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.

Prospective monitoring of adverse events following vaccination with Modified vaccinia Ankara - Bavarian Nordic (MVA-BN) administered to a Canadian population at risk of Mpox: A Canadian Immunization Research Network study.

MVA-BN is an orthopoxvirus vaccine that provides protection against both smallpox and mpox. In June 2022, Canada launched a publicly-funded vaccination campaign to offer MVA-BN to at-risk populations including men who have sex with men (MSM) and sex workers. The safety of MVA-BN has not been assessed in this context. To address this, the Canadian National Vaccine Safety Network (CANVAS) conducted prospective safety surveillance during public health vaccination campaigns in Toronto, Ontario and in Vancouver, British Columbia. Vaccinated participants received a survey 7 and 30 days after each MVA-BN dose to elicit adverse health events. Unvaccinated individuals from a concurrent vaccine safety project evaluating COVID-19 vaccine safety were used as controls. Vaccinated and unvaccinated participants that reported a medically attended visit on their 7-day survey were interviewed. Vaccinated participants and unvaccinated controls were matched 1:1 based on age group, gender, sex and provincial study site. Overall, 1,173 vaccinated participants completed a 7-day survey, of whom 75 % (n = 878) also completed a 30-day survey. Mild to moderate injection site pain was reported by 60 % of vaccinated participants. Among vaccinated participants 8.4 % were HIV positive and when compared to HIV negative vaccinated individuals, local injection sites were less frequent in those with HIV (48 % vs 61 %, p = 0.021), but health events preventing work/school or requiring medical assessment were more frequent (7.1 % vs 3.1 %, p = 0.040). Health events interfering with work/school, or requiring medical assessment were less common in the vaccinated group than controls (3.3 % vs. 7.1 %, p < 0.010). No participants were hospitalized within 7 or 30 days of vaccination. No cases of severe neurological disease, skin disease, or myocarditis were identified. Our results demonstrate that the MVA-BN vaccine appears safe when used for mpox prevention, with a low frequency of severe adverse events and no hospitalizations observed.

Background rates of adverse events of special interest for COVID-19 vaccines: A multinational Global Vaccine Data Network (GVDN) analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Vaccine acceptance, hesitancy and refusal in Canada: Challenges and potential approaches.

"Vaccine hesitancy" is a concept used frequently in vaccination discourse and is challenging previously held perspective that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. Given the importance of achieving high vaccine coverage in Canada to avoid vaccine preventable diseases and their consequences, vaccine hesitancy is an important issue that needs to be addressed. This article describes the scope and causes of vaccine hesitancy in Canada and proposes potential approaches to address it.

Outbreak of measles in an unvaccinated population, British Columbia, 2014.

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

What do we know about how to improve vaccine uptake?

Over the past 100 years, an increasing array of vaccines has been introduced into the Canadian market and yet optimal use depends on public demand and acceptance of these products. In the 1990s, research focused on key barriers to vaccine uptake, highlighting the importance of barriers to access and "missed opportunities" for vaccination. In this century the focus is on vaccine hesitancy, which is influenced by factors such as complacency, convenience and confidence. This phenomenon is not new but some of its drivers include an increasingly crowded immunization schedule, heightened societal concerns about risk over benefit, and a rise in health consumerism. Understanding and addressing vaccine hesitancy will be critical to preventing it from undermining the success of immunization in the future. While more research is needed, there are both practitioner-based resources to optimize dialogue with vaccine-hesitant parents and program-based resources to address vaccine hesitancy at a population-based and societal level.

Behind the scenes in public health: Adverse events following immunization (AEFI) signal investigation in British Columbia.

BACKGROUND: In British Columbia, vaccine safety is monitored through a passive surveillance system with voluntary reporting of adverse events following immunization (AEFIs) from immunizers to five regional health authorities and onward to the British Columbia Centre for Disease Control (BCCDC). OBJECTIVE: To review and summarize all documented AEFI cluster or signal investigations carried out by BCCDC between November 2007 and July 2014. METHOD: Documented cluster or signal investigations were reviewed to summarize year, alerting mechanism, event type and vaccine, investigative analysis approach, results, and public health actions. The findings and public health actions of two cluster investigations are described in detail. RESULTS: There were two fatality investigations and thirteen cluster investigations. The two fatalities were found to be due to sudden infant death syndrome and were not vaccine-related. Clusters were predominantly identified through notification from regional medical health officers or public health nurses, and the majority were local injection site reactions (54%), or allergic events (39%). Most investigations did not identify a specific association to a vaccine or a lot of vaccine, and no public health actions were taken. Two recent investigations-reports of hypotonic-hyporesponsive episodes with or without severe vomiting and diarrhea following receipt of a single lot of DPT-IPV/Hib/hepatitis B vaccine, and reports of severe pain past nearest joint following administration of a single lot of influenza vaccine-were thought to be vaccine-related. The former investigation did not find an association to vaccine, while the severe local reactions post-influenza immunization were determined to be a result of improper injection technique. Public health actions included communication to federal/provincial/territorial vaccine safety partners and additional injection technique training. CONCLUSION: This investigative aspect of public health immunization programs is often not in the public eye but is an important component of behind the scenes activities that serve to protect public safety.

