Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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A systematic knowledge synthesis on the spatial dimensions of Q fever epidemics
Rooij, Myrna M.T. de; Leuken, Jeroen P.G. van; Swart, Arno ; Kretzschmar, Mirjam E.E. ; Nielen, Mirjam ; Koeijer, Aline A. de; Janse, Ingmar ; Wouters, Inge M. ; Heederik, Dick J.J. - \ 2018
Zoonoses and Public Health (2018). - ISSN 1863-1959
airborne exposure - Coxiella burnetii - epidemiology - Q fever - risk assessment - spatial analysis

From 2007 through 2010, the Netherlands experienced the largest Q fever epidemic ever reported. This study integrates the outcomes of a multidisciplinary research programme on spatial airborne transmission of Coxiella burnetii and reflects these outcomes in relation to other scientific Q fever studies worldwide. We have identified lessons learned and remaining knowledge gaps. This synthesis was structured according to the four steps of quantitative microbial risk assessment (QMRA): (a) Rapid source identification was improved by newly developed techniques using mathematical disease modelling; (b) source characterization efforts improved knowledge but did not provide accurate C. burnetii emission patterns; (c) ambient air sampling, dispersion and spatial modelling promoted exposure assessment; and (d) risk characterization was enabled by applying refined dose–response analyses. The results may support proper and timely risk assessment and risk management during future outbreaks, provided that accurate and structured data are available and exchanged readily between responsible actors.

Prevalence of Leptospira spp. and Seoul hantavirus in brown rats (Rattus norvegicus) in four regions in the Netherlands, 2011-2015
Maas, Miriam ; Vries, Ankje De; Reusken, Chantal ; Buijs, Jan ; Goris, Marga ; Hartskeerl, Rudy ; Ahmed, Ahmed ; Tulden, Peter van; Swart, Arno ; Pijnacker, Roan ; Koene, Miriam ; Lundkvist, Åke ; Heyman, Paul ; Rockx, Barry ; Giessen, Joke Van Der - \ 2018
Infection Ecology and Epidemiology 8 (2018)1.
epidemiology - hantavirus - Leptospirosis - prevalence - Rattus norvegicus - Seoul virus

Background: Brown rats (Rattus norvegicus) may carry pathogens that can be a risk for public health. Brown rats in the Netherlands were tested for the zoonotic pathogens Leptospira spp. and Seoul hantavirus (SEOV), in order to obtain insight in their prevalence. Methods and results: Cross-sectional studies were performed at four locations from 2011 to 2015. The rats were tested for Leptospira spp. using real-time PCR and/or culture resulting in a prevalence ranging between 33–57%. Testing for SEOV was done through an adapted human Seoul hantavirus ELISA and real-time RT-PCR. Although at several locations the ELISA indicated presence of SEOV antibodies, none could be confirmed by focus reduction neutralization testing. Conclusion: The results indicate a widespread presence of Leptospira spp. in brown rats in the Netherlands, including areas with a low leptospirosis incidence in humans. No evidence for circulation of SEOV was found in this study.

On the role of vaccine dose and antigenic distance in the transmission dynamics of Highly Pathogenic Avian Influenza (HPAI) H5N1 virus and its selected mutants in vaccinated animals
Sitaras, Ioannis - \ 2017
University. Promotor(en): Mart de Jong, co-promotor(en): Ben Peeters. - Wageningen : Wageningen University - ISBN 9789463438063 - 209
avian influenza viruses - avian influenza - disease transmission - vaccines - vaccination - dosage - antigenic variation - mutants - mutations - immunity - vaccine development - virology - epidemiology - aviaire influenzavirussen - aviaire influenza - ziekteoverdracht - vaccins - vaccinatie - dosering - antigene variatie - mutanten - mutaties - immuniteit - vaccinontwikkeling - virologie - epidemiologie

Influenza virus infections can cause high morbidity and mortality rates among animals and humans, and result in staggering direct and indirect financial losses amounting to billions of US dollars. Ever since it emerged in 1996 in Guangdong province, People’s Republic of China, one particular highly pathogenic avian influenza (HPAI) H5N1 virus has spread globally, and is responsible for massive losses of poultry, as well as human infections. For these reasons, HPAI H5N1 is considered as one of the viruses possible to cause a future influenza pandemic.

One of the main reasons why influenza is a recurring problem is its ability to constantly evolve through the selection of mutants that are able to avoid immunity (be it natural or acquired). Due to the accumulation of mutations during genome replication, diverse/variant influenza genome sequences co-exist in a virus pool (quasispecies). These sequences can contain mutations that are able to confer selective advantages to the influenza virus given the opportunity. As a consequence, whenever a situation arises that places the virus under any type of pressure that the dominant virus sequence cannot cope with (i.e. immune pressure, selective receptor binding, etc.), the virus with the genome sequence that allows it to better adapt to that particular pressure becomes selected and takes over.

Because of the influenza virus’s high rate of mutations, a global surveillance network is in place to monitor changes in circulating strains among humans that would warrant an update of the vaccines used. For human influenza strains, vaccines are updated frequently (every one or two years) and a similar situation holds true for racehorse vaccination. For avian influenza vaccination, however, the situation is different. In most countries, vaccination against avian influenza is not used, and in the countries where vaccines are used (either as routine or emergency measures), they are not updated as frequently as human vaccines are. In addition, in many instances vaccination against avian influenza viruses has met with some spectacular failures, since it failed to produce a level of immunity that would protect against circulating field strains. These vaccination failures have often been attributed to the fact that without constant vaccine updating (as is done for human influenza), the vaccines used are not able to keep up with continuously evolving antigenic variants selected in the field, and thus to protect poultry against them. In addition, since it is known that immune pressure resulting from vaccination can be a driving force in the evolution of influenza viruses and the selection of immune-escape mutants, there is a school of thought that posits that vaccination against avian influenza is not only a very expensive affair (especially if vaccines need to be frequently updated), but can also lead to selection of mutants that are able to avoid vaccination-induced immunity.

