC] = 88% [95% CI: 80 to 95%]). In coronavirus disease 2019 (COVID-19) vaccine dose one or two recipients, the sensitivity of DBS testing increased to 97% (95% CI: 83 to 99%) and 100% (95% CI: 88 to 100%). Modeling found that DBS testing possesses a high positive predictive value (98% [95% CI: 97 to 98%]) in a population with 75% seroprevalence. We demonstrate that DBS testing should be considered to reliably detect SARS-CoV-2 seropositivity from natural infection or vaccination. IMPORTANCE Dried blood spot samples have comparable diagnostic accuracy to serum collected by venipuncture when tested by an electrochemiluminescent assay for antibodies and should be considered to reliably detect seropositivity following SARS-CoV-2 infection and/or vaccination.

BackgroundOlder adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age.MethodsTo assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets.ResultsSamples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally.ConclusionMost people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.

Background: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,’ gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning. Methods: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics. Results: The six-class model was the best fit and had the following names and characteristics:‘Younger PWID’ (n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%).‘Older PWID’ (n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%).‘Other Middle-Aged People’ (n = 9019): gbMSM (26%), material privilege (31%), people born between 1965−1974 (47%).‘People of Asian backgrounds’ (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born

BackgroundAs part of the public health outbreak investigations, serological surveys were carried out following two COVID-19 outbreaks in April 2020 and October 2020 in one long term care facility (LTCF) in British Columbia, Canada. This study describes the serostatus of the LTCF residents and monitors changes in their humoral response to SARS-CoV-2 and other human coronaviruses (HCoV) over seven months.MethodsA total of 132 serum samples were collected from all 106 consenting residents (aged 54-102) post-first outbreak (N=87) and post-second outbreak (N=45) in one LTCF; 26/106 participants provided their serum following both COVID-19 outbreaks, permitting longitudinal comparisons between surveys. Health-Canada approved commercial serologic tests and a pan-coronavirus multiplexed immunoassay were used to evaluate antibody levels against the spike protein, nucleocapsid, and receptor binding domain (RBD) of SARS-CoV-2, as well as the spike proteins of HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43. Statistical analyses were performed to describe the humoral response to SARS-CoV-2 among residents longitudinally.FindingsSurvey findings demonstrated that among the 26 individuals that participated in both surveys, all 10 individuals seropositive after the first outbreak continued to be seropositive following the second outbreak, with no reinfections identified among them. SARS-CoV-2 attack rate in the second outbreak was lower (28.6%) than in the first outbreak (40.2%), though not statistically significant (P>0.05). Gradual waning of anti-nucleocapsid antibodies to SARS-CoV-2 was observed on commercial (median Δ=-3.7, P=0.0098) and multiplexed immunoassay (median Δ=-169579, P=0.014) platforms; however, anti-spike and anti-receptor binding domain (RBD) antibodies did not exhibit a statistically significant decline over 7 months. Elevated antibody levels for beta-HCoVs OC43 (P

Current liver transplantation societies recommend recipients with active coronavirus disease 2019 (COVID-19) be deferred from transplantation for at least 2 wks, have symptom resolution and at least 1 negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test.1 This approach does not address patients who require urgent transplantation and will otherwise die from liver failure. We report a successful orthotopic liver transplant (OLT) in a patient with active COVID-19 infection. This is only the second to be reported worldwide and the first in Canada.

