HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines.

Pandemic's influence on parents' attitudes and behaviors toward meningococcal vaccination.

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents' attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0-4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11-18 years from US. Data collection took place 19 January-16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks.

What is the context? Invasive meningococcal disease (IMD) is an uncommon infection that can lead to permanent disabilities and even death.Meningitis vaccination can prevent IMDs caused by Neisseria meningitidis.Vaccination rates have declined during the coronavirus (COVID-19) pandemic.What is new? We collected opinion of parents from the UK, France, Germany, Italy, Brazil, Argentina, Australia, and the US, to understand their attitudes and behaviors toward meningitis vaccination during the COVID-19 pandemic.Results were reviewed by health care professional experts as well as by patient authors (IMD survivors).Most (83%) of the 4,962 parents believed that it is important for their child to continue receiving recommended vaccines during the COVID-19 pandemic.Half of the scheduled appointments for meningitis vaccination were canceled or delayed during the COVID-19 pandemic, mainly due to lockdown regulations and fear of catching COVID-19.Twenty-one percent of the parents who had their child's meningitis vaccination appointment canceled, did not intend to reschedule it.What is the impact? It is crucial that clear information is communicated by health care authorities and practitioners about the availability of vaccination during pandemic and the safety precautions that are taken.Collected opinions emphasize the importance of continuing vaccinations against infectious diseases during a pandemic.

Influence of Digital Intervention Messaging on Influenza Vaccination Rates Among Adults With Cardiovascular Disease in the United States: Decentralized Randomized Controlled Trial.

BACKGROUND: Seasonal influenza affects 5% to 15% of Americans annually, resulting in preventable deaths and substantial economic impact. Influenza infection is particularly dangerous for people with cardiovascular disease, who therefore represent a priority group for vaccination campaigns. OBJECTIVE: We aimed to assess the effects of digital intervention messaging on self-reported rates of seasonal influenza vaccination. METHODS: This was a randomized, controlled, single-blind, and decentralized trial conducted at individual locations throughout the United States over the 2020-2021 influenza season. Adults with self-reported cardiovascular disease who were members of the Achievement mobile platform were randomized to receive or not receive a series of 6 patient-centered digital intervention messages promoting influenza vaccination. The primary end point was the between-group difference in self-reported vaccination rates at 6 months after randomization. Secondary outcomes included the levels of engagement with the messages and the relationship between vaccination rates and engagement with the messages. Subgroup analyses examined variation in intervention effects by race. Controlling for randomization group, we examined the impact of other predictors of vaccination status, including cardiovascular condition type, vaccine drivers or barriers, and vaccine knowledge. RESULTS: Of the 49,138 randomized participants, responses on the primary end point were available for 11,237 (22.87%; 5575 in the intervention group and 5662 in the control group) participants. The vaccination rate was significantly higher in the intervention group (3418/5575, 61.31%) than the control group (3355/5662, 59.25%; relative risk 1.03, 95% CI 1.004-1.066; P=.03). Participants who were older, more educated, and White or Asian were more likely to report being vaccinated. The intervention was effective among White participants (P=.004) but not among people of color (P=.42). The vaccination rate was 13 percentage points higher among participants who completed all 6 intervention messages versus none, and at least 2 completed messages appeared to be needed for effectiveness. Participants who reported a diagnosis of COVID-19 were more likely to be vaccinated for influenza regardless of treatment assignment. CONCLUSIONS: This personalized, evidence-based digital intervention was effective in increasing vaccination rates in this population of high-risk people with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584645; https://clinicaltrials.gov/ct2/show/NCT04584645.

Lessons learned from 2 years of influenza vaccinations in the UK and USA during the COVID-19 pandemic as respiratory viruses return.

During the COVID-19 pandemic, immunization programs for other respiratory infections, notably influenza continued worldwide but attracted less public or political attention than COVID-19 vaccinations. Due to non-pharmaceutical intervention measures the global influenza burden decreased substantially; but with lifting of restrictions a rebound in other respiratory virus pathogens is both plausible and likely. This article discusses lessons identified from the UK and USA, and provides recommendations for future influenza vaccination programs in light of emerging data from the southern hemisphere and the need for harmonization with COVID-19 vaccination, focusing on operational delivery and messaging to practitioners and the public.

Vaccination in pregnancy against pertussis and seasonal influenza: key learnings and components from high-performing vaccine programmes in three countries: the United Kingdom, the United States and Spain.