The research reported in this thesis started with addressing the gaps in the knowledge regarding the role of vaccination-induced immunity in the selection of immune-escape mutants of HPAI H5N1, and if there is a way for vaccines to still be able to protect against antigenically-distant variants of the vaccine seed strain, without the need for frequent vaccine updates.

Our first step in studying influenza virus evolution and selection of immune-escape mutants was to investigate how antigenic pressure may drive the selection of such mutants, and what the effect of the selected mutations on the pathogenicity and transmissibility of the mutants may be. Although there exist a variety of methods to select for influenza virus mutations (i.e. monoclonal antibodies, site-directed mutagenesis, reverse genetics, etc.), none of them is representative of selection as it happens in a vaccinated animal. In Chapter 2, we discuss in detail a laboratory-based system we have developed, in which immune-escape mutants are selected using homologous polyclonal chicken sera, similar to how they are selected in the field due to vaccination- induced immune pressure. We find that selection takes place early on, and additional mutations are selected when immune pressure is increased. Antigenic distances between the selected mutants and their parent strains are also increased throughout the selection process, but not in a linear fashion. Our selection system proved to be robust and replicable, and to be representative of selection in the field, since the mutations we selected for are also found in naturally-selected field isolates, and the antigenic distances between our selected mutants and their parent strains are similar to antigenic distances between vaccine strains and field isolates.

We continued our research by addressing the roles played by vaccine dose (and resulting immunity) and antigenic distance between vaccine and challenge strains, in the transmission of HPAI H5N1 viruses, by employing transmission experiments using vaccinated chickens (Chapter 3). To our surprise, we found that the effect of antigenic distances between vaccine and challenge strains on transmission is very small compared to the effect of vaccine dose. We then quantified, for the first time, the minimum level of immunity and minimum percentage of the vaccinated population exhibiting said immunity, in order for vaccines to be able to protect against transmission even of strains that are antigenically distant to the vaccine seed strain. Transmission of such strains in well-vaccinated populations would allow for a scenario where vaccination- induced immunity may drive the selection of immune-escape mutants. Our results show that in order for vaccines to prevent transmission of antigenically distant strains (such as the ones resulting from selection due to immune pressure), the threshold level of immunity against these strains should be ≥23 haemagglutination inhibition units (HIU), in at least 86.5% of the vaccinated population. This level of immunity can be estimated by knowing the antigenic distance between the vaccine and challenge (field) strain, and the HI titre against the vaccine strain, which would then allow the approximate level of immunity against the field strain to be deduced. For example, assuming the HI titre against a vaccine strain is 210 HIU, and the distance with the challenge (field) strain is 24 HIU, according to our results the vaccine should be able to protect against the challenge strain, because the difference in HI titres should be around 26 HIU (i.e. above 23 HIU). These results, taken together with our previous work on selection of mutants, where we showed that the antigenic distances between our mutants and their parent strains are representative of distances found in the field, point to the fact that it is unlikely that vaccination-induced immunity can lead to selection of mutants able to escape it, given that a threshold level of immunity in a minimum percentage of the vaccinated population is achieved. As a consequence, we believe that constant vaccine updating may not be necessary for avian influenza viruses, as long as a threshold level of immunity is maintained. This makes vaccination a more attractive control measure, both from a health perspective and a financial one, than just applying biosecurity measures.

To examine the effect the mutations in the haemagglutinin protein of our selected mutants may have in their transmission among chickens vaccinated with the parent strain, we used reverse genetics techniques to insert the HA gene of our most antigenically distant mutant into the parent strain backbone (Chapter 4). We vaccinated animals with a sub-optimal dose of vaccine, and we concluded that the mutations we selected for did not allow the mutant to avoid even low levels of immunity, such as the ones resulting from a sub-optimal vaccine dose (which resembles a poor field vaccination scenario). At the same time, the HA mutations we selected for did not appear to have a negative effect either on the pathogenicity of the mutant, or its ability to transmit to unvaccinated animals, since both parameters were comparable to the parent strain.

Finally, we studied the role inter-animal variation in immunity – as measured by HI titres – has in the accuracy of antigenic cartography calculations (Chapter 5). We found that using sera from more than one animal significantly increased the accuracy of antigenic distance calculations, since it takes into account individual differences in immune responses to vaccination, an inevitable phenomenon documented in both humans and animals. In addition, we increased the accuracy of antigenic maps by avoiding the use of dimension-reducing algorithms as is currently done. By not reducing the dimensionality of virus positioning in space, our maps retain the original geometry between strains or sera, leading to more accurate positioning (Chapters 2 and 5). We hope that improving the accuracy of antigenic cartography can lead to a more precise surveillance of influenza evolution and better informed decisions regarding the need to update vaccines.

Taken collectively, our results can improve field vaccination outcomes, since they provide guidelines on how to increase vaccination efficiency in stopping transmission of even antigenically-distant strains. In addition, our method for selecting for immune- escape mutants can be a valuable addition to research on influenza virus evolution. Moreover, policy making decisions regarding vaccination against any type of influenza can also benefit from our improvement on antigenic cartography accuracy, saving unnecessary costs in vaccine updating, and reducing morbidity and mortality of both animals and humans.

