GlycoNote with Iterative Decoy Searching and Open-Search Component Analysis for High-Throughput and Reliable Glycan Spectral Interpretation.

Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.

Factors associated with HPV vaccination decision-making among Korean American women.

Despite a significant reduction of human papillomavirus (HPV) infection in the United States in the past decade, Korean American (KA) women experience a disproportionately high cervical cancer burden due to low HPV vaccination rates. Given associations between parental decision-making and adolescent vaccination, it is crucial to identify and address factors influencing parental HPV vaccination decision-making for their children. The purpose of this study was to examine the sociodemographic characteristics and health literacy factors in relation to KA women's willingness to allow their daughters to receive HPV vaccination. We used baseline data collected from 560 KA women who participated in a cluster-randomized trial designed to promote mammography and Pap test screening. Participants answered study questionnaires measuring individual characteristics, cancer literacy, HPV knowledge, and HPV vaccination decision-making for their daughters. Multivariate logistic regression analysis was conducted to identify the correlates of HPV vaccination decision-making among participants. Over half of the participants (54%) endorsed HPV vaccination for their daughters. Low knowledge, compared to high and medium HPV knowledge (aOR 3.48, CI 2.01-6.04 and aOR 2.14, CI 1.46-3.12, respectively), were significantly associated with higher odds of participants' intention to vaccinate their daughters. Additionally, in comparison to low cancer literacy, middle-range cancer literacy (aOR 1.70, CI 1.08-2.68) was significantly associated with higher odds of participants' intention to vaccinate their daughters. Misperceptions about cancer and low HPV knowledge among KA women should be considered when providing vaccine counseling and developing interventions to promote cervical health in this population.

Human Milk Oligosaccharide Compositions Illustrate Global Variations in Early Nutrition.

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Human Milk Proteins and Their Glycosylation Exhibit Quantitative Dynamic Variations during Lactation.

BACKGROUND: Proteins in human milk are essential and known to support the growth, development, protection, and health of the newborn. These proteins are highly modified by glycans that are currently being recognized as vital to protein structure, stability, function, and health of the intestinal mucosa. Although milk proteins have been studied, the quantitative changes in milk proteins and their respective site-specific glycosylation are unknown. OBJECTIVE: This study expanded the analytical tools for milk proteins and their site-specific glycosylation and applied these tools to a large cohort to determine changes in individual protein concentrations and their site-specific N-glycosylation across lactation. DESIGN: A tandem mass spectrometry method was applied to 231 breast-milk samples from 33 mothers in Davis, California, obtained during 7 different periods of lactation. Dynamic changes in the absolute abundances of milk proteins, as well as variation in site-specific N-glycosylation of individual proteins, were quantified. RESULTS: α-Lactalbumin, ß-casein, k-casein, and α-antitrypsin were significantly increased from colostrum to transitional milk (4.37 ± 1.33 g/L to 6.41 ± 0.72 g/L, 2.25 ± 0.86 g/L to 2.59 ± 0.78 g/L, 1.33 ± 0.44 g/L to 1.60 ± 0.39 g/L, and 0.09 ± 0.10 g/L to 0.11 ± 0.04 g/L, respectively; P < 0.002). α-Lactalbumin (37%), ß-casein (9%), and lysozyme (159%) were higher in mature milk than in colostrum. Glycans exhibited different behavior. Fucosylated glycans of lactoferrin and high-mannose, undecorated, fucosylated, sialylated, and combined fucosylated + sialylated glycans of secretory immunoglobulin A increased during lactation even when the concentrations of the parent proteins decreased. CONCLUSIONS: Proteins in healthy mothers vary dynamically through lactation to support the development of infants. Individual milk proteins carried unique glycan modifications that varied systematically in structure even with site specificity. The role of glycosylation in human milk proteins will be important in understanding the functional components of human milk. This trial was registered at clinicaltrials.gov as NCT01817127.

Identification of Oligosaccharides in Feces of Breast-fed Infants and Their Correlation with the Gut Microbial Community.

