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.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Neurodevelopmental and behavioural outcomes of HIV-exposed uninfected and HIV-unexposed children at 2-3 years of age in Cape Town, South Africa.

Successful vertical HIV transmission prevention programmes (VTP) have resulted in an expanding population of HIV-exposed uninfected (HEU) infants whose growth, health and neurodevelopmental outcomes could have consequences for future resource allocation. We compared neurodevelopmental and behavioural outcomes in a prospective cohort of 2-3 year old HEU and HIV-unexposed uninfected (HU) children.Women living with and without HIV and their infants were enrolled within three days of birth from a low-risk midwife obstetric unit in Cape Town, South Africa during 2012 and 2013, under WHO Option A VTP guidelines. HIV-uninfected children aged 30-42 months were assessed using the Bayley scales of Infant Development-Third edition (BSID) and Strengths and Difficulties questionnaire (SDQ).Thirty-two HEU and 27 HU children (mean birth weight 3048g vs 3096g) were assessed. HEU children performed as well as HU children on BSID cognitive, language and motor domains. Mean scores fell within the low average range. Mothers of HEU children reported fewer conduct problems but stunting was associated with increased total difficulties on the SDQ.HEU and HU children's performance on the BSID was similar. In this low-risk cohort, HIV exposure did not confer additional risk. Stunting was associated with increased behavioural problems irrespective of HIV exposure.

Irinotecan-induced muscle twitching from a possible drug interaction: A case report.

We report the case of a 50-year-old human immunodeficiency virus-positive patient with stage IV KRAS-mutated colorectal cancer who experienced visible muscle twitching in the right lateral triceps brachii from irinotecan administration for which typical supportive care measures were unsuccessful, including the administration of atropine and slowing down the infusion rate. The patient was able to tolerate this reaction and received 20 cycles of irinotecan-based chemotherapy despite experiencing the muscle twitching with every cycle at the same onset, duration, and severity. It is possible that competitive metabolism by concomitant medications metabolized by CYP3A4 or UGT1A1 was responsible for this event. Due to ethical concerns, we were unable to formally assess the drug interaction by discontinuing the suspected interacting medications and re-initiating them to evaluate the effects. A formal pharmacokinetic study may be warranted to better elucidate these potential drug interactions.

Serotonin-norepinephrine reuptake inhibitors and the influence of binding affinity (Ki) on analgesia.

WHAT IS KNOWN AND OBJECTIVE: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used for various psychiatric conditions and neuropathic pain syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine (NE); however, NE reuptake inhibition is thought to be the primary mediator for their analgesic effect. COMMENT: Key differences in pharmacodynamics and receptor affinities exist between SNRIs. The selectivity for each monoamine differs among SNRIs based on the agent's affinity and activity at the monoamine reuptake transporter. We review differences in receptor affinities and monoamine selectivity among SNRIs and the corresponding clinical impact. WHAT IS NEW AND CONCLUSION: The varying selectivity for 5-HT and NE among the SNRIs may help explain the therapeutic dosing required for neuropathic pain as well as dose-related adverse effects. It is important to understand the pharmacologic differences among SNRIs, in addition to the data from clinical trials, to guide their safe and effective use.

Knowledge, attitudes, beliefs, and behaviors of university students, faculty, and staff during a meningococcal serogroup B outbreak vaccination program.

OBJECTIVES: During an outbreak of invasive meningococcal B disease on a university campus, we explored the knowledge, attitudes, beliefs, and behaviors of members of the university community in relation to the disease, the vaccine, and the vaccination program. DESIGN: All students, faculty and staff were invited by email to participate in a 71-item online survey, which was administered after completion of the mass clinics for the first and second doses of a meningococcal B vaccination program. RESULTS: A total of 404 individuals responded to the survey; 75.7% were students. Knowledge about meningococcal disease and vaccine was generally high; more than 70% correct responses were received on each knowledge question except for one question about the different meningococcal serogroups. Gender (female) and higher knowledge scores were significantly associated with either being immunized or intending to be immunized (p<0.05). Positive attitudes about immunization, concern about meningococccal infection, a sense of community responsibility, and trust in public health advice also correlated with being vaccinated or intending to be vaccinated (p<0.05). CONCLUSIONS: A successful mass vaccination program in a Nova Scotia university was associated with high levels of knowledge, positive attitudes toward vaccination, and positive attitudes toward public health recommendations.

