Can the booster interval for the tick-borne encephalitis (TBE) vaccine 'FSME-IMMUN' be prolonged? - A systematic review.

Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, field effectiveness of FSME-IMMUN remains high in irregularly vaccinated subjects and thus does not correlate well with the percentage of subjects achieving an arbitrarily defined threshold of persisting antibodies. FSME-IMMUN booster doses led to increases in antibody responses within 7 days. VB are rare and remain poorly understood. VB did not increase, and vaccine effectiveness did not significantly decrease with time since completion of the primary vaccination series or with the time since administration of the last vaccine dose. For all these reasons, data identified from this systematic review suggest that seropersistence alone does not explain the high effectiveness of FSME-IMMUN irrespective of the time since the last vaccine dose was administered. Induction of immunological memory characterized by a rapid and sustained secondary immune response is proving to be an alternative mechanism of action for protection against TBE. In this context Switzerland and Finland have adopted a longer booster interval (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years.

Performance of full scale constructed wetlands in removing antibiotics and antibiotic resistance genes.

Additional treatment of wastewater, such as constructed wetlands (CWs), is a possible solution to reduce the discharge of antibiotics and antibiotic resistance genes (ARGs) from households and industry to the environment. This study aims to investigate the occurrence and removal of antibiotics and ARGs by two full scale CWs operated at different hydraulic retention times (HRT), namely 1 day and 3 days. Both CWs were receiving the same wastewater treatment plant (WWTP) effluent. Temporally and spatially distributed sampling of water and sediment was conducted for one year and samples were analyzed for antibiotics and ARGs by using LC-MS/MS and qPCR. Results showed that both CWs removed antibiotics significantly with a comparable overall removal of 28%-100%, depending on the type of antibiotics. However, some of the antibiotics showed higher concentration after the CW treatment. Five antibiotics (tiamulin, tylosin, oxytetracycline, sulfamethoxazole and trimethoprim) were the most abundant (>1500 ng/l on average) in winter. Meanwhile, ermB was the most abundant (average of 5.0 log) in winter compared to summer (average of 3.5 log). Other ARGs did not show a significant increase or decrease between winter and summer. ARGs were removed from the wastewater by 0.8 to 1.5 log. The HRT did not influence the removal of either the antibiotics or the ARGs. A strong correlation was found between sul genes and intI1. The results also revealed a positive and a negative relationship from sampling point 1 to sampling point 5: a positive relation between abundance of antibiotics, ARGs, and of NO3-N, NH4-N, TP, COD and a negative relation between antibiotics, ARGs and temperature. This relationship showed the effect between antibiotics and ARGs concentrations with physicochemical parameters and nutrients. The ability of CWs to reduce the input of micropollutants into the environment makes CWs a potential post treatment to WWTP.

Fate of antibiotics and antibiotic resistance genes during conventional and additional treatment technologies in wastewater treatment plants.

Information on the removal of antibiotics and ARGs in full-scale WWTPs (with or without additional treatment technology) is limited. However, it is important to understand the efficiency of full-scale treatment technologies in removing antibiotics and ARGs under a variety of conditions relevant for practice to reduce their environmental spreading. Therefore, this study was performed to evaluate the removal of antibiotics and ARGs in a conventional wastewater treatment plant (WWTP A) and two full-scale combined with additional treatment technologies. WWTP B, a conventional activated sludge treatment followed by an activated carbon filtration step (1-STEP® filter) as a final treatment step. WWTP C, a treatment plant using aerobic granular sludge (NEREDA®) as an alternative to activated sludge treatment. Water and sludge were collected and analysed for 52 antibiotics from four target antibiotic groups (macrolides, sulfonamides, quinolones, tetracyclines) and four target ARGs (ermB, sul 1, sul 2 and tetW) and integrase gene class 1 (intI1). Despite the high removal percentages (79-88%) of the total load of antibiotics in all WWTPs, some antibiotics were detected in the various effluents. Additional treatment technology (WWTP C) showed antibiotics removal up to 99% (tetracyclines). For ARGs, WWTP C reduced 2.3 log followed by WWTP A with 2.0 log, and WWTP B with 1.3 log. This shows that full-scale WWTP with an additional treatment technology are promising solutions for reducing emissions of antibiotics and ARGs from wastewater treatment plants. However, total removal of the antibiotics and ARGS cannot be achieved for all types of antibiotics and ARGs. In addition, the ARGs were more abundant in the sludge compared to the wastewater effluent suggesting that sludge is an important reservoir representing a source for later ARG emissions upon reuse, i.e. as fertilizer in agriculture or as resource for bioplastics or bioflocculants. These aspects require further research.

