The persistence of seroprotective levels of antibodies after vaccination with PreHevbrio, a 3-antigen hepatitis B vaccine.

Prevention of hepatitis B virus (HBV) infection by vaccination can potentially eliminate HBV-related diseases. PreHevbrio™/PreHevbri® is a 3-antigen (S, preS1, preS2) HBV vaccine (3A-HBV) recently licensed for adults in the US, EU and Canada. This study evaluated antibody persistence in a subset of fully vaccinated and seroprotected (anti-HBs ≥ 10 mIU/mL) Finnish participants from the phase 3 trial (PROTECT) of 3A-HBV versus single-antigen HBV vaccine (1A-HBV). 465/528 eligible subjects were enrolled (3A-HBV: 244; 1A-HBV: 221). Baseline characteristics were balanced. After 2.5 years, more 3A-HBV subjects remained seroprotected (88.1 % [95 %CI: 84.1,92.2]) versus 1A-HBV (72.4 % [95 %CI: 66.6,78.3)], p < 0.0001) and had higher mean anti-HBs [1382.9 mIU/mL (95 %CI: 1013.8,1751.9) versus 252.6 mIU/mL (95 %CI: 127.5,377.6), p < 0.0001]. In multiple variable logistic regression analysis including age, vaccine, initial vaccine response, sex and BMI, only higher post dose 3 (Day 196) antibody titers significantly reduced the odds of losing seroprotection.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial.

INTRODUCTION/HYPOTHESIS: Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014-2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study. METHODS: An online survey which included participants' prior experience with clinical trials, motivations to participate (including financial incentives), and demographic information was developed to examine the motivations of healthy participants in two phase 1 clinical vaccine trials conducted at the Canadian Center for Vaccinology in Halifax, Nova Scotia. Participants were invited via email to complete the online survey. Readability and clarity were assessed through pilot testing. RESULTS: A total of 49 (55.7%) of 88 participants of the two studies completed the survey (22 [55%] of 40 participants from the Ebola vaccine study and 27 [56.3%] of 48 from the adjuvanted influenza vaccine study). Motivations that were most frequently ranked among participants' top three in both trials were (1) wanting to contribute to the health of others, (2) wanting to participate in something important, (3) wanting to contribute to the advancement of science, and (4) wanting to receive an incentive such as money or a tablet. CONCLUSIONS/RECOMMENDATIONS: Although media attention and financial compensation were more often cited by Ebola vaccine trial participants as a reason to participate, both altruistic and self-interested factors were important motivations for participants in their decision to participate in a phase 1 vaccine clinical trial.

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.

Routine immunization of adults by pharmacists: Attitudes and beliefs of the Canadian public and health care providers.

Vaccine coverage among adults for recommended vaccines is generally low. In Canada and the US, pharmacists are increasingly becoming involved in the administration of vaccines to adults. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults and health care providers regarding pharmacists as immunizers. Geographically representative samples of Canadian adults (n = 4023) and health care providers (n = 1167) were surveyed, and 8 focus groups each were conducted nationwide with adults and health care providers. Provision of vaccines by pharmacists was supported by 64.6% of the public, 82.3% of pharmacists, 57.4% of nurses, and 38.9% of physicians; 45.7% of physicians opposed pharmacist-delivered vaccination. Pharmacists were considered a trusted source of vaccination information by 75.0% of the public, exceeding public health officials (68.3%) and exceeded only by doctors and nurses (89.2%). Public concerns about vaccination in pharmacies centered on safety (management of adverse events), record keeping (ensuring their family physician was informed), and cost (should be no more expensive than vaccination at public health or physicians' offices). Concerns about the logistics of vaccination delivery were expressed more frequently in regions where pharmacists were not yet immunizing than in jurisdictions with existing pharmacist vaccination programs. These results suggest that the expansion of pharmacists' scope of practice to include delivery of adult vaccinations is generally accepted by Canadian health care providers and the public. Acceptance of this expanded scope of pharmacist practice may contribute to improvements in vaccine coverage rates by improving vaccine accessibility.

The challenge of vaccinating adults: attitudes and beliefs of the Canadian public and healthcare providers.