Rapid surveillance for health events following a mass meningococcal B vaccine program in a university setting: A Canadian Immunization Research Network study.

An outbreak of Neisseria meningitidis serotype B infection occurred at a small residential university; public health announced an organizational vaccination program with the 4-component Meningococcal B (4CMenB) vaccine (Bexsero(TM), Novartis/GlaxoSmithKline Inc.) several days later. Since there were limited published data on reactogenicity of 4CMenB in persons over 17years of age, this study sought to conduct rapid surveillance of health events in vaccinees and controls using an online survey. Vaccine uptake was 84.7% for dose 1 (2967/3500) and 70% (2456/3500) for dose 2; the survey response rates were 33.0% (987/2967) and 18.7% (459/2456) in dose 1 and dose 1 recipients respectively, and 12% in unvaccinated individuals (63/533). Most students were 20-29years of age (vaccinees, 64.0%; controls, 74.0). A new health problem or worsening of an existing health problem was reported by 30.0% and 30.3% of vaccine recipients after doses 1 and 2 respectively; and by 15.9% of controls. These health problems interfered with the ability to perform normal activities in most vaccinees reporting these events (74.7% post dose 1; 62.6% post dose 2), and in 60% of controls. The health problems led to a health care provider visit (including emergency room) in 12.8% and 14.4% of vaccinees post doses 1 and 2, respectively and in 40% of controls. The most common reactions in vaccinees were injection site reactions (20.6% post dose 1, 16.1% post dose 20 and non-specific systemic complaints (22.6% post dose 1, 17.6% post dose 2). No hospitalizations were reported. An online surveillance program during an emergency meningococcal B vaccine program was successfully implemented, and detected higher rates of health events in vaccinees compared to controls, and high rates of both vaccinees and controls seeking medical attention. The types of adverse events reported by young adult vaccinees were consistent with those previously.

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.

Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Canadian vaccine research networks: Vaccine safety resources for Canada.

The Public Health Agency of Canada / Canadian Institutes of Health Research Influenza Research Network (PCIRN), established in 2009 to undertake evaluative research to inform public health decision making in Canada, is now being replaced by the Canadian Immunization Research Network (CIRN), which will retain the mandate of PCIRN but expand it to all vaccines including influenza vaccine. CIRN is organized as a network of networks focusing on undertaking research in the areas of vaccine safety, adverse events following immunization (AEFIs), vaccine hesitancy, vaccine effectiveness, and vaccine coverage. CIRN's networks include: a clinical trial network; a laboratory network; a modelling and economics network; a network of social science and humanities researchers; a vaccine safety surveillance network; a hospital-based surveillance network; a clinic network to evaluate serious AEFIs; and a network that links vaccine research capacity in provincial health agencies and departments. PCIRN has contributed to Canada's vaccine safety surveillance system and has facilitated the translation of safety research into policy. Vaccine safety surveillance and research will remain a focus of the newly formed Canadian Immunization Research Network.

Home environmental tobacco smoke exposure in Canadian children.

BACKGROUND: Children living with a smoker experience increased environmental tobacco smoke (ETS) exposure, even when the smoker refrains from smoking inside the house, compared to children not living with a smoker. Given the risks of ETS in children, it was hypothesized that households with children are less likely than those without children to experience home ETS exposure. DESIGN: Cross-sectional analysis of the Canadian Community Health Survey 2009-2010 for the association between children aged <12 years in the household and home ETS exposure, using logistic regression and considering household education and income as confounders or effect modifiers. A subgroup analysis was conducted comparing younger child households (at least one child aged <6 years) to older child households (only children aged 6-11 years). RESULTS: Of 66 631 households included, home ETS exposure occurred in 25% of households without children and 22% of households with children. Households with children were less likely than those without children to experience ETS exposure (OR 0.83, 95%CI 0.80-0.87). Effect modification by education and income was observed. No difference was observed in ETS exposure between older child and younger child households (OR 0.98, 95%CI 0.91-1.05). CONCLUSION: Households with children are marginally less likely than households without children to experience home ETS exposure.

The Canadian Immunization Monitoring Program, ACTive (IMPACT): Active surveillance for vaccine adverse events and vaccine-preventable diseases.

