The effect of cool water pack preparation on vaccine vial temperatures in refrigerators

Cool water packs are a useful alternative to ice packs for preventing unintentional freezing of vaccines during outreach in some situations. Current guidelines recommend the use of a separate refrigerator for cooling water packs from ambient temperatures to prevent possible heat degradation of adjacent vaccine vials. To investigate whether this additional equipment is necessary, we measured the temperatures that vaccine vials were exposed to when warm water packs were placed next to vials in a refrigerator. We then calculated the effect of repeated vial exposure to those temperatures on vaccine vial monitor status to estimate the impact to the vaccine. Vials were tested in a variety of configurations, varying the number and locations of vials and water packs in the refrigerator. The calculated average percentage life lost during a month of repeated warming ranged from 20.0% to 30.3% for a category 2 (least stable) vaccine vial monitor and from 3.8% to 6.0% for a category 7 (moderate stability) vaccine vial monitor, compared to 17.0% for category 2 vaccine vial monitors and 3.1% for category 7 vaccine vial monitors at a constant 5 °C. The number of vials, number of water packs, and locations of each impacted vial warming and therefore percentage life lost, but the vaccine vial monitor category had a higher impact on the average percentage life lost than any of the other parameters. The results suggest that damage to vaccines from repeated warming over the course of a month is not certain and that cooling water packs in a refrigerator where vaccines are being stored may be a useful practice if safe procedures are established.     

Addition of C3d-P28 adjuvant to a rabies DNA vaccine encoding the G5 linear epitope enhances the humoral immune response and confers protection

Rabies DNA vaccines based on full-length glycoprotein (G) induce virus neutralizing antibody (VNA) responses and protect against the virus challenge. Although conformational epitopes of G are the main target of VNAs, some studies have shown that a polypeptide linear epitope G5 is also able to induce VNAs. However, a G5 DNA vaccine has not been explored. While multiple doses of DNA vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of C3d-P28, a molecular adjuvant is know to improve the antibody response in several anti-viral vaccine models. To induce and enhance the immune response against rabies in mice, we evaluated two DNA vaccines based on the linear epitope G5 of Rabies Virus (RABV) glycoprotein (pVaxG5 vaccine) and another vaccine consisting of G5 fused to the molecular adjuvant C3d-P28 (pVaxF1 vaccine). VNA responses were measured in mice immunized with both vaccines. The VNA levels from the group immunized with pVaxG5 decreased gradually, while those from the group vaccinated with pVaxF1 remained high throughout the experimental study. After challenge with 22 LD50 of the Challenge Virus Strain (CVS), the survival rate of mice immunized with pVaxG5 and pVaxF1 was increased by 27% and 50% respectively, in comparison to the PBS group. Furthermore, the in vitro proliferation of anti-rabies specific spleen CD4+ and CD8+ T cells from mice immunized with pVaxF1 was observed. Collectively, these results suggest that the linear G5 epitope is a potential candidate vaccine. Furthermore, the addition of a C3d-P28 adjuvant contributed to enhanced protection, the sustained production of VNAs, and a specific T-cell proliferative response.     

Immunologic non-inferiority and safety of the investigational pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) 4-dose vial presentation compared to the licensed PHiD-CV 1-dose vial presentation in infants: A phase III randomized study

BackgroundTo support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants.MethodsIn this phase III, mono-center, observer-blind study in Bangladesh, 6–10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV] <2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated.ResultsOf 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, ≥97.9% of infants in each group had antibody concentrations ≥0.2 μg/mL; for 19A ≥ 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations.ConclusionImmunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries.Clinical Trial Registry: NCT02447432.     

Cost-effectiveness of dengue vaccination in ten endemic countries

Following publication of results from two phase-3 clinical trials in 10 countries or territories, endemic countries began licensing the first dengue vaccine in 2015. Using a published mathematical model, we evaluated the cost-effectiveness of dengue vaccination in populations similar to those at the trial sites in those same Latin American and Asian countries. Our main scenarios (30-year horizon, 80% coverage) entailed 3-dose routine vaccinations costing US$20/dose beginning at age 9, potentially supplemented by catch-up programs of 4- or 8-year cohorts. We obtained illness costs per case, dengue mortality, vaccine wastage, and vaccine administration costs from the literature. We estimated that routine vaccination would reduce yearly direct and indirect illness cost per capita by 22% (from US$10.51 to US$8.17) in the Latin American countries and by 23% (from US$5.78 to US$4.44) in the Asian countries. Using a health system perspective, the incremental cost-effectiveness ratio (ICER) averaged US$4,216/disability-adjusted life year (DALY) averted in the five Latin American countries (range: US$666/DALY in Puerto Rico to US$5,865/DALY in Mexico). In the five Asian countries, the ICER averaged US$3,751/DALY (range: US$1,935/DALY in Malaysia to US$5,101/DALY in the Philippines). From a health system perspective, the vaccine proved to be highly cost effective (ICER under one times the per capita GDP) in seven countries and cost effective (ICER 1–3 times the per capita GDP) in the remaining three countries. From a societal perspective, routine vaccination proved cost-saving in three countries. Including catch-up campaigns gave similar ICERs. Thus, this vaccine could have a favorable economic value in sites similar to those in the trials.     

