A behavior change model to address caregiver hesitancy around COVID-19 vaccination in pediatrics

IntroductionMany families express hesitancy around immunizing their children against COVID-19. We sought to better understand the perspectives of vaccine hesitant caregivers, and develop targeted recommendations for health care workers and policymakers to engage in more effective vaccine discussions.MethodsWe conducted semi-structured telephone interviews with 23 caregivers recruited from a pediatric infectious diseases clinic, including a subset of patients referred to discuss vaccine hesitancy. Thematic analysis of the interviews identified themes that were mapped using behavior change models to identify perceived barriers and facilitators towards COVID-19 immunization.ResultsBarriers and facilitators were mapped to the WHO (World Health Organization) 3C’s (confidence, complacency, convenience) model of vaccine hesitancy as well as the COM-B (capability, opportunity, motivation) behavior change model. Barriers included mistrust in authorities, misperception of the risk of COVID-19 in children, and perceived health contraindications and negative previous vaccine experiences. Facilitators included positive relationships with healthcare workers, the promise of a “return to normal”, and societal pressures to immunize.ConclusionsEfforts to increase vaccine uptake in the pediatric population must target specific barriers and facilitators to immunization expressed by caregivers. To address these concerns, we suggest: 1. Educating hesitant caregivers by highlighting the long-term pandemic effects on children and the threat of COVID-19 to children’s health, 2. Building on the trust caregivers have in healthcare workers by involving frontline workers in public health policy, and 3. Harnessing the power of peer pressure by mobilization of societal pressures and establishing COVID-19 vaccination as the norm in children.     

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE).MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals.ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01).ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.     

Disparities in COVID-19 vaccine uptake among health care workers

BackgroundCOVID-19 vaccine uptake by healthcare workers (HCWs) is critical to protect HCWs, the patients they care for, and the healthcare infrastructure. Our study aims to examine the actual COVID-19 vaccination rate among HCWs and identify risk factors associated with vaccine nonacceptance.Study Design and MethodsA retrospective analysis of COVID-19 vaccinations for HCWs at a large multi-site US academic medical center from 12/18/2020 through 05/04/2021. Comparisons between groups were performed using unpaired student t-test for continuous variables and the chi-square test for categorical variables. A logistic regression analysis was used to assess the associations between vaccine uptake and risk factor(s).ResultsOf the 65,270 HCWs included in our analysis, the overall vaccination rate was 78.6%. Male gender, older age, White and Asian race, and direct patient care were associated with higher vaccination rates (P <.0001). Significant differences were observed between different job categories. Physicians and advanced practice staff, and healthcare professionals were more likely to be vaccinated than nurses and support staff.ConclusionsOur data demonstrated higher initial vaccination rates among HCWs than the general population national average during the study period. We observed significant disparities among different high-risk HCWs groups, especially among different job categories, black HCWs and younger HCWs despite their high risk of contracting the infection. Interventions to address lower vaccination rate and vaccine hesitancy should be built with these disparities and differences in mind to create more targeted interventions.     

Pre-implementation evaluation for an HPV vaccine provider communication intervention among primary care clinics

ObjectivesInterventions to improve health care provider communication about HPV vaccination can increase vaccine acceptance. Our objectives were to (1) identify clinics in locations with high HPV-associated cancer and low HPV-vaccination rates that would potentially benefit from dissemination of a proposed HPV Provider Communication intervention and (2) use qualitative interviews and a dissemination and implementation framework to assess readiness for change and fit of the HPV Provider Communication intervention to the context of these clinics.MethodsLocal HPV-associated cancer and HPV vaccination rates were assigned to Practice-Based Research Network clinics using data from the Colorado Central Cancer Registry, the Colorado Immunization Information System, and the American Community Survey. Staff from 38 clinics located in areas with high numbers of adolescents not up-to-date for HPV vaccine and high rates of HPV-associated cancers were recruited for qualitative interviews. Interview questions used the Promoting Action on Research Implementation in Health Services (PARIHS) conceptual framework and addressed the proposed intervention, current vaccination practices and prior quality improvement (QI) experience.ResultsTwenty-seven interviews were completed with clinicians, clinic managers, and other staff across 17 clinics (9 pediatric, 5 family medicine, 3 public/school-based health). Most clinics had some prior QI experience and there were few thematic differences between sites with more or less foundation for QI/immunization work. Participants were motivated to improve the health of their patients and valued both guidelines and local experience as important evidence to consider adopting an intervention. Interviewees were more interested in implementing the proposed intervention if it aligned with existing priorities and fit within clinic workflows. Facilitation needs included adequate time and external facilitation support for data tracking and analysis.ConclusionsQualitative interviews to understand clinic context and fit of an HPV Provider Communication intervention can inform implementation in settings with the highest potential for clinical impact.     

