Biomedical subjects

D Klinkenberg

Publications and source records attributed to D Klinkenberg.

13 recordsLinked to original sources

PubMed2006

The effect of a live vaccine on the horizontal transmission of Mycoplasma gallisepticum.

The effect of a live Mycoplasma gallisepticum vaccine on the horizontal transmission of this Mycoplasma species was quantified in an experimental animal transmission model in specific pathogen free White Layers. Two identical trials were performed, each consisting of two experimental groups and one control group. The experimental groups each consisted of 20 birds 21 weeks of age, which were housed following a pair-wise design. One group was vaccinated twice with a commercially available live attenuated M. gallisepticum vaccine, while the other group was not vaccinated. Each pair of the experimental group consisted of a challenged chicken (10(4) colony-forming units intratracheally) and a susceptible in-contact bird. The control group consisted of 10 twice-vaccinated birds housed in pairs and five individually housed non-vaccinated birds. The infection was monitored by serology, culture and quantitative polymerase chain reaction. The vaccine strain and the challenge strain were distinguished by a specific polymerase chain reaction and by random amplified polymorphic DNA analysis. In both experiments, all non-vaccinated challenged chickens and their in-contact 'partners' became infected with M. gallisepticum. In the vaccinated challenged and corresponding in-contact birds, a total of 19 and 13 chickens, respectively, became infected with M. gallisepticum. Analysis of the M. gallisepticum shedding patterns showed a significant effect of vaccination on the shedding levels of the vaccinated in-contact chickens. Moreover, the Cox Proportional Hazard analysis indicated that the rate of M. gallisepticum transmission from challenged to in-contact birds in the vaccinated group was 0.356 times that of the non-vaccinated group. In addition, the overall estimate of R (the average number of secondary cases infected by one typical infectious case) of the vaccinated group (R = 4.3, 95% confidence interval = 1.6 to 49.9) was significantly lower than that of the non-vaccinated group (R = infinity, 95% confidence interval = 9.9 to infinity). However, the overall estimate of R in the vaccinated group still exceeded 1, which indicates that the effect of the vaccination on the horizontal transmission M. gallisepticum is insufficient to stop its spread under these experimental conditions.

Animals↗

PubMed2005

A simple model for the within-host dynamics of a protozoan parasite.

The dynamics of parasite-host systems can be complicated if the parasite life cycle contains an obligatory environmental stage and if the hosts' immunity increases upon re-infection. The dynamics then greatly depend on the relation between infection history and parasite uptake and excretion of individual hosts. In an effort to better understand such systems, we study Eimeria spp. in chickens as our model. In this paper we take a first step and study the within-host dynamics of Eimeria spp. transmitted through oocysts in the environment, with a mathematical model for the parasite life cycle in discrete time, interacting with a single variable describing the immune response. The model can explain various types of oocyst input-output behaviour as described in previous experiments, in particular the characteristic crowding effect, which causes a decreasing oocyst production with increasing single dose oocyst uptake. Oocyst excretion during constant oocyst uptake (trickle infection) and the immunizing effect of single and trickle infections also appears in accordance with published experiments. The model seems a good description of oocyst input-output behaviour in individual hosts; it provides a solid basis for the study of between-host dynamics, where individuals interact in a common environment, thereby affecting their own and each other's infection pattern.

Animals↗

PubMed2005

An experimental model to quantify horizontal transmission of Mycoplasma gallisepticum.

Before interventions to control horizontal transmission of Mycoplasma gallisepticum can be tested, a suitable experimental model should be available. Transmission dynamics in a flock can be quantified by two parameters: the average number of secondary cases infected by one typical infectious case (R0) and the number of new infections that occur due to one infectious animal per unit of time (beta). The transmission dynamics of M. gallisepticum have not been studied experimentally, so the aim of this study was to examine the horizontal transmission of M. gallisepticum. The study was carried out using a pairwise design with three different inoculation doses. Every pair consisted of an inoculated chicken and a susceptible in-contact chicken. Five susceptible individually housed chickens were placed in between pairs in order to measure airborne transmission. Infection was detected by serology, quantitative polymerase chain reaction and culture. The inoculated and in-contact chickens were equally infectious and the pairs could be regarded as independent. The R0 was estimated to be greater than 1 (infinity; 95% confidence interval, 4.5 to infinity), the estimated beta was 0.22 per day and there was no significant difference between the different inoculation doses. It was concluded that the animal model as described in this study meets the conditions for the establishment of transmission dynamics of M. gallisepticum and therefore can be used to establish the quantitative effect of intervention measures on horizontal transmission.