ESBL Evaluation framework
Bondt, N. ; Asseldonk, M.A.P.M. van; Bergevoet, R.H.M. - \ 2016
The Hague : LEI Wageningen UR (Report / LEI Wageningen UR 2016-020) - ISBN 9789462578517 - 45 p.
extended spectrum beta-lactamases - livestock - epidemiology - animal welfare - animal health - public health - food safety - risk management - verbreed spectrum bèta-lactamases - vee - epidemiologie - dierenwelzijn - diergezondheid - volksgezondheid - voedselveiligheid - risicobeheersing
Extended-spectrum bèta-lactamases (ESBL)-producing bacteria have become increasingly common in animals and humans. The goal of the presented ESBL evaluation framework is to help policy makers to evaluate the effectiveness of possible interventions aimed to reduce ESBL levels in livestock. An objective-driven ESBL policy approach (i.e., setting more clear and stringent objectives, for example maximum ESBL prevalence on national level) is preferable since much is unknown about other potential relevant measures and moreover the accountability of individual agents is hampered, which are both requisites for a measure-driven policy approach. In addition, for the nearby future, an additional measure is to extend the ban on some other antibiotics that are related to ESBLs.
Statistical modelling for exposure measurement error with application to epidemiological data
Agogo, G.O. - \ 2016
University. Promotor(en): Hendriek Boshuizen; Fred van Eeuwijk, co-promotor(en): Hilko van der Voet. - Wageningen : Wageningen University - ISBN 9789462576223 - 160 p.
calibration - regression analysis - exposure assessment - validity - simulation models - statistical bias - epidemiology - kalibratie - regressieanalyse - blootstellingsbepaling - geldigheid - simulatiemodellen - statistische vertekening - epidemiologie

Background Measurement error in exposure variables is an important issue in epidemiological studies that relate exposures to health outcomes. Such studies, however, usually pay limited attention to the quantitative effects of exposure measurement error on estimated exposure-outcome associations. Therefore, the estimators for exposure-outcome associations are prone to bias. Existing methods to adjust for the bias in the associations require a validation study with multiple replicates of a reference measurement. Validation studies with multiple replicates are quite costly and therefore, in some cases only a single–replicate validation study is conducted besides the main study. For a study that does not include an internal validation study, the challenge in dealing with exposure measurement error is even bigger. The challenge is how to use external data from other similar validation studies to adjust for the bias in the exposure-outcome association. In accelerometry research, various accelerometer models have currently been developed. However, some of these new accelerometer models have not been properly validated in field situations. Despite the widely recognized measurement error in the accelerometer, some accelerometers have been used to validate other instruments, such as physical activity questionnaires, in measuring physical activity. Consequently, if an instrument is validated against the accelerometer, and the accelerometer itself has considerable measurement error, the observed validity in the instrument being validated will misrepresent the true validity.

Methodology In this thesis, we adapted regression calibration to adjust for exposure measurement error for a single-replicate validation study with zero-inflated reference measurements and assessed the adequacy of the adapted method in a simulation study. For the case where there is no internal validation study, we showed how to combine external data on validity for self-report instruments with the observed questionnaire data to adjust for the bias in the associations caused by measurement error in correlated exposures. In the last part, we applied a measurement error model to assess the measurement error in physical activity as measured by an accelerometer in free-living individuals in a recently concluded validation study.

Results The performance of the proposed two-part model was sensitive to the form of continuous independent variables and was minimally influenced by the correlation between the probability of a non-zero response and the actual non-zero response values. Reducing the number of covariates in the model seemed beneficial, but was not critical in large-sample studies. We showed that if the confounder is strongly linked with the outcome, measurement error in the confounder can be more influential than measurement error in the exposure in causing the bias in the exposure-outcome association, and that the bias can be in any direction. We further showed that when accelerometers are used to monitor the level of physical activity in free-living individuals, the mean level of physical activity would be underestimated, the associations between physical activity and health outcomes would be biased, and there would be loss of statistical power to detect associations.

Conclusion The following remarks were made from the work in this thesis. First, when only a single-replicate validation study with zero-inflated reference measurements is available, a correctly specified regression calibration can be used to adjust for the bias in the exposure-outcome associations. The performance of the proposed calibration model is influenced more by the assumption made on the form of the continuous covariates than the form of the response distribution. Second, in the absence of an internal validation study, carefully extracted validation data that is transportable to the main study can be used to adjust for the bias in the associations. The proposed method is also useful in conducting sensitivity analyses on the effect of measurement errors. Lastly, when “reference” instruments are themselves marred by substantial bias, the effect of measurement error in an instrument being validated can be seriously underestimated.

Transmission of antibiotic resistance from animals to humans : Broilers as a reservoir of ESBL-producing bacteria
Huijbers, P.M.C. - \ 2016
University. Promotor(en): Mart de Jong; Lisette Graat; E. van Duijkeren. - Wageningen : Wageningen University - ISBN 9789462576216 - 156 p.
broilers - man - disease transmission - antibiotic resistance - bacteria - enterobacteriaceae - poultry farming - epidemiology - vleeskuikens - mens - ziekteoverdracht - antibioticaresistentie - bacteriën - pluimveehouderij - epidemiologie

Huijbers, P.M.C. (2016). Transmission of antibiotic resistance from animals to humans: Broilers as a reservoir of ESBL-producing bacteria. PhD thesis, Wageningen University, Wageningen, the Netherlands.

Antibiotic resistance in animals becomes a public health issue when there is transmission of antibiotic resistant bacteria, or their resistance genes, from animals to humans. β-lactam antibiotics are critically important for the treatment of human bacterial infections. Resistance to this class of antibiotics, mediated by extended-spectrum β-lactamases (ESBL) has emerged. Broilers might contribute to transmission to humans due to the high prevalence of ESBL-producing Enterobacteriaceae among their intestinal biome, compared to other livestock species, companion animals, and wildlife. Transmission to humans might occur via the food chain, by direct contact or via the environment. The aim was to investigate transmission of antibiotic resistant bacteria between animals and humans, and more specifically transmission of ESBL-producing E. coli between broilers, and between broilers and humans in varying degrees of contact with these animals. Systematically collected and categorised evidence from literature showed that clinically relevant antibiotic resistant bacteria were present in the natural environment, that is in soil, water, air and wildlife. It was therefore hypothesised that humans in areas with high broiler densities might have an increased risk for carriage of ESBL-producing Enterobacteriaceae. This hypothesis was rejected, as the observed risk was lower for these individuals. The situation might be different for individuals living on broiler farms as ESBL-producing E. coli were detected on all investigated farms. Among broilers, the within farm prevalence approached 100%, and there was no difference between conventional and organic farms at five weeks, i.e. just before slaughter on conventional farms. On organic farms, the prevalence decreased to 80.0% at 70 days, i.e. slaughter age. Not only transmission to humans via the farm environment, but close physical contact with broilers might, therefore, lead to increased risk for carriage. Prevalence among farmers, their family members and employees on both conventional (19.1%) and organic (18.5%) broiler farms was higher compared to humans in the general population (5.1%). Moreover, people in close contact with live broilers showed the highest risk (27.1 vs. 14.3%). Evidence for clonal transmission of ESBL-producing E. coli between humans and broilers was found on conventional farms, and horizontal gene transfer was suspected on both conventional and organic farms. Even without selection pressure from antibiotics ESBL-producing E. coli were able to transmit and persist in an organic broiler flock, which shows that broilers form a reservoir of antibiotic resistance genes. This leads to an increased risk of carriage of humans on farms through direct contact with broilers and possibly via the direct farm environment. As only a very small percentage of the general population is exposed to live broilers, direct contact with broilers does not appear to be important for carriage in the general human population.