BACKGROUND: Pertussis and seasonal influenza are responsible for significant maternal, neonatal, and infant morbidity and mortality, but vaccine coverage rates (VCR) for both pertussis (administered as a tetanus, diphtheria, acellular pertussis [Tdap] vaccination) and seasonal influenza in pregnancy remain generally low. Only a small number of countries, including Spain, the United Kingdom (UK), and the United States (US), have high Tdap and seasonal influenza VCRs in pregnancy. The purpose of this study was to identify the key factors that contributed to the high VCRs observed in these countries. METHODS: The experience from both Tdap and seasonal influenza vaccination programmes during pregnancy were documented in Spain, the UK, and the US using a three-step approach. A literature review yielded 157 publications, and a further 117 documents were selected through desk research. A published five-pillar VCR framework for influenza was amended to evaluate the specific contributing factors leading to high Tdap and seasonal influenza VCRs among pregnant women. RESULTS: The analysis identified components that contributed to higher VCR in pregnant women across three different healthcare systems in Spain, UK, and US. The combination of several key interventions in each country led to a rapid increase in VCR that reached near-optimal levels (i.e. 75% for seasonal influenza) within a few years. As well as inclusion in national immunisation programme and vaccine reimbursement, key components that were identified included the mobilisation of health authorities, prenatal care Healthcare Professionals (HCP) and scientific societies, the inclusion of vaccination in antenatal medical guidance, the provision of educational material to HCPs, and a strong disease awareness driven by recent pertussis outbreaks in each country. CONCLUSIONS: Although there is no simple, universal solution to improving sub-optimal VCRs, the list of components identified in this study from three countries with high-performing Tdap and seasonal influenza vaccination programmes provides a basis for public health and medical stakeholders in other countries to define strategies to successfully implement national vaccination programmes for pregnant women.

Key policy and programmatic factors to improve influenza vaccination rates based on the experience from four high-performing countries.

BACKGROUND: Many countries consistently fail to achieve the target influenza vaccine coverage rate (VCR) of 75% for populations at risk of complications, recommended by the World Health Organization and European Council. We aimed to identify factors for achieving a high VCR in the scope of four benchmark countries with high influenza VCRs: Australia, Canada, UK and USA. METHODS: Publicly available evidence was first reviewed at a global level and then for each of the four countries. Semi-structured interviews were then conducted with stakeholders meeting predefined criteria. Descriptive cluster analyses were performed to identify key factors and pillars for establishing and maintaining high VCRs. RESULTS: No single factor led to a high VCR, and each benchmark country used a different combination of tailored approaches to achieve a high vaccine coverage. In each country, specific triggers were important to stimulate changes that led to improved vaccine coverage. A total of 42 key factors for a successful influenza vaccination programme were identified and clustered into five pillars: (1) Health Authority accountability and strengths of the influenza programme, (2) facilitated access to vaccination, (3) healthcare professional accountability and engagement, (4) awareness of the burden and severity of disease and (5) belief in influenza vaccination benefit. Each benchmark country has implemented multiple factors from each pillar. CONCLUSION: A wide range of factors were identified from an evaluation of four high-performing benchmark countries, classified into five pillars, thus providing a basis for countries with lower VCRs to tailor their own particular solutions to improve their influenza VCR.

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

Pharmacy-based interventions to increase vaccine uptake: report of a multidisciplinary stakeholders meeting.

BACKGROUND: Despite the existence of efficacious vaccines, the burden of vaccine-preventable diseases remains high and the potential health benefits of paediatric, adolescent and adult vaccination are not being achieved due to suboptimal vaccine coverage rates. Based on emerging evidence that pharmacy-based vaccine interventions are feasible and effective, the European Interdisciplinary Council for Ageing (EICA) brought together stakeholders from the medical and pharmacy professions, the pharmaceutical industry, patient/ageing organisations and health authorities to consider the potential for pharmacy-based interventions to increase vaccine uptake. We report here the proceedings of this 3-day meeting held in March 2018 in San Servolo island, Venice, Italy, focussing firstly on examples from countries that have introduced pharmacy-based vaccination programmes, and secondly, listing the barriers and solutions proposed by the discussion groups. CONCLUSIONS: A range of barriers to vaccine uptake have been identified, affecting all target groups, and in various countries and healthcare settings. Ease of accessibility is a potentially modifiable determinant in vaccine uptake, and thus, improving the diversity of settings where vaccines can be provided to adults, for example by enabling community pharmacists to vaccinate, may increase the number of available opportunities for vaccination.

Cognitive Improvements in Children with Prader-Willi Syndrome Following Pitolisant Treatment-Patient Reports.

