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BACKGROUND: Evidence shows that activation of pulmonary vascular endothelium and neutrophils are involved in the pathophysiology of acute bronchiolitis. We hypothesized that levels of markers of endothelial activation and leukocyte counts are associated with requirement and duration of respiratory support.METHODS: Thirty-four infants with bronchiolitis and eight controls were included. Nasopharyngeal swabs and blood samples were taken at admission. Serum levels of Angiopoietin (Ang)-1, Ang-2, sP-selectin, sE-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and leukocyte counts were measured. For univariate analysis, bronchiolitis cases were grouped into two groups, namely those not requiring and those requiring any form of respiratory support. To control for known risk factors for poor outcome (i.e., age, prematurity, and congenital heart disease), and for days post symptom onset, linear regression analysis was performed with duration of any type of respiratory support in days.RESULTS: Ang-2 levels, Ang-2/Ang-1 ratios, sE-selectin levels, immature neutrophil count, and neutrophil/lymphocyte ratio (NLR) were higher in acute bronchiolitis versus controls. Ang-2, and NLR levels were significantly higher, and lymphocyte counts significantly lower, in infants that required respiratory support versus those that did not. Ang-2 levels (β: .32, 95% confidence interval [CI]: 0.19-1.19) and NLR (β: .68, 95% CI: 0.17-1.19) were positive predictors for the duration of respiratory support.CONCLUSIONS: Markers of endothelial and neutrophil activation are associated with respiratory support for acute bronchiolitis. Admission Ang-2 levels and NLR may be promising markers to determine requirement of respiratory support and deserve further study.

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies., Graphical Abstract, Komdeur, Singh, et al. report on a first-in-human phase I clinical trial of a Semliki Forest virus-based cancer vaccine. The trial shows that the vaccine is safe and well tolerated, inducing strong HPV16 E6- and E7-specific CD8 and CD4 T cell responses.

Background The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. Methods An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios: i no intervention, i.e., the current practice, ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, and iii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1–F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. Results For all cohorts, comparison between scenarios (ii) and (i) resulted in ICERs between €9,306 and €10,173 per QALY gained and 5 year budget impacts varying between €6,283,830 and €19,220,405. For all cohorts, comparison between scenarios (iii) and (i) resulted in ICERs between €1,739 and €2,749 per QALY gained and budget impacts varying between €1,468,670 and €5,607,556. For all cohorts, the ICERs (scenario iii versus ii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between €56,607 and €56,892, well above the willingness-to-pay (WTP) threshold of €20,000 per QALY gained and even above a threshold of €50,000 per QALY gained. Conclusion Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention.

Objective This study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account. Methods An age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually. Results At an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine. Conclusion Modeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially.

Objective: We aimed to assess the cost-effectiveness of hepatitis C virus (HCV) screening strategies among recently arrived migrants in the Netherlands. Methods: A Markov model was used to estimate the health effects and costs of HCV screening from the healthcare perspective. A cohort of 50,000 recently arrived migrants was used. In this cohort, three HCV screening strategies were evaluated: (i) no screening, (ii) screening of migrants from HCV-endemic countries and (iii) screening of all migrants. Results: Strategy (ii) screening of migrants from HCV-endemic countries compared to strategy (i) no screening, yielded an incremental cost-effectiveness ratio (ICER) of &euro, 971 per quality-adjusted life-years (QALYs) gained. Strategy (iii) screening of all migrants compared with strategy (ii) screening of migrants from HCV-endemic countries yielded an ICER of &euro, 1005 per QALY gained. The budget impact of strategy (ii) screening of migrants from HCV-endemic countries and strategy (iii) screening of all migrants was &euro, 13,752,039 and &euro, 20,786,683, respectively. Conclusion: HCV screening is cost-effective. However, the budget impact may have a strong influence on decision making.