Bioeconomic modelling of foot and mouth disease and its control in Ethiopia
Jemberu, W.T. - \ 2016
University. Promotor(en): Henk Hogeveen, co-promotor(en): Monique Mourits. - Wageningen : Wageningen University - ISBN 9789462576872 - 175 p.
foot-and-mouth disease virus - economic models - mathematical models - epidemiology - animal diseases - cattle - cattle diseases - ethiopia - mond- en klauwzeervirus - economische modellen - wiskundige modellen - epidemiologie - dierziekten - rundvee - rundveeziekten - ethiopië

Keywords: Control, cost-benefit, economic impact, epidemiology, Ethiopia, Foot and mouth disease, intention, modelling, production system.

Bioeconomic Modelling of Foot and Mouth Disease and Its control in Ethiopia

Foot and mouth disease (FMD) is a highly contagious viral disease which affects cloven hoofed animals. FMD is endemic in Ethiopia with potential impact both on national and household economies because of its effect on production and trade. The general objective of this PhD research was to provide insight into the epidemiology and economics of FMD and its control in Ethiopia to support decision making in the control of the disease.

A study of the national incidence of FMD outbreak revealed that the disease is endemic in all regional states affecting more than a quarter of the country every year, with the highest frequency of outbreaks occurring in the central, southern and southeastern parts of the country. The type of production system, presence of a major livestock market and/or route, and adjacency to a national parks or wildlife sanctuary were associated with the risk of outbreaks in the districts.

Field outbreak study indicated that FMD morbidity rates of 85% and 95 % at herd level; and 74% and 61% at animal level in the affected herds in the crop–livestock mixed system (CLM) and pastoral system, respectively. The herd level economic loss estimates were on average USD 76 per affected herd in CLM and USD 174 per affected herd in the pastoral production system.

Study of motivation of farmers to implement FMD control, through the Health Belief Model (HBM) framework, revealed that almost all farmers had high intention to implement FMD vaccination free of charge, which decreases, especially in CLM system, if the vaccine is charged. Farmers in the pastoral and crop-livestock mixed production systems had low intention to implement herd isolation and animal movement restriction control measure. Among the HBM perception constructs perceived barrier was found to be the most important predictor of the intention to implement FMD control measures.

A modelling study on the national economic impact and cost-benefit analysis FMD control strategies showed that the annual cost of the disease is about 1,354 million birr. A stochastic cost-benefit analysis of three potential FMD control strategies indicated that all the strategies on average have a positive economic return but with variable degree of uncertainty including possibility of loss. Targeted vaccination strategy gives relatively the best economic return with relatively less risk of loss.

Abstract P407: Epicatechin intake and markers of glucose and insulin metabolism: the Zutphen elderly study
Obura, M. ; Dower, J.I. ; Kromhout, D. ; Hollman, P.C.H. ; Geleijnse, J.M. ; Soedamah-Muthu, S.S. ; Goede, J. de - \ 2015
European Journal of Epidemiology 30 (2015)6. - ISSN 0393-2990 - p. 915 - 915.
epidemiology - diabetes
Background: Consumption of flavonoid-rich foods like cocoa and tea
is associated with a reduced risk of type 2 diabetes and improved
glycemic control. Cocoa and tea are both important dietary sources of
the flavonoid epicatechin. Our objective therefore was to examine
whether dietary epicatechin intake is associated with markers of
glucose and insulin metabolism.
Methods: We conducted a prospective study in 437 men from the
Zutphen Elderly Study aged 65–84 years at baseline (1985), free of
diabetes and cancer. Dietary epicatechin and other nutrients were
assessed at baseline using a validated cross-check dietary history
method. Glucose and insulin areas under the curve (AUC) were
determined in response to an oral glucose tolerance test (OGTT)
performed in 1990. Homeostasis model assessment of insulin resistance
(HOMA-IR) as well as Matsuda index were calculated from
fasting glucose (mmol/l) and insulin (mU/l) levels. Glycated hemoglobin
(HbA1c) was measured in 1993. Adjusted means and 95 %
confidence intervals (95 % CI) across quintiles of epicatechin intake
and trend analysis were calculated using multivariable linear regression.
Models were adjusted for age, BMI, socioeconomic status,
family history of diabetes, lifestyle (smoking, physical activity and
alcohol consumption), dietary factors (total energy and dietary fiber)
and cardiovascular disease.
Results: The median intake of epicatechin in the highest quintile (Q5)
was 26.6 mg/day compared to 5.5 mg/day in the lowest quintile (Q1).
Tea contributed 50 % of epicatechin intake, followed by apples
(29 %), cocoa (8 %) and red wine (2 %). Epicatechin intake was not
associated with any of the markers of glucose and insulin metabolism
(p trends[0.05 for all). The adjusted mean (95 % CI) for HbA1c (%)
was 4.9 (4.7–5.1) in Q1 and 4.7 (4.5–4.9) in Q5 (p trend = 0.32). The
adjusted means (95 % CI) for Q1 and Q5 were 90.5 (81.4–100.6)and
93.4 (83.6–104.4) (p trend = 0.52) for the Matsuda index, 891
(842–942) and 882 (832–935) (p trend = 0.94) for glucoseAUC
(mmol/L min), 4777 (4323–5279) and 4995 (4498.8–5547.4)
(p trend = 0.86) for insulinAUC (mU/L min) and 2.3 (2.0–2.5) and
2.1 (1.9–2.4) (p trend = 0.29) for HOMA-IR. There was no interaction
with age, family history of diabetes, smoking status and BMI.
Excluding men with cardiovascular disease (n = 57) did not alter the
associations.
Conclusions: In Dutch elderly non-diabetic men, epicatechin intake
was not associated with markers of glucose and insulin metabolism.
Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality
Sijtsma, F.P.C. - \ 2015
University. Promotor(en): Daan Kromhout; D.R. Jacobs, co-promotor(en): Sabita Soedamah-Muthu. - Wageningen : Wageningen University - ISBN 9789462575493 - 207
dieet - hart- en vaatziekten - atherosclerose - prognostische merkers - ziektemerkers - mortaliteit - classificatiesystemen - epidemiologie - longitudinaal onderzoek - diet - cardiovascular diseases - atherosclerosis - prognostic markers - disease markers - mortality - classification systems - epidemiology - longitudinal studies