Strategic silences,eroded trust: The impact of divergent COVID-19 vaccine sentiments on healthcare workers' relations with peers and patients

BackgroundPolarized debates about Covid-19 vaccination and vaccine mandates for healthcare workers (HCWs) challenge Belgian HCWs ability to discuss Covid-19 vaccine sentiments with peers and patients. Although studies have identified drivers of HCWs vaccine hesitancy, they do not include effects of workplace interactions and have not addressed consequences beyond vaccine coverage.MethodsInterviews and focus group discussions with 74 HCWs practicing in Belgium addressed Covid-19 vaccine sentiments and experiences of discussing vaccination with peers and patients.ResultsMost participating HCWs reported difficulties discussing Covid-19 vaccination with peers and patients. Unvaccinated HCWs often feared that expressing their vaccine sentiments might upset patients or peers and that they would be suspended. Consequently, they used social cues to evaluate others’ openness to vaccine-skeptical discourses and avoided discussing vaccines. Surprisingly, some vaccine-confident HCWs hid their vaccine sentiments to avoid peer and patient conflicts. Both vaccinated and unvaccinated HCWs observed that unvaccinated patients occasionally received suboptimal care. Suboptimal care was central in unvaccinated HCW unwillingness to express their vaccine sentiments to peers. Both vaccinated and unvaccinated HCWs described loss of trust and ruptured social relations with peers and patients holding divergent vaccine sentiments.DiscussionBelgian HCW perceived Covid-19 vaccines as a risky discussion topic and engaged in “strategic silences” around vaccination to maintain functional work relationships and employment in health institutions. Loss of trust between HCW and peers or patients, along with suboptimal patient care based on vaccination status, threaten to weaken Belgium’s, and by implication, other health systems, and to catalyze preventable disease outbreaks.     

Vaccine administration error rates at a large academic medical center and its affiliated clinics – Familiarity matters

ObjectiveThe purpose of this study was to track and describe the absolute number of vaccine administration errors and corresponding error rates over time and by patient age and vaccine type.MethodsTotal vaccines administered to patients aged 0 through 19 years 364 days from 1/1/2006 through 12/31/2017 at a large academic health system in the Midwest United States with primary, specialty and school-based clinics, and a pediatric hospital were obtained from an electronic medical record. Vaccine administration errors over the same time period for the same patient criteria were analyzed from the health system’s incident reporting system and further compared to the frequency of all incidents reported. Vaccine administration error rates were calculated. Data were analyzed by patient age, vaccine type and year administered.ResultsOf the 1,431,206 vaccine doses given, 552 vaccine administration errors were identified (0.04%). The highest error rates occurred in children aged 2, 3, and 19 years. Vaccine types with the highest error rate were Td, rabies and pneumococcal polysaccharide vaccines. Overall vaccine doses given and errors reported increased over the study period. However, the increase was disproportionate, resulting in an increase in the error rate initially followed by a stabilization at the end of the study period.ConclusionsVaccine administration errors are uncommon. The error rate appears to be stabilizing. Errors are more likely at ages when vaccines are not commonly given, with vaccines that have age-specific dosing and with vaccines that are given less often. This suggests more safety checks are needed for vaccines that are rarely used or given off-schedule, and manufacturers should avoid vaccines with age-specific dosing.     

Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study

BackgroundRotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016.MethodsA national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area.ResultsSignificant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847).ConclusionsIn New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.     