Motion estimation and correction in cardiac CT angiography images using convolutional neural networks.

Cardiac motion artifacts frequently reduce the interpretability of coronary computed tomography angiography (CCTA) images and potentially lead to misinterpretations or preclude the diagnosis of coronary artery disease (CAD). In this paper, a novel motion compensation approach dealing with Coronary Motion estimation by Patch Analysis in CT data (CoMPACT) is presented. First, the required data for supervised learning is generated by the Coronary Motion Forward Artifact model for CT data (CoMoFACT) which introduces simulated motion to 19 artifact-free clinical CT cases with step-and-shoot acquisition protocol. Second, convolutional neural networks (CNNs) are trained to estimate underlying 2D motion vectors from 2.5D image patches based on the coronary artifact appearance. In a phantom study with computer-simulated vessels, CNNs predict the motion direction and the motion magnitude with average test accuracies of 13.37°±1.21° and 0.77 ±â€¯0.09 mm, respectively. On clinical data with simulated motion, average test accuracies of 34.85°±2.09° and 1.86 ±â€¯0.11 mm are achieved, whereby the precision of the motion direction prediction increases with the motion magnitude. The trained CNNs are integrated into an iterative motion compensation pipeline which includes distance-weighted motion vector extrapolation. Alternating motion estimation and compensation in twelve clinical cases with real cardiac motion artifacts leads to significantly reduced artifact levels, especially in image data with severe artifacts. In four observer studies, mean artifact levels of 3.08 ±â€¯0.24 without MC and 2.28 ±â€¯0.29 with CoMPACT MC are rated in a five point Likert scale.

Seropersistence and booster response following vaccination with FSME-IMMUN in children, adolescents, and young adults.

BACKGROUND: Tick-borne encephalitis (TBE) is a viral disease that can have a severe clinical course and considerable long-term morbidity. As no curative treatment exists, vaccination is the primary means of prevention. Long-term antibody seropersistence 2-5 years after the 3-dose primary immunization and 3-10 years after first booster was evaluated, as well as booster responses in children, adolescents and young adults. METHODS: Subjects who participated in these phase 4 prospective, open-label follow-up studies received all vaccinations with FSME-IMMUN. After 3-dose primary immunization, subjects were followed for 2-5 years. Overall, 205 out of 358 subjects (57%) received the first booster and 179 of these subjects (87%) enrolled in a further 10-year follow-up. Antibody seropersistence was assessed annually. Subjects with a TBE antibody titer below a pre-specified cut-off at the yearly blood draw received a booster. Seropositivity rates and geometric mean fold rises (GMFRs) were assessed. RESULTS: In children who received their 3-dose primary immunization between 1 and 15 years of age, the seropositivity rate 5 years after the 3rd dose was 84.9% by NT and 72.0% by ELISA. One month post-first booster, all subjects were seropositive by NT and 98.5% by ELISA. Response to first booster by GMFR ranged from 3.7 to 11.4. At 5 years post-first booster, seropositivity was 99.4% by NT and 97.5% by ELISA, and at 10 years, was 90.3% by NT and 87.7% by ELISA. Although seropositivity rates differed between age groups, all subjects (100%) who received a second booster responded with a robust increase of TBEV antibodies. DISCUSSION: Long-lasting seropersistence of TBEV antibodies after the 3-dose primary immunization and first booster was demonstrated as well as a competent immune memory response in those who received a first or second booster at any time during the 15-year follow-up. Therefore, an extension of FSME-IMMUN booster interval up to 10 years after the 3-dose primary immunization seems warranted. ClinicalTrials.gov Identifier: NCT00894686.