OBJECTIVES: Vaccine coverage for recommended vaccines is low among adults. The objective of this study was to assess the knowledge, attitudes, beliefs and behaviours of adults and healthcare providers related to four vaccine-preventable diseases and vaccines (diphtheria-tetanus-pertussis, zoster, pneumococcus and influenza). DESIGN: We undertook a survey and focus groups of Canadian adults and healthcare providers (doctors, nurses, pharmacists). A total of 4023 adults completed the survey and 62 participated in the focus groups; 1167 providers completed the survey and 45 participated in the focus groups. RESULTS: Only 46.3% of adults thought they were up-to-date on their vaccines; 30% did not know. In contrast, 75.6% of providers reported being up-to-date. Only 57.5% of adults thought it was important to receive all recommended vaccines (compared to 87.1-91.5% of providers). Positive attitudes towards vaccines paralleled concern about the burden of illness and confidence in the vaccines, with providers being more aware of disease burden and confident in vaccine effectiveness than the public. Between 55.0% and 59.7% of adults reported willingness to be vaccinated if recommended by their healthcare provider. However, such recommendations were variable; while 77.4% of the public reported being offered and 52.8% reported being recommended the influenza vaccine by their provider, only 10.8% were offered and 5.6% recommended pertussis vaccine. Barriers and facilitators to improved vaccine coverage in adults, such as trust-mistrust of health authorities, pharmaceutical companies and national recommendations, autonomy versus the public good and logistical issues (such as insufficient time and lack of vaccination status tracking), were identified by both the public and providers. CONCLUSIONS: Despite guidelines for adult vaccination, there are substantial gaps in knowledge and attitudes and beliefs among both the public and healthcare providers that lead to low vaccine coverage. A systematic approach that involves education, elimination of barriers and establishing and improving infrastructure for adult immunisation is required.

Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What the Canadian public knows and wants to know.

Tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in Canada but uptake is low. This study measured the knowledge, attitudes, beliefs, and behaviors of Canadian adults to identify potential barriers and facilitators to Tdap uptake. A survey was undertaken on a geographically representative sample of Canadian adults (n=4023) and 8 focus groups (62 participants) were conducted nationwide. The survey revealed that knowledge about pertussis and Tdap was low (38.3% correct answers). Only 36.0% of respondents reported being aware that all adults were recommended to receive Tdap and only 10.7% reported being immunized; 36.7% did not know whether they had received Tdap. Respondents who were aware of the immunization recommendations were twice as likely to be immunized (16.6% vs. 8.3%; p<0.001). Only 9.3% believed that their health care provider thought that Tdap was important for adults. The focus group data supported the survey results. Participants wanted information about pertussis and Tdap communicated through multiple modalities, but a recommendation by their family physician was most important to their decision to be immunized or not. This study demonstrates that current recommendations for universal adult vaccination with Tdap are not reaching the general public in Canada and an alternative strategy will be required to improve Tdap vaccine uptake.

Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What Canadian health care providers know and need to know.

The tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (N =1,167). In addition, 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was awareness of and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients are at significant risk of getting pertussis, and to feel that they have sufficient information (p < 0.0001 for each statement). Focus group data supported the survey results and indicated that there are substantial gaps in knowledge of pertussis and Tdap among Canadian HCPs. Lack of public knowledge about adult immunization, lack of immunization registries, a costing differential between Td and Tdap, workload required to deliver the vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization, and suggestions were provided to better translate recommendations to front-line practitioners.

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.

Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis vaccine in women of childbearing age and postpartum women.

BACKGROUND: Because adolescents and adults act as a primary source of pertussis infection for infants, vaccination of mothers immediately postpartum is a potential strategy to reduce transmission (cocoon strategy). For this to be effective, high levels of antibodies must be achieved rapidly after vaccination. We sought to determine whether the antibody response to tetanus-diphtheria-acellular pertussis vaccine (Tdap) is sufficiently rapid to support the cocoon strategy. METHODS: Two sequential studies were performed. The first was a nonrandomized, open study of a 5-pertussis-component Tdap vaccine (tetanus toxoid, diphtheria toxoid, pertussis toxoid [PT], filamentous hemagglutinin [FHA], fimbriae types 2 and 3 [FIM], and pertactin [PRN]) given to women of childbearing age; the second was a randomized, open study of Tdap or no vaccine in postpartum women. Serum levels of immunoglobin (Ig) G and IgA against pertussis antigens, serum levels of IgG against diphtheria and tetanus, and breast milk levels of IgA against pertussis antigens were measured at various times after vaccination. RESULTS: In both studies, the antibody response was relatively rapid, with serum IgG and IgA levels beginning to increase noticeably by days 5-7 and approaching peak levels by day 14. Greater than 68% and 84.4% of IgG and IgA responders, respectively, achieved ≥ 90% of their maximum titer by day 14. The diphtheria and tetanus antibody kinetics followed a similar time course. Breast milk levels of IgA against PT, FHA, and FIM were first detectable at day 7, peaked by day 10, and then slowly decreased through day 28. Antibodies against PRN showed a similar response, although the peak occurred at day 14. There were no significant antibody responses in the control group. CONCLUSIONS: Although the antibody response to a dose of Tdap in healthy nonpregnant women of child-bearing age and postpartum women occurs by day 14 and is suggestive of an anamnestic immune response, it may not be sufficiently rapid to protect infants in the first weeks of life.