Summary belonging to the thesis entitled ‘Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality’

The long history of epidemiologic studies on diet and cardiovascular disease (CVD) has traditionally relied on analysis of specific nutrients or foods. Dietary patterns are multiple dietary components operationalized as a single exposure; they reflect the entire diet. In general, two methods are used to define dietary patterns: 1) theoretically, or a priori, defined dietary scores and 2) empirically, or a posteriori, derived dietary patterns. A priori dietary scores were developed to assess diet quality based on adherence to dietary patterns or recommendations. An example of an ‘a posteriori’ approach is factor analysis (e.g. principal components analysis (PCA)). Factor analysis reduces data into patterns based upon intercorrelations between nutrients or foods. The aim of this thesis was to create, examine and compare several dietary patterns and indices and assess these in relation to both early stage markers of CVD (markers of endothelial function and oxidative stress) and to mortality from CVD and all-causes.

In chapter 2 we described the creation of the A Priori Diet Quality Score, representing overall diet quality in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The CARDIA study included 5115 black and white men and women, aged 18-30 at baseline (1985-86). Diet was assessed diet at baseline, year 7(1992-93) and 20 (2005-06) examinations. The A Priori Diet Quality Score summed 46 food groups rated by investigators as positive or negative on the basis of hypothesized health effects. In 2652 participants with 3 diet assessments, the mean (±SD) A Priori Diet Quality Score increased from 64.1± 13.0 at year 0 to 71.1 ± 12.6 at year 20, which was primarily attributable to increased age. However, the secular trend, which was estimated from differences of dietary quality scores across time at a fixed age (age matched time trend), decreased. The diet score was higher in whites than in blacks and in women than in men and increased with education, but demographic gaps in the score narrowed over 20 y. Consumption of positively rated food groups tended to increase and negatively rated food groups tended to decrease, and were similar in direction across demographic groups.

In chapter 3 we used the ‘A Priori Diet Quality Score’ and two dietary patterns derived using principal components analysis (PCA) the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern in the CARDIA study. We studied prospective associations of the ‘A Priori Diet Quality Score’, the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern with cellular adhesion molecules (CAMs). The ‘Fruit and Vegetables’ dietary pattern was characterized by high intakes of fruit, vegetables, and whole grains and the ‘Meat’ dietary pattern by high intakes of red meat, refined grain, and butter. The ‘A Priori Diet Quality Score’ was related to all CAMs. The ‘Fruit and Vegetables’ dietary pattern was related to E-selectin and sICAM-1 but not to P-selectin and VCAM. The ‘Meat’ dietary pattern was related to all CAMs except VCAM. Strongest associations were for the ‘Meat’ dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the ‘A Priori Diet Quality Score’ with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)).

Chapter 4 described prospective associations of the A Priori Diet Quality Score, ‘Fruit and Vegetables’ dietary pattern and ‘Meat’ dietary pattern and a plasma biomarker of lipid peroxidation, F2-isoprostanes also in the CARDIA study. We estimated associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718). In the cross-sectional analysis, the A Priori Diet Quality Score and the ‘Fruit and Vegetables’ dietary pattern were inversely, and the ‘Meat’ dietary pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations were also statistically significant in prospective analysis.

In chapter 5 we described a food classification system derived from the Food-based Dietary Guidelines in the Netherlands that can be used to systematically and objectively classify foods in relation to their effects on health. Classification criteria for each food group were developed based on presumed positive, neutral or negative effects on chronic diseases of five nutrients: four that likely increase (saturated fatty acids, mono-trans unsaturated fatty acids, sodium, and added sugar) and one that likely decreases (dietary fiber) the risk of chronic diseases. This classification system also provided a framework to create food-based dietary scores for epidemiologic research on diet and chronic disease relationships.

Chapter 6 describes the creation of two dietary scores the ‘Dutch Healthy Nutrient and Food Score’ and the ‘Dutch Undesirable Nutrient and Food Score’ based on the food classification system described in chapter 5 in the Alpha Omega Trial. The Alpha Omega Trial is a randomized controlled trial; however the current analyses were done from an observational prospective cohort perspective (with adjustment for intervention groups). We included 4307 cardiac patients aged 60-80 years and monitored mortality for 10 years. Patients in the highest quintile of the ‘Dutch Healthy Nutrient and Food Score’ had 30% (HR 0.70; 95% CI 0.55-0.91) lower CVD and 32% (HR 0.68; 95%CI 0.47-0.99) lower all-cause mortality risk compared to patients in the first quintile. The ‘Dutch Undesirable Nutrient and Food Score’ was unrelated to both CVD and all-cause mortality.