Billing and payment of commercial and Medicaid health plan adult vaccination claims in Michigan since the Affordable Care Act

BackgroundProvider concern regarding insurance non-payment for vaccines is a common barrier to provision of adult immunizations. We examined current adult vaccination billing and payment associated with two managed care populations to identify reasons for non-payment of immunization insurance claims.MethodsWe assessed administrative data from 2014 to 2015 from Blue Care Network of Michigan, a nonprofit health maintenance organization, and Blue Cross Complete of Michigan, a Medicaid managed care plan, to determine rates of and reasons for non-payment of adult vaccination claims across patient-care settings, insurance plans, and vaccine types. We compared commercial and Medicaid payment rates to Medicare payment rates and examined patient cost sharing.ResultsPharmacy-submitted claims for adult vaccine doses were almost always paid (commercial 98.5%; Medicaid 100%). As the physician office accounted for the clear majority (79% commercial; 69% Medicaid) of medical (non-pharmacy) vaccination services, we limited further analyses of both commercial and Medicaid medical claims to the physician office setting. In the physician office setting, rates of payment were high with commercial rates of payment (97.9%) greater than Medicaid rates (91.6%). Reasons for non-payment varied, but generally related to the complexity of adult vaccine recommendations (patient diagnosis does not match recommendations) or insurance coverage (complex contracts, multiple insurance payers). Vaccine administration services were also generally paid. Commercial health plan payments were greater for both vaccine dose and vaccine administration than Medicare payments; Medicaid paid a higher amount for the vaccine dose, but less for vaccine administration than Medicare. Patients generally had very low (commercial) or no (Medicaid) cost-sharing for vaccination.ConclusionsAdult vaccine dose claims were usually paid. Medicaid generally had higher rates of non-payment than commercial insurance.     

Pneumococcal vaccination in older adults: An initial analysis of social determinants of health and vaccine uptake

ObjectivesTo examine the potential influence of social determinants of health on pneumococcal vaccination in older American adults.MethodsThis study used nationwide, US Medicare claims data from 2013 to 2016 to assess uptake of pneumococcal vaccination among adults in the first year after turning age 65. Patients were followed from the point of being 65 years of age and initially enrolled in traditional fee-for-service Medicare or a Medicare Advantage plan through the subsequent year and observed for pneumococcal vaccination in outpatient clinics and pharmacies. Publicly-available data on select social determinants of health were incorporated and guided by the World Health Organization vaccine hesitancy matrix. Logistic regression determined predictors of vaccination while controlling clinical and demographic characteristics.ResultsA total of 307,488 and 74,995 adults aged 65 years were identified from Medicare Advantage and Medicare fee-for-service claims, respectively, and 21.1% of Medicare Advantage and 38.2% of Medicare fee-for-service patients received a pneumococcal vaccine in the first year after turning 65. Those residing in urban areas had a higher likelihood of pneumococcal vaccination in both the Medicare Advantage (OR: 1.31; 95% CI: 1.267–1.344) and Medicare fee-for-service (OR: 1.53; 95% CI: 1.450–1.615) cohorts. Additionally, residing in areas of higher health literacy or communities with more democratic voters were consistently associated with a higher odds of pneumococcal vaccination regardless of Medicare type. Results also pointed to a synergistic relationship between receiving the influenza vaccine and also being vaccinated against pneumococcal disease.ConclusionSocial determinants of health, including local health literacy, poverty, residing in more liberal areas, and access to information, may be influencing the pneumococcal vaccine-related decisions of older adults. However, additional factors associated with the vaccine hesitancy matrix and more granular data (e.g., zip code-level) are needed to fully determine the impact in this and other vaccines recommended in older adults.     

Using economic and social data to improve veterinary vaccine development: Learning lessons from human vaccinology

The drivers of vaccine development are many and varied. They include, for example, recognition of the burden of a vaccine-targeted disease, prioritisation of the multiple problems associated with a disease, consideration of the differing socio-economic situations under which vaccines are used, the influence of advocacy groups, and assessment of the feasibility of large-scale vaccine manufacture and distribution. In the field of human health, data-driven development of vaccines is becoming increasingly common through the availability of reliable information on the Global Burden of Disease (GBD) and stringent evaluations of vaccination programmes utilising empirical data on costing and effectiveness, and standardised cost-effectiveness thresholds. The data generated from such analyses allow policymakers, implementing partners, industries and researchers to make decisions based on the best, and most contextually relevant, available evidence. In this paper, we wish to explore the current use of economic and social data for the development of veterinary vaccines. Through comparison with the development of human vaccines, we will look for opportunities in animal health sciences to better integrate socio-economic data and analyses into the process of veterinary vaccine selection, development, and field implementation. We believe that more robust animal health impact assessments could add value to veterinary vaccine development by improving resource allocation and animal disease management.     