A nasally administered trivalent inactivated influenza vaccine is well tolerated, stimulates both mucosal and systemic immunity, and potentially protects against influenza illness.

A randomized placebo-controlled double-blind trial of a nasally administered inactivated trivalent influenza vaccine formulated with partially purified meningococcal outer membrane proteins (OMP-TIV) was conducted in 1349 healthy adults aged 18-64 years. Subjects received either vaccine containing 15 µg of haemagglutinin (HA) of each of three influenza strains for the 2003-2004 season on days 0 and 14, or 30 µg on day 0 and saline placebo on day 14, or placebo on days 0 and 14. Vaccination was well tolerated, with similar reactogenicity as placebo. Compared to placebo, statistically significant increases in mean serum haemagglutinin inhibition reciprocal titers and salivary secretory IgA to all 3 antigens were seen on day 28 for both vaccine dose groups. The incidence of culture-positive influenza and fever >37.8°C and cough and one or more of sore throat, runny nose or nasal congestion, muscle or joint ache, headache, fatigue, or chills or culture positive influenza and at least two of these symptoms was low (16/1349; 1.2%). In the intent-to-immunize population too few febrile culture-confirmed illness events (n=4) occurred to perform analysis. Fever occurred infrequently, even in the presence of positive cultures and disabling multi-symptom disease. In participants receiving all doses of either vaccine regimen the incidence of culture-confirmed influenza with respiratory symptoms and with or without fever was 0.77% (7/904) vs. 2.03% (9/443) in placebo recipients (p=0.045, Fisher's exact test; relative risk reduction 62%), despite circulation of a drift variant A/H3N2 that was poorly matched to vaccine. An OMP-TIV vaccine was well tolerated and reduced risk of symptomatic culture confirmed influenza. Vaccine efficacy will need to be validated in a season with a higher attack rate.

Influenza-attributable deaths, Canada 1990-1999.

The number of deaths attributable to influenza is believed to be considerably higher than the number certified by vital statistics registration as due to influenza. Weekly mortality data for Canada from the 1989/1990 to the 1998/1999 influenza seasons were analysed by cause of death, age group, and place of death to estimate the impact of influenza on mortality. A Poisson regression model was found to accurately predict all-cause, as well as cause-specific mortality, as a function of influenza-certified deaths, after controlling for seasonality, and trend. Influenza-attributable deaths were calculated as predicted less baseline-predicted deaths. In summary, throughout the 1990s there were on average just under 4000 deaths attributable to influenza annually (for an influenza-attributable mortality rate of 13/100,000 persons), varying from no detectable excess mortality for the 1990/1991 influenza season, to 6000-8000 influenza-attributable deaths for the more severe influenza seasons of 1997/1998 and 1998/1999. On average, 8% (95% CI 7-10) of influenza-attributable deaths were certified as influenza, although this percentage varied from 4% to 12% from year to year. Only 15% of the influenza-attributable deaths were certified as pneumonia, and for all respiratory causes, 40%. Deaths were distributed over most causes. The weekly pattern of influenza-certified deaths was a good predictor of excess all-cause mortality.

Unique epidemiology of nosocomial urinary tract infection in children.

