Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D3 and simulated sunlight supplementation trial in healthy adults.

PURPOSE: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. RESULTS: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41-71 nmol/L mean difference [95% confidence interval] - 15% [- 26, - 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L - 12% [- 24%, - 1%]). Vaccine response was also poorer in winter than summer (- 18% [- 31%, - 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [- 21%, 14%]). CONCLUSION: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. CLINICAL TRIAL REGISTRY NUMBER: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103

Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus Infection

BACKGROUND: Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc. METHODS: We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals. RESULTS: In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011). CONCLUSION: This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination

Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach

Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections

Handhaving van een rookvrij binnenmilieu

Abstract niet beschikbaarAbstract not availableVW

What do Dutch adolescents smoke and why?

Volgens rokende jongeren kiezen zij hun sigarettenmerk in twee derde van de gevallen vanwege de smaak. Daarnaast bepalen merktrouw, de verkrijgbaarheid van het merk en de prijs de keuze. De meerderheid van de rokende jongeren zegt te willen stoppen, vooral vanwege de kosten en het negatieve effect op hun gezondheid. Dit blijkt uit een online enquete door het RIVM naar het rookgedrag en de productkeuze van jongeren tot en met 18 jaar. De vragenlijst is uitgezet op scholen en op de websites van STIVORO en Scholieren.com, wat resulteerde in bijna vijfduizend ingevulde vragenlijsten. Uit de enquete blijkt ook dat de belangrijkste redenen om te beginnen met roken nieuwsgierigheid, rokers in de sociale omgeving en een positieve verwachting van de smaak zijn. Rokers steken meestal een sigaret op omdat ze er zin in hebben en omdat ze het ontspannend vinden. Ook zeggen ze zich lekker en voldaan te voelen door te roken. Omdat roken aanzienlijke gezondheidschade veroorzaakt bij zowel de roker als zijn omgeving, is het van groot belang met beleidsmaatregelen te voorkomen dat jongeren roken. Op grond van de resultaten van de enquete en literatuuronderzoek doet het RIVM enkele aanbevelingen. Aangezien smaak mede wordt bepaald door additieven in tabak, wordt aanbevolen om het gebruik van additieven die de smaak van rook verbeteren te beperken. Daarnaast is het van belang tegemoet te komen aan de informatiebehoefte van jongeren over de samenstelling en de effecten van tabaksproducten. Tot slot is het belangrijk om naast primaire preventie sterk in te zetten op stoppen-met-rokenprogramma's bij jongeren, vooral bij beginnende rokers. Hierbij lijkt een doelgroepgerichte aanpak, bijvoorbeeld gericht op jongeren met een lager opleidingsniveau, effectief.More than two thirds of smoking adolescents report that they choose their brand of cigarettes on the basis of taste. Additional factors influencing their choice are brand loyalty, availability of the brand and price. Most adolescent smokers say that they want to quit smoking, mainly because of the costs and the negative effects on their health. These are the conclusions drawn from the results of an online survey carried out by the RIVM on smoking behaviour and product choice of adolescents up to 18 years of age. The questionnaire was announced on schools and on the websites of STIVORO and Scholieren.com. Almost 5000 questionnaires were completed. The answers to the survey indicate that curiosity, smokers in their social circle and positive expectations of the taste are the most important reasons for adolescents to start smoking. Smokers usually light up a cigarette because they feel like having one and because smoking relaxes them. The respondents also reported that smoking makes them feel good and gives them a feeling of satisfaction. Smoking causes severe health damage to both the smoker and his environment. It is therefore of major importance that there are adequate policy measures to prevent adolescents from starting to smoke. Based on the survey results and on a literature search, RIVM has made a number of recommendations. As taste is also determined by tobacco additives, one recommendation is that the use of additives that migitate the taste of smoke be restricted. It is also of the greatest importance to satisfy the adolescent's need for information on the composition and the effects of tobacco products. Finally, in addition to measures aimed at the primary prevention of smoking, stop smoking programmes directed towards adolescents, especially the starting smoker, are of major importance. In the latter case, the most effective approach appears to be that of focusing on a target group, such as a stop smoking programme aimed at youth with a low level of education.VWS-VG