Glycans in breast milk are abundant and found as either free oligosaccharides or conjugated to proteins and lipids. Free human milk oligosaccharides (HMOs) function as prebiotics by stimulating the growth of beneficial bacteria while preventing the binding of harmful bacteria to intestinal epithelial cells. Bacteria have adapted to the glycan-rich environment of the gut by developing enzymes that catabolize glycans. The decrease in HMOs and the increase in glycan digestion products give indications of the active enzymes in the microbial population. In this study, we quantitated the disappearance of intact HMOs and characterized the glycan digestion products in the gut that are produced by the action of microbial enzymes on HMOs and glycoconjugates from breast milk. Oligosaccharides from fecal samples of exclusively breast-fed infants were extracted and profiled using nanoLC-MS. Intact HMOs were found in the fecal samples, additionally, other oligosaccharides were found corresponding to degraded HMOs and non-HMO based compounds. The latter compounds were fragments of N-glycans released through the cleavage of the linkage to the asparagine residue and through cleavage of the chitobiose core of the N-glycan. Marker gene sequencing of the fecal samples revealed bifidobacteria as the dominant inhabitants of the infant gastrointestinal tracts. A glycosidase from Bifidobacterium longum subsp. longum was then expressed to digest HMOs in vitro, which showed that the digested oligosaccharides in feces corresponded to the action of glycosidases on HMOs. Similar expression of endoglycosidases also showed that N-glycans were released by bacterial enzymes. Although bifidobacteria may dominate the gut, it is possible that specific minority species are also responsible for the major products observed in feces. Nonetheless, the enzymatic activity correlated well with the known glycosidases in the respective bacteria, suggesting a direct relationship between microbial abundances and catabolic activity.

Lipid-Based Nutrient Supplements During Pregnancy and Lactation Did Not Affect Human Milk Oligosaccharides and Bioactive Proteins in a Randomized Trial.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied. OBJECTIVE: We aimed to determine whether lipid-based nutrient supplements (LNSs) affect milk bioactive protein and HMO concentrations at 6 mo postpartum in women in rural Malawi. These are secondary outcomes of a previously published randomized controlled trial. METHODS: Women were randomly assigned to consume either an iron and folic acid capsule (IFA) daily from ≤20 wk gestation until delivery, followed by placebo daily from delivery to 6 mo postpartum, or a multiple micronutrient (MMN) capsule or LNS daily from ≤20 wk gestation to 6 mo postpartum. Breast milk concentrations of total HMOs, sialylated HMOs, fucosylated HMOs, lactoferrin, lactalbumin, lysozymes, antitrypsin, immunoglobulin A, and osteopontin were analyzed at 6 mo postpartum (n = 647). Between-group differences in concentrations and in proportions of women classified as having low concentrations were tested. RESULTS: HMO and bioactive protein concentrations did not differ between groups (P > 0.10 for all comparisons). At 6 mo postpartum, the proportions of women with low HMOs or bioactive proteins were not different between groups except for osteopontin. A lower proportion of women in the IFA group had low osteopontin compared with the LNS group after adjusting for covariates (OR: 0.5; 95% CI: 0.3, 0.9; P = 0.016). CONCLUSION: The study findings do not support the hypothesis that supplementation with an LNS or MMN capsule during pregnancy and postpartum would increase HMO or bioactive milk proteins at 6 mo postpartum among Malawian women. This trial was registered at clinicaltrials.gov as NCT01239693.

Portable acuity screening for any school: validation of patched HOTV with amblyopic patients and Bangerter normals.

BACKGROUND: We needed to validate and calibrate our portable acuity screening tools so amblyopia could be detected quickly and effectively at school entry. METHODS: Spiral-bound flip cards and download pdf surround HOTV acuity test box with critical lines were combined with a matching card. Amblyopic patients performed critical line, then threshold acuity which was then compared to patched E-ETDRS acuity. 5 normal subjects wore Bangerter foil goggles to simulate blur for comparative validation. RESULTS: The 31 treated amblyopic eyes showed: logMAR HOTV = 0.97(logMAR E-ETDRS)-0.04 r2 = 0.88. All but two (6%) fell less than 2 lines difference. The five showed logMAR HOTV = 1.09 ((logMAR E-ETDRS) + .15 r2 = 0.63. The critical-line, test box was 98% efficient at screening within one line of 20/40. CONCLUSION: These tools reliably detected acuity in treated amblyopic patients and Bangerter blurred normal subjects. These free and affordable tools provide sensitive screening for amblyopia in children from public, private and home schools. Changing "pass" criteria to 4 out of 5 would improve sensitivity with somewhat slower testing for all students.

Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo.

Rapid-throughput glycomics applied to human milk oligosaccharide profiling for large human studies.

Glycomic analysis is the comprehensive determination of glycan (oligosaccharide) structures with quantitative information in a biological sample. Rapid-throughput glycomics is complicated due to the lack of a template, which has greatly facilitated analysis in the field of proteomics. Furthermore, the large similarities in structures make fragmentation spectra (as obtained in electron impact ionization and tandem mass spectrometry) less definitive for identification as it has been in metabolomics. In this study, we develop a concept of rapid-throughput glycomics on human milk oligosaccharides, which have proven to be an important bioactive component of breast milk, providing the infant with protection against pathogenic infection and supporting the establishment of a healthy microbiota. To better understand the relationship between diverse oligosaccharides structures and their biological function as anti-pathogenic and prebiotic compounds, large human studies are needed, which necessitate rapid- to high-throughput analytical platforms. Herein, a complete glycomics methodology is presented, evaluating the most effective human milk oligosaccharide (HMO) extraction protocols, the linearity and reproducibility of the nano-liquid chromatography chip time-of-flight mass spectrometry (nano-LC chip-TOF MS) method, and the efficacy of newly developed, in-house software for chromatographic peak alignment that allows for rapid data analysis. High instrument stability and retention time reproducibility, together with the successful automated alignment of hundreds of features in hundreds of milk samples, allow for the use of an HMO library for rapid assignment of fully annotated structures.

Second National Immunization Congress 2010: addressing vaccine financing for the future in the US.

At the 2nd National Immunization Congress held in Chicago, IL, from August 31-September 2, 2010, partners from government, provider groups, academia, and manufacturers gathered to discuss the progress made and the future of financing child, adolescent, and adult vaccines. The meeting is a continuation of a solution-oriented vaccine financing dialogue held in February 2007 at the 1st Immunization Congress. The need for this forum arose from concerns that increased costs of immunization could hinder the ability of current financing and delivery systems to maintain access without financial barriers. Preventive care and additional financial coverage for vaccines are key points in federal health reform but some populations, especially adolescents and adults, could continue to experience challenges in accessing vaccines. Congress participants discussed adequate reimbursement in the public and private sectors for vaccine delivery and the potential financial resources, data, and infrastructure needed to increase vaccine uptake in the US. Participants agreed that partners from all sectors--manufacturers, providers, public health, employers, payors, insurers, and consumers--will collectively need to leverage their efforts to address financial gaps not covered by health care reform law to ensure the preventive benefits of vaccines are fully realized for all Americans.

