Influenza Vaccine Distribution Research Articles

Time lapses between distribution of influenza vaccines to health authorities and their administration by General Practitioners (GPs) to older adults: a retrospective study over five influenza seasons in Italy

ABSTRACTBackgroundDelays in influenza vaccine delivery and administration can hinder vaccine coverage and protection. This study examines the differentials in distributing and administering adjuvanted trivalent (aTIV) and quadrivalent influenza vaccines (aQIV) to older adults in Italy’s primary care setting and its potential impact on hospitalization risk over 5 epidemic seasons.MethodsUsing a primary care database, individuals aged ≥ 65 years were selected. The proportion of vaccine distribution to regional authorities and subsequent administration by GPs was estimated using census data. Using quantile (median) regression, we examined the relationship between velocities of vaccine distribution and administration (doses/week) and the incidence of hospitalizations.ResultsOver the 5 influenza seasons, the velocity of distribution and administration of aTIV/aQIV ranged 341–833 and 152–270 median doses/week; no trend was yielded for the difference between these velocities (p = 0.189) or vaccine coverage (p = 0.142). An association was observed for each differential dose/week between distributed and administered vaccines and all-cause hospitalizations with a 10% increase in 2017–2018, 54% in 2018–2019, and 12% in 2020–2021 season.ConclusionsThese findings highlight the importance of minimizing the time lapse between vaccine distribution and administration to mitigate the impact of influenza and address factors that contribute to vaccination barriers.

Having a real say: findings from first nations community panels on pandemic influenza vaccine distribution

BackgroundRecent deliberations by Australian public health researchers and practitioners produced an ethical framework of how decisions should be made to distribute pandemic influenza vaccine. The outcome of the deliberations was that the population should be considered in two categories, Level 1 and Level 2, with Level 1 groups being offered access to the pandemic influenza vaccine before other groups. However, the public health researchers and practitioners recognised the importance of making space for public opinion and sought to understand citizens values and preferences, especially First Nations peoples.MethodsWe conducted First Nations Community Panels in two Australian locations in 2019 to assess First Nations people’s informed views through a deliberative process on pandemic influenza vaccination distribution strategies. Panels were asked to make decisions on priority levels, coverage and vaccine doses.ResultsTwo panels were conducted with eighteen First Nations participants from a range of ages who were purposively recruited through local community networks. Panels heard presentations from public health experts, cross-examined expert presenters and deliberated on the issues. Both panels agreed that First Nations peoples be assigned Level 1 priority, be offered pandemic influenza vaccination before other groups, and be offered two doses of vaccine. Reasons for this decision included First Nations people’s lives, culture and families are important; are at-risk of severe health outcomes; and experience barriers and challenges to accessing safe, quality and culturally appropriate healthcare. We found that communication strategies, utilising and upskilling the First Nations health workforce, and targeted vaccination strategies are important elements in pandemic preparedness and response with First Nations peoples.ConclusionsFirst Nations Community Panels supported prioritising First Nations peoples for pandemic influenza vaccination distribution and offering greater protection by using a two-dose full course to fewer people if there are initial supply limitations, instead of one dose to more people, during the initial phase of the vaccine roll out. The methodology and findings can help inform efforts in planning for future pandemic vaccination strategies for First Nations peoples in Australia.

111. Influenza and Pneumococcal vaccination rate in a cohort of adults with chronic comorbid conditions in Colombia.

Abstract Background Lower respiratory tract infections (LRTI) are the leading cause of mortality and morbidity worldwide. Elderly and patients with comorbid conditions are at higher risk of developing LRTI and systemic complications. Therefore, the Centers for Disease Control and Prevention (CDC) and the United States National Center for Immunization and Respiratory Diseases (US-NCIRD) recommend that patients older than 19 be vaccinated for influenza annually. Patients older than 65 or with comorbid conditions (of any age) should be vaccinated for the pneumococcal vaccine. Low-middle-income countries like Colombia do not have strong policies for adults to get vaccinated. According to CDC recommendations, this study aims to determine the vaccination rate in a Colombian cohort. Figure 1. Panel A illustrates patients’ distribution of influenza vaccine in the cohort, while Panel B shows the distribution of pneumococcal vaccine Methods This is the description of a prospective cohort of patients with chronic comorbid conditions between 2020-and 2022 in Bogotá, Colombia. We compared the number of patients vaccinated against Influenza and S. pneumoniae, according to CDC recommendations, to determine the adherence to international guidelines. Results The cohort was composed of 810 patients. The median [IQR] age was 63 [53-62] and the most common comorbidities were 52.2% [423/810] arterial hypertension, 21.7% [176/810] coronary disease, 19.0% [154/810] congestive heart failure, and 17.4% [141/810] chronic kidney disease. According to CDC recommendations, 808 patients should have been vaccinated against influenza (Figure 1A), but only 31.7% [256/808] were immunized last year. Also, 17.8% [144/810] of the whole cohort were 65 years old and should have received the quadrivalent flu shot. Moreover, 86.4% [700/810] patients meet the criteria for pneumococcal vaccination (Figure 1B), but only 11.9% [83/700] received at least one shot. Conclusion Vaccination rates in our cohort of adult patients with chronic comorbidities were meager. Therefore, these patients are at higher risk of developing LRTI complications. More robust vaccination programs for adults are required in Colombia. Disclosures All Authors: No reported disclosures.