While children with Prader-Willi Syndrome (PWS), a rare genetic disease with an incidence of 1:15,000, typically present with hypotonia and hyperphagia, their lives are made more difficult by an ever-present sleepiness as well as multiple neuro-cognitive dysfunctions, including cognitive defects. We describe a case series of 3 children who were treated with the histamine 3 receptor inverse agonist pitolisant. While this first-in-class inverse agonist is approved for another orphan disease (i.e., narcolepsy with or without cataplexy), we have observed that pediatric patients with PWS prescribed pitolisant demonstrate decreased daytime sleepiness and improved cognition, as evidenced by increased processing speed and improved mental clarity. Pitolisant may represent a novel therapeutic option that might relieve substantial PWS disease burden, including cognitive disability, excessive daytime sleepiness, and poor-quality nighttime sleep.

A pathway to developing and testing quality measures aimed at improving adult vaccination rates in the United States.

Despite recommendations for vaccinating adults and widespread availability of immunization services (e.g., pharmacy venues, workplace wellness clinics), vaccination rates in the United States remain low. The U.S. National Adult Immunization Plan identified the development of quality measures as a priority and key strategy to address low adult vaccination coverage rates. The use of quality measures can provide incentives for increased utilization of preventive services. To address the lack of adult immunization measures, the National Adult and Influenza Immunization Summit, a coalition of adult immunization partners led by the Immunization Action Coalition, Centers for Disease Control and Prevention, and National Vaccine Program Office, spearheaded efforts to (1) identify gaps and priorities in adult immunization quality performance measurement; (2) explore feasibility of data collection on adult immunizations through pilot testing and engaging stakeholders; and (3) develop and test quality measure specifications. This paper outlines the process by which a public-private partnership drove the development of two adult immunization performance measures-an adult immunization status measure for influenza, tetanus and diphtheria (Td) and/or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), herpes zoster and pneumococcal vaccines, and a prenatal immunization status measure for influenza and Tdap vaccinations in pregnant women. These measures have recently been added to the 2019 Healthcare Effectiveness Data and Information Set (HEDIS®), a widely used set of performance measures reportable by private health plans.

Dissemination and implementation of the ICAMP.

The current rate of immunizations for older adults does not meet the immunization goals for Healthy People 2020. Using a Social Ecological Model and Social Cognitive Theory, the purpose of this study was to disseminate and implement the Immunization Champions, Advocates and Mentors Program (ICAMP) into a variety of health care settings. This study used a single group pre-/post-test design. Champions were recruited nationally. Five geographically diverse face-to-face meetings were held to train health care providers to be ICAMP immunization champions. Dissemination and implementation of ICAMP was evaluated using the Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model. Participants were surveyed at baseline for descriptive information and were asked to gather immunization rates for at least one particular vaccine and provide follow-up data on progress toward goal achievement. A total of 212 champions from 82 settings participated in ICAMP. The majority were nurses (111/212, 52%). With regard to reach, we obtained 212 applications from individuals in a variety of settings interested in becoming champions. With regard to effectiveness, the majority of the champions (n = 178/212, 84%) used ICAMP material, 88% (n = 186/212) made changes related to immunization processes within their setting, and all reported that immunization practices improved. The majority used the toolkit materials up through 60 days following ICAMP. Sustained use of materials after the 60-day follow-up was less evident. ICAMP was implemented as intended and was effective in changing processes around immunizations. Ongoing work is needed to determine whether ICAMP improves immunization rates.

A review of the key factors to improve adult immunization coverage rates: What can the clinician do?

Adult immunization coverage rates remain low in the United States and internationally, despite obvious benefits to vaccinating and maintaining a well-vaccinated adult population. Broad policy changes are required to identify and address gaps in financing, in immunization infrastructure, and patient and provider awareness and knowledge to improve the protection of our adult and aging population from vaccine-preventable diseases. There is good evidence that efforts are now underway both within the United States and across the world to advance these policy changes. There are successful interventions that have been demonstrated to improve rates in the pediatric population that must be translated into the adult patient population to meet the critical gaps that remain at the interface of the delivery of vaccinations to adults. Improvements in overall policy will only increase adult immunization coverage rates if interventions are adapted and implemented for adult patients. Often, these same interventions will be applicable to adolescent patients as well. These interventions have been reviewed by the United States Preventive Services Task Force and recommended interventions fall into three categories: (1) Enhancing Patient Access to Vaccination; (2) Improving community/patient demand; and (3) Provider- and healthcare system-directed interventions. Specific interventions that have been demonstrated successful for the adult population include interventions such as reducing patient out-of-pocket costs for vaccinations, patient or family incentive rewards, and implementation of quality measures and quality improvement interventions. Addressing the poor performance in adult immunizations requires approaches predicated on not repeating previous efforts and will require innovative thinking to integrate multiple interventions that have been successful separately, into a holistic approach to support and automate immunization assessment, recommendation, and administration. This can then lead to increased valuation of adult and adolescent immunizations within the priorities of a healthcare system, and improvements in clinic efficiency within a practice.

