In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A ...(H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.
(1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.
Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.
•We estimated the vaccine effectiveness (VE) against SARS-CoV-2 infection in people living with HIV (PLWH).•The VE estimates in PLWH were compared with a matched HIV-negative comparator.•Two doses of ...COVID-19 vaccines were effective against SARS-CoV-2 infection among PLWH.•However, the VE in PLWH appeared to peak later, and the degree of waning was quicker.
We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared the estimates with a matched HIV-negative cohort.
We used the British Columbia COVID-19 Cohort, a population-based data platform, which integrates COVID-19 data on SARS-CoV-2 tests, laboratory-confirmed cases, and immunizations with provincial health services data. The vaccine effectiveness (VE) was estimated with a test-negative design using the multivariable logistic regression.
The adjusted VE against SARS-CoV-2 infection was 71.1% (39.7, 86.1%) 7-59 days after two doses, rising to 89.3% (72.2, 95.9%) between 60 and 89 days. VE was preserved 4-6 months after the receipt of two doses, after which noticeable waning was observed (51.3% 4.8, 75.0%). In the matched HIV-negative cohort (n = 375,043), VE peaked at 91.4% (90.9, 91.8%) 7-59 days after two doses and was sustained for up to 4 months, after which evidence of waning was observed, dropping to 84.2% (83.4, 85.0%) between 4 and 6 months.
The receipt of two COVID-19 vaccine doses was effective against SARS-CoV-2 infection among PLWH pre-Omicron. VE estimates appeared to peak later in PLWH than in the matched HIV-negative cohort and the degree of waning was relatively quicker in PLWH; however, peak estimates were comparable in both populations.
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•DAA therapies are an important component of HCV elimination strategies.•Larger population-level reports of reinfection rates after DAA therapy are lacking.•HCV reinfection rates ...remain elevated among people who recently injected drugs.•Opioid-agonist therapy mitigates reinfection risk.
Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. Therefore, we estimated HCV reinfection rates among DAA-treated individuals, including PWID.
We analyzed data from the British Columbia Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWID were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% CIs.
Of 4,114 individuals who met the inclusion criteria, most were male (n = 2,692, 65%), born before 1965 (n = 3,411, 83%) and were either recent (n = 875, 21%) or former PWID (n = 1,793, 44%). Opioid-agonist therapy (OAT) was received by 19% of PWID. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR 6.7; 95% CI 1.9–23.5) and former PWID (1.4/100 PYs; IRR 3.7; 95% CI 1.1–12.9) than non-PWID (0.3/100 PYs). Among recent PWID, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection.
Population-level reinfection rates remain elevated after DAA therapy among PWID because of ongoing exposure risk. Engagement of PWID in harm-reduction and support services is needed to prevent reinfections.
Direct-acting antivirals are an effective tool for the treatment of hepatitis C virus, enabling the elimination of the virus. However, some patients who have been successfully treated with direct-acting antivirals are at risk of reinfection. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection.
Sofosbuvir and ledipasvir-sofosbuvir are both newer direct-acting antiviral agents for the treatment of hepatitis C. The high list prices for both drugs have led to concern about the budget impact ...for public drug coverage programs. Therefore, we studied the impact of public prescription drug coverage for both drugs on utilization, adherence, and public and private expenditure in British Columbia, Canada.
We used provincial administrative claims data from January 2014 to June 2017 for all individuals historically tested for either hepatitis C and/or human immunodeficiency virus. Using interrupted time series analysis, we examined the impact of public insurance coverage on treatment uptake, adherence (proportion of days covered), and public and private expenditures.
Over our study period, 4,462 treatment initiations were eligible for analysis (1,131 sofosbuvir and 3,331 ledipasvir-sofosbuvir, which include 19 patients initiated on both treatments). We found the start of public coverage for sofosbuvir and ledipasvir-sofosbuvir increased treatment uptake by 154%. Adherence rates were consistently high and did not change with public coverage. Finally, public expenditure increased after the policy change, and crowded out some private expenditure.
Public coverage for high-cost drugs for hepatitis C dramatically increased use of these drugs, but did not reduce adherence. From a health policy perspective, public payers should be prepared for increased treatment uptake following the availability of public coverage. However, they should not be concerned that populations without private insurance coverage will be less adherent and not finish their treatment course.
Background
Population‐level monitoring of hepatitis C virus (HCV) infected people across cascades of care identifies gaps in access and engagement in care and treatment. We characterized the ...population‐level care cascade for HCV in British Columbia (BC), Canada before and after introduction of Direct Acting Antiviral (DAA) treatment.
Methods
BC Hepatitis Testers Cohort (BC‐HTC) includes 1.7 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2018 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV care cascade stages: (a) antibody diagnosed; (b) RNA tested; (c) RNA positive; (d) genotyped; (e) initiated treatment; and (f) achieved sustained virologic response (SVR).
Results
We estimated 61 127 people were HCV antibody positive in BC in 2018 (undiagnosed: 7686, 13%; diagnosed: 53 441, 87%). Of those diagnosed, 83% (44 507) had HCV RNA testing, and of those RNA positive, 90% (28 716) were genotyped. Of those genotyped, 61% (17 441) received therapy, with 90% (15 672) reaching SVR. Individuals from older birth cohorts had lower progression to HCV RNA testing. While people who currently inject drugs had the highest proportional progression to RNA testing, this group had the lowest proportional treatment uptake.
Conclusions
Although gaps in HCV RNA and genotype testing after antibody diagnosis exist, the largest gap in the care cascade is treatment initiation, despite introduction of DAA treatment and removal of treatment eligibility restrictions. Further interventions are required to ensure testing and treatment is equitably accessible in BC.
Background
To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease‐2019 (COVID‐19), a systematic review and meta‐analysis were conducted ...on the association between admission laboratory values in hospitalized COVID‐19 patients and subsequent disease severity and mortality.
Material and Methods
Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta‐analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta‐regression techniques for 11 markers.
Results
In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109/L (2.76, 4.87), lymphocytes (ALC) at −0.34 × 109/L (−0.45, −0.23), interleukin‐6 (IL‐6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C‐reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D‐dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non‐severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta‐regression.
Conclusion
The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID‐19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.
High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to ...estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence.
HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence.
57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio aOR 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98).
These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination.
To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.
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•People who inject drugs are a key population for hepatitis C elimination.•Australia has provided universal access to direct-acting antiviral therapy since 2016.•Data linkage was used to assess population-level direct-acting antiviral uptake.•Those with evidence of recent drug dependence had the highest treatment uptake.•Despite higher direct-acting antiviral uptake among those with recent drug dependence, gaps remain.
The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly ...introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring.
Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015–19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios.
An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015–19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 95% CI 19.01–25.65 to 278.82 278.20–279.44 per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 95% CI 44.85–45.84 to 93.77 95% CI 93.46–94.08 per 100,000 person-years). The IR of myocarditis ranged from 1.60 (95% CI 1.45–1.76) to 7.76 (95% CI 7.46–8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015–19.
Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.
Current 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.
BC 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.
In 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 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019.
Prenatal 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.
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