Objective To study participant’s acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in future acceptability of screening.Design Cross-sectional online survey of clinical trial participants.Setting Primary care, population-based Cervix Screening Program, British Columbia, Canada.Participants A total of 5532 participants from the HPV FOCAL trial, in which women received HPV and cytology testing at study exit, were included in the analysis. Median age was 54 years. The median time of survey completion was 3 years after trial exit.Outcome measures Acceptability of HPV testing for primary cervical cancer screening (primary); attitudes and patient perceptions towards HPV testing and receipt of HPV positive screen results (secondary).Results Most respondents (63%) were accepting of HPV testing, with the majority (69%) accepting screening to begin at age 30 years with HPV testing. Only half of participants (54%) were accepting of an extended screening interval of 4–5 years. In multivariable logistic regression, women who received an HPV positive screen test result during the trial (OR=1.41 95% CI 1.11 to 1.80) or were older (OR=1.01, 95% CI 1.00 to 1.02) were more likely to report HPV testing as acceptable.Conclusions In this evaluation of acceptability and attitudes regarding HPV testing for cervix screening, most are accepting of HPV testing for screening; however, findings indicate heterogeneity in concerns and experiences surrounding HPV testing and receipt of HPV positive results. These findings provide insights for the development of education, information and communication strategies during implementation of HPV-based cervical cancer screening.Trial registration numbers ISRCTN79347302 and NCT00461760.

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine–Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.

Introduction Increasing evidence indicates that chronic hepatitis C virus (HCV) infection is associated with higher risk of diabetes. Previous studies showed ethnic disparities in the disease burden of diabetes, with increased risk in Asian population. We described the incidence of type 2 diabetes related to HCV infection and assessed the concurrent impact of HCV infection and ethnicity on the risk of diabetes.Research design and methods In British Columbia Hepatitis Testers Cohort, individuals were followed from HCV diagnosis to the earliest of (1) incident type 2 diabetes, (2) death or (3) end of the study (December 31, 2015). Study population included 847 021 people. Diabetes incidence rates in people with and without HCV were computed. Propensity scores (PS) analysis was used to assess the impact of HCV infection on newly acquired diabetes. PS-matched dataset included 117 184 people. We used Fine and Gray multivariable subdistributional hazards models to assess the effect of HCV and ethnicity on diabetes while adjusting for confounders and competing risks.Results Diabetes incidence rates were higher among people with HCV infection than those without. The highest diabetes incidence rate was in South Asians with HCV (14.7/1000 person-years, 95% CI 12.87 to 16.78). Compared with Others, South Asians with and without HCV and East Asians with HCV had a greater risk of diabetes. In the multivariable stratified analysis, HCV infection was associated with increased diabetes risk in all subgroups: East Asians, adjusted HR (aHR) 3.07 (95% CI 2.43 to 3.88); South Asians, aHR 2.62 (95% CI 2.10 to 3.26); and Others, aHR 2.28 (95% CI 2.15 to 2.42).Conclusions In a large population-based linked administrative health data, HCV infection was associated with higher diabetes risk, with a greater relative impact in East Asians. South Asians had the highest risk of diabetes. These findings highlight the need for care and screening for HCV-related chronic diseases such as type 2 diabetes among people affected by HCV.

Acute hepatitis A viral (HAV) infection is rare in the liver transplant population due to recommended pre-transplant vaccinations. We report a case of acute hepatitis A infection in a liver transplant recipient. This individual had immunity to hepatitis A with protective IgG antibodies and presented with abnormal liver biochemistry in the post-transplant in-patient setting. Hepatitis A infection was confirmed by positive HAV IgM whereas other etiologies, including acute cellular rejection, were ruled out by laboratory tests and liver biopsies. He was treated conservatively with supportive care and liver enzymes recovered to normal baseline. Despite adequate pre-transplant immunity, in the post-transplant setting there may be loss of protective immunity due to profound immunosuppression and hence hepatitis A should remain an important differential diagnosis in the setting of acute hepatitis.

Background: Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of: (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. Methods: A cross-sectional study of n = 424 “participants” aged 1–104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. Findings: Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0•092). Mean relative transcription of transmembrane (P = 0•00012) and soluble (P

Introduction: Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings. Methods: In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry. Results: Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55–3.51), HBV (HR 2.47; 95% CI 1.85–3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47–3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01–3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39–5.71), and HCV/HBV co-infection. Discussion/Conclusion: Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.

