Efficacy of m-Health for the detection of adverse events following immunization – The stimulated telephone assisted rapid safety surveillance (STARSS) randomised control trial

IntroductionPassive surveillance is recommended globally for the detection of adverse events following immunisation (AEFI) but this has significant challenges. Use of Mobile health for vaccine safety surveillance enables a consumer-centred approach to reporting. The Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) a randomised control trial (RCT) sought to evaluate the efficacy and acceptability of SMS for AEFI surveillance.MethodsMulti-centre RCT, participants were adult vaccinees or parents of children receiving any vaccine at a trial site. At enrolment randomisation occurred to one of two SMS groups or a control group. Prompts on days 2, 7 and 14 post-immunisation, were sent to the SMS group, to ascertain if a medical event following immunisation (MEFI) had occurred. No SMS’s were sent to the control participants. Those in the SMS who notified an MEFI were pre-randomised to complete a computer assisted telephone interview or a web based report to determine if an AEFI had occurred whilst an AEFI in the controls was determined by a search for passive reports. The primary outcome was the AEFI detection rate in the SMS group compared to controls.ResultsWe enrolled 6,338 participants, who were equally distributed across groups and who received 11,675 vaccines. The SMS group (4,225) received 12,675 surveillance prompts with 9.8% being non-compliant and not responding. In those that responded 90% indicated that no MEFI had been experienced and 184 had a verified AEFI. 6 control subjects had a reported AEFI. The AEFI detection rate was 13 fold greater in the SMS group when compared with controls (4.3 vs 0.3%).ConclusionWe have demonstrated that the STARSS methodology improves AEFI detection. Our findings should inform the wider use of SMS-based surveillance which is particularly relevant since establishing robust and novel pharmacovigilance systems is critical to monitoring novel vaccines which includes potential COVID vaccines.     

Understanding the messages and motivation of vaccine hesitant or refusing social media influencers

BackgroundWhile anti-vaccine messages on social media have been studied for content, reach, and effectiveness, less is known about those who create and promote the messages. Online influencers, or ‘everyday people who are influential within their online social networks’, are viewed as trusted voices who are often making similar life decisions as their followers. Therefore, their experiences with and perspectives on health issues can be persuasive.MethodsWe collaborated with a formal network of online influencers to interview, using a semi-structured interview guide, vaccine hesitant influencer mothers about their views on vaccination; their process for developing health-related social media content; their motivation to promote anti-vaccine messages; and their opinions on current vaccination messaging. Prescreening ensured a diverse sample by race/ethnicity, age, education, number of children, and geographic residence. Interviews occurred by telephone, were audio recorded, and transcribed. Themes were generated independently by two coders using a deductive coding approach.ResultsWe interviewed 15 online influencer mothers from across the U.S. (average age 39 years old; all married; 13 Caucasian, 1 African American, 1 Hispanic). In some capacity, 5 of the 15 wrote about vaccination on their blog. Those who chose not to post anti-vaccine content did so for fear of alienating followers or having their platform be the site of combative discourse among readers. When researching their social media posts, the influencers did not trust mainstream sources of health information and relied on alternative sources and search engines.Implications: This exploratory study interviewed influential mothers who have the ability to spread anti-vaccine messages on social media. While most do not contribute to the anti-vaccine sentiment, understanding the motivation and practices of those that do assists the public health community in better understanding the online vaccination communication environment, leading to more effective messages to counterbalance anti-vaccine content on social media.     

Bivalent non-typhoidal Salmonella outer membrane vesicles immunized mice sera confer passive protection against gastroenteritis in a suckling mice model