Background Adults 65 years and older (seniors) experience more complications following influenza infection than younger adults. We estimated the relative vaccine effectiveness (rVE) of a trivalent high dose (HD-IIV3) versus an adjuvanted trivalent influenza vaccine (aIIV3) in seniors for respiratory-related hospitalizations. Methods We conducted a retrospective cohort study using claims data from Optum’s Clinformatics® Data Mart to compare outcome rates between seniors who received HD-IIV3 versus aIIV3 during the 2016/17 and 2017/18, predominantly A/H3N2 respiratory seasons. Rates were adjusted for demographic characteristics, comorbid conditions, previous influenza vaccination, and geography. We used the previous event rate ratio (PERR) approach to address bias by time-fixed unmeasured confounders. Results We identified 842,282 HD-IIV3 and 34,157 aIIV3 recipients for the 2016/17 season and 1,058,638 HD-IIV3 and 189,636 aIIV3 recipients for the 2017/18 season. The pooled rVE of HD-IIV3 versus aIIV3 for respiratory-related hospitalizations over both seasons was 12% (95% confidence interval: 3.3%–20%); 13% (−6.4% to 32%) for the 2016/17 season and 12% (2.1%–21%) for the 2017/18 season. Conclusions Pooled over two predominantly A/H3N2 respiratory seasons, HD-IIV3 was associated with fewer respiratory hospital admissions than aIIV3 in senior members of large national managed health care company in the U.S.

Two influenza vaccines are licensed in the U.S. exclusively for the 65 years and older population: a trivalent inactivated high-dose influenza vaccine (HD-IIV3) and a trivalent inactivated adjuvanted influenza vaccine (aIIV3). In a recent publication, we estimated a relative vaccine effectiveness (rVE) of HD-IIV3 vs. aIIV3 of 12% (95% CI: 3.3–20%) for influenza-related hospitalizations using a retrospective study design, but did not report the number of prevented hospitalizations nor the associated avoided cost. In this paper we report estimations for both. Methods: Leveraging the rVE of a cohort study over two influenza seasons (2016/17 and 2017/18), we collected cost data for healthcare provided to the same study population. Vaccine costs were obtained from the Medicare pricing schedule. Our economic assessment compared cost of vaccination and hospital care for patients experiencing acute respiratory or cardiovascular illness. Results: We analyzed 1.9 million HD-IIV3 and 223,793 aIIV3 recipients. Average vaccine list prices were $46.23 for HD-IIV3 and $48.26 for aIIV3. The hospitalization rates for respiratory disease in HD-IIV3 and aIIV3 recipients were 187 (95% CI: 185–189) and 212 (195–231) per 10,000 persons-years, respectively. Attributing the average cost per hospitalization of $12,652 ($12,214–$13,090) to the difference in hospitalization rates, we estimate net savings of HD-IIV3 to be $34 ($10–$62) per recipient. Conclusion: Pooled over two predominantly A/H3N2 respiratory seasons, vaccination with HD-IIV3 was associated with lower hospitalization rates and associated costs compared to aIIV3 in senior members of a large national managed health care company in the U.S. Reduced hospitalizations affect healthcare utilization overall, and therefore other costly health outcomes.

Introduction: Respiratory syncytial virus (RSV) causes high morbidity and mortality rates among infants, young children, and the elderly worldwide. Unfortunately, a safe and effective vaccine is still unavailable. In 1966, a formalin-inactivated RSV vaccine failed and resulted in the death of two young children. This failure shifted research toward the development of subunit-based vaccines for pregnant women (to passively vaccinate infants) and the elderly. Among these subunit-based vaccines, the viral envelope glycoproteins show great potential as antigens. Areas covered: In this review, progress in the development of safe and effective subunit RSV vaccines based on the viral envelope glycoproteins and intended for pregnant women and the elderly, are reviewed and discussed. Studies published in the period 2012-2018 were included. Expert opinion: Researchers are close to bringing safe and effective subunit-based RSV vaccines to the market using the viral envelope glycoproteins as antigens. However, it remains a major challenge to elicit protective immunity, with a formulation that has sufficient (storage) stability. These issues may be overcome by using the RSV fusion protein in its pre-fusion conformation, and by formulating this protein as a dry powder. It may further be convenient to administer this powder via the pulmonary route.