Animals↗

PubMed2005

Quantifying transmission of Campylobacter spp. among broilers.

Campylobacter species are frequently identified as a cause of human gastroenteritis, often from eating or mishandling contaminated poultry products. Quantitative knowledge of transmission of Campylobacter in broiler flocks is necessary, as this may help to determine the moment of introduction of Campylobacter in broiler flocks more precisely. The aim of this study was to determine the transmission rate parameter in broiler flocks. Four experiments were performed, each with four Campylobacter-inoculated chicks housed with 396 contact chicks per group. Colonization was monitored by regularly testing fecal samples for Campylobacter. A mathematical model was used to quantify the transmission rate, which was determined to be 1.04 new cases per colonized chick per day. This would imply that, for example, in a flock of 20,000 broilers, the prevalence of Campylobacter would increase from 5% to 95% within 6 days after Campylobacter introduction. The model and the estimated transmission rate parameter can be used to develop a suitable sampling scheme to determine transmission in commercial broiler flocks, to estimate whether control measures can reduce the transmission rate, or to estimate when Campylobacter was introduced into a colonized broiler flock on the basis of the time course of transmission in the flock.

Animals↗

PubMed2004

The effectiveness of classical swine fever surveillance programmes in The Netherlands.

Consequences of classical swine fever (CSF) epidemics depend on the control measures, but also on the number of infected herds at the end of the high-risk period (HRP). Surveillance programmes aim to keep this number as low as possible, so the effectiveness of surveillance programmes can be measured by the number of infected herds at the end of the HRP. In this paper, an evaluation of the effectiveness of the following five Dutch CSF surveillance programmes is presented: (1) routine gross pathology of severely diseased pigs; (2) routine virological tests of tonsils of all pigs, submitted under 1; (3) daily clinical observation by the farmer; (4) periodic clinical inspection by a veterinarian; (5) leucocyte counts in blood samples from diseased animals on a herd where antimicrobial 'group therapy' is started. The evaluation was done by a modelling study, in which virus transmission, disease development, and actions and diagnostic tests in surveillance programmes were simulated. Also, the yearly costs of the programmes were calculated, and direct costs of CSF epidemics were related to the number of infected herds at the end of the HRP. It appeared that the current Dutch surveillance programmes, without the leucocyte counts, keep the number of infected herds at the end of the HRP below 20 with 95% probability. Leaving out the most-expensive programme of periodic inspection (12.5M per year) does not change this result - indicating that (for CSF surveillance) the programme could well be stopped. If the leucocyte programme, which is currently not effective due to the low sample submission rate, optimally were applied, the 95th percentile could be reduced to 10 infected herds. However, whether application is beneficial is unclear, because of uncertainty of the economic benefits due to the many expected false-positive herds each year.

Animal Husbandry↗

PubMed2003

Quantification of the effect of control strategies on classical swine fever epidemics.

Emergency vaccination during an epidemic of classical swine fever virus (CSFV) has become a serious option because of the ethical problems of strategies with massive culling and the availability of a marker vaccine that reduces virus transmission. Here we present a model of between-herd CSFV transmission, which quantifies the effect of control strategies with and without vaccination. We estimate the model parameters from data of the Dutch CSFV epidemic of 1997/1998. With the model, a set of control strategies is compared, consisting of five control measures in several combinations. Consequently, the following general requirements of successful strategies can be formulated. First, to achieve extinction of a CSFV epidemic, transmission through transport should be prevented and the indirect virus transmission, i.e. all transmission not through animal contacts, should at least be halved, either by vaccination or by culling of the susceptible pig population. Second, to minimize the size and duration of an epidemic, the extinction requirements should be met quickly and indirect virus transmission should be reduced by far more than a half. Although the origin of the model parameters let the requirements in fact be only applicable for the south-eastern part of the Netherlands, it is argued that epidemics in other areas will not need stricter control strategies.