Association of provider recommendation and offer and influenza vaccination among adults aged ≥18 years – United States

BackgroundInfluenza vaccination has been recommended for all persons aged ≥6 months since 2010.MethodsData from the 2016 National Internet Flu Survey were analyzed to assess provider vaccination recommendations and early influenza vaccination during the 2016–17 season among adults aged ≥18 years. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with early vaccine uptake by provider vaccination recommendation status.ResultsOverall, 24.0% visited a provider who both recommended and offered influenza vaccination, 9.0% visited a provider who only recommended but did not offer, 25.1% visited a provider who neither recommended nor offered, and 41.9% did not visit a doctor from July 1 through date of interview. Adults who reported that a provider both recommended and offered vaccine had significantly higher vaccination coverage (66.6%) compared with those who reported that a provider only recommended but did not offer (48.4%), those who neither received recommendation nor offer (32.0%), and those who did not visit a doctor during the vaccination period (28.8%). Results of multivariable logistic regression indicated that having received a provider recommendation, with or without an offer for vaccination, was significantly associated with higher vaccination coverage after controlling for demographic and access-to-care factors.ConclusionsProvider recommendation was significantly associated with influenza vaccination. However, overall, 67.0% of adults did not visit a doctor during the vaccination period or did visit a doctor but did not receive a provider recommendation. Evidence-based strategies such as client reminder/recall, standing orders, provider reminders, or health systems interventions in combination should be undertaken to improve provider recommendation and influenza vaccination coverage. Other factors significantly associated with a higher level of influenza vaccination included age ≥50 years, being Hispanic, having a college or higher education, having a usual place for medical care, and having public health insurance.     

Why do we not want to recommend influenza vaccination to young children? A qualitative study of Australian parents and primary care providers

IntroductionInfluenza vaccination has been shown to be safe and effective against influenza and in the prevention of complicating secondary respiratory illnesses. However, its uptake in young children remains low. This study explored the views, attitudes and practices of parents and primary care providers (PCPs) on their knowledge and acceptance of influenza vaccination in children under 5.MethodsUsing a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs (i.e., general practitioners, practice nurses, maternal and child health nurses, and pharmacists) and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed.ResultsParents thought the vaccine could cause influenza, and influenza vaccination was not necessary for their children as they needed to build their own ‘immunity’. Parents said that they would consider vaccinating their children if recommended by their GP and if the influenza vaccine was part of the immunisation schedule. PCPs also expressed concerns regarding the efficacy of the vaccine as well as out-of-pocket costs incurred by families, and uncertainty regarding the mortality and morbidity of influenza in otherwise healthy children. However, they said they would recommend the vaccine to high-risk groups (e.g. children with chronic disease(s), and asthma).ConclusionDespite the established safety of influenza vaccines, barriers to uptake include concerns regarding the iatrogenic effects of vaccination, its administration schedule, and knowledge of influenza severity. Updated information on influenza and the efficacy of the vaccine, and incorporating influenza vaccination into the immunisation schedule may overcome some of these barriers to increase influenza vaccination in this vulnerable cohort.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

Maximum likelihood estimation of influenza vaccine effectiveness against transmission from the household and from the community

Influenza vaccination is recommended as the best way to protect against influenza infection and illness. Due to seasonal changes in influenza virus types and subtypes, a new vaccine must be produced, and vaccine effectiveness (VE) must be estimated, annually. Since 2010, influenza vaccination has been recommended universally in the United States, making randomized clinical trials unethical. Recent studies have used a monitored household cohort study design to determine separate VE estimates against influenza transmission from the household and community. We developed a probability model and accompanying maximum likelihood procedure to estimate vaccine‐related protection against transmission of influenza from the household and the community. Using agent‐based stochastic simulations, we validated that we can obtain maximum likelihood estimates of transmission parameters and VE close to their true values. Sensitivity analyses to examine the effect of deviations from our assumptions were conducted. We used our method to estimate transmission parameters and VE from data from a monitored household study in Michigan during the 2012‐2013 influenza season and were able to detect a significant protective effect of influenza vaccination against community‐acquired transmission.     

2016年上海市浦东新区高东社区儿童青少年乙肝病毒感染及乙肝疫苗接种状况调查

目的 调查上海市浦东新区高东社区儿童青少年乙肝病毒感染现状及乙肝疫苗接种状况,为该社区的乙肝防控工作提供依据。 方法 2016年3-4月,随机抽取高东社区幼儿园、小学及初级中学各1所,对每所学校每个年级抽取的1个班级中所有学生开展乙肝病毒感染及乙肝疫苗接种相关问卷调查,同时采集静脉血进行乙肝血清指标及HBV DNA定量检测,分析该社区儿童青少年乙肝疫苗接种情况、乙肝病毒感染血清标志物分布情况及其影响因素。 结果 高东社区儿童青少年乙肝疫苗接种率95.50%(276/289),年龄组越小的儿童青少年乙肝疫苗接种率越高(P<0.01);10岁以下学生接种率高于≥10岁学生(P<0.01);HBsAg、HBcAb和HBsAb阳性率分别为1.04%(3/289)、1.38%(4/289)和32.18%(93/289);未接种乙肝疫苗及未全程接种者HBsAg和HBcAb阳性率均高于接种乙肝疫苗及全程接种者(P<0.05);女性HBcAb阳性率高于男性(P<0.05);≥10岁学生HBcAb阳性率高于3~＜10岁学生(P<0.05);年龄组越大的儿童青少年HBsAb阳性率越低(P<0.01);HBsAb阳性学生抗体滴度水平分布以低水平(10 mIU/ml≤HBsAb<100 mIU/ml)为主(占81.33%,61/75),无年龄分布差异(P>0.05)。 结论 2016年该社区儿童青少年的乙肝疫苗接种率高于95%,HBsAg、HBcAb阳性率较2012年上海市的调查结果下降明显。