Mapping the inequality of the global distribution of seasonal influenza vaccine

With an estimated annual worldwide death toll of between 290 000 and 650 000, seasonal influenza remains one of the deadliest respiratory diseases. Influenza vaccines provide moderate to high protection and have been on the World Health Organization’s Model List of Essential Medicines since 1979. Approximately 490 million doses of influenza vaccine are produced per year, but an investigation of geographic allocation reveals enormous disparities. Here, we present two maps that visualise the inequality of the distribution across 195 countries: a conventional choropleth map and a cartogram. In combination, these two maps highlight the widespread lack of coverage in Africa and many parts of Asia. As COVID-19 vaccines are now being distributed in developed countries, data for seasonal influenza vaccine distribution emphasises the need for policymakers to ensure equitable access to COVID-19 vaccines.

An inventory-location optimization model for equitable influenza vaccine distribution in developing countries during the COVID-19 pandemic

The addition of other respiratory illnesses such as flu could cripple the healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. An annual seasonal influenza vaccine is the best way to help protect against flu. Fears of coronavirus have intensified the shortage of influenza shots in developing countries that hope to vaccinate many populations to reduce stress on their health services. We present an inventory-location mixed-integer linear programming model for equitable influenza vaccine distribution in developing countries during the pandemic. The proposed model utilizes an equitable objective function to distribute vaccines to critical healthcare providers and first responders, elderly, pregnant women, and those with underlying health conditions. We present a case study in a developing country to exhibit efficacy and demonstrate the optimization model’s applicability.

Global influenza vaccine distribution survey demonstrates urgency of implementation of objective 3 of WHO influenza strategy 2019-2030.

Global influenza vaccine distribution survey demonstrates urgency of implementation of objective 3 of WHO influenza strategy 2019-2030.

Hemagglutinin Quantitative ELISA-based Potency Assay for Trivalent Seasonal Influenza Vaccine Using Group-Specific Universal Monoclonal Antibodies

The assurance of vaccine potency is important for the timely release and distribution of influenza vaccines. As an alternative to Single Radial Immunodiffusion (SRID), we report a new quantitative enzyme-linked immunosorbent assay (ELISA) for seasonal trivalent influenza vaccine (TIV). The consensus hemagglutinin (cHA) stalks for group 1 influenza A virus (IAV), group 2 IAV, and influenza B virus (IBV) were designed and produced in bacterial recombinant host in a soluble form, and monoclonal antibodies (mAbs) were generated. The group-specific ‘universal’ mAbs (uAbs) bound to various subtypes of HAs in the same group from recombinant hosts, embryonated eggs, and commercial vaccine lots. The calibration curves were generated to assess the sensitivity, specificity, accuracy, and linear dynamic range. The quantitative ELISA was validated for the potency assay of individual components of TIV- H1, H3, and IBV- with good correlation with the SRID method. This new assay could be extended to pandemic or pre-pandemic mock-up vaccines of H5 of group 1 and H7 virus of group 2, and novel HA stalk-based universal vaccines.

Optimal influenza vaccine distribution with equity

This paper is concerned with the optimal influenza vaccine distribution in a heterogeneous population consisting of multiple subgroups. We employ a compartmental model for influenza transmission and formulate a mathematical program to minimize the number of vaccine doses distributed to effectively extinguish an emerging outbreak in its early stages. We propose an equity constraint to help public health authorities consider fairness when making vaccine distribution decisions. We develop an exact solution approach that generates a vaccine distribution policy with a solution quality guarantee. We perform sensitivity analyses on key epidemic parameters in order to illustrate the application of the proposed model. We then analyze the scalability of the solution approach for a population consisting of subgroups based on geographic location and age. We finally demonstrate the proposed model’s ability to consider vaccine coverage inequity and discuss a derivative-free optimization approach, as an alternative solution method which can consider various different objective functions and constraints. Our results indicate that consideration of group-specific transmission dynamics is paramount to the optimal distribution of influenza vaccines.

