A comparative cost analysis of the Vaccination Program for US-bound Refugees

BackgroundVaccination Program for US-bound Refugees (VPR) currently provides one or two doses of some age-specific Advisory Committee on Immunization Practices (ACIP)-recommended vaccines to US-bound refugees prior to departure.MethodsWe quantified and compared the full vaccination costs for refugees using two scenarios: (1) the baseline of no VPR and (2) the current situation with VPR. Under the first scenario, refugees would be fully vaccinated after arrival in the United States. For the second scenario, refugees would receive one or two doses of selected vaccines before departure and complete the recommended vaccination schedule after arrival in the United States. We evaluated costs for the full vaccination schedule and for the subset of vaccines provided by VPR by four age-stratified groups; all costs were reported in 2015 US dollars. We performed one-way and probabilistic sensitivity analyses and break-even analyses to evaluate the robustness of results.ResultsVaccination costs with the VPR scenario were lower than costs of the scenario without the VPR for refugees in all examined age groups. Net cost savings per person associated with the VPR were ranged from $225.93 with estimated Refugee Medical Assistance (RMA) or Medicaid payments for domestic costs to $498.42 with estimated private sector payments. Limiting the analyses to only the vaccines included in VPR, the average costs per person were 56% less for the VPR scenario with RMA/Medicaid payments. Net cost savings with the VPR scenario were sensitive to inputs for vaccination costs, domestic vaccine coverage rates, and revaccination rates, but the VPR scenario was cost savings across a range of plausible parameter estimates.ConclusionsVPR is a cost-saving program that would also reduce the risk of refugees arriving while infected with a vaccine preventable disease.     

Why France is making eight new vaccines mandatory

France is one of the countries with the highest prevalence of vaccine hesitancy in the world. In an attempt to raise vaccination coverages, the French government made on January 1, 2018 eight more vaccines mandatory in addition to the three required until then. The process that led to this policy choice is of particular interest. We describe how vaccines became contentious in France and how French authorities came to view mandatory vaccination as the solution to the rise in vaccine hesitancy. In a bold move, French public health authorities turned to a new type of institutional device grounded in the ideal of democracy and public participation to political decision-making: “a citizen consultation”. This consultation anchored the idea that legal coercion could be the solution to France’s crisis with vaccines. Time will tell whether the French extension of mandatory vaccination will reduce tensions around vaccines.     

Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: The NSW Public Health Network case-control study

BackgroundInfants are at the highest risk of severe complications – including death – as a result of pertussis infection. Controlling pertussis in this group has been challenging, particularly in those too young to be vaccinated. Following revised national recommendations in March 2015, the state of New South Wales, Australia, introduced a funded maternal vaccination campaign at 28 – 32 weeks of gestation using a 3-component tetanus-diphtheria-acellular pertussis vaccine (dTpa; Boostrix, GSK). This study aimed to assess the effectiveness of maternal vaccination and add to the growing body of evidence for this strategy.MethodsA 1:1 matched case-control study was conducted between 16 August 2015 and 17 August 2016. Cases were laboratory or doctor notified, laboratory confirmed (nucleic acid testing or culture) and aged <6 months at onset. Each control infant was randomly selected from public hospital births in the same geographical area in the period up to 3 days before and after the case’s birthdate. Odds ratios (OR) were calculated using conditional logistic regression. Vaccine effectiveness (VE) was calculated as 1 – OR.FindingsIn total, 117 cases and 117 controls were recruited. The overall VE estimate was non-significantly protective for infants <6 months old (VE 39%, 95% CI −12 to 66%). Higher VE was observed for infants <3 months old (VE 69%, 95% CI 13–89%) and against hospitalisation (VE 94%, 95% CI 59–99%).InterpretationMaternal pertussis vaccination with a 3-component acellular vaccine was found to be highly effective at preventing severe disease in infants, but was less effective at preventing disease which did not require hospitalisation. The overall VE reported in this study was lower than in prior studies and suggests that maternal vaccination, while an effective strategy at preventing severe pertussis, is less effective at protecting against infection or mild disease.     

Breaking the inertia in coverage: Mainstreaming under-utilized immunization strategies in the Middle East and North Africa region

Vaccination coverage rates have stagnated in the past several years in many middle-income countries (MICs), especially in the UNICEF Middle East and North Africa region, with political and economic turmoil as contributing factors. This paper reviews country experiences with three under-utilized strategies aimed at increasing vaccination coverage and reducing disparities between socio-economic and geographic groups in MICs. These strategies include: (1) identifying and accounting for displaced, mobile and neglected populations; (2) assessing and addressing missed opportunities for vaccination, including by expanding immunization into the second year of life and beyond; and (3) engaging effectively with the private/nongovernmental health providers in the coordination, provision and reporting of immunization services. The examples focus primarily on quality data collection, analysis, use and reporting aspects of the strategies. While data are limited, there is evidence from MICs that each of these strategies can have a positive impact on vaccination coverage, especially among marginalized populations.     

Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany

ObjectiveTo identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany.MethodsActive surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997–2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data.Results96–97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (−48% [95% CI: −55%; −39%]) with a rebound to −26% [95% CI: −36%; −16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0–1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases.ConclusionThe maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.     

Impact of live attenuated influenza vaccination programme for healthy children in Northern Ireland: A comparison of seven influenza seasons, 2010/11–2016/17

Seasonal influenza vaccination for healthy children was introduced in Northern Ireland in the 2013/14 flu season, with an initial pilot year involving two specific cohorts, followed by rollout to all children aged 4–11 years in subsequent seasons. This study aimed to examine the impact of that programme on the burden of flu in primary care over the study period 2010/11–2016/17.Two routine indicators were used to measure impact – GP in-hour consultations and out-of-hour calls for influenza and influenza-like-illness (ILI). Analysis was conducted overall and stratified by age; rates in children under 14 years of age to measure direct impact and rates in individuals 14 years and over to measure indirect impact. Seven influenza seasons were included, three pre-programme seasons (2010/11–2012/13: phase 0), one pilot season (2013/14: phase 1), and three post-programme seasons (2014/15–2016/17: phase 2).High uptake of vaccination was observed from the programme introduction, with consistent uptake of over 50% in pre-school age groups and over 75% in primary school age groups. Statistically significant reductions were found in GP in-hours consultations and in out-of-hour calls in phase 2 compared to phase 0, both overall (GP in-hours RR 0.61, 95% CI 0.38–0.98, p = .040; out-of-hours RR 0.51, 95% CI 0.27–0.97, p = .041) and in the under 14 years group (GP in-hours RR 0.38, 95% CI 0.19–0.75, p = .006; out-of-hours RR 0.39, 95% CI 0.19–0.83, p = .014).Our results suggest that there have been reductions in the burden of flu in primary care settings overall and in children aged under 14 years in the seasons since the introduction of healthy children influenza vaccination. Further seasons should be added to subsequent analyses to strengthen this evidence.     

Safety,tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch™)

BackgroundInjection using needle and syringe (N&S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine.MethodsHealthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 µg haemagglutinin (HA) per dose), applied to the volar forearm (NP-HA/FA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 µg HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvax® 2016 containing 15 µg of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays.FindingsNP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with N&S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p < 0.0001), with no statistical differences between the treatment groups (p > 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189–593 95% CI), 160 (74–345 95% CI), and 221 (129–380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection.InterpretationInfluenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection.     

Intranasal vaccination with ebola virus GP amino acids 258–601 protects mice against lethal challenge

Ebola virus (EBOV) disease (EVD) leads to lethal hemorrhagic fever with a case fatality rate as high as 90%, thus posing a serious global public health concern. However, while several vaccines based on the EBOV glycoprotein have been confirmed to be effective in animal experiments, no licensed vaccines or effective treatments have been approved since the first outbreak was reported in 1976. In this study, we prepared the extracellular domain of the EBOV GP protein (designated as N20) by prokaryotic expression and purification via chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we evaluated the immunogenicity of N20 by intranasal administration and the associated protective efficacy against mouse-adapted EBOV challenge in mice. We found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on IgG subclasses and IFN-γ/IL-4 secreting cells; and mucosal immunity, based on the presence of anti-EBOV IgA in vaginal lavages. We also confirmed that the vaccine could completely protect mice against a lethal mouse-adapted EBOV (MA-EBOV) challenge with few side effects (based on weight loss). In comparison, mice that received N20 or H45 alone succumbed to lethal MA-EBOV challenge. Therefore, mucosal vaccination with H45-adjuvanted N20 represents a potential vaccine candidate for the prevention of EBOV in an effective, safe, and convenient manner.     

Local thermal reaction after influenza vaccination: Quantification by infrared imaging and biometric considerations

BackgroundExtensive clinical investigations are mandatory to evaluate the safety and reactogenicity of vaccines. The recording of common adverse events like injection site soreness or general discomfort derives from individual subjective perceptions. Thermal imaging at the injection site possibly provides a non-subjective and a non-invasive approach to supplement this evaluation.ResultsA protocol for quantified injection-site infrared imaging included 86 participants during a flu vaccine campaign, 40% of whom had a thermal reaction of 1 °C; 25–30% had no thermal response. There was little subjective pain reporting and no clinical correlations were observed except with post-vaccination erythema.Higher responses were linked with advanced age and multiple previous vaccinations.ConclusionEvan if influenza vaccine was only moderately reactogenic, a thermal response was detectable in about 70% of vaccinees, though no relationship to reactogenicity was seen.Infrared imaging might however be a prospective tool for individual studies of vaccine-induced vascular responses.