Animals↗

PubMed2002

Influence of maternal antibodies on efficacy of a subunit vaccine: transmission of classical swine fever virus between pigs vaccinated at 2 weeks of age.

This study shows the effectiveness of vaccination with an E2 subunit vaccine against classical swine fever (CSF) in 2-week-old piglets. Half of the piglets were carrying maternally derived antibodies (MDAs) at the time of vaccination. Three and 6 months later, antibody levels were compared between the two treatments. Moreover, reduction of virus transmission was investigated at 3 and 6 months by doing transmission experiments. The vaccine was found to be capable of reducing virus transmission significantly at both time intervals. Maternal immunity reduced vaccination-induced antibody levels after 3 and 6 months and possibly led to a less effective protection against virus transmission after 6 months.

Animals↗

PubMed2002

Within- and between-pen transmission of Classical Swine Fever Virus: a new method to estimate the basic reproduction ratio from transmission experiments.

We present a method to estimate basic reproduction ratio R0 from transmission experiments. By using previously published data of experiments with Classical Swine Fever Virus more extensively, we obtained smaller confidence intervals than the martingale method used in the original papers. Moreover, our method allows simultaneous estimation of a reproduction ratio within pens R0w and a modified reproduction ratio between pens R'0b. Resulting estimates of R0w and R'0b for weaner pigs were 100 (95% CI 54.4-186) and 7.77 (4.68-12.9), respectively. For slaughter pigs they were 15.5 (6.20-38.7) and 3.39 (1.54-7.45), respectively. We believe, because of the smaller confidence intervals we were able to obtain, that the method presented here is better suited for use in future experiments.

Animals↗

PubMed2001

Classical swine fever (CSF) marker vaccine. Trial II. Challenge study in pregnant sows.

The efficacy of two marker vaccines against classical swine fever (CSF) was tested in a large scale laboratory trial in several National Swine Fever Laboratories (NSFL) of the EU member states. The vaccines were: BAYOVAC CSF Marker (Vaccine A) from Bayer, Leverkusen, Germany and PORCILIS PESTI (Vaccine B) from Intervet, Boxmeer, The Netherlands. At the NSFL of Belgium, The Netherlands and Germany experiments were carried out to examine the ability of the vaccines to prevent transplacental transmission of CSF virus. In Belgium and The Netherlands pregnant sows were vaccinated once and challenged with virulent CSF virus 14 days later, which was around day 60 of gestation. At the NSFL in Germany sows were vaccinated twice, on days 25 and 46 of pregnancy and were challenged fourteen days after booster vaccination (day 60 of gestation). Apart from minor inflammatory reactions in some sows, no reactions post vaccination were noticed in either vaccine group. Sows vaccinated with Vaccine A were better protected against clinical CSF than sows vaccinated with Vaccine B. The antibody response after vaccination with Vaccine A was more pronounced than after vaccination with Vaccine B. After single vaccination six out of eight sows vaccinated with Vaccine A and all eight sows vaccinated with Vaccine B had viraemic piglets. After double vaccination one out of four litters from sows vaccinated with Vaccine A and four out of five litters from sows vaccinated with Vaccine B were found to be viraemic. However, both vaccines reduced the transmission probability significantly (Vaccine A: P=0.004, Vaccine B: P=0.024) after booster vaccination. However, Vaccine A appeared in this regard more potent as the estimated probability of fetal infections was lower. Nevertheless the risk of virus spreading after vaccination via transplacental transmission is still present and has to be addressed from an epidemiological point of view.

Animals↗

PubMed2001

Spatial and stochastic simulation to compare two emergency-vaccination strategies with a marker vaccine in the 1997/1998 Dutch Classical Swine Fever epidemic.