[Catheterization of the subclavian vein and the risk of pneumothorax : Mechanical ventilation increases the risk of pneumothorax during infraclavicular landmark-guided subclavian vein puncture: a prospective randomized study]. / Vena-subclavia-Katheter und Pneumothoraxrisiko : Maschinelle Beatmung erhöht das Pneumothoraxrisiko während infraklavikulärer landmarkengestützter V.­subclavia-Punktion: eine prospektive randomisierte Studie.

BACKGROUND: Infraclavicular subclavian vein (SCV) catheterization is a standard procedure in anesthesia and intensive care. There is a lack of evidence on how mechanical ventilation during venipuncture of the SCV influences pneumothorax rates. OBJECTIVE: Primary hypothesis: non-inferiority of continuing vs. discontinuing mechanical ventilation during infraclavicular puncture of the SCV with respect to the pneumothorax rate. MATERIAL AND METHODS: This prospective, randomized and single-blinded study was approved by the local ethics committee. A total of 1021 eligible patients who underwent cranial neurosurgery in 2 different university hospitals were assessed between August 2014 and October 2017. Patients were randomly assigned to two groups directly before induction of anesthesia. Intervention groups for venipuncture of the SCV were mechanical ventilation: tidal volume 7 ml/kg ideal body weight, positive end expiratory pressure (PEEP) ideal body weight/10, n = 535, or apnea: manual/spontaneous, APL valve 0 mbar, n = 486. Patients and the physicians who assessed pneumothorax rates were blinded to the intervention group. Venipuncture was carried out by both inexperienced and experienced physicians. RESULTS: The pneumothorax rate was significantly higher in the mechanical ventilation group (2.2% vs. 0.4%; p = 0.012) with an odds ratio (OR) of 5.63 (95% confidence interval, CI: 1.17-27.2; p = 0.031). A lower body mass index (BMI) was associated with a higher pneumothorax rate, OR 0.89 (95% CI: 0.70-0.96; p = 0.013). CONCLUSION: In this study landmark-guided infraclavicular SCV catheterization was associated with a significantly higher rate of pneumothorax when venipuncture was performed during mechanical ventilation and not in apnea. If a short phase of apnea is justifiable in the patient, mechanical ventilation should be discontinued during the venipuncture procedure.

Motion artifact recognition and quantification in coronary CT angiography using convolutional neural networks.

Excellent image quality is a primary prerequisite for diagnostic non-invasive coronary CT angiography. Artifacts due to cardiac motion may interfere with detection and diagnosis of coronary artery disease and render subsequent treatment decisions more difficult. We propose deep-learning-based measures for coronary motion artifact recognition and quantification in order to assess the diagnostic reliability and image quality of coronary CT angiography images. More specifically, the application, steering and evaluation of motion compensation algorithms can be triggered by these measures. A Coronary Motion Forward Artifact model for CT data (CoMoFACT) is developed and applied to clinical cases with excellent image quality to introduce motion artifacts using simulated motion vector fields. The data required for supervised learning is generated by the CoMoFACT from 17 prospectively ECG-triggered clinical cases with controlled motion levels on a scale of 0-10. Convolutional neural networks achieve an accuracy of 93.3% ±â€¯1.8% for the classification task of separating motion-free from motion-perturbed coronary cross-sectional image patches. The target motion level is predicted by a corresponding regression network with a mean absolute error of 1.12 ±â€¯0.07. Transferability and generalization capabilities are demonstrated by motion artifact measurements on eight additional CCTA cases with real motion artifacts.