Objectives The COVID-19 pandemic has underscored the need for rapid novel diagnostic strategies. Metagenomic Next-Generation Sequencing (mNGS) may allow for the detection of pathogens that can be missed in targeted assays. The goal of this study was to assess the performance of nanopore-based Sequence-Independent Single Primer Amplification (SISPA) for the detection and characterization of SARS-CoV-2. Methods We performed mNGS on clinical samples and designed a diagnostic classifier that corrects for barcode crosstalk between specimens. Phylogenetic analysis was performed on genome assemblies. Results Our assay yielded 100% specificity overall and 95.2% sensitivity for specimens with a RT-PCR cycle threshold value less than 30. We assembled 10 complete, and one near-complete genomes from 20 specimens that were classified as positive by mNGS. Phylogenetic analysis revealed that 10/11 specimens from British Columbia had a closest relative to another British Columbian specimen. We found 100% concordance between phylogenetic lineage assignment and Variant of Concern (VOC) PCR results. Our assay was able to distinguish between the Alpha and Gamma variants, which was not possible with the current standard VOC PCR being used in British Columbia. Conclusions This study supports future work examining the broader feasibility of nanopore mNGS as a diagnostic strategy for the detection and characterization of viral pathogens.

The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada’s public health policy in response to COVID-19.

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches—NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.

Background: Most public health datasets do not include sexual orientation measures, thereby limiting the availability of data to monitor health disparities, and evaluate tailored interventions. We therefore developed, validated, and applied a novel computable phenotype model to classify men who have sex with men (MSM) using multiple health datasets from British Columbia, Canada, 1990–2015.Methods: Three case surveillance databases, a public health laboratory database, and five administrative health databases were linked and deidentified (BC Hepatitis Testers Cohort), resulting in a retrospective cohort of 727,091 adult men. Known MSM status from the three disease case surveillance databases was used to develop a multivariable model for classifying MSM in the full cohort. Models were selected using “elastic-net” (GLMNet package) in R, and a final model optimized area under the receiver operating characteristics curve. We compared characteristics of known MSM, classified MSM, and classified heterosexual men.Findings: History of gonorrhea and syphilis diagnoses, HIV tests in the past year, history of visit to an identified gay and bisexual men's clinic, and residence in MSM-dense neighborhoods were all positively associated with being MSM. The selected model had sensitivity of 72%, specificity of 94%. Excluding those with known MSM status, a total of 85,521 men (12% of cohort) were classified as MSM.Interpretation: Computable phenotyping is a promising approach for classification of sexual minorities and investigation of health outcomes in the absence of routinely available self-report data.

ObjectiveCurrent guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women.MethodsBC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses.ResultsIn 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (pConclusionPrenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.

Background: Limited data are available on HBV, HCV, and HIV co-infections and triple infection. We characterized co-occurrence of HIV, HBV, and HCV infections at the population level in British Columbia (BC) to identify patterns of predisposing factors unique to co-infection subgroups. Methods: We analyzed data from the BC Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV in BC between 1992 and 2013, or included in provincial public health registries of HIV, HCV, HBV, and active tuberculosis. Individuals were classified as negative, mono-, and co-infection groups based on HIV, HBV, and HCV status. We evaluated associations between risk factors (injection drug use, sexual orientation etc.) and co-infection groups using multivariate multinomial logistic regression. Findings: Of a total of 1,376,989 individuals included in the analysis, 1,276,290 were negative and 100,699 were positive for HIV, HBV, and/or HCV. Most cases (91,399, 90.8%) were mono-infected, while 3991 (4.0%) had HBV/HCV, 670 HBV/HIV (0.7%), 3459 HCV/HIV (3.4%), and 1180 HBV/HCV/HIV (1.2%) co-infection. Risk factor and demographic distribution varied across co-infection categories. MSM classification was associated with higher odds of all HIV co-infection groups, particularly HBV/HIV (OR 6.8; 95% CI: 5.6, 8.27), while injection drug use was most strongly associated with triple infection (OR 64.19; 95% CI: 55.11, 74.77) and HIV/HCV (OR 23.23; 95% CI: 21.32, 25.31). Interpretation: Syndemics of substance use, sexual practices, mental illness, socioeconomic marginalization, and co-infections differ among population groups, highlighting avenues for optimal composition and context for health services to meet each population's unique needs. Funding: BC Centre for Disease Control and Canadian Institutes of Health Research. Keywords: Hepatitis B, Hepatitis C, HIV, Substance use, Syndemics, Co-infection