Objective To compare the economic impact of high-dose trivalent (HD) versus standard-dose trivalent (SD) influenza vaccination on direct medical costs for cardio-respiratory hospitalizations in adults aged 65 years or older enrolled in the United States (US) Veteran’s Health Administration (VHA). Methods Leveraging a relative vaccine effectiveness study of HD versus SD over five respiratory seasons (2010/11 through 2014/15), we collected cost data for healthcare provided to the same study population both at VHA and through Medicare services. Our economic assessment compared the costs of vaccination and hospital care for patients experiencing acute cardio-vascular or respiratory illness. Results We analyzed 3.5 million SD and 158,636 HD person-seasons. The average cost of HD and SD vaccination was $23.48 (95% CI: $21.29 - $25.85) and $12.21 (95% CI: $11.49 - $13.00) per recipient, respectively, while the hospitalization rates for cardio-respiratory disease in HD and SD recipients were 0.114 (95% CI: 0.108–0.121) and 0.132 (95% CI: 0.132–0.133) per person-season, respectively. Attributing the average cost per hospitalization of $11,796 (95% CI: $11,685 - $11,907) to the difference in hospitalization rates, we estimated savings attributable to HD to be $202 (95% CI: $115 – $280) per vaccinated recipient. Conclusions For the five-season period of 2010/11 through 2014/15, HD influenza vaccination was associated with net cost savings due to fewer hospitalizations, and therefore lower direct medical costs, for cardio-respiratory disease as compared to SD influenza vaccination in the senior US VHA population.

Background Viruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries. Methods Between 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS). Results Of a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS. Conclusions Viruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks.

In this study, we estimated the benefits of rotavirus vaccination for infants had the rotavirus vaccine been introduced in the Netherlands as of its market authorization in 2006. An age-structured, deterministic cohort model was developed to simulate different birth cohorts over a period of 15 years from 2006 until 2021, comparing both universal and targeted high-risk group vaccination to no vaccination. Different scenarios for the duration of protection (5 or 7 years) and herd immunity (only for universal vaccination) were analyzed. All birth cohorts together included 2.6 million infants, of which 7.9% were high-risk individuals, and an additional 13.2 million children between 1–15 years born prior to the first cohort in 2006. The costs and health outcomes associated with rotavirus vaccination were calculated per model scenario and discounted at 4% and 1.5%, respectively. Our analysis reveals that, had rotavirus vaccination been implemented in 2006, it would have prevented 356,800 (51% decrease) and 32,200 (5% decrease) cases of rotavirus gastroenteritis after universal and targeted vaccination, respectively. Over the last 15 years, this would have led to significant avoided costs and quality-adjusted life year losses for either vaccination strategy with the most favorable outcomes for universal vaccination. Clearly, an opportunity has been lost.