Two alternative emergency-vaccination strategies with a marker vaccine that could have been applied in the 1997/1998 Dutch Classical Swine Fever (CSF) epidemic were evaluated in a modified spatial, temporal and stochastic simulation model: InterCSF. In strategy 1, vaccination would be applied only to overcome a shortage in destruction capacities. Destruction of all pigs on vaccinated farms distinguishes this strategy from strategy 2, which assumes intra-Community trade of vaccinated pig meat. InterCSF simulates the spread of CSF between farms through local spread and three contact types. Disease spread is affected by control measures implemented through different mechanisms. Economic results were generated by a separate model that calculated the direct costs (including the vaccination costs) and consequential losses for farmers and related industries subjected to control measures. The comparison (using epidemiological and economic results) between the different emergency-vaccination strategies with an earlier simulated preventive-slaughter scenario led to some general conclusions on the Dutch CSF epidemic. Both emergency-vaccination strategies were hardly more efficient than the non-vaccination scenario. The intra-Community trade strategy (vaccination-strategy 2) was the least costly of all three scenarios.

Animals↗

PubMed1999

A mathematical model for the intracellular circadian rhythm generator.

A mathematical model for the intracellular circadian rhythm generator has been studied, based on a negative feedback of protein products on the transcription rate of their genes. The study is an attempt at examining minimal but biologically realistic requirements for a negative molecular feedback loop involving considerably faster reactions, to produce (slow) circadian oscillations. The model included mRNA and protein production and degradation, along with a negative feedback of the proteins upon mRNA production. The protein production process was described solely by its total duration and a nonlinear term, whereas also the feedback included nonlinear interactions among protein molecules. This system was found to produce robust oscillations in protein and mRNA levels over a wide range of parameter values. Oscillations were slow, with periods much longer than the time constants of any of the individual system parameters. Circadian oscillations were obtained for realistic values of the parameters. The system was readily entrainable to external periodic perturbations. Two distinct classes of phase response curves were found, viz. with or without a time domain within the circadian cycle in which external perturbations fail to induce a phase shift ("dead zone"). The delay and nonlinearity in the protein production and the cooperativity in the negative feedback (Hill coefficient) were for this model found to be necessary and sufficient to generate robust circadian oscillations. The similarities between model outcomes and empirical findings establish that circadian rhythmicity at the cellular level can plausibly emerge from interactions among molecular systems which are not in themselves rhythmic.

Biological Transport↗

PubMed1999

A model of molecular circadian clocks: multiple mechanisms for phase shifting and a requirement for strong nonlinear interactions.

A fundamental question in the field of circadian rhythms concerns the biochemical and molecular nature of the oscillator. There is strong evidence that circadian oscillators are cell autonomous and rely on periodic gene expression. In Drosophila, Neurospora, Aplysia, and vertebrates, circadian oscillators are thought to be based on molecular autoregulatory loops composed of transcription, translation, and negative feedback by proteins on nuclear transcription. By studying a mathematical model of molecular clocks based on this general concept, the authors sought to determine which features such clocks must have to generate robust and stable oscillations and to allow entrainment by external stimuli such as light. The model produced circadian oscillations as an emergent property even though a time delay in protein synthesis and rate constants of the feedback loop were much shorter than 24 h. Along with the delay in protein production, strong nonlinear interactions in macromolecular synthesis and nuclear feedback appeared to be required for the model to show well-behaved oscillatory behavior. Realistic phase-shifting patterns induced by external stimuli could be achieved by multiple mechanisms-namely, up- and downward perturbations of protein or mRNA synthesis or degradation rates. The model makes testable predictions about interactions between clock elements and mechanisms of entrainment and may help to understand the functions of the intricate molecular interactions governing circadian rhythmogenesis.

Animals↗

PubMed1994

Dating scripts of gay men and lesbians.

Scripts for a first date for 51 gay men and 44 lesbians were explored. Well-defined scripts were found for both hypothetical and actual accounts. Hypothetical scripts contained fourteen actions for gay men and lesbians; eleven were common to both. Gay men's actual scripts had eighteen actions and lesbians' had nineteen, with twelve common to both. Gay men's scripts were more sexually oriented and less intimacy-focused than lesbians'. However, scripts for both genders were free of many other aspects of traditional heterosexual roles and involved some actions unique to this population.

Adult↗