Seasonal and pandemic influenza: global fatigue versus global preparedness

Seasonal and pandemic influenza: global fatigue versus global preparedness

Broad cross-protective anti-hemagglutination responses elicited by influenza microconsensus DNA vaccine

Despite the routine development and distribution of seasonal influenza vaccines, influenza remains an important pathogen contributing to significant human morbidity as well as mortality each year. The seasonal variability of influenza creates a significant issue for vaccine development of seasonal strains that can afford protection from infection or disease based on serotype matching. It is appreciated that the globular head of the HA antigen contained in the vaccines generates antibodies that result in HAI activity that are a major correlates of the protection against a particular strain. Due to seasonal genetic changes in the HA protein, however, new vaccine strains are needed to be developed continually to match the new HA antigen of that seasons virus. A distinct advantage in seasonal vaccine development would be if a small group of antigens could be developed that could span many seasons without needed to be replaced due to this genetic drift. Here we report on a synthetic microconsensus approach that relies on a small collection of 4 synthetic H1HA DNA antigens which together induce broad protective HAI immunity spanning decades of H1 influenza viruses in mice, guinea pigs and non-human primates. The protective HAI titers induced by microconsensus immunogens are fully functional in vivo as immunized ferrets were completely protected from A/Mexico/InDRE4487/2009 virus infection and morbidity associated with lethal challenge. These results are encouraging that a limited easy-to-formulate collection of invariant antigens can be developed which can span seasonal vaccine changes allowing for continued immune protection.

A network flow model for inventory management and distribution of influenza vaccines through a healthcare supply chain

Influenza epidemics impose great losses in both human and financial terms. Billions of dollars are spent annually on vaccination programs aimed at fighting seasonal influenza outbreaks. A key question arising in large-scale vaccination programs is how to minimize the program costs while maintaining a required standard of public benefits. We suggest an operational research approach for solving this problem using supply chain concepts and techniques. Specifically, we consider a constrained cost minimization problem from the perspective of a healthcare organization (HCO). The HCO is assumed to consist of distribution centers clinics and to be a major provider of vaccination services. We seek to decrease the total monetary expenses of the HCO while taking into account public benefits of the vaccination program. A mathematical model based on network flow analysis is suggested. A real-world application of the developed methodology is presented.

Development of a Thermostable Microneedle Patch for Influenza Vaccination

The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane (PDMS) led to increased stability compared with drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for 6 months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain.

Distribution of Pandemic Influenza Vaccine and Reporting of Doses Administered, New York, New York, USA

In 2009, the New York City Department of Health and Mental Hygiene delivered influenza A(H1N1)pdm09 (pH1N1) vaccine to health care providers, who were required to report all administered doses to the Citywide Immunization Registry. Using data from this registry and a provider survey, we estimated the number of all pH1N1 vaccine doses administered. Of 2.8 million doses distributed during October 1, 2009–March 4, 2010, a total of 988,298 doses were administered and reported; another 172,289 doses were administered but not reported, for a total of 1,160,587 doses administered during this period. Reported doses represented an estimated 80%–85% of actual doses administered. Reporting by a wide range of provider types was feasible during a pandemic. Pediatric-care providers had the highest reporting rate (93%). Other private-care providers who routinely did not report vaccinations indicated that they had few, if any, problems, thereby suggesting that mandatory reporting of all vaccines would be feasible.

Evaluating the Most Effective Distribution Strategies to Assure Administration of Pandemic H1N1 Influenza Vaccine to New York State Children and Adolescents