Associations of Human Milk Oligosaccharides and Bioactive Proteins with Infant Morbidity and Inflammation in Malawian Mother-Infant Dyads.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relations is sparse. OBJECTIVES: We aimed to examine associations of milk content of HMOs and bioactive proteins with incidence and longitudinal prevalence of infant morbidity (any illness, fever, diarrhea, acute respiratory infection, and loss of appetite) and markers of inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)]. These are secondary analyses of a randomized controlled trial. METHODS: Breast milk samples at 6 mo postpartum (n  = 659) were analyzed to quantify absolute abundance of HMOs, relative abundance of fucosylated HMOs, sialylated HMOs, and 51 individual HMOs, and concentrations of 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of these constituents with infant morbidity from 6 to 7 and 6 to 12 mo, and CRP and AGP at 6 and 18 mo, considering maternal secretor status [presence or absence of the functional enzyme encoded by the fucosyltransferase 2 gene (FUT2) ] and adjusting for covariates and multiple hypothesis testing. RESULTS: In secretors there were positive associations between total HMOs and longitudinal prevalence of fever (P = 0.032), between fucosylated HMOs and incidence of diarrhea (P = 0.026), and between lactoferrin and elevated CRP at 18 mo (P = 0.011). In nonsecretors, there were inverse associations between lactoferrin and incidence of fever (P  = 0.007), between osteopontin and longitudinal prevalence of lost appetite (P  = 0.038), and between fucosylated HMOs and incidence of diarrhea (P = 0.025), lost appetite (P = 0.019), and concentrations of AGP and CRP at 6 mo (P = 0.001 and 0.010); and positive associations between total HMOs and incidence of lost appetite (P = 0.024) and elevated CRP at 18 mo (P  = 0.026), between lactalbumin and incidence of diarrhea (P = 0.006), and between lactoferrin and elevated CRP at 18 mo (P = 0.015). CONCLUSIONS: Certain HMOs and bioactive proteins were associated with infant morbidity and inflammation, particularly in nonsecretors. Further research is needed to elucidate the causality of these relations.This trial was registered at clinicaltrials.gov as NCT01239693.

Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries. OBJECTIVES: We aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi. METHODS: Breast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing. RESULTS: Among all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors. CONCLUSIONS: Certain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.

Analysis of Milk Oligosaccharides by Mass Spectrometry.

Human milk oligosaccharides (HMOs) are a highly abundant constituent in human milk, and its protective and prebiotic properties have attracted considerable attention. HMOs have been shown to directly and indirectly benefit the overall health of the infant due to a number of functions including serving as a beneficial food for gut bacteria, block to pathogens, and aiding in brain development. Researchers are currently exploring whether these structures may act as possible disease and nutrition biomarkers. Because of this, rapid-throughput methods are desired to investigate biological activity in large patient sets. We have optimized a rapid-throughput protocol to analyze human milk oligosaccharides using micro-volumes of human breast milk for nutritional biomarkers. This method may additionally be applied to other biological fluid substrates such as plasma, urine, and feces. The protocol involves lipid separation via centrifugation, protein precipitation using ethanol, alditol reduction with sodium borohydride, and a final solid-phase extraction purification step using graphitized carbon cartridges. Samples are analyzed using HPLC-Chip/TOF-MS and data filtered on Agilent MassHunter using an in-house library. Individual structural identification is matched against a previously developed HMO library using accurate mass and retention time. Using this method will allow in-depth characterization and profiling of HMOs in large patient sets, and will ease the process of discovering significant nutritional biomarkers in human milk.

The Serum Immunoglobulin G Glycosylation Signature of Gastric Cancer.

Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). Serum IgG was released and analyzed using nano-LC-TOF mass spectrometry. Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG and GC, three that distinguished NAG from DU, and eight that differed between DU and GC. The IgG glycosylation signature may be useful as a predictive marker for gastric cancer.

Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth.

OBJECTIVES: Curcumin (CUR), the active chemical of the Asian spice turmeric, has strong anti-oxidant and anti-inflammatory properties. CUR inhibits proliferation and growth of several cell types, e.g. cancer cells. While CUR inhibitory effects on microglial cells are demonstrated, little is known of its effects on neuroglia, astrocytes (AST) and oligodendrocytes (OLG). Our work focuses on CUR's effects on neuroglial proliferation and growth in vitro, utilizing C-6 rat glioma 2B-clone cells, a mixed colony of both neuroglial cells, in 6 day trials. METHODS: The doses studied included 4, 5, 10, 15, and 20 microM - concentrations slightly smaller than those shown to stimulate protein expression in ASTs. Automated particle counter was used to determine proliferation, and marker enzyme assays were used to determine AST and OLG activity. RESULTS: CUR inhibited neuroglial proliferation, with the degree of inhibition correlated directly with the CUR concentration. Proliferative inhibition was observed after a concentration as low as 5 microM by day 6, while inhibition of 20 microM doses occurred by day 2 of culture. Proliferative inhibition is associated with morphological changes, e.g. cell elongation and neurite prolongation, and increased activity of a marker enzyme corresponding to differentiation of OLG and with a reduced activity of the marker enzyme for AST. CONCLUSIONS: Our data suggests CUR acts continuously over a period of time, with low doses being as effective as higher doses given a longer period of treatment. It has been suggested that CUR's anti-inflammatory and anti-oxidant actions may be useful in the prevention-treatment of neurodegenerative diseases, e.g. Alzheimer's and Parkinson's Diseases. Given neuroglial involvement in these diseases, and CUR's observed actions on neuroglia, the data presented here may provide further explanations of CUR's preventative-therapeutic role in these diseases.