BACKGROUND: Nosocomial urinary tract infection (NUTI) occurs with varying frequency in children and is thought to be associated with urethral instrumentation. In response to changing infection control resources at our facility, we reviewed NUTI to determine whether the frequency of NUTI, associated complications, or presence of a remediable risk factor (instrumentation) justified ongoing routine infection control surveillance. METHODS: Prospective surveillance was conducted on all wards 8 months per year from January 1991 through December 1997 by an infection control nurse coordinator. NUTI was defined by laboratory evidence according to Center for Disease Control and Prevention definitions and detected 48 hours after admission. Urinary catheterization in the previous 7 days was categorized as continuous/indwelling or intermittent. RESULTS: NUTI was the fifth most common nosocomial infection (129/1375; approximately 9%) and decreased in frequency during the decade from 0.9 to approximately 0.6 cases/1000 patient days. Incidence was equal among men and women. Only 50% of cases had prior instrumentation of the urinary tract. NUTI occurred disproportionately in newborns and infants (P <.001). The most common pathogen was Escherichia coli (28%; 38/132), followed by Candida sp (18%; 24/134), Enterococcus (13%; 18/134), gram-negative nonfermenters (13%; 17/132), Enterobacter (approximately 10%; 13/134), Pseudomonas (9.7%; 13/134), and other (16%; 22/134). Three cases of secondary bacteremia occurred (2.3%; 95% confidence interval 0.5-6.6); there was no mortality. CONCLUSIONS: NUTI poses a less significant burden of illness (incidence, associated morbidity) than other nosocomial infection in children. If resources do not permit hospital-wide surveillance, high-risk children with urethral instrumentation and newborns and infants could be targeted. Although E coli remains the most common cause of pediatric NUTI, fungi have become the second most common pathogen in this tertiary care population. Risk factors for NUTI in noncatheterized children remain to be delineated.

Evaluation of the notification of hepatitis C risk to children who received unscreened blood or blood products.

Parents of children who received blood or blood products between 1984 and 1990 were notified about the potential risk of hepatitis C virus (HCV) infection. Data were collected about knowledge, attitudes and intended behaviours to determine the acceptability of the notification process. Demographic variables that may predict responses to notification were also recorded and analysed. Recipients were sent couriered letters explaining HCV risk, and the survey questionnaire. Sera were screened for HCV antibody and reactive samples confirmed with a recombinant immunoblot assay (RIBA). Four letter recipients were RIBA positive for a prevalence of 1.1% (4/358) in the notification group. Thirty-two percent of respondents did not know their child had been transfused and 58% did not know about the potential risk of HCV infection. Although 90% (165/185) felt the notification was valuable, 65% reported emotional distress (fear, worry, anger, very depressed). Responders were similar to non-responders except for HCV testing rate (76.2% v. 59.8%, p < 0.0002). Parents of children at risk of transfusion-acquired HCV virus approved of notification programs, but experienced some emotional distress. Awareness of transfusion history or risk of HCV was not universal, indicating the need to address notification to individuals, rather than through public education campaigns alone.

Canadian Acute Respiratory Illness and Flu Scale (CARIFS): development of a valid measure for childhood respiratory infections.

Although acute respiratory infection (ARI) is the most frequent clinical syndrome in childhood, there is no validated measure of its severity. Therefore a parental questionnaire was developed: the Canadian Acute Respiratory Illness Flu Scale (CARIFS). A process of item generation, item reduction, and scale construction resulted in a scale composed of 18 items covering three domains; symptoms (e.g., cough); function (e.g., play), and parental impact (e.g., clinginess). The validity of the scale was evaluated in a study of 220 children with ARI. Construct validity was assessed by comparing the CARIFS score with physician, nurse, and parental assessment of the child's health. Data were available from 206 children (94%). The CARIFS correlated well with measures of the construct (Spearman's correlations between 0.36 and 0.52). Responsiveness was shown, with 90% of children having a CARIFS score less than a quarter of its initial value, by the tenth day.

Variation in risk for nosocomial chickenpox after inadvertent exposure.

Inadvertent exposure to chickenpox in the healthcare setting results in time-consuming and expensive infection control management strategies. In households, secondary cases occur in up to 96% of susceptibles, but transmission risk after exposure in an occupational setting is less well defined. In this prospective cohort study of inadvertent exposures in a 180-bed paediatric hospital, the secondary transmission rate was 4.5% (4/89; 95% confidence interval 1.2, 11.1%). Fourteen index cases exposed 158 patients and 93 healthcare workers over a 36-month study period. Exposures occurred in inpatient and ambulatory settings, with patients, staff and siblings serving as index cases. Transmission only occurred when the index case and contacts were in the same room and not in a multi-room setting (12% v. 0%, Fisher exact test, P = 0.02). Occupational exposures present a lesser transmission risk than those in households. Definition of those exposure variables that increase risk of transmission in the occupational setting should be explored in future studies.