BackgroundThis study evaluates the cost-effectiveness of extending the Dutch influenza vaccination programme for elderly and clinical risk groups to include paediatric influenza vaccination, taking indirect protection into account.MethodsAn age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over four seasons (2010/11 to 2013/14). The clinical and economic impact of different paediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children and the vaccine type for elderly and clinical risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life years (QALYs), incremental cost-effectiveness ratios, and net health benefits (NHBs), using a willingness-to-pay threshold of €20,000 per QALY gained.ResultsAt an assumed coverage of 50%, adding vaccination of 2- to 17-year-olds with quadrivalent-live-attenuated influenza vaccine (Q-LAIV) to the current influenza vaccination programme was estimated to avert on average 406,270 symptomatic cases and 83 deaths per season compared to vaccination of elderly and risk groups with trivalent inactivated vaccine (TIV), and was cost-saving (cumulative 20-year savings of 36,396 QALYs and €1,680 million; NHB: 120,411 QALYs). This strategy dominated paediatric vaccination strategies targeting 2- to 6-year-olds or 2- to 12-year-olds, or paediatric vaccination strategies with TIV. The highest NHB was obtained when 2- to 17-year-olds were vaccinated with Q-LAIV and existing target groups switched from TIV to quadrivalent inactivated vaccine (NHB: 132,907 QALYs).ConclusionModelling indicates that paediatric influenza vaccination reduces the disease burden of influenza substantially and is cost-saving.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes significant morbidity and mortality among young infants worldwide. It is currently widely accepted that neutrophil influx into the airways is a hallmark of the pathophysiology. However, the exact mechanism of neutrophil migration from the vasculature into the alveolar space in RSV LRTI has received little attention. Data shows that endothelial cells become activated upon RSV infection, driving a 'pro-adhesive state' for circulating neutrophils with upregulation of endothelial intercellular adhesion molecule-1 (ICAM-1). During RSV LRTI different subsets of immature and mature neutrophils are present in the bloodstream, that upregulate integrins lymphocyte-function associated antigen (LFA)-1 and macrophage (Mac)-1, serving as ICAM-1 ligands. An alveolar gradient of interleukin-8 may serve as a potent chemoattractant for circulating neutrophils. Neutrophils from lung aspirates of RSV-infected infants show further signs of inflammatory and migratory activation, while soluble endothelial cell adhesion molecules (sCAMs), such as sICAM-1, have become measurable in the systemic circulation. Whether these mechanisms are solely responsible for neutrophil migration into the alveolar space remains under debate. However, data indicate that the currently postulated neutrophil influx into the lungs should rather be regarded as a neutrophil efflux from the vasculature, involving substantial neutrophil-endothelial interactions. Molecular patterns of these interactions may be clinically useful to predict outcomes of RSV LRTI and deserve further study.

To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers.Prospective cohort study.Two University Medical Centers in The Netherlands.Healthcare workers receiving an influenza vaccination.Healthcare workers that were vaccinated during the influenza vaccination season of 2012-2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination.Side effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, p0.001). Local side effects were perceived as more severe in healthcare workers receiving the intradermal vaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated.This study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine.

Acute Zika virus (ZIKV) infection is usually mild and self-limiting. Earlier, we reported three cases of fatal acute ZIKV infection in patients without typical signs of ZIKV, but rather with criteria of systemic inflammation response syndrome (SIRS). To follow up these observations, we prospectively included patients at the emergency room with temperature instability and suspected to have acute ZIKV infection, SIRS, or both. A total of 102 patients were included of whom N = 21 (21%) were suspected of acute ZIKV infection, N = 56 (55%) of acute ZIKV infection with SIRS criteria, and N = 25 (24%) of SIRS alone. ZIKV-PCR was positive in N = 21 (20%) patients. Eight (38%) ZIKV-positive patients needed admission to the hospital of whom four (50%) presented with SIRS alone. One ZIKV-positive patient had vascular co-morbidity and died following shock and severe coagulopathy. We confirm the hypothesis that acute ZIKV infection can present atypical and severely with systemic inflammation and have lethal course particularly amongst patients with significant prior disease.