In Chapter 7 we also created a ‘Dutch Healthy Nutrient and Food Score’ and a ‘Dutch Undesirable Nutrient and Food Score’ in the Zutphen Elderly Study. We assessed the association of these scores with 25 year CVD and all-cause mortality and life-years gained. We divided the men (age 65-84 years) into those with (n=210) and without (n=616) cardiovascular-metabolic diseases at baseline in 1985. During a median follow-up of 10.6 years (IQR 5.8-15.9) 806 participants died, of whom 359 from CVD. Diet scores did not predict death in all men. Among men with cardiovascular-metabolic diseases, ‘Dutch Healthy Nutrient and Food Score’ was associated with lower CVD (HR: 0.57; 95%CI: 0.35-0.93) and all-cause mortality risk (HR: 0.64; 95% CI: 0.44-0.94) comparing highest vs. lowest tertiles of the score. Men with cardiovascular-metabolic diseases in the highest vs. lowest tertile of the ‘Dutch Healthy Nutrient and Food Score’ lived 2.5 year longer. The ‘Dutch Healthy Nutrient and Food Score’ was not associated with CVD and all-cause mortality in men without cardiovascular-metabolic diseases. The ‘Dutch Undesirable Nutrient and Food Score’ was not associated with any of the outcomes.

In Chapter 8 we summarized the main findings of this thesis and reflected on some methodological considerations. First, we discussed the different approaches to derive dietary scores and patterns and the advantages and disadvantages of these methods. Second, we reflected on important aspects for creating a priori dietary scores and on further research. Finally, the general conclusions and implications were presented.

From the results presented in this thesis we conclude that adherence to a healthy diet is inversely associated with early stage markers of CVD (markers of endothelial function and oxidative stress), CVD and all-cause mortality. In summary, a healthy diet consists of plenty of vegetables and fruit, legumes, whole grains, nuts and seeds, moderate intake of fish/poultry/lean meats and low fat dairy, and limited intake of processed meats, refined grains, sugar sweetened beverages, ready meals and snacks. However, this thesis also showed that a high quality dietary pattern can be achieved in several different ways, and may differ among populations.

Elucidating the Ramularia eucalypti species complex
Videira, S.I.R. ; Groenewald, J.Z. ; Kolecka, A. ; Haren, L. van; Boekhout, T. ; Crous, P.W. - \ 2015
Persoonia 34 (2015). - ISSN 0031-5850 - p. 50 - 64.
desorption ionization-time - flight mass-spectrometry - primer sets - identification - phylogeny - pathogens - fungi - dna - epidemiology - punctiformis
The genus Ramularia includes numerous phytopathogenic species, several of which are economically important. Ramularia eucalypti is currently the only species of this genus known to infect Eucalyptus by causing severe leaf-spotting symptoms on this host. However, several isolates identified as R. eucalypti based on morphology and on nrDNA sequence data of the ITS region have recently been isolated from other plant hosts, from environmental samples and also from human clinical specimens. Identification of closely related species based on morphology is often difficult and the ITS region has previously been shown to be unreliable for species level identification in several genera. In this study we aimed to resolve this species-complex by applying a polyphasic approach involving morphology, multi-gene phylogeny and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Six partial genes (ITS, ACT, TEF1-a, HIS3, GAPDH and RPB2) were amplified and sequenced for a total of 44 isolates representing R. eucalypti s.lat. and closely related species. A multi-gene Bayesian phylogenetic analysis and parsimony analysis were performed, and both the resulting trees showed significant support for separation of seven species in R. eucalypti s.lat., including two previously described (R. eucalypti and R. miae), four novel species here described (R. haroldporteri, R. glennii, R. mali and R. plurivora) and one undescribed Ramularia species (sterile). Additionally, Mycosphaerella nyssicola is newly combined in Ramularia as R. nyssicola. Main mass spectra (MSPs) of several R. eucalypti s.lat. strains were generated using MALDI-TOF MS and were compared through a Principal Component Analysis (PCA) dendogram. The PCA dendrogram supported three clades containing R. plurivora, R. glenni/R. mali and R. eucalypti/R. miae. Although the dendrogram separation of species differed from the phylogenetic analysis, the clinically relevant strains were successfully identified by MALDI-TOF MS
Foot-and-mouth disease virus : the role of infection routes and species differences in the transmission of FMDV
Bravo De Rueda Cabrera, C. - \ 2015
University. Promotor(en): Mart de Jong, co-promotor(en): Aldo Dekker; Phaedra Eble. - Wageningen : Wageningen University - ISBN 9789462573284 - 137
mond- en klauwzeervirus - mond- en klauwzeer - infectieziekten - ziekteoverdracht - ziektebestrijding - infectiebestrijding - soortverschillen - epidemiologie - diergeneeskunde - foot-and-mouth disease virus - foot and mouth disease - infectious diseases - disease transmission - disease control - infection control - species differences - epidemiology - veterinary science

ÁFoot-and-mouth disease is a contagious viral disease of cloven-hoofed animals (e.g. cattle, sheep, pigs) and can cause severe economic losses to the farm animal industries. The aim of this thesis was to quantify underlying mechanisms regarding transmission of FMDV. With data from past animal experiments we identified the factors which are associated with the amount of virus shed by infected animals and thus may be of importance for transmission of the virus. In an experimental study, the contribution of the environment on the transmission of FMDV was investigated by using a new mathematical model in which the contribution of the environment on transmission was incorporated. Roughly 44% of the transmission of FMDV occurred through the environment that was contaminated with se-excretions from FMDV infected animals. The role of the different species on the transmission of FMDV was investigated with a transmission study of FMDV between infected sheep and naïve cattle. Sheep were found to be less infectious than cattle but similarly susceptible. Using a so-called next-generation matrix, transmission of FMDV in mixed cattle-sheep populations (with different proportions of cattle and different proportions of vaccinated animals) was quantified and the effects of different vaccination strategies against FMDV were analysed. In mixed populations of cattle and sheep, transmission of FMDV is higher when more cattle are present. In populations with more than 14% cattle, targeting vaccination to cattle only can be sufficient to control FMDV.