To examine differences in H1N1 influenza vaccine distribution strategies that may impact the ability to rapidly administer vaccine during a pandemic or public health emergency. Retrospective evaluation of immunization data in the New York State Immunization Information System (NYSIIS). Analysis of existing NYSIIS data. Children and adolescents younger than 19 years for whom information on at least 1 H1N1 influenza vaccine was present in NYSIIS. Median time to administer vaccines to children and adolescents younger than 19 years by December 31, 2009, by county; venue of H1N1 vaccine administration (local health department [LHD] or private medical provider); comparison of immunization-seeking behavior for routine childhood vaccinations and H1N1 vaccine. A total of 459 189 first or only doses of H1N1 influenza vaccine were recorded in NYSIIS as being administered to New York State, outside of New York City, children aged less than 19 years, between October 2, 2009, and December 31, 2009. Overall, LHD administered 31% of H1N1 vaccine doses; in counties having population less than 100,000, LHD administered 63% of H1N1 doses compared with 23% in counties having population more than 100,000. Time to median administration was faster for LHD in smaller counties and similar for LHD and private medical providers in larger counties. Children who always received routine childhood immunizations either within or outside of their county of residence often had the same practice for H1N1 vaccine, with 85% of children following these patterns. Children who did not follow these patterns were more likely to receive H1N1 influenza vaccine through LHD. Local health departments were able to rapidly administer large quantities of H1N1 influenza vaccine, and patterns of health care seeking relying on increased use of LHD needs to be further studied for future public health emergency planning.

Extended antigen sparing potential of AS03-adjuvanted pandemic H1N1 vaccines in children, and immunological equivalence of two formulations of AS03-adjuvanted H1N1 vaccines: results from two randomised trials

BackgroundPandemic influenza vaccine manufacturing capacity and distribution agility is enhanced through the availability of equivalent antigen-sparing vaccines. We evaluated equivalence in terms of immunogenicity between GlaxoSmithKline Vaccines’ A/California/7/2009 (H1N1)v-like-AS03 vaccines manufactured in Dresden (D-Pan), and Quebec (Q-Pan).MethodsIn two studies, 334 adults 18-60 years of age received 2 doses of D-Pan or Q-Pan containing 3.75 μg haemagglutinin antigen (HA) adjuvanted with AS03A administered 21 days apart, and 209 children 3-9 years of age received 1 reduced dose of D-Panor Q-Pan (0.9 μg HA) or Q-Pan (1.9 μg HA) with AS03B. Haemagglutination inhibition (HI) titres were assessed before and 21 days post-vaccination. HI persistence was assessed after 12 months in adults and 6 months in children.ResultsPre-defined criteria for immunological equivalence of Q-Pan versus D-Pan were achieved in both populations. After one vaccine dose, ≥97.6% of adults and children had HI titres ≥1:40, with increases in titre ≥25.7-fold. CHMP and CBER regulatory acceptance criteria for influenza vaccines were exceeded by all groups in both studies at Day 21. In adults,the percentage with HI titres ≥1:40 at Month 12 was 82.9% (Q-Pan) and 84.0% (D-Pan). In children, the percentages at Month 6 were 75.3.3% (Q-Pan0.9), 85.1% (D-Pan0.9) and 79.3% (Q-Pan1.9). Safety profile of the study vaccines was consistent with previously published data.ConclusionTwo studies indicate that A/California/7/2009 (H1N1)v-like HA manufactured at two sites and combined with AS03 are equivalent in terms of immunogenicity in adults and children and highly immunogenic. Different HA doses elicited an adequate immune response through 180 days post-vaccination in children 3-9 years of age.Trial registrationClinicalTrials.gov: NCT00979407 and NCT01161160.

Climate change and influenza: the likelihood of early and severe influenza seasons following warmer than average winters

The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, which can lead to early and severe epidemics. In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to mitigate the severity of future influenza epidemics.

Geographic prioritization of distributing pandemic influenza vaccines.

Pandemic influenza is an international public health concern. In light of the persistent threat of H5N1 avian influenza and the recent pandemic of A/H1N1swine influenza outbreak, public health agencies around the globe are continuously revising their preparedness plans. The A/H1N1 pandemic of 2009 demonstrated that influenza activity and severity might vary considerably among age groups and locations, and the distribution of an effective influenza vaccine may be significantly delayed and staggered. Thus, pandemic influenza vaccine distribution policies should be tailored to the demographic and spatial structures of communities. Here, we introduce a bi-criteria decision-making framework for vaccine distribution policies that is based on a geospatial and demographically-structured model of pandemic influenza transmission within and between counties of Arizona in the Unites States. Based on data from the 2009-2010 H1N1 pandemic, the policy predicted to reduce overall attack rate most effectively is prioritizing counties expected to experience the latest epidemic waves (a policy that may be politically untenable). However, when we consider reductions in both the attack rate and the waiting period for those seeking vaccines, the widely adopted pro rata policy (distributing according to population size) is also predicted to be an effective strategy.

