COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Impact of availability of direct-acting antivirals for hepatitis C on Canadian hospitalization rates, 2012-2016.

BACKGROUNDS: Hospitalizations associated with hepatitis C virus (HCV) infection and liver disease increased on average by 6.0% per year from 2004 to 2010 in Canada and were projected (in 2010) to increase by another 4% by 2016. The first generation of direct-acting antivirals (DAAs) became available in 2012. In 2014, a second generation of effective and well-tolerated DAA therapy was authorized in Canada. The impact of DAA therapy on the HCV-associated disease burden in Canada has not been documented. OBJECTIVES: To assess the potential impact of DAA therapy on the disease burden by a) comparing the actual hospitalization rates associated with HCV infection and liver disease following the introduction of DAAs in Canada with the 2010 baseline projection and b) documenting the associated uptake of anti-HCV therapy. METHODS: The hospital records of inpatients diagnosed with chronic HCV and chronic liver disease were extracted from the Canadian Discharge Abstract Database (DAD) by fiscal year for 2004-2016. We compared the actual number of hospitalizations to the baseline projection by year and for selected 5-year birth cohorts (1925-1989). The monthly number of new prescriptions for anti-HCV regimens was extracted from the IQVIA CDH CompuScript database (formerly IMS Health), aggregated to annual levels by age group and compared with hospitalization trends. RESULTS: Compared to the baseline projection, there was a slight reduction in hospitalizations in 2014/15 and 2015/16. This slight reduction was followed by a more significant decline in 2016/17 (32% below expected; 95% confidence interval [CI]: 27%-37%). The largest declines were observed for patients born before 1960 (age 55 or older) at 40% below expected in 2016/17. The number of new anti-HCV prescriptions increased from 5,484 in fiscal year 2012/13 to a peak of 17,775 in 2015/2016. The number of new prescriptions corresponds to approximately 1.3 and five times the number of hospitalizations in 2012/13 and 2015/16, respectively. CONCLUSIONS: In Canada there has been a modest decrease in HCV and liver-related hospitalizations following a significant increase in uptake of second-generation DAAs in 2015. However, the burden is still high. Linked health administrative databases created to monitor the disease burden in the new treatment era should provide additional insight with the linkage of treatment history and disease stage to individual outcomes.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

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

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

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

Role of primary T-cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.

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

Interim estimates of influenza vaccine effectiveness in 2012/13 from Canada's sentinel surveillance network, January 2013.

The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13-66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.

Use of biomass fuel and acute respiratory infections in rural Pakistan.

OBJECTIVE: To evaluate the association between use of biomass fuel and acute respiratory infection (ARI) episodes in children aged ≤5 years in Pakistan. DESIGN: Cross-sectional study. METHODS: Cluster sampling was used to select 566 children from 379 households in August-September 2007 in a rural setting in Pakistan. Information was collected on ARI episodes during the previous month and type of fuel used for cooking. Poisson regression with robust variance estimation was used to assess the association between use of biomass fuel and ARI episodes, adjusting for potential confounders. RESULTS: The incidence of ARI was 7 episodes/child/year. In the adjusted model, the incidence of ARI was higher in children living in houses where biomass fuel was used and who accompanied their mothers while cooking compared with children living in houses where fossil fuel was used and who did not accompany their mothers while cooking [rate ratio (RR) 2.6, 95% confidence interval (CI) 1.5-4.5]. Compared with the latter group, the incidence of ARI was also higher in children living in houses where biomass fuel was used but who did not accompany their mothers during cooking (RR 1.5, 95% CI 1.2-1.9), and in children living in houses where fossil fuel was used and who accompanied their mothers while cooking (RR 1.9, 95% CI 1.3-2.8). CONCLUSION: Use of biomass fuel and presence of a child in the kitchen during cooking were associated with increased incidence of ARI in children aged ≤5 years.

Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010.

In pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross-reactive antibodies to a representative swine H3N2 (swH3N2) and a related ancestral human H3N2 (A/Sydney/5/1997) influenza virus. Few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres ≥40 to either virus. Titres increased with age among children but decreased in adults. Fewer than 20% showed a four-fold rise in antibody titres to either virus following immunisation. Further investigation is warranted to guide ongoing risk assessment and response to emerging swine H3N2 viruses.

Health care risk factors among women and personal behaviours among men explain the high prevalence of hepatitis C virus infection in Karachi, Pakistan.