Prevalence of small-for-gestational-age and its mortality risk varies by choice of birth-weight-for-gestation reference population.

BACKGROUND: We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations. METHODS: We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality. RESULTS: The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in India, depending on the reference population. Females had higher rates of SGA than males using reference populations that were not sex specific. SGA prevalence was lowest when using reference populations from low-income countries. Infants who were both preterm and SGA had much higher mortality risk than those who were term and appropriate-for-gestational-age. Risk ratios for those who are both preterm and SGA ranged from 7.34-17.98 in Nepal and 5.29-11.98 in India, depending on the reference population. CONCLUSIONS: These results demonstrate the value of a common birth-weight-for-gestation reference population that will facilitate comparisons of SGA prevalence and mortality risk across research studies.

Adult immunization policies in advanced economies: vaccination recommendations, financing, and vaccination coverage.

OBJECTIVES: While many countries have robust child immunization programs and high child vaccination coverage, vaccination of adults has received less attention. The objective of this study was to describe the adult vaccination policies in developed countries. METHODS: From 2010 to 2011, we conducted a survey of 33 advanced economies as defined by the International Monetary Fund. The survey asked about national recommendations for adults for 16 vaccines or vaccine components, funding mechanisms for recommended adult vaccines, and the availability of adult vaccination coverage estimates. RESULTS: Thirty-one of 33 (93.9 %) advanced economies responded to the survey. Twelve of 31 (38.7 %) reported having a comprehensive adult immunization schedule. The total number of vaccines or vaccine components recommended for adults ranged from one to 15 with a median of 10. Seasonal influenza (n = 30), tetanus (n = 28), pneumococcal polysaccharide (n = 27), and hepatitis B (n = 27) were the most frequently recommended vaccines or components. CONCLUSIONS: Approximately two-thirds of survey respondents do not have a comprehensive adult vaccine schedule, and most do not measure vaccination coverage. We found that a funding mechanism is available for most recommended adult vaccines.

Variation in adult vaccination policies across Europe: an overview from VENICE network on vaccine recommendations, funding and coverage.

BACKGROUND: In 2010-2011, in the framework of the VENICE project, we surveyed European Union (EU) and Economic Area (EEA) countries to fill the gap of information regarding vaccination policies in adults. This project was carried out in collaboration with the United States National Vaccine Program Office, who conducted a similar survey in all developed countries. METHODS: VENICE representatives of all 29 EU/EEA-countries received an online questionnaire including vaccination schedule, recommendations, funding and coverage in adults for 17 vaccine-preventable diseases. RESULTS: The response rate was 100%. The definition of age threshold for adulthood for the purpose of vaccination ranged from 15 to 19 years (median=18 years). EU/EEA-countries recommend between 4 and 16 vaccines for adults (median=11 vaccines). Tetanus and diphtheria vaccines are recommended to all adults in 22 and 21 countries respectively. The other vaccines are mostly recommended to specific risk groups; recommendations for seasonal influenza and hepatitis B exist in all surveyed countries. Six countries have a comprehensive summary document or schedule describing all vaccines which are recommended for adults. None of the surveyed countries was able to provide coverage estimates for all the recommended adult vaccines. CONCLUSIONS: Vaccination policies for adults are not consistent across Europe, including the meaning of "recommended vaccine" which is not comparable among countries. Coverage data for adults should be collected routinely like for children vaccination.