Modeling Optimal Age-Specific Vaccination Strategies Against Pandemic Influenza

In the context of pandemic influenza, the prompt and effective implementation of control measures is of great concern for public health officials around the world. In particular, the role of vaccination should be considered as part of any pandemic preparedness plan. The timely production and efficient distribution of pandemic influenza vaccines are important factors to consider in mitigating the morbidity and mortality impact of an influenza pandemic, particularly for those individuals at highest risk of developing severe disease. In this paper, we use a mathematical model that incorporates age-structured transmission dynamics of influenza to evaluate optimal vaccination strategies in the epidemiological context of the Spring 2009 A (H1N1) pandemic in Mexico. We extend previous work on age-specific vaccination strategies to time-dependent optimal vaccination policies by solving an optimal control problem with the aim of minimizing the number of infected individuals over the course of a single pandemic wave. Optimal vaccination policies are computed and analyzed under different vaccination coverages (21%-77%) and different transmissibility levels ([Formula: see text] in the range of 1.8-3). The results suggest that the optimal vaccination can be achieved by allocating most vaccines to young adults (20-39yr) followed by school age children (6-12yr) when the vaccination coverage does not exceed 30%. For higher [Formula: see text] levels ([Formula: see text]), or a time delay in the implementation of vaccination (>90days), a quick and substantial decrease in the pool of susceptibles would require the implementation of an intensive vaccination protocol within a shorter period of time. Our results indicate that optimal age-specific vaccination rates are significantly associated with [Formula: see text], the amount of vaccines available and the timing of vaccination.

Modeling the Effects of H1N1 Influenza Vaccine Distribution in the United States

ObjectiveWe analyzed the effects of the timing of vaccine distribution in 11 US states during the 2009 H1N1 influenza pandemic. MethodsBy using reported data on the fraction of patients presenting with flu-related symptoms, we developed a transformation that allowed estimation of the state-specific temporal flu wave curve, representing the number of new infections during each week. We also utilized data describing the weekly numbers of vaccine doses delivered and administered. By using a simple difference equations model of flu progression, we developed two influenza wave curves: first, an “observable” curve that included the beneficial effects of vaccinations, and second, an unobservable curve that depicted how the flu would have progressed with no vaccine administered. We fit the observable curve to match the estimated epidemic curve and early exponential growth associated with R0, the reproductive number. By comparing the number of infections in each scenario, we estimated the infections averted by the administration of vaccine. ResultsSouthern states experienced peak infection several weeks before northern states, and most of the vaccine was delivered well after the peak of the southern flu wave. Our models suggest that the vaccine had minimal ameliorative impact in the southern states and measurable positive impact in the northern states. Vaccine delivery after peak also results in a smaller fraction of the population's seeking the vaccine. ConclusionsOur analysis suggests that current Centers for Disease Control and Prevention policy of allocating flu vaccine over time in direct proportion to states' populations may not be best in terms of averting nationally the maximum possible number of infections.

Evaluation of a Legislatively Mandated Influenza Vaccination Program for Adults in Rhode Island, USA

There have been disruptions in influenza vaccine supply in the United States during the 2000-2001, 2001-2002, 2004-2005, and 2005-2006 influenza seasons. Some providers received limited or no vaccine, while others obtained their order in full, depending on with whom the order was placed. A state law was passed that mandates the Rhode Island Department of Health to include the purchase and distribution of influenza vaccine for adults in its immunization program. To evaluate the first 2 years of the statewide adult influenza immunization program. We conducted key informant interviews of 25 providers in 2008 and surveyed all enrolled providers in 2008 (year 1) and 2009 (year 2). State of Rhode Island. Physician practices and facilities that provide influenza vaccination to adults, including private practices, nursing homes, health centers, urgent care facilities, hospitals, mass immunizers, and businesses. Enrolled providers received influenza vaccines free and billed insurers, Medicare, and Medicaid for vaccine administration costs. Provider satisfaction with different program components and overall satisfaction. For year 1, there was higher satisfaction with enrollment, training, vaccine ordering, and vaccine shipment than with paperwork and claims. Of the survey respondents, 71% reported that the program paperwork was reasonable and 30% reported difficulties in receiving reimbursement. Satisfaction with the vaccination start date of October 17, 2007, was 80%. There was high overall satisfaction (94%). In response to streamlining of reporting requirements and setting an earlier start date of October 7, 2008, for year 2, there was a significant increase in satisfaction with paperwork (89%) and with vaccination start date (90%). The findings may be useful in guiding the development of vaccination programs to provide influenza and other vaccines for adults at the state or national level.