OBJECTIVES: Cost savings associated with high-dose (HD) as compared to standard-dose (SD) influenza vaccination in the United States (US) Veteran's Health Administration (VHA) population have been attributed to better protection against hospitalization for cardiac and respiratory diseases. The relative contribution of each of these disease categories to the reported savings remains to be explored.METHODS: During a recently completed study of HD versus SD vaccine effectiveness (conducted in the VHA over five respiratory seasons from 2010/11 through 2014/15), we collected cost data for all healthcare services provided at both VHA and Medicare-funded facilities. In that analysis, we compared the costs of vaccination and hospital care for patients admitted with either cardiovascular or respiratory disease. Treatment selection bias and other confounding factors were adjusted using an instrumental variable (IV) method. In this brief report we use the same study cohort and methods to stratify the results by patients admitted for cardiovascular disease (CVD) and those admitted for respiratory disease.RESULTS: We analyzed 3.5 million SD and 0.16 million HD person-seasons. The IV-adjusted rVEs were 14% (7-20%) against hospitalizations for CVD and 15% (5-25%) against respiratory hospitalizations. Net cost savings per HD recipient were $138 ($66-$200) for CVD related hospitalizations and $62 ($10-$107) for respiratory disease related hospitalizations.CONCLUSIONS: In the US VHA population, the reduction in hospitalizations for CVD over five respiratory seasons contributed twice the cost savings (per HD recipient) of the reduction in hospitalizations for respiratory disease.

Background Childhood immunization programmes have made substantial contributions to lowering the burden of disease among children in developing countries, however a large proportion of children still remain unimmunized. This study aimed to explore the determinants of rotavirus vaccine (RVV) and pneumococcal conjugate vaccine (PCV) uptake in Ethiopia. Methods The 2016 Ethiopian demographic and health survey dataset was used in this analysis. A total of 2004 children aged 12–23 months were included in the analysis. A multivariable logistic regression model was employed to identify the determinants of uptake of the complete schedules of RVV (two doses) and PCV (three doses). Crude and adjusted odds ratios with 95% confidence intervals (CIs) were calculated. Results The uptakes of the complete schedules of RVV and PCV among children aged 12–23 months were 56 and 49.1%, respectively. The likelihood of immunization with the complete schedule of RVV was significantly lower among children from the relatively poor Afar region in Ethiopia (AOR 0.16; 95%-CI 0.04–0.61). Similarly, children living in not only the Afar region (AOR 0.10; 95%-CI 0.03–0.38), but also the Gambela region (AOR 0.25; 95%-CI 0.08–0.83), were less likely to be vaccinated with PCV. On the other hand, children from more wealthy households had higher odds of vaccination with RVV (AOR 1.69; 95%-CI 1.04–2.75). Also attending antenatal care (ANC) was found to be significantly associated with uptake of the complete schedule of RVV and PCV. Conclusions The uptake of RVV and PCV is suboptimal in Ethiopia. The uptake of the vaccines were found to be associated with region, ANC use and wealth status.

Influenza is an acute respiratory infection primarily caused by influenza virus types A or B [1]. Next to occasional pandemics, influenza virus causes annual seasonal outbreaks. Globally, these ann...

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL.METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective.RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy.CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHADA (R) adjuvant.Virosomes were initially formed by contacting a lipid film containing 3D-PHADA (R) with viral membranes solubilized with the short chain phospholipid DCPC, followed by dialysis, later by adding solubilized 3D-PHAD to viral membranes, or to preformed virosomes from DMSO.Virosomes formed from lipid films contained the membrane glycoproteins G and F, at similar F to G ratios but lower concentrations than in virus, and the added lipids, but only a fraction of the 3D-PHADA (R). By single particle tracking (SPT), the virosome size distribution resembled that seen by cryo-electron microscopy, but dynamic light scattering showed much larger particles. These differences were caused by small virosome aggregates. Measured by SPT, virosomes were stable for 300 days. 3DPHAD A (R) incorporation in virosomes could be enhanced by providing the adjuvant from DCPC solubilized stock, but also by adding DMSO dissolved adjuvant to pre-formed virosomes. Virosomes with 0.1 mg/mg of 3D-PHADA (R)/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHADA (R).Stable 3D-PHADA (R) adjuvanted RSV virosomes can be formulated.