The results of this thesis show that transmission of FMDV can occur via a contaminated environment, (without animal presence) and that sheep seem to play a limited role in the transmission of FMDV. These results can be used to improve the control measures to prevent and control FMDV in different animal populations.

The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project-design, population and data harmonization of a large-scale, international study
Boffetta, P. ; Bobak, M. ; Borsch-Supan, A. ; Brenner, H. ; Eriksson, S. ; Grodstein, F. ; Jansen, E. ; Jenab, M. ; Juerges, H. ; Kampman, E. ; Kee, F. ; Kuulasmaa, K. ; Park, Y. ; Tjonneland, A. ; Duijn, C. van; Wilsgaard, T. ; Wolk, A. ; Trichopoulos, D. ; Bamia, C. ; Trichopoulou, A. - \ 2014
European Journal of Epidemiology 29 (2014)12. - ISSN 0393-2990 - p. 929 - 936.
osteoporotic fractures - cardiovascular-disease - life-style - epidemiology - mortality - women - diet - consumption - disability - cancer
There is a public health demand to prevent health conditions which lead to increased morbidity and mortality among the rapidly-increasing elderly population. Data for the incidence of such conditions exist in cohort studies worldwide, which, however, differ in various aspects. The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project aims at harmonizing data from existing major longitudinal studies for the elderly whilst focussing on cardiovascular diseases, diabetes mellitus, cancer, fractures and cognitive impairment in order to estimate their prevalence, incidence and cause-specific mortality, and identify lifestyle, socioeconomic, and genetic determinants and biomarkers for the incidence of and mortality from these conditions. A survey instrument assessing ageing-related conditions of the elderly will be also developed. Fourteen cohort studies participate in CHANCES with 683,228 elderly (and 150,210 deaths), from 23 European and three non-European countries. So far, 287 variables on health conditions and a variety of exposures, including biomarkers and genetic data have been harmonized. Different research hypotheses are investigated with meta-analyses. The results which will be produced can help international organizations, governments and policy-makers to better understand the broader implications and consequences of ageing and thus make informed decisions.
Comparative population structure analysis of Campylobacter jejuni from human and poultry origin in Bangladesh
Islam, Z. ; Belkum, A. van; Wagenaar, J.A. ; Cody, A.J. ; Boer, A.G. de; Sarker, S.K. ; Jacobs, B.C. ; Talukder, K.A. ; Endtz, H.P. - \ 2014
European Journal of Clinical Microbiology and Infectious Diseases 33 (2014)12. - ISSN 0934-9723 - p. 2173 - 2181.
fragment-length polymorphism - guillain-barre-syndrome - field gel-electrophoresis - miller-fisher-syndromes - sequence typing system - short variable region - genetic diversity - molecular characterization - strains - epidemiology
Campylobacter jejuni is the most important cause of antecedent infections leading to Guillain-Barr, syndrome (GBS) and Miller Fisher syndrome (MFS). The objective of the present study was to define the genetic diversity, population structure, and potential role of poultry in the transmission of Campylobacter to humans in Bangladesh. We determined the population structure of C. jejuni isolated from poultry (n = 66) and patients with enteritis (n = 39) or GBS (n = 10). Lipooligosaccharide (LOS) typing showed that 50/66 (76 %) C. jejuni strains isolated from poultry could be assigned to one of five LOS locus classes (A-E). The distribution of neuropathy-associated LOS locus classes A, B, and C were 30/50 (60 %) among the typable strains isolated from poultry. The LOS locus classes A, B, and C were significantly associated with GBS and enteritis-related C. jejuni strains more than for the poultry strains [(31/38 (82 %) vs. 30/50 (60 %), p <0.05]. Multilocus sequence typing (MLST) defined 15 sequence types (STs) and six clonal complexes (CCs) among poultry isolates, including one ST-3740 not previously documented. The most commonly identified type, ST-5 (13/66), in chicken was seen only once among human isolates (1/49) (p <0.001). Amplified fragment length polymorphism (AFLP) revealed three major clusters (A, B, and C) among C. jejuni isolated from humans and poultry. There seems to be a lack of overlap between the major human and chicken clones, which suggests that there may be additional sources for campylobacteriosis other than poultry in Bangladesh.
Aziatisch vliegje zet fruitteelt op stelten
Sikkema, A. ; Helsen, H.H.M. - \ 2014
Resource: weekblad voor Wageningen UR 9 (2014)7. - ISSN 1874-3625 - p. 10 - 10.
drosophila suzukii - fruitteelt - insectenplagen - plantenplagen - epidemiologie - gewasbescherming - bestrijdingsmethoden - fruit growing - insect pests - plant pests - epidemiology - plant protection - control methods
De Suzuki-fruitvlieg uit Azië is een ramp voor de Nederlandse fruitsector: ‘We raken dit Aziatische vliegje nooit meer kwijt.’
Schmallenberg virus : technical and scientific studies
Poel, W.H.M. van der - \ 2014
Lelystad : Central Veterinary Institute of Wageningen UR - 67
dierpathologie - schmallenbergvirus - epidemiologie - pathogenese - transmissie - vectoren - diagnose - reverse transcriptase pcr - serologie - wilde dieren - huisdieren - kalveren - lammeren - koeien - schapen - animal pathology - schmallenberg virus - epidemiology - pathogenesis - transmission - vectors - diagnosis - serology - wild animals - domestic animals - calves - lambs - cows - sheep
Schmallenberg virus primarily infects domestic and wild ruminants. Cattle and sheep seem to be the most susceptible species. Goats, pigs and camelids seem to be less susceptible. In pregnant cattle and sheep, the virus can infect multiple organs of the un-borne fetus. However, this infection often does not cause major lesions and infrequently leads to malformations.
Campylobacteriosis in returning travellers and potential secondary transmission of exocit strains.
Mughini-Gras, L. ; Smid, J.H. ; Wagenaar, J.A. ; Boer, A. de; Havelaar, A.H. ; Friesema, I.H.M. ; French, N.P. ; Graziani, C. ; Busani, L. ; Pelt, W. van - \ 2014
Epidemiology and Infection 142 (2014)6. - ISSN 0950-2688 - p. 1277 - 1288.
risk-factors - household outbreaks - salad vegetables - jejuni - netherlands - coli - infection - epidemiology - disease - identification
Multilocus sequence types (STs) were determined for 232 and 737 Campylobacter jejuni/coli isolates from Dutch travellers and domestically acquired cases, respectively. Putative risk factors for travel-related campylobacteriosis, and for domestically acquired campylobacteriosis caused by exotic STs (putatively carried by returning travellers), were investigated. Travelling to Asia, Africa, Latin America and the Caribbean, and Southern Europe significantly increased the risk of acquiring campylobacteriosis compared to travelling within Western Europe. Besides eating chicken, using antacids, and having chronic enteropathies, we identified eating vegetable salad outside Europe, drinking bottled water in high-risk destinations, and handling/eating undercooked pork as possible risk factors for travel-related campylobacteriosis. Factors associated with domestically acquired campylobacteriosis caused by exotic STs involved predominantly person-to-person contacts around popular holiday periods. We concluded that putative determinants of travel-related campylobacteriosis differ from those of domestically acquired infections and that returning travellers may carry several exotic strains that might subsequently spread to domestic populations even through limited person-to-person transmission.
Infection of great apes and a zoo keeper with the same Mycobacterium tuberculosis spoligotype
Akkerman, O.W. ; Werf, T.S. van de; Rietkerk, F. ; Eger, A. ; Soolingen, D. ; Loo, K. v.d.; Zanden, A.G.M. v.d. - \ 2014
Medical Microbiology and Immunology 203 (2014)2. - ISSN 0300-8584 - p. 141 - 144.
resistant tuberculosis - transmission - outbreak - epidemiology - school
An animal keeper was diagnosed with pulmonary tuberculosis (TB) after bi-annual screening for latent TB infection in zoo employees. In the same period, several bonobos of the zoo were suffering from TB as well. The Mycobacterium tuberculosis strains from both the animal keeper and the bonobos appeared identical. We provide evidence that the animals infected their keeper.
Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States
Schottker, B. ; Jorde, R. ; Peasey, A. ; Thorand, B. ; Jansen, E.H.J.M. ; Groot, C.P.G.M. de; Streppel, M.T. ; Feskens, E.J.M. ; Kampman, E. - \ 2014
BMJ: British Medical Journal 348 (2014). - ISSN 0959-8138 - 15 p.
serum 25-hydroxyvitamin d - all-cause mortality - monica/kora augsburg - cardiovascular-disease - general-population - older-adults - risk - cancer - intervention - epidemiology
Objective - To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. Design - Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. Setting - General population. Participants - 26 018 men and women aged 50-79 years
Mechanisms underlying disease transmission between spatially separated animals
Bunnik, B.A.D. van - \ 2014
University. Promotor(en): Mart de Jong, co-promotor(en): Thomas Hagenaars; Gonnie Nodelijk. - Wageningen : Wageningen University - ISBN 9789461739537 - 150
dieren - vleeskuikens - infectieziekten - ziekteoverdracht - gastheren (dieren, mensen, planten) - wiskundige modellen - epidemiologie - diergeneeskunde - animals - broilers - infectious diseases - disease transmission - hosts - mathematical models - epidemiology - veterinary science