Defining the multiplicity and time of infection for the production of Zaire Ebola virus-like particles in the insect cell-baculovirus expression system

The Ebola virus disease is a public health challenge. To date, the only available treatments are medical support or the emergency administration of experimental drugs. The absence of licensed vaccines against Ebola virus impedes the prevention of infection. Vaccines based on recombinant virus-like particles (VLP) are a promising alternative. The Zaire Ebola virus serotype (ZEBOV) is the most aggressive with the highest mortality rates. Production of ZEBOV-VLP has been accomplished in mammalian and insect cells by the recombinant coexpression of three structural proteins, the glycoprotein (GP), the matrix structural protein VP40, and the nucleocapsid protein (NP). However, specific conditions to manipulate protein concentrations and improve assembly into VLP have not been determined to date. Here, we used a design of experiments (DoE) approach to determine the best MOI and TOI for three recombinant baculoviruses: bac-GP, bac-VP40 and bac-NP, each coding for one of the main structural proteins of ZEBOV. We identified two conditions where the simultaneous expression of the three recombinant proteins was observed. Interestingly, a temporal and stoichiometric interplay between the three structural proteins was observed. VP40 was required for the correct assembly of ZEBOV-VLP. High NP concentrations reduced the accumulation of GP, which has been reported to be necessary for inducing a protective immune response. Electron microscopy showed that the ZEBOV-VLP produced were morphologically similar to the native virus micrographs previously reported in the literature. A strategy for producing ZEBOV in insect cells, which consists in using a high MOI of bac-VP40 and bac-GP, and reducing expression of NP, either by delaying infection or reducing the MOI of bac-NP, was the most adequate for the production of VLP.     

Vaccination against cocaine using a modifiable dendrimer nanoparticle platform

Pharmacological therapies for the treatment of cocaine addiction have had disappointing efficacy, and the lack of recent developments in the clinical care of cocaine-addicted patients indicates a need for novel treatment strategies. Recent studies have shown that vaccination against cocaine to elicit production of antibodies that reduce concentrations of free drug in the blood is a promising method to protect against the effects of cocaine and reduce rates of relapse. However, the poorly immunogenic nature of cocaine remains a major hurdle to active immunization. Therefore, we hypothesized that strategies to increase targeted exposure of cocaine to the immune system may produce a more effective vaccine. To specifically direct an immune response against cocaine, in the present study we have conjugated a cocaine analog to a dendrimer-based nanoparticle carrier with MHC II-binding moieties that previously has been shown to activate antigen-presenting cells necessary for antibody production. This strategy produced a rapid, prolonged, and high affinity anti-cocaine antibody response without the need for an adjuvant. Surprisingly, additional evaluation using multiple adjuvant formulations in two strains of inbred mice found adjuvants were either functionally redundant or deleterious in the vaccination against cocaine using this platform. The use of conditioned place preference in rats after administration of this vaccine provided proof of concept for the ability of this vaccine to diminish cocaine reward. Together these data demonstrate the intrinsic efficacy of an immune-targeting dendrimer-based cocaine vaccine, with a vast potential for design of future vaccines against other poorly immunogenic antigens by substitution of the conjugated cargo.     

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.     

Preclinical safety assessment of a combined vaccine against Hepatitis a virus and enterovirus 71