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27; 95% CI = 1.17–1.37), older age (p-trend < 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30–39 years = 3.06; 95% CI = 2.32–4.03, to aRR 80+ years = 43.68; 95% CI = 33.41–57.10 compared to 20–29 years-old]), asthma (aRR = 1.15; 95% CI = 1.04–1.26), cancer (aRR = 1.19; 95% CI = 1.09–1.29), chronic kidney disease (aRR = 1.32; 95% CI = 1.19–1.47), diabetes (treated without insulin aRR = 1.13; 95% CI = 1.03–1.25, requiring insulin aRR = 5.05; 95% CI = 4.43–5.76), hypertension (aRR = 1.19; 95% CI = 1.08–1.31), injection drug use (aRR = 2.51; 95% CI = 2.14–2.95), intellectual and developmental disabilities (aRR = 1.67; 95% CI = 1.05–2.66), problematic alcohol use (aRR = 1.63; 95% CI = 1.43–1.85), immunosuppression (aRR = 1.29; 95% CI = 1.09–1.53), and schizophrenia and psychotic disorders (aRR = 1.49; 95% CI = 1.23–1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69; 95% CI = 1.42–5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n = 72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis — circulating miR-24, miR-223 and PCSK9 — whose regulation is affected by HCV infection and treatment-based viral cure.

Abstract Background Every year, over 1 million people develop isoniazid (INH) resistant tuberculosis (TB). Yet, the optimal treatment regimen remains unclear. Given increasing prevalence, the clinical efficacy of regimens used by physicians is of interest. This study aims to examine treatment outcomes of INH resistant TB patients, treated under programmatic conditions in British Columbia, Canada. Methods Medical charts were retrospectively reviewed for cases of culture-confirmed INH mono-resistant TB reported to the BC Centre for Disease Control (BCCDC) from 2002 to 2014. Treatment regimens, patient and strain characteristics, and clinical outcomes were analysed. Results One hundred sixty five cases of INH mono-resistant TB were included in analysis and over 30 different treatment regimens were prescribed. Median treatment duration was 10.5 months (IQR 9–12 months) and treatment was extended beyond 12 months for 26 patients (15.8%). Fifty six patients (22.6%) experienced an adverse event that resulted in a drug regimen modification. Overall, 140 patients (84.8%) had a successful treatment outcome while 12 (7.2%) had an unsuccessful treatment outcome of failure (n = 2; 1.2%), relapse (n = 4; 2.4%) or all cause mortality (n = 6; 3.6%). Conclusion Our treatment outcomes, while consistent with findings reported from other studies in high resource settings, raise concerns about current recommendations for INH resistant TB treatment. Only a small proportion of patients completed the recommended treatment regimens. High quality studies to confirm the effectiveness of standardized regimens are urgently needed, with special consideration given to trials utilizing fluoroquinolones.

Background: Population-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each stage. Methods: The BC Hepatitis Testers Cohort (BC-HTC) includes 1.5 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV cascade of care stages: 1) estimated population prevalence; 2) HCV diagnosed; 3) HCV RNA tested; 4) genotyped; 5) initiated treatment; and 6) achieved sustained virologic response (SVR). Results: We estimated that 73,203 people were HCV antibody positive in BC in 2012 (undiagnosed: 18,301, 25%; diagnosed: 54,902, 75%). Of these, 56%(40,656) had HCV RNA testing; 34%(26,300) were genotyped; 12%( 8532 ) had received interferon-based therapy and 7%(5197) had SVR. Males, older birth cohorts, and HBV coinfected were less likely to undergo HCV RNA testing. Among those with chronic HCV infection, 32% had received liver-related care. Retention in liver care was more likely in those with HIV, cirrhosis, and drug/alcohol use and less likely in males and HBV coinfected. Conclusions: Although there are gaps in HCV RNA testing and genotyping after HCV diagnosis, the major gap in the cascade of care was low treatment initiation. People with comorbidities progressed through the cascade of testing and care but few received treatment.