Addition of the HPV vaccine to available cytological screening has been proposed to increase HPV-related cancer prevention. A comprehensive review on this combined strategy implemented in the Netherlands is lacking. For this review, we therefore analyzed all relevant studies on cost-effectiveness of HPV vaccines in combination with cervical screening in the Netherlands. Most of the studies agree that vaccination in pre-sexual-activity periods of life is cost-effective. Based on published sensitivity analyses, the incremental cost-effectiveness ratio was found to be mainly driven by vaccine cost and discount rates. Fewer vaccine doses, inclusion of additional benefits of these vaccines to prevent HPV-related non-cervical cancers and vaccination of males to further reduce the burden of HPV-induced cancers are three relevant options suggested to be investigated in upcoming economic evaluations.

International audience; Quadrivalent influenza vaccines (QIVs) contain antigens derived from an additional influenza type B virus as compared with currently used trivalent influenza vaccines (TIVs). This should overcome a potential reduced vaccine protection due to mismatches between TIV and circulating B viruses. In this study, we systematically reviewed the available literature on health economic evaluations of switching from TIV to QIV. Areas covered: The databases of Medline and Embase were searched systematically to identify health economic evaluations of QIV versus TIV published before September 2016.A total of sixteen studies were included, thirteen cost-effectiveness analyses and three cost-comparisons. Expert commentary: Published evidence on the cost-effectiveness of QIV suggests that switching from TIV to QIV would be a valuable intervention from both the public health and economic viewpoint. However, more research seems mandatory. Our main recommendations for future research include: 1) more extensive use of dynamic models in order to estimate the full impact of QIV on influenza transmission including indirect effects, 2) improved availability of data on disease outcomes and costs related to influenza type B viruses, and 3) more research on immunogenicity of natural influenza infection and vaccination, with emphasis on cross-reactivity between different influenza B viruses and duration of protection.

Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information for Asian populations is lacking. We searched four electronic databases including PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov. We reviewed selected manuscripts and extracted the pooled relative risk (RR) from immunogenicity and safety information on HPV vaccination among women in Asian countries. We identified two quadrivalentvaccine studies and eight bivalent-vaccine studies conducted in Asian countries. Analysis across these studies suggested that the HPV vaccines significantly enhanced HPV16- and HPV18-specific antibody among both uninfected (RR 85.69; 95% confidence interval (CI) 31.51-233.04 and 62.77; 95% CI 37.4-105.51) and infected individuals (RR 8.60; 95% CI 6.95-10.64 and RR 8.13; 95% CI 5.96-11.11). Furthermore, HPV vaccination among Asian populations has a favorable safety profile, with only slightly higher risks of local (RR: 1.89; 95% CI 1.65-2.17) and systemic (RR: 1.33; 95% CI 1.18-1.50) adverse events in vaccinated individuals compared with controls. For Asian populations, HPV vaccines enhance the level of HPV16- and HPV18-specific antibodies for both uninfected and infected individuals. Also, the risk of adverse events related to vaccination are acceptable. More data are needed to establish vaccine efficacy with regard to prevention of HPV infection and further outcomes including cervical intraepithelial neoplasia (CIN) and cervical cancer.

Dengue transmission in Venezuela has become perennial and a major public health problem. The increase in frequency and magnitude of recent epidemics prompted a comprehensive community-based cross-sectional study of 2,014 individuals in high-incidence neighborhoods of Maracay, Venezuela. We found a high seroprevalence (77.4%), with 10% of people experiencing recent infections. Multivariate logistic regression analysis showed that poverty-related socioeconomic factors (place and duration of residence, crowding, household size, and living in a shack) and factors/constraints related to intradomiciliary potential mosquito breeding sites (storing water and used tires) were linked with a greater risk of acquiring a dengue infection. Our results also suggest that transmission occurs mainly at home. The combination of increasingly crowded living conditions, growing population density, precarious homes, and water storage issues caused by enduring problems in public services in Maracay are the most likely factors that determine the permanent dengue transmission and the failure of vector control programs.