[Joint pain and consumption of analgesics among young elite athletes : Nationwide data from youth basketball]. / Gelenkschmerzen und Analgetikakonsum bei jungen Leistungssportlern : Bundesweite Daten aus dem Jugendbasketball.

BACKGROUND: Joint pain may be an early indicator of biomechanical stress. During adolescence the physical development, including the development of the musculoskeletal system, is still ongoing and joint pain requires special attention, especially among young athletes. OBJECTIVE: Young athletes from the highest national basketball leagues in Germany were questioned about prevalence, location, context and coping strategies concerning joint pain. MATERIAL AND METHODS: Data were derived from the German "Adolescents' and Childrens' Health in Elite Basketball study" (ACHE study). Analyses were based on an online survey of 182 elite basketball players between 13 and 19 years of age from 46 German teams, conducted between April 2016 and June 2016. RESULTS: In the highest German leagues 2 out of 3 players suffered from joint pain at the time of the survey (7-day prevalence 64.6%). Pain in the lower extremities occurred most frequently. The 7­day prevalence for knee and leg pain reached up to 40% and foot pain up to 21%. For 84% of all players, occasional consumption of analgesics was the norm and 40% took them frequently. The consumption of several medicinal substances, especially of cyclooxygenase inhibitors, such as ibuprofen and diclofenac, is widespread among adolescent elite basketball players as 1 out of 7 athletes (13%) used medicinal substances despite being pain-free and 5% used it prophylactically with the purpose of preventing pain. CONCLUSION: From the point of view of pain medicine, it is not only the high prevalence of pain that is remarkable but also the widespread use of analgesics without a prescription and the misguided conception of adolescent competitive athletes that such medications have preventive effects.

Review of basal-plus insulin regimen options for simpler insulin intensification in people with Type 2 diabetes mellitus.

AIMS: To identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities. METHODS: Using randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta-analyses and proof-of-concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal-plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short-acting insulin injections/day) vs a basal-bolus regimen (basal insulin plus three short-acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal-plus regimens, differences among insulin titration algorithms, and the importance of self-motivation and autonomy in achieving optimum glycaemic control. RESULTS: A basal-plus regimen can provide glycaemic control equivalent to that obtained with a full basal-bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day. CONCLUSIONS: Compared with a basal-bolus regimen, a basal-plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world.

ESBL carriage in pig slaughterhouse workers is associated with occupational exposure.

We investigated the prevalence of extended-spectrum ß-lactamase (ESBL) carriage in slaughterhouse workers and the association with occupational exposure to slaughter animals and products. Stool samples from 334 employees in a Dutch pig slaughterhouse were obtained. Presence of ESBL was determined by selective plating, microarray analysis, and gene sequencing. Questionnaires were used to collect personal and occupational information. The overall prevalence of ESBL carriage was 4·8% (16/334). All ESBL-producing isolates were Escherichia coli. The ESBL genes detected were bla CTX-M-1 (n = 8), bla CTX-M-15 (n = 3), bla CTX-M-27 (n = 2), bla CTX-M-24 (n = 1), bla CTX-M-55 (n = 1), and bla SHV-12 (n = 1). A higher prevalence of ESBL was seen in workers in jobs with as tasks 'removal of lungs, heart, liver, tongue' (33%), and 'removal of head and spinal cord' (25%). For further analysis, participants were divided in two groups based on potential exposure to ESBL as related to their job title. One group with an assumed higher exposure to ESBL (e.g. stable work, stabbing, dehairing, removal of organs) and another group with an assumed lower exposure to ESBL (e.g. refrigeration, packaging and expedition). In the 'higher exposure' group, ten out of 95 (10·5%) were carrying ESBL vs. six out of 233 (2·6%) in the 'lower exposure' group. Human ESBL carriage was significantly associated with job exposure in the slaughterhouse (OR 4·5, CI 1·6-12·6). Results suggest that ESBL carriage in slaughterhouse workers overall is comparable with the Dutch population. Within the slaughterhouse population a difference in carriage exists depending on their position along the slaughter line and tasks involved.