Moving the needle on nursing staff influenza vaccination in long-term care: Results of an evidence-based intervention.

PURPOSE: Influenza vaccination rates among healthcare providers (HCPs) in long-term care facilities (LTCFs) are commonly below the Healthy People 2020 goal of 90%. This study was conducted to develop and evaluate an intervention program designed to increase influenza uptake among HCPs in LTCFs. METHODS: This study was conducted in four Midwestern LTCFs. Baseline interviews, surveys, and administrative data analysis were performed following the 2013-2014 influenza season. Interventions implemented during the 2014-2015 season were based on the health belief and ecological models and included goal-setting worksheets, policy development, educational programs, kick-off events, incentives, a vaccination tracking roster, and facility-wide communication about vaccine uptake among HCPs. Outcomes were evaluated in 2015. RESULTS: At baseline, 50% of 726 nursing staff employed during the 2013-2014 influenza season had documented receipt of influenza vaccine (Site A: 34%; Site B: 5%; Site C: 75%; Site D: 62%), and 31% of 347 survey respondents reported absenteeism due to respiratory illness. At follow-up, 85% of HCPs had documented receipt of influenza vaccine (p<0.01) and 19% of 323 survey respondents reported absenteeism due to respiratory illness (p<0.01). Vaccination rates among respondents' family members increased from 31% at baseline to 44% post-intervention (p<0.01). Reasons for declining vaccination did not change following exposure to educational programs, but HCPs were more likely to recommend vaccination to others after program implementation. CONCLUSIONS: Vaccination rates among long-term care HCPs and their family members increased significantly and HCP absenteeism decreased after the implementation of multifaceted interventions based on an ecological model. The findings suggest that major increases in HCP vaccination can be achieved in LTCFs. More research is needed to evaluate the impact of increased HCP vaccination on the health and productivity of LTCF employees, their family members, and residents.

A Novel Dynamic Model for Health Economic Analysis of Influenza Vaccination in the Elderly.

INTRODUCTION: New vaccines are being developed to improve the efficacy of seasonal influenza immunization in elderly persons aged ≥65 years. These products require clinical and economic evaluation to aid policy decisions. METHODS: To address this need, a two-part model has been developed, which we have applied to examine the potential clinical and economic impact of vaccinating elderly persons with adjuvanted trivalent inactivated influenza vaccine (aTIV) relative to conventional trivalent (TIV) and quadrivalent (QIV) vaccines. We compared outcomes in the US population for (1) aTIV in persons aged ≥65 years and QIV in all other age cohorts; (2) QIV in all cohorts; (3) TIV in all cohorts. Low, average, and high intensity seasons with low, average, and high vaccine match scenarios were compared. Probabilistic sensitivity analysis was conducted within each discrete scenario to explore the impact of variation in model inputs on potential outcomes. RESULTS: Assuming current vaccination coverage rates in the US population with (a) 25% better efficacy of adjuvanted versus non-adjuvanted vaccine against any strain and (b) 35% better efficacy of non-adjuvanted vaccine against matched B versus mismatched B strains, use of aTIV in persons aged ≥65 years and QIV in persons <65 years could reduce influenza cases by 11,166-1,329,200, hospitalizations by 1365-43,674, and deaths by 421-11,320 versus use of QIV in all cohorts. These outcomes are reflected in a corresponding increase in quality-adjusted life-years (QALYs) of 3003-94,084. If the prevalence of mismatched influenza B was >54.5% of all circulating strains, use of QIV in all cohorts would offset the clinical benefits of aTIV. Elderly aTIV or QIV vaccination was associated with improved outcomes over non-adjuvanted TIV in many of the scenarios, particularly in low match seasons of any intensity. Total cost savings (including direct and indirect healthcare costs plus productivity impacts) with aTIV in the elderly versus QIV in the whole population ranged from $27 million (low intensity, low match) to $934 million (high intensity, high match). Univariate sensitivity analysis of relative vaccine prices in the average intensity, average match scenario indicated that aTIV could be marginally cost saving relative to QIV at the currently published Medicare price for influenza vaccines offering enhanced efficacy in the elderly. Elderly vaccination with aTIV was associated with a higher overall cost compared with TIV in only two scenarios (low intensity with average or high match); the incremental cost/QALY relative to TIV was $9980 in the average match scenario and $28,800 in the high match scenario. CONCLUSIONS: Vaccination of persons aged ≥65 years with aTIV has the potential to provide clinical and economic benefit relative to QIV and TIV. The new model allows the assessment of various alternative strategies for available influenza vaccines. FUNDING: Novartis Vaccines.