Environmental tobacco smoke and alternatives for smoking rooms

Door het roken en smeulen van tabaksproducten ontstaat omgevingstabaksrook. Door TNO en RIVM is aan de hand van een aantal indicatorstoffen onderzocht hoeveel omgevingstabaksrook uit rookruimten van horecagelegenheden kan weglekken. De aanwezigheid van rookruimten in horecagelegenheden zorgt ervoor dat concentraties omgevingstabaksrook in de rookvrije ruimten ongeveer een factor 10 tot 100 lager zijn dan in gelegenheden zonder rookverboden. Rookruimten in de negentien onderzochte Nederlandse horecagelegenheden kunnen de concentraties omgevingstabaksrook in de rookvrije ruimte niet op het niveau brengen van volledig rookvrije horeca. De bezetting bij grote drukte, het gebruik van klapdeuren en het wegstromen van vervuilde lucht uit de rookkamer richting rookvrije ruimte door het aangelegde ventilatiesysteem, kunnen bijdragen aan aanzienlijke lekkage van zwerfrook, en dus belasting van de rookvrije ruimte. De gevonden concentraties in de rookvrije ruimten zijn ongeveer een factor 10 hoger dan in volledig rookvrije horeca. Zwerfrook uit rookruimten zorgt voor achtergrondconcentraties omgevingstabaksrook in de rookvrije ruimten. Er zijn alternatieven voor rookruimten beschikbaar en te ontwikkelen die deze achtergrondconcentraties in principe ook kunnen beperken. Om bij toepassing van deze alternatieve systemen de kwaliteit van de binnenlucht in horecagelegenheden te waarborgen, zou certificering toegepast kunnen worden op ontwerp, aanleg, onderhoud, gebruik en toezicht van deze systemen.Environmental tobacco smoke (ETS) is produced during smoking and smoldering of tobacco products. Based on several marker compounds TNO and RIVM have investigated how much ETS is leaking from smoking rooms into smoke free areas. The use of smoking rooms in the hospitality venues which have been investigated causes that ETS concentrations in smoke free areas of cafés are 10 to 100 times lower than those observed in hospitality industry where smoking is allowed. However, smoking rooms do not reduce ETS concentrations in the smoke free area to levels found in smoke free hospitality industry without smoking rooms. In particular high density of customers, de intensity of the smoking, the use of swing doors and transfer of smoke from the smoking room to the smoke free area by the ventilation system, are the cause of the 10 to 20 times elevated ETS concentrations. ETS from smoking rooms thus causes background concentrations in the smoke free areas of hospitality industry. Alternatives for the use of smoking rooms are available or can be developed. These alternatives may in principle be able to reduce the ETS background concentrations to the same levels. Certification may help to ensure the quality of the indoor air with respect to ETS concentrations in the future. Certification should not be limited to design, manufacture and use of equipment howver, since application, users density and control are of paramount importance.VW

Ultraviolet light and resistance to infectious diseases

Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune responses in animals and humans. This immunomodulation can lead to positive health effects especially with respect to certain autoimmune diseases and allergies. However, UV-induced immunomodulation has also been shown to be deleterious. Experimental animal studies have revealed that UV exposure can impair the resistance to many infectious agents, such as bacteria, parasites, viruses, and fungi. Importantly, these effects are not restricted to skin-associated infections, but also concern systemic infections. UV radiation induces a multistep process, locally in the skin as well as systemically, that ultimately leads to immunosuppression. The first event is the absorption of "UV" photons by chromophores, or so-called photoreceptors, such as DNA and urocanic acid (UCA) in the upper cell layers of the skin. Upon absorption of UV radiation, trans-UCA isomerizes to the cis-isomer. Cis-UCA is likely the most important mediator of UV-induced immunosuppression, as this compound has been shown to modulate the induction of contact type hypersensitivity and delayed type hypersensitivity, allograft rejection, and the functions of monocytes and T-lymphocytes as well as natural killer cells. The real consequences of UV-induced immunomodulation on resistance to infectious diseases for humans are not fully known. Risk estimations have been performed through extrapolation of animal data, obtained from infection models, to the human situation. This estimation indicated that UV doses relevant to outdoor exposure can impair the human immune system sufficiently to have effects on resistance to infections, but also indicated that human data are necessary to further quantify and validate this risk estimation. Further information has been obtained from vaccination studies in human volunteers as ethical reasons prohibit studies with infectious agents. Studies in mice and human volunteers on the effects of prior UVB exposure on hepatitis B vaccination responses revealed suppressed cellular and humoral immune responses in mice but not in human volunteers. However, subgroups within the performed human volunteer study made by determination of cytokine polymorphisms or UVB-induced mediators, revealed that some individuals have suppressed hepatitis B vaccination responses after UVB exposure. Thus, it might be concluded that the human immune system can be affected by UVB exposure, and decreased resistance to infectious diseases can be expected after sun exposure