Osteoarthritis and joint replacements of the lower limb and spine in ex-professional soccer players: A systematic review.

After a professional career as a soccer player, the risk of developing osteoarthritis (OA) in different joints of the spine and lower limb might be increased. The extent of this problem to date is not clear. Therefore, the aim of this systematic review is to summarize the prevalence of OA and joint replacement of the lower limb and spine in former professional soccer players. Relevant databases were searched with different combinations of key words: for example, OA, hip, knee, ankle, foot, joint replacement, soccer. Studies were included if they were original research, included a sample of former professional male soccer players, and had OA in the lower limb and/or spine; OA was diagnosed either through questionnaires or X-rays; and the article is in English, Dutch, or German. Sixteen studies with 1576 former players and 2153 control subjects were included in the review. Studies agreed that the prevalence of hip OA and hip replacements is significantly higher in former players compared to the control group. For the ankle and spine, there is only limited information, and for the prevalence of knee OA and knee replacement, the results are contradictory. The quality of the included studies was moderate. Future studies should have a prospective design to control for confounding factors, to identify possible risk factors and consequences for the individuals, and to be able to develop a prevention program.

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

AIMS: To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. METHODS: This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of <7.0% (<53mmol/mol) per baseline HbA1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. RESULTS: Patients had comparable demographic characteristics and similar HbA1c and FHG values at baseline in each HbA1c quartile regardless of whether they reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. CONCLUSION: Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens.

Effect of kinesiotaping, non-elastic taping and bracing on segmental foot kinematics during drop landing in healthy subjects and subjects with chronic ankle instability.

OBJECTIVE: To evaluate the effects of kinesiotape, non-elastic tape, and soft brace on segmental foot kinematics during drop landing in subjects with chronic ankle instability and healthy subjects. DESIGN: Controlled study with repeated measurements. SETTING: Three-dimensional motion analysis laboratory. PARTICIPANTS: Twenty participants with chronic ankle instability and 20 healthy subjects. INTERVENTIONS: The subjects performed drop landings with 17 retroreflective markers on the foot and lower leg in four conditions: barefoot, with kinesiotape, with non-elastic tape and with a soft brace. MAIN OUTCOME MEASURES: Ranges of motion of foot segments using a foot measurement method. RESULTS: In participants with chronic ankle instability, midfoot movement in the frontal plane (inclination of the medial arch) was reduced significantly by non-elastic taping, but kinesiotaping and bracing had no effect. In healthy subjects, both non-elastic taping and bracing reduced that movement. In both groups, non-elastic taping and bracing reduced rearfoot excursion in inversion/eversion significantly, which indicates a stabilisation effect. No such effect was found with kinesiotaping. All three methods reduced maximum plantar flexion significantly. CONCLUSIONS: Non-elastic taping stabilised the midfoot best in patients with chronic ankle instability, while kinesiotaping did not influence foot kinematics other than to stabilise the rearfoot in the sagittal plane. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01810471.

Formation of polycyclic aromatic hydrocarbons from bimolecular reactions of phenyl radicals at high temperatures.

The self-reaction of the phenyl radical is one of the key reactions in combustion chemistry. Here we study this reaction in a high-temperature flow reactor by IR/UV ion dip spectroscopy, using free electron laser radiation as mid-infrared source. We identified several major reaction products based on their infrared spectra, among them indene, 1,2-dihydronaphthalene, naphthalene, biphenyl and para-terphenyl. Due to the structural sensitivity of the method, the reaction products were identified isomer-selectively. The work shows that the formation of indene and naphthalene, which was previously considered to be evidence for the HACA (hydrogen abstraction C2H2 addition) mechanism in the formation of polycyclic aromatic hydrocarbons and soot can also be understood in a phenyl addition model.