To estimate the prevalence and identify factors associated with hepatitis C virus (HCV) infection among men and women in Karachi, Pakistan. We conducted a cross-sectional study of adult men and women in a peri-urban community of Karachi (Jam Kandah). Households were selected through systematic sampling from within all villages in the study area. All available adults within each household were interviewed about potential HCV risk factors. A blood specimen was collected to test for anti-HCV antibodies by enzyme immunoassay. We used generalized estimating equations while accounting for correlation of responses within villages to identify the factors associated with HCV infection. Of 1997 participants, 476 (23.8%) were anti-HCV positive. Overall, HCV infection was significantly associated with increasing age, ethnicity, and having received > or =2 blood transfusions, > or =3 hospitalizations, dental treatment and >5 injections among women. Among women, > or =2 blood transfusions [adjusted odds ratio (aOR) = 2.32], >5 injections during the past 6 months (aORs = 1.47), dental treatment (aOR = 1.31) and increasing age(aOR = 1.49), while among men, extramarital sexual intercourse (aOR = 2.77), at least once a week shave from barber (aOR = 5.04), > or =3 hospitalizations (aOR = 2.50) and increasing age (aOR = 1.28) were associated with HCV infection. A very high prevalence of HCV was found in the study population. Among women, unsafe health care practices, while among men extramarital sex, shaving from a barber and hospitalizations were associated with HCV infection. Efforts are needed to improve the safety of medical procedures to reduce the transmission of HCV in Pakistan [Corrections made in Summary after initial online publication.].

High-risk behaviours among juvenile prison inmates in Pakistan.

OBJECTIVES: To assess the sexual- and drug-use-related risk behaviours of male juvenile detainees in Karachi, Pakistan. DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted of prison inmates aged 15-21 years in Karachi Juvenile Prison in 2002. In total, 321 inmates were interviewed about sexual orientation and behaviours, and knowledge about human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). Urine specimens were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction. RESULTS: A substantial proportion (n=111, 34.6%) of the participants were sexually active. Sixty-two (19%) and 67 (21%) had had sex with a male or female before incarceration, respectively. Twenty-seven (8.4%) participants had an STI, and 50% of the 109 sexually active participants had had multiple sexual partners. Use of addictive substances was associated with sexual activity. The mean knowledge score computed from the sum of 16 items was 4.7, with a median of 2.9. A large proportion (40%) of participants knew about condoms, but very few (3.4%) had ever used one. The mean+/-standard deviation risk score from nine items was 2.4+/-1.7. On the basis of behavioural and biological markers, 117 (36.4%) participants had high-risk behaviour. In multivariate logistic regression analysis, knowledge, risk perception and age were predictive of higher risk. CONCLUSIONS: HIV risk behaviours are common among adolescent inmates. Although inmates do have knowledge about modes of transmission and condom use, the use of condoms is significantly low. Interventions are needed for behavioural change among this group.

Knowledge and practices of barbers about hepatitis B and C transmission in Rawalpindi and Islamabad.

OBJECTIVE: To assess the knowledge and practices of barbers regarding transmission risk of HBV and HCV viruses. METHODS: A cross-sectional survey of barber's shops in Rawalpindi and Islamabad was conducted during September- November1998. Barbers were queried about hepatitis, knowledge regarding hepatitis transmission through razor, vaccination, sterilization, and the form of media they use for information and entertainment. Use of instruments on at least 2 clients were observed in each shop. Proportion and their 95% confidence intervals were computed. RESULTS: Of 96 barbers approached, 12 (13%) knew that hepatitis is a disease of the liver, causing jaundice, it is transmitted through parenteral route and could also be transmitted by razor. During the actual observation of 192 clients, razors were cleaned with antiseptic solution for 22 (11.4%) and reused for 88 (46%) shaves. CONCLUSION: Level of awareness among barbers about hepatitis and risks of transmission is very low, and their practice of razor reuse that may spread hepatitis is very common. Messages about hepatitis need to be incorporated in media campaigns, in addition to regulation of practices.

Injection practices and sharp waste disposal by general practitioners of Murree, Pakistan.

OBJECTIVE: To describe the injection and sharp waste disposal practices of general practitioners of Murree, Pakistan. METHODOLOGY: In-depth interviews of all general practitioners available between 10th to 20th July 2000 were conducted. Practitioners were interviewed about injection administration and disposal of waste due to injections and other sharp material. RESULTS: Twenty general practitioners out of 25 were interviewed. All claimed using disposable syringes only once. None of them was disposing off syringes in sharp containers in the clinic. Of 20, 12 (60%) were throwing syringes at open places and 5 (25%) in municipal waste bins. Most of the injections by general practitioners were administered for fever, body aches, diarrhea and respiratory tract infection. CONCLUSION: Sharp waste disposal is not safe in Murree. Improper disposal of sharp waste needs development of cost effective methods that are applicable at a small scale. Larger studies are required to quantify the gravity of the problem.