Since 2007, Hepatitis A (HAV) vaccination has been a part of the National Immunization Program of China. Recognizing enterovirus 71 (EV71) as the most important pathogen in severe hand, foot and mouth disease, an inactivated EV71 vaccine was successfully marketed in 2015. Based on the concept of one vaccine preventing two diseases and owing to similarities in vaccine preparation and the overlap of the eligible population, a combination of the inactivated HAV vaccine and inactivated EV71 vaccine is theoretically feasible and desirable. However, the optimal vaccination schedule for this combination vaccine has yet to be optimized. Use of this combined vaccine would not only decrease the number of vaccinations, but also lower associated cost. This study aimed to investigate the toxicity and adverse reactions of the combined HAV-EV71 vaccine under Good Laboratory Practice conditions to provide a reference for clinical studies/applications in the future. CD®(Sprague Dawley) IGS rats were employed for single-dose toxicity testing using a high dose, and repeated-dose toxicity testing using high, as well as low doses. Animals that received only a single dose showed no obvious clinical symptoms nor abnormal body weight, and no significant gross pathological change at the experimental endpoint at necropsy. In the rats injected with three doses, phagocytosis of basophilic granules by macrophages was observed in the inguinal, mesenteric, and local lymph nodes, besides irritation at the administration site. At 56 days after the last dose, no significant histopathological change was observed in the lymph nodes, and local irritation gradually faded. Further, systematic allergy testing was performed in guinea pigs. After systemic sensitization and challenge with the HAV-EV71 vaccine, animals showed normal weight gain and no allergic reactions. This study, therefore, confirmed a good safety profile of the inactivated HAV and EV71 combined vaccine.     

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.     

Empowering Health Workers to Build Public Trust in Vaccination: Experience from the International Pediatric Association’s Online Vaccine Trust Course, 2020–2021

BackgroundThe quality of interactions between health workers (HWs) and caregivers is key in vaccine acceptance. To optimize this, HWs need knowledge about best vaccine communication practices in person and on social media. Most pre-service curricula do not include such approaches. COVID-19 necessitated the International Pediatric Association (IPA) to shift from in-person train the trainer workshops to developing an online Vaccine Trust Course to address these gaps.MethodThe seven-module, 8-hour Vaccine Trust Course was offered online in seven languages and promoted globally. Course outcomes for participants between September 1, 2020 and September 30, 2021 were assessed using enrollment, participation, and completion data; pre-and post-training surveys of attitudes, knowledge, and practice skills; and follow-up practice surveys 3 months post course completion.ResultsOf the 4,926 participants across 137 countries who registered; 2,381 (48.3 %) started the course, with 1,217 (51.1 %) completing. The majority were 25 – 39 years (57 %), female (57 %), and in pediatrics (70 %); 31 % came from India. 62 % of completers rated course structure/design as excellent, 36 % as good. Over 80 % rated the content as the most valuable aspect. Three months post training, 61 % HWs reported increased empathy towards caregivers, confidence while counseling and increased vaccine acceptance amongst their patients. 21 % identified the course as the only factor in these positive changes.ConclusionShifting from face-to-face to online training due to the COVID-19 pandemic helped increase the global reach of HWs course engagement and uptake. Trained HWs reported increased empathy towards caregivers and confidence while counseling and increased patient vaccine acceptance.     

A place for neutrophils in the beneficial pathogen-agnostic effects of the BCG vaccine

The BCG vaccine has long been recognized for reducing the risk to suffer from infectious diseases unrelated to its target disease, tuberculosis. Evidence from human trials demonstrate substantial reductions in all-cause mortality, especially in the first week of life. Observational studies have identified an association between BCG vaccination and reduced risk of respiratory infectious disease and clinical malaria later in childhood. The mechanistic basis for these pathogen-agnostic benefits, also known as beneficial non-specific effects (NSE) of BCG have been attributed to trained immunity, or epigenetic reprogramming of hematopoietic cells that give rise to innate immune cells responding more efficiently to a broad range of pathogens. Furthermore, within trained immunity, the focus so far has been on enhanced monocyte function. However, polymorphonuclear cells, namely neutrophils, are not only major constituents of the hematopoietic compartment but functionally as well as numerically represent a prominent component of the immune system. The beneficial NSEs of the BCG vaccine on newborn sepsis was recently demonstrated to be driven by a BCG-mediated numeric increase of neutrophils (emergency granulopoiesis (EG)). And experimental evidence in animal models suggest that BCG can modulate neutrophil function as well. Together, these findings suggest that neutrophils are crucial to at least the immediate beneficial NSE of the BCG vaccine. Efforts to uncover the full gamut of mechanisms underpinning the broad beneficial effects of BCG should therefore include neutrophils at the forefront.