Invasive non-typhoidal Salmonella (iNTS) serovars, especially Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE), cause gastroenteritis worldwide. Due to the emergence of multi-drug resistance in iNTS, a broad-spectrum vaccine is urgently needed for the prevention of iNTS infection. Currently, there is no effective licensed vaccine against iNTS available in the market. We have formulated an outer membrane vesicles (OMVs) based bivalent immunogen as a vaccine candidate to generate broad-spectrum protective immunity against both recently circulating prevalent ST and SE. We have isolated OMVs from ST and SE and formulated the immunogen by mixing both OMVs (1:1 ratio). Three doses of bivalent immunogen significantly induced humoral immune responses against lipopolysaccharides (LPSs) and outer membrane proteins (OMPs) as well as a cell-mediated immune response in adult mice. We also observed that proteins of OMVs act as an adjuvant for generation of high levels of anti-LPS antibodies through T cell activation. We then characterized the one-day old suckling mice model for both ST and SE mediated gastroenteritis and used the model for a passive protection study. In the passive protection study, we found the passive transfer of bivalent OMVs immunized sera significantly reduced ST and SE mediated colonization and gastroenteritis symptoms in the colon of suckling mice compared to non-immunized sera recipients. The overall study demonstrated that OMVs based bivalent vaccine could generate broad-spectrum immunity against prevalent iNTS mediated gastroenteritis. This study also established the suckling mice model as a suitable animal model for vaccine study against iNTS mediated gastroenteritis.     

Trends in the uptake of pediatric measles-containing vaccine in the United States: A Disneyland effect?

BackgroundThe measles outbreak that began in December 2014 at the California Disneyland theme park in the United States (U.S.) received a high amount of media attention. Media attention can influence health-related behaviors. We investigated the effect of the Disneyland outbreak on measles-containing vaccine (MCV) uptake among U.S. children.MethodsWe used 2012–2017 National Immunization Survey-Child (NIS-Child) data to examine MCV uptake among U.S. children by 19 months of age. We classified MCV coverage among birth cohorts as exposed based on age at the time of the outbreak. A difference-in-differences design with adjustment for categorical birth cohort was implemented in base models to estimate the exposure effect on the outcomes, ≥1-dose MCV coverage or age at first MCV dose, with pneumococcal conjugate vaccination as a control. Primary analyses included this model adjusted for geographic region, maternal education, race/ethnicity, household income, and insurance status, and an exposure-interaction term with maternal education. All analyses included sampling weights.ResultsThe study population represented 34,471,357 children. In base models, the Disneyland outbreak was associated with a 1.0% (95% CI: 0.2%, 1.8%) increase in ≥1-dose MCV coverage and a 6.6 (95% CI: 4.8, 8.5)-day decrease in MCV administration age. In primary analyses, the outbreak was associated with a 3.9% (95% CI: 3.1%, 4.8%) increase in ≥1-dose MCV coverage among children of college-educated mothers, and a 3.2% (95% CI: 0.6%, 5.9%) decrease among children of mothers earning less than a high school degree. Decreases in MCV administration age ranging from 5.9 (95% CI: 3.3, 8.5) to 9.1 (95% CI: 6.8, 11.4) days were observed across maternal education categories.ConclusionsThe Disneyland outbreak was associated with differential effects on MCV coverage by maternal education and decreases in MCV administration age among U.S. children. These findings may provide useful insights to inform methods to address pediatric MCV undervaccination.     

Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

Comparison of local influenza vaccine effectiveness using two methods

BackgroundIn some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases.MethodsUsing the test-negative, case-control design, data for 2017–2018 and 2018–2019 influenza seasons were collected using: 1) consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 ? aOR) × 100.ResultsResearch participants were significantly younger (P < 0.001), more often white (69% vs. 59%; P < 0.001) than non-white and less frequently enrolled through the emergency department (35% vs. 72%; P < 0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37–49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P < 0.001) and influenza A (67% research vs. 49% administrative; P < 0.001) in the emergency department.Conclusions:The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost.     

Vaccine coverage in children born to migrant mothers in Australia: A population-based cohort study

BackgroundOverall, infant immunisation coverage is currently >90% in Australia, but there are pockets of under-immunised children including children from migrant backgrounds. This study aimed to examine whether on-time vaccination coverage of diphtheria-tetanus-pertussis dose 3 (DTP3) for children born in Australia differed by mother’s region of birth and if so, what factors were associated with these differences.MethodsWe conducted a population-based cohort study using linked data on perinatal, immunisation and birth records for 2 million children born in Western Australia and New South Wales between 1996 and 2012. We assessed on-time coverage of DTP3 (vaccination from 2 weeks prior to, and up until 30 days after, the due date) in children with mothers born overseas. Logistic regression models were developed to determine factors associated with on-time coverage for each maternal region of birth and all regions combined, adjusting for a range of demographic factors. Adjusted estimates of coverage were calculated for the different regions of birth.ResultsOn-time DTP3 coverage was 76.2% in children of Australian born mothers, lower in children of mothers from Oceania (66.7%) and North America (68%), and higher in children born to mothers from South-East Asia (79.9%) and Southern Asia (79.3%). While most variables were consistently associated with lower coverage in all regions of birth, higher socioeconomic status and jurisdiction of birth showed varied results. Adjusted estimates of DTP3 coverage increased in children born to mothers from Australia (78.3%), Oceania (70.5%), Northern Africa (81.5%) and the Middle East (79.6%). DTP3 coverage decreased in children born to mothers from Europe and former USSR (74.6%), North-east Asia (75.2%), Southern Asia (76.7%), North America (65.5) and South/Central America and the Caribbean (73.2%).ConclusionsOn-time vaccination rates differed by mother’s region of birth. More research is needed to determine the main reasons for these remaining differences to improve vaccine uptake and also help guide policy and practice.     

Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques

Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.     

National decision-making for the introduction of new vaccines: A systematic review, 2010–2020

BackgroundCompeting priorities make using a transparent and evidence-based approach important when deciding to recommend new vaccines. We conducted a literature review to document the processes and frameworks for national decision-making on new vaccine introductions and explored which key features have evolved since 2010.MethodsWe searched literature published on policymaking related to vaccine introduction from March 2010 to August 2020 in six databases. We screened articles for eligibility with the following exclusion criteria: non-human or hypothetical vaccines, the sole focus on economic evaluation or decision to adopt rather than policy decision-making. We employed nine broad categories of criteria from the 2012 review for categorization and abstracted data on the country, income level, vaccine, and other relevant criteria.ResultsOf the 3808 unique references screened, 116 met eligibility criteria and were classified as: a) framework of vaccine adoption decision-making (27), b) studies that analyse empirical data on or examples of vaccine adoption decision-making (45), c) theoretical and empirical articles that provide insights into the vaccine policymaking process (44 + 17 already included in the previous categories). Commonly reported criteria for decision-making were the burden of disease; vaccine efficacy/effectiveness, safety; impact on health and non-health outcomes; economic evaluation and cost-effectiveness of alternative interventions. Programmatic and acceptability aspects were not as often considered. Most (50; 82%) of the 61 articles describing the process of vaccine introduction policymaking highlighted the role of country, regional, or global evidence-informed recommendations and a robust national governance as enabling factors for vaccine adoption.ConclusionsThe literature on vaccine adoption decision-making has expanded since 2010. We found that policymakers and expert advisory committee members (e.g., National Immunization Technical Advisory Group [NITAG]) increasingly value the interventions based on economic evaluations. The results of this review could guide discussions on evidence-informed immunization decision-making among country, sub-regional, and regional stakeholders.     

Social norms and vaccine uptake: College students’ COVID vaccination intentions,attitudes, and estimated peer norms and comparisons with influenza vaccine

BackgroundVaccination may be critical to curtailing the spread of the SARS-CoV-2 virus responsible for the COVID-19 pandemic, but herd immunity can only be realized with high vaccination coverage. There is a need to identify empirically supported strategies to increase uptake, especially among young adults as this subpopulation has shown relatively poor adherence to physical distancing guidelines. Social norms – estimates of peers’ behavior and attitudes – are robust predictors of health behaviors and norms-based intervention strategies may increase COVID vaccine uptake, once available. This study examined the extent that vaccination intentions and attitudes were associated with estimated social norms as an initial proof-of-concept test.MethodIn November of 2020, 647 undergraduate students (46.21% response rate) completed online surveys in which they reported intentions to get COVID and influenza vaccines, perceived importance of these vaccines for young adults, and estimated social norms regarding peers’ vaccination behaviors and attitudes.ResultsStudents reported significantly greater intentions to get a COVID vaccine (91.64%) than an influenza vaccine (76.04%), and perceived COVID vaccination as significantly more important than influenza vaccination. The sample generally held strong intentions to receive a COVID vaccine and thought that doing so was of high importance, but participants, on average, perceived that other young adults would be less likely to be vaccinated and would not think vaccination was as important. Multiple regression models indicated that estimated social norms were positively associated with participants’ own intentions and perceived importance of getting a COVID vaccine.ConclusionsThese significant associations highlight the potential value in developing and testing norms-based intervention strategies, such as personalized normative feedback, to improve uptake of forthcoming COVID vaccines among young adults.