In January 2015, British Columbia, Canada, reported avian influenza A(H7N9) virus infection in 2 travelers returning from China who sought outpatient care for typical influenza-like illness. There was no further spread, but serosurvey findings showed broad population susceptibility to H7N9 virus. Travel history and timely notification are critical to emerging pathogen detection and response.

Introduction Most chronic hepatitis B virus (HBV) infections in Canada are diagnosed among immigrants from endemic countries and lack traditional risk factors while most acute infections are usually diagnosed in Caucasian population with co-occurring risk factors. Thus, understanding geographical distribution of HBV infection by ethnicity could inform screening and care strategies. Objectives and Approach We identified geographic clusters of HBV infection in British Columbia by ethnicity during the years 1990-2015 using the BC Hepatitis Testers Cohort (BC-HTC). The BC-HTC includes ~1.7 million individuals tested for HCV or HIV at the BC Public Health Laboratory or reported as a case of HCV, HIV, or HBV linked to healthcare administrative databases. We plotted maps of HBV diagnoses (acute and chronic) rate at the Dissemination Area level between 1990-2015 stratified by ethnicity and compared this distribution with injection drug use (IDU) distribution in BC. Results The distribution of HBV varied considerably by ethnicity. From 1990 to 2015, a higher rate of HBV infection was found among East Asians and Caucasians followed by South Asians and other ethnicities. East Asians with highest rates were mainly concentrated in Vancouver city, Burnaby and Richmond (Metro Vancouver) while South Asians with highest rates were mostly concentrated in urban areas in Surrey and Abbotsford. Caucasians with higher rates were clustered in Downtown Eastside in Vancouver, Surrey and Abbotsford (Metro Vancouver) and urban areas in Greater Victoria (Vancouver Island), Prince George (Northern BC) and Kamloops (Interior BC). The distribution of IDU closely followed the distribution of HBV among Caucasians but did not align with other ethnic groups. Conclusion/Implications Results highlight distinct areas of HBV infection clustering by ethnicity, which differ from areas with high IDU distribution except in Caucasians. Findings support ethnicity-based HBV screening/prevention and care services to areas with immigrants from HBV-endemic countries and integrated HBV and harm reduction services for early diagnosis and treatment in Caucasians.

Background. The goal of treating chronic hepatitis C virus (HCV) infection is sustained virologic response (SVR). There is concern that despite achieving SVR, replication-competent HCV may be sequestered at low levels within the liver and could theoretically reactivate with immunosuppression. We report transplantation of a HCV-seropositive liver donor, who achieved SVR, into a seronegative patient without HCV reactivation despite profound immunosuppression. Method. Retrospective chart review. Results. We present a 21-year-old male who was HCV seronegative and received a liver transplant from a donor who had been treated for HCV and achieved SVR. The liver recipient, despite developing severe acute graft rejection and undergoing intense immunosuppression with T cell–depleting antibodies, did not become HCV RNA-positive with a follow up period of 8 months. The recipient was HCV seronegative before transplant, but became HCV seropositive immediately posttransplant. The antibodies were undetectable after 97 days, in keeping with a passive antibody transmission or B lymphocyte transmission with the graft. Conclusions. To the best of our knowledge, this is the first reported case of an HCV seropositive liver allograft transplanted into an HCV-negative recipient who subsequently received intense immunosuppression. This case, therefore, is an encouraging and novel step in liver transplantation, and demonstrates that SVR may be closer to a true “cure” of HCV in the donor population and that, even in circumstances of very potent immunosuppression in the recipient, this SVR is sustained.

BACKGROUND: The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) are 0.4% and 0.8%, respectively, in Canada, but varying rates have been reported in different populations.