Transmission of infections between spatially separated hosts is a common problem, not only during major outbreaks of livestock diseases, but also in many other settings such as the transmission of infectious diseases between plants and crops or in healthcare settings. During the last major epidemics of livestock diseases in the Netherlands and abroad, disease transmission events occurred despite movement bans and other (bio-)security measures, implying that indirect transmission plays a major role. A better understanding of indirect transmission is necessary to put in place evidence based bio-security measures against neighbourhood (indirect) transmission. To gain more insight in the mechanisms underlying indirect transmission a series of experimental studies combined with mathematical modelling were conducted of which the results are presented in this thesis. First the effect of acidification of drinking water on the transmission parameters of direct and indirect transmission of Campylobacter jejuni (C. jejuni) between broilers was studied. It was shown that acidified drinking water has an effect on indirect transmission but not on direct transmission of C. jejuni between broilers. The sender and receiver sub-process of indirect transmission was then studied in more detail and it was shown that a significant negative interaction effect between acidification of the sender and receiver sub-processes exists, indicating that there is no additional effect of acidification of the drinking water on both sides of the transmission process compared to acidified drinking water only on one side. To study the transport of the pathogen in the environment in more detail, a series of indirect transmission experiments was carried out and a model framework was developed to study indirect transmission between spatially separated hosts. These studies showed that indirect transmission of C. jejuni between broilers is best described by a multistage environmental route from sending to receiving animal, suggesting that indirect transmission occurs through progressive (but slow) contamination of the environment surrounding the source. Indirect transmission experiments where repeated with both C. jejuni and Escherichia coli and the results showed that for C. jejuni it takes much longer for the first effective (viable) bacterium to cross the small distance of approximately 75 cm than it does for Escherichia coli. A new modelling approach to study indirect transmission was developed guided by these indirect transmission experiments. This model is capable of accurately describing the pathogen dispersal process by a diffusive transport mechanism which includes pathogen mortality. Lastly, a range of dose-response models were compared and tested how well these fitted to the data from a dose-response experiment. Here it was shown that for interpolation purposes two relatively simple models are best capable of describing the data from the dose-response experiment. For extrapolation purposes, however, it was shown that from the models that were studied a model that abides by the independent action hypothesis is best.

Bloedingsziekte in paardenkastanje werkgroep Aesculaap
Os, Gera van - \ 2014
aesculus - hippocastanaceae - plant pathogenic bacteria - infection - epidemiology - susceptibility - varietal susceptibility - site factors - tree care - disease control
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