Intention of parents to have male children vaccinated with the human papillomavirus vaccine.

BACKGROUND: Although already approved for use in males in some jurisdictions, there is little information about parental attitudes toward having their sons receive the human papillomavirus (HPV) vaccine. The goal of this study was to ascertain parental intentions to vaccinate their sons with an HPV vaccine and to determine factors that predict this intention. METHODS: Parents of children aged 8-18 years were recruited from across Canada through random digit dialling. Participants were asked to respond to a series of questions in the context of a Grade 6 (age 11/12 years old), publicly funded school-based HPV vaccine programme, including their intention to vaccinate their sons with the HPV vaccine. Parents were also asked about a series of characteristics thought to predict intention to vaccinate as well as demographic characteristics. Backwards logistic regression was conducted to calculate adjusted odds ratios (AOR) to identify the factors that are predictive of parents' intention to vaccinate their son(s) against HPV. RESULTS: Of the 1381 respondents with male children, 67.8% (95% CI 65.3 to 70.3) intend to vaccinate their son(s) against HPV. Parents who had positive attitudes toward vaccines and the HPV vaccine in particular (AOR 41.5, 95% CI 9.5 to 181.7), parents who were influenced by subjective norms (AOR 7.8, 95% CI 5.8 to 10.5), parents who felt that the vaccine had limited influence on sexual behaviour (AOR 2.3, 95% CI 1.6 to 3.3) and parents who were aware of HPV (AOR 1.4, 95% CI 1.1 to 2.0) were significantly more likely to report an intention to vaccinate boys against HPV. In contrast, residence in British Columbia compared to Atlantic Canada (AOR 0.4, 95% CI 0.2 to 0.8) and higher education (AOR 0.7, 95% CI 0.5 to 0.9) were negatively associated with intention to vaccinate. Parents who reported an intention to vaccinate their daughters were also highly likely to report an intention to vaccinate their sons (kappa = 0.9, p<0.001). DISCUSSION: The majority of Canadian parents would intend to have their male children receive the HPV vaccine in the context of a publicly funded school-based immunisation programme. Overall attitudes toward vaccine, recommendations from health professionals and impact of the vaccine on sexual practices are important predictors of intention to have a male child receive the HPV vaccine.

Health behavior associated with influenza vaccination among healthcare workers in long-term-care facilities.

OBJECTIVE: To investigate the health behavior associated with influenza vaccination among healthcare workers (HCWs) in long-term-care facilities. DESIGN: A cross-sectional, self-administered survey of HCWs, augmented with focus groups to further examine attitudes toward influenza vaccination. SETTING: Two long-term-care facilities participated in the survey. The focus groups were held at one of the two facilities. PARTICIPANTS: All HCWs were invited to participate in the survey and all nonmanagerial staff members were invited to participate in the focus groups. The response rate for the survey was 58% (231 of 401). RESULTS: Vaccinated HCWs had a more positive attitude toward influenza vaccination and a greater belief that the vaccine is effective. This was not accompanied by differences in vaccine knowledge or values of potential preventive outcomes. Nonvaccinated respondents were more likely to believe that other preventive measures, such as washing hands, taking vitamins and supplements, eating a nutritious diet, exercising, and taking homeopathic or naturopathic medications, were more effective than vaccination. Additional findings from the focus groups suggest that HCWs believe that the main purpose of influenza vaccination programs is to protect residents' health at the expense, potential harm, and burden of responsibility of the staff. CONCLUSIONS: This study identifies challenges to and opportunities for improving vaccination rates among HCWs. A message that emphasizes the health benefits of vaccination to staff members, such as including vaccination as part of a staff "wellness" program, may improve the credibility of influenza immunization programs and coverage rates.

Prevention of influenza and pneumococcal pneumonia in Canadian long-term care facilities: how are we doing?