For almost 25 years the Canadian Immunization Monitoring Program, ACTive (IMPACT) has been conducting active surveillance for severe adverse events following immunization (AEFIs) and vaccine-preventable diseases in children. The network, which consists of volunteer paediatric infectious diseases investigators at 12 tertiary care paediatric hospitals, is an important component of Canada's AEFI monitoring. The network employs nurses at each of the sites to search for and report possible AEFIs to local, provincial and national public health authorities. The active nature of the surveillance ensures a high level of vigilance for severe AEFIs in children.

Determinants of parents' decision to vaccinate their children against rotavirus: results of a longitudinal study.

Rotavirus disease is a common cause of health care utilization and almost all children are affected by the age of 5 years. In Canada, at the time of this survey (2008-09), immunization rates for rotavirus were <20%. We assessed the determinants of a parent's acceptance to have their child immunized against rotavirus. The survey instruments were based on the Theory of Planned Behavior. Data were collected in two phases. In all, 413 and 394 parents completed the first and second interviews, respectively (retention rate 95%). Most parents (67%) intended to immunize their child against rotavirus. Factors significantly associated with parental intentions (Phase 1) were as follows: perception of the moral correctness of having their child immunized (personal normative belief) and perception that significant others will approve of the immunization behavior (subjective norm), perceived capability of having their child immunized (perceived behavioral control) and household income. At Phase 2, 165 parents (42%) reported that their child was immunized against rotavirus. The main determinant of vaccination behavior was parental intention to have their child vaccinated, whereas personal normative beliefs influenced both intention and behavior. The acceptability of the rotavirus vaccine will be higher if health promotion addresses parental knowledge, attitudes and beliefs regarding the disease and the vaccine.

Clinicians' opinions on new vaccination programs implementation.

In Canada, several new vaccines were recently approved for clinical use or are expected to be soon. Decision-makers are faced with the choice whether or not to include these vaccines in publicly funded vaccination programs. The aim of this study was to assess Canadian pediatricians' and family physicians' opinions regarding 7 new vaccines, and perceived priority for the introduction of new programs. A self-administered, anonymous, mail-based questionnaire was sent during fall 2009 to a random sample of 1182 family physicians and to all 1852 Canadian pediatricians. Responses to 8 statements regarding frequency and severity of the diseases, efficacy and safety of the vaccines as well as feasibility of immunization programs were used to calculate priority scores to rank the 7 potential new vaccination programs (calculated scores ranging from 0 to 100). Overall response rate was 43%. The majority of respondents perceived the health and economic burden of diseases prevented by the seven new vaccines as important and considered new vaccines to be safe and effective. More than 90% of physicians strongly agreed or agreed that the new vaccines would be or are currently well accepted by the public and by the health professionals who administer vaccines, except for the HPV and rotavirus vaccines (respectively 30% and 29% strongly agreed or agreed). Mean priority scores were: 77.4 out of 100 for the measles, mumps, rubella and varicella (MMRV) combined vaccine; 75.6 for the hexavalent (DTaP-IPV-Hib-HBV) vaccine; 73.1 for the new pneumococcal conjugate vaccines; 69.8 for the meningococcal ACYW135; 68.9 for the combined hepatitis A and B; 63.5 for the human papillomavirus vaccine and 56.9 for the rotavirus vaccine. Health professionals' opinion is an important element to consider in the decision-making process regarding implementation of new immunization programs. Without health professional support, the introduction of a new vaccination program may be unsuccessful. In this study, the MMRV and the hexavalent (DTaP-IPV-Hib-HBV) vaccines received the highest ratings.

Chloride intracellular channels modulate acute ethanol behaviors in Drosophila, Caenorhabditis elegans and mice.