Individualizing treatment of type 2 diabetes by targeting postprandial or fasting hyperglycaemia: Response to a basal vs a premixed insulin regimen by HbA1c quartiles and ethnicity.

AIM: This study evaluated the proportions of prandial (PHG) vs fasting hyperglycaemia (FHG) over 24h in a group of patients with type 2 diabetes (overall and for Caucasian vs Asian patients), and tested the hypothesis that an insulin regimen with a prandial component allows a greater response than basal insulin at low glycated haemoglobin (HbA1c) levels with a higher proportion of PHG than FHG. METHODS: Relative contributions of PHG and FHG to overall hyperglycaemia were analyzed by baseline HbA1c quartiles and by ethnicity at baseline and after 24-week treatment with either insulin glargine or insulin lispro mix 25 in the DURABLE study. RESULTS: With increasing baseline HbA1c, the mean relative contribution of PHG to the total area under the curve decreased (from 41% to 27%) while FHG was increased (from 59% to 73%). Both insulins decreased FHG, but only insulin lispro mix 25 decreased PHG. More patients with baseline HbA1c < 9%, where PHG was more relevant, achieved the target HbA1c of < 7% at endpoint with insulin lispro mix 25 compared with glargine. On average, Asians had a 10% larger contribution of PHG at all HbA1c quartiles, and a lower proportion of Asians reached the HbA1c target of < 7% with either insulin treatment compared with Caucasians. CONCLUSION: At baseline, the contribution of FHG to overall hyperglycaemia predominated at all HbA1c quartiles, whereas PHG was more clinically relevant at lower HbA1c levels and with a greater response to insulin lispro mix 25. Asians had a greater proportion of PHG and a lesser response to either insulins compared with Caucasians. Thus, responses to diabetes drugs by baseline HbA1c and ethnicity are worth investigating to better target and individualize treatment.

Studies on the effect of storage time and plasticizers on the structural variations in thermoplastic starch.

Starch was combined with plasticizers such as glycerol, sorbitol, glycerol/sorbitol and urea/ethanolamine blends by means of high shear extrusion process to prepare thermoplastic starch (TPS). Effect of storage time and plasticizers on the structural stability of melt processed TPS was investigated. Morphological observation, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy reveal that melt extrusion process is efficient in transforming granular starch into a plasticized starch for all plasticizer compositions. XRD analysis highlights major changes in the microstructure of plasticized starch, and dependence of crystalline type and degree of crystallinity mainly on the plasticizer composition and storage time. Dynamical mechanical analysis (DMA) yields a decrease of the peak intensity of loss factor with aging time. The effect of ageing on tensile strength also appears to be highly dependent on the plasticizer composition. Thus, through different plasticizer combinations and ageing, starch-based materials with significant differences in tensile properties can be obtained, which may be tuned to meet the requirements of a wide range of applications.

Adult vaccination.

Vaccination of children has had a major impact on the morbidity and mortality of many infectious diseases globally. However, with age, immune responses to vaccines can be less robust, which can be further enhanced by underlying diseases that are common in the older adult. In many countries around the globe booster vaccinations against diphtheria, tetanus, and pertussis are recommended for adults. For the older adult, vaccination against pneumococcal diseases, influenza and herpes zoster are also recommended. Despite these recommendations, the widespread use of these vaccines in the adult population clearly lags behind the vaccine uptake and successes documented for pediatric vaccination programs. Furthermore, extensive and sometimes inappropriate use of antibiotics have fostered the emergence of antibiotic-resistant bacteria (e.g., methicillin resistant Staphylococcus aureus (MRSA)) as well as increased susceptibility in the elderly to bacterial species such as Clostridium difficile. Infectious diseases remain an important unmet medical need and new concepts to successfully implement vaccination of adults are urgently needed.