BACKGROUND: Influenza and pneumococcal pneumonia are serious health problems among elderly people and a major cause of death in long-term care facilities. We describe the results of serial surveys of vaccination coverage and influenza outbreak management in Canadian long-term care facilities over the last decade. METHODS: Cross-sectional surveys consisting of questionnaires mailed to all Canadian residential long-term care facilities for elderly people in 1991 and to a random sample of respondents in 1995 and 1999. RESULTS: The response rates were 83% (430/515) in 1995 and 75% (380/506) in 1999. In 1999 the mean reported rates of influenza vaccination were 83% among residents and 35% among staff, and the mean rate of pneumococcal vaccination among residents was 71%; all 3 rates were significantly higher than those in 1991. The rates were also higher in facilities with an infection control practitioner than in those without such an individual (88% v. 82% for influenza vaccination among residents [p < 0.001], 42% v. 35% for influenza vaccination among staff [p = 0.008] and 75% v. 63% for pneumococcal vaccination among residents [p < 0.001]). Obtaining consent for vaccination on admission to the facility was associated with higher influenza and pneumococcal vaccination rates among residents (p = 0.04 and p < 0.001 respectively). Facilities with higher influenza vaccination rates among residents and staff reported lower rates of influenza outbreaks (p = 0.08 and 0.03 respectively). Despite recommendations from the National Advisory Committee on Immunization, only 50% of the facilities had policies for amantadine prophylaxis during influenza A outbreaks. Amantadine was judged effective in controlling 76% of the influenza A outbreaks and was discontinued because of side effects in 3% of the residents. INTERPRETATION: Influenza and pneumococcal vaccination rates among residents and staff in Canadian long-term care facilities have increased over the last decade but remain suboptimal. Vaccination of residents and staff against influenza is associated with a reduced risk of influenza outbreaks. Amantadine is effective in controlling influenza outbreaks in long-term care facilities.

High critical current density and enhanced irreversibility field in superconducting MgB2 thin films.

The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. This compound has twice the transition temperature of Nb3Sn and four times that of Nb-Ti alloy, and the vital prerequisite of strongly linked current flow has already been demonstrated. One possible drawback, however, is that the magnetic field at which superconductivity is destroyed is modest. Furthermore, the field which limits the range of practical applications-the irreversibility field H*(T)-is approximately 7 T at liquid helium temperature (4.2 K), significantly lower than about 10 T for Nb-Ti (ref. 6) and approximately 20 T for Nb3Sn (ref. 7). Here we show that MgB2 thin films that are alloyed with oxygen can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding an H* value at 4.2 K greater than 14 T. In addition, very high critical current densities at 4.2 K are achieved: 1 MA cm-2 at 1 T and 105 A cm-2 at 10 T. These results demonstrate that MgB2 has potential for high-field superconducting applications.

Strongly linked current flow in polycrystalline forms of the superconductor MgB2.

The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered.

Expanding the epidemiologic profile: risk factors for active tuberculosis in people immigrating to Ontario.

BACKGROUND: Many people immigrating to Canada come from countries with a high burden of tuberculosis. The aim of this study was to develop a detailed epidemiologic profile of foreign-born people with tuberculosis living in Ontario. METHODS: In this population-based case-control study, cases of tuberculosis diagnosed in 1994-1995 were identified from the database of the Ontario Reportable Disease Information Service and were considered eligible for analysis if a record of landing (receipt of permission to establish residence in Canada) from the period 1986-1995 was found in the Citizenship and Immigration Canada (CIC) database, if the person was at least 11 years of age at the time their visa was issued, and if the person had not been diagnosed with tuberculosis before becoming legally landed in Canada. Control subjects, who met the same criteria as the case subjects but who did not have tuberculosis in 1994-1995, were identified from a CIC database for landed immigrants. RESULTS: A total of 1341 cases of tuberculosis in foreign-born people were reported in Ontario in 1994-1995. A record of landing was found in CIC databases for 1099 of these people, 224 of whom were not legally landed at the time of diagnosis. In total, 602 cases met the inclusion criteria. The 2 strongest determinants of risk among those who had become landed within the preceding 10 years were referral for medical surveillance by immigration officials (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.6-6.0) and world region of origin (Somalia [OR 67.7, 95% CI 31.3-154.9], Vietnam [OR 25.0, 95% CI 12.5-50.0], the Philippines [OR 11.9, 95% CI 6.0-23.3], other sub-Saharan African countries [OR 11.6, 95% CI 5.7-23.2], India [OR 9.7, 95% CI 4.9-18.9], China [OR 6.1, 95% CI 3.1-12.1], other Asian countries [OR 4.7, 95% CI 2.4-9.1], the Middle East [OR 4.1, 95% CI 2.0-8.3], Latin America [OR 1.9, 95% CI 0.9-3.8), and the former socialist countries of Europe [OR 1.8, 95% CI 0.8-3.8]; the reference category was countries with established market economies). Low socioeconomic status was an independent risk factor. INTERPRETATION: The risk of tuberculosis in groups of people migrating to Ontario is highly variable and is influenced by several factors. Successful population-based tuberculosis prevention strategies will need to accommodate this variability.