Ultraviolet B radiation induces upregulation of calcitonin gene-related peptide levels in human Finn chamber skin samples

Ultraviolet B radiation induces upregulation of calcitonin gene-related peptide levels in human Finn chamber skin samples. Sleijffers A, Herreilers M, van Loveren H, Garssen J. Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands. [email protected] One of the neuropeptides that plays a role in UVB-induced immunomodulation is calcitonin gene-related peptide (CGRP), as demonstrated in several animal studies. CGRP can be detected in human skin, but effects of UVB exposure on CGRP levels in human skin are not known. We determined CGRP levels in human Finn chamber skin samples of 15 UVB-irradiated and 10 control volunteers. Filter samples were collected prior to and immediately after a UVB exposure protocol (5 consecutive days, with one personally determined minimal erythema dose (MED(jp)) per day). CGRP levels in filter samples were determined using a commercially available radioimmunoassay kit. CGRP could be detected in the filter samples and volunteers showed statistically significantly increased levels after UVB exposure. In addition, the CGRP levels of UVB-exposed volunteers were positively correlated with the dose of UVB in J/m(2) that they received on 5 consecutive days. In other words, higher UVB doses resulted in higher CGRP levels. In summary, CGRP, a mediator in UVB-induced immunomodulation, could be detected in human Finn chamber skin samples, and was significantly increased after UVB exposure. The CGRP level appeared to depend on the amount of UVB the volunteers received

Environmental tobacco smoke and alternatives for smoking rooms

Door het roken en smeulen van tabaksproducten ontstaat omgevingstabaksrook. Door TNO en RIVM is aan de hand van een aantal indicatorstoffen onderzocht hoeveel omgevingstabaksrook uit rookruimten van horecagelegenheden kan weglekken. De aanwezigheid van rookruimten in horecagelegenheden zorgt ervoor dat concentraties omgevingstabaksrook in de rookvrije ruimten ongeveer een factor 10 tot 100 lager zijn dan in gelegenheden zonder rookverboden. Rookruimten in de negentien onderzochte Nederlandse horecagelegenheden kunnen de concentraties omgevingstabaksrook in de rookvrije ruimte niet op het niveau brengen van volledig rookvrije horeca. De bezetting bij grote drukte, het gebruik van klapdeuren en het wegstromen van vervuilde lucht uit de rookkamer richting rookvrije ruimte door het aangelegde ventilatiesysteem, kunnen bijdragen aan aanzienlijke lekkage van zwerfrook, en dus belasting van de rookvrije ruimte. De gevonden concentraties in de rookvrije ruimten zijn ongeveer een factor 10 hoger dan in volledig rookvrije horeca. Zwerfrook uit rookruimten zorgt voor achtergrondconcentraties omgevingstabaksrook in de rookvrije ruimten. Er zijn alternatieven voor rookruimten beschikbaar en te ontwikkelen die deze achtergrondconcentraties in principe ook kunnen beperken. Om bij toepassing van deze alternatieve systemen de kwaliteit van de binnenlucht in horecagelegenheden te waarborgen, zou certificering toegepast kunnen worden op ontwerp, aanleg, onderhoud, gebruik en toezicht van deze systemen.Environmental tobacco smoke (ETS) is produced during smoking and smoldering of tobacco products. Based on several marker compounds TNO and RIVM have investigated how much ETS is leaking from smoking rooms into smoke free areas. The use of smoking rooms in the hospitality venues which have been investigated causes that ETS concentrations in smoke free areas of cafés are 10 to 100 times lower than those observed in hospitality industry where smoking is allowed. However, smoking rooms do not reduce ETS concentrations in the smoke free area to levels found in smoke free hospitality industry without smoking rooms. In particular high density of customers, de intensity of the smoking, the use of swing doors and transfer of smoke from the smoking room to the smoke free area by the ventilation system, are the cause of the 10 to 20 times elevated ETS concentrations. ETS from smoking rooms thus causes background concentrations in the smoke free areas of hospitality industry. Alternatives for the use of smoking rooms are available or can be developed. These alternatives may in principle be able to reduce the ETS background concentrations to the same levels. Certification may help to ensure the quality of the indoor air with respect to ETS concentrations in the future. Certification should not be limited to design, manufacture and use of equipment howver, since application, users density and control are of paramount importance.VW