Identifying genes that influence behavioral responses to alcohol is critical for understanding the molecular basis of alcoholism and ultimately developing therapeutic interventions for the disease. Using an integrated approach that combined the power of the Drosophila, Caenorhabditis elegans and mouse model systems with bioinformatics analyses, we established a novel, conserved role for chloride intracellular channels (CLICs) in alcohol-related behavior. CLIC proteins might have several biochemical functions including intracellular chloride channel activity, modulation of transforming growth factor (TGF)-ß signaling, and regulation of ryanodine receptors and A-kinase anchoring proteins. We initially identified vertebrate Clic4 as a candidate ethanol-responsive gene via bioinformatic analysis of data from published microarray studies of mouse and human ethanol-related genes. We confirmed that Clic4 expression was increased by ethanol treatment in mouse prefrontal cortex and also uncovered a correlation between basal expression of Clic4 in prefrontal cortex and the locomotor activating and sedating properties of ethanol across the BXD mouse genetic reference panel. Furthermore, we found that disruption of the sole Clic Drosophila orthologue significantly blunted sensitivity to alcohol in flies, that mutations in two C. elegans Clic orthologues, exc-4 and exl-1, altered behavioral responses to acute ethanol in worms and that viral-mediated overexpression of Clic4 in mouse brain decreased the sedating properties of ethanol. Together, our studies demonstrate key roles for Clic genes in behavioral responses to acute alcohol in Drosophila, C. elegans and mice.

Canadian paediatricians' opinions on rotavirus vaccination.

Rotavirus is the leading cause of dehydration and hospitalization due to gastroenteritis (GE) in young children. Almost all children are affected by the age of 5 years. Two safe and effective rotavirus vaccines are available for clinical use in Canada. In the context where rotavirus vaccination is recommended, but not publicly funded, we have assessed paediatricians' knowledge, attitudes and beliefs (KAB) regarding rotavirus disease and its prevention by vaccination. A self-administered anonymous questionnaire based upon the Health Belief Model and the Analytical framework for immunization programs was mailed to all 1852 Canadian paediatricians. The response rate was 50%. The majority of respondents rated consequences of rotavirus infection for young patients as moderate. Sixty-six percent considered that rotavirus disease occur frequently without vaccination and 62% estimated that the disease generates a significant economic burden. Sixty-nine percent of respondents considered rotavirus vaccines to be safe and 61%, to be effective. The reduction of severe GE cases was seen as the main benefit of rotavirus vaccination, while the risk of adverse events was the principal perceived barrier. Fifty-three percent (53%) indicated a strong intention to recommend rotavirus vaccines. In multivariate analysis, main determinant of paediatricians' intention to recommend rotavirus vaccines was the perceived health and economic burden of rotavirus diseases (partial R(2)=0.49, p<0.0001). More than half of surveyed paediatricians were willing to recommend rotavirus vaccines to their patients, but the proportion of respondents who had a strong intention to do so remains low when compared to several other new vaccines. As with other new vaccines, rotavirus vaccine uptake risks to remain low in Canada as long as it is not publicly funded.

Loss of RAB-3/A in Caenorhabditis elegans and the mouse affects behavioral response to ethanol.

The mechanisms by which ethanol induces changes in behavior are not well understood. Here, we show that Caenorhabditis elegans loss-of-function mutations in the synaptic vesicle-associated RAB-3 protein and its guanosine triphosphate exchange factor AEX-3 confer resistance to the acute locomotor effects of ethanol. Similarly, mice lacking one or both copies of Rab3A are resistant to the ataxic and sedative effects of ethanol, and Rab3A haploinsufficiency increases voluntary ethanol consumption. These data suggest a conserved role of RAB-3-/RAB3A-regulated neurotransmitter release in ethanol-related behaviors.

State-dependency in C. elegans.

Memory and the expression of learned behaviors by an organism are often triggered by contextual cues that resemble those that were present when the initial learning occurred. In state-dependent learning, the cue eliciting a learned behavior is a neuroactive drug; behaviors initially learned during exposure to centrally acting compounds such as ethanol are subsequently recalled better if the drug stimulus is again present during testing. Although state-dependent learning is well documented in many vertebrate systems, the molecular mechanisms underlying state-dependent learning and other forms of contextual learning are not understood. Here we demonstrate and present a genetic analysis of state- dependent adaptation in Caenorhabditis elegans. C. elegans normally exhibits adaptation, or reduced behavioral response, to an olfactory stimulus after prior exposure to the stimulus. If the adaptation to the olfactory stimulus is acquired during ethanol administration, the adaptation is subsequently displayed only if the ethanol stimulus is again present. cat-1 and cat-2 mutant animals are defective in dopaminergic neuron signaling and are impaired in state dependency, indicating that dopamine functions in state-dependent adaptation in C. elegans.