Biomedical subjects

J A P Heesterbeek

Publications and source records attributed to J A P Heesterbeek.

18 recordsLinked to original sources

PubMed2006

Classification of temporal profiles of F4+ E. coli shedding and faecal dry matter in experimental post-weaning diarrhoea of pigs.

Enterotoxigenic F4+ Escherichia coli can colonize the intestine of pigs and cause diarrhoea. Our primary goal was to find a discriminant rule to discriminate between F4+ E. coli shedding profiles as this may reflect differences in the infectiousness of pigs. Our secondary goal was to find a discriminant rule to discriminate between diarrhoeic and non-diarrhoeic pigs. Repeated measurements (bacterial shedding and percentage dry matter of faeces) were taken of 74 weaned pigs that were infected experimentally with F4+ E. coli. These measurements were summarized into two new variables by means of a principal components analysis. Discriminant rules were derived based on these summary variables by fitting a mixture of normal distributions. Finally, the association between the classifications (as derived from the discriminant rules) and the occurrence in the pigs of the F4 receptor, an adhesion site for F4+ E. coli, was studied. We found that only the classification based on bacterial shedding allowed us to distinguish two significantly different groups of pigs (high and low shedders). Presence of the F4 receptor was associated strongly with pigs being high shedders.

Adhesins, Escherichia coli↗

PubMed2006

The CHRNE 470del20 mutation causing congenital myasthenic syndrome in South African Brahman cattle: prevalence, origin, and association with performance traits.

Genotyping of the South African, registered, Brahman cattle population for the 470del20 mutation in the CHRNE gene causing congenital myasthenic syndrome (CMS) was carried out in 1,453 animals. Overall prevalence of carriers was 0.97% (0.50 to 1.68%, 95% confidence interval). Carrier prevalence among breeding bulls in 2004 was 1.22% (0.65 to 2.15%, 95% confidence interval), and had not changed significantly since 2000. Using segregation analysis, CMS genotype probabilities were calculated for all 612,219 animals in the pedigree, leading to the identification of 2 founder animals as the most likely original carriers. Pedigree analysis revealed no ancestors common to all known carriers, but rather that the mutation had been introduced at least twice into the South African Brahman population, probably via animals imported from the United States. The effects of CMS genotype probability on adjusted birth, 200-d, 400-d, and 600-d BW, as well as on EBV for birth, 200-d, 400-d, and 600-d BW, and milk, were estimated, accounting for effects of sire. Heterozygosity for the CHRNE 470del20 mutation was associated with a 13.3-kg increase in adjusted 600-d BW (P = 0.03). Positive effects of CMS carrier status on all BW EBV were found, but no effect was found on milk EBV. We conclude that CMS carriers have a BW advantage at 600 d and possibly also at birth, 200 d, and 400 d. This may confer a selective advantage and tend to increase the frequency of the mutation.

Animals↗

PubMed2006

A stochastic exposure assessment model to estimate vanadium intake by beef cattle used as sentinels for the South African vanadium mining industry.

This paper presents an environmental exposure assessment model for estimating chronic intake of vanadium (a transition metal) by cattle farmed extensively in areas contaminated by vanadium pollutants. The exposure model differs from most other models in several ways: (1) it does not rely heavily on extrapolating information from the point source (e.g. stack height, exit velocity, exit diameter) to the point of exposure. (2) It incorporates the physiological constraints of the species exposed. (3) It takes into account oral as well as inhalation exposure. (4) It addresses terrain, by using measurements at the point of exposure. (5) It accounts for existing background concentrations of pollutants and pollutants from multiple sources. (6) It uses a stochastic process with distribution functions to account for variability in the data over time. Environmental inputs into the model included aerial fall-out sample vanadium (n=566), unwashed grass sample vanadium (n=342) and soluble soil sample vanadium (n=342). Physiological cattle inputs were derived from two cohorts of Brahman-cross sentinel cattle (n=30). The model provided an estimate of the chronic external exposure dose of vanadium for two separate groups of cattle grazing over a 5-year period (1999-2004) immediately adjacent (median dose=2.14mg vanadium/kg body weight/day) and 2km away (median dose=1.07mg/kg/day) from a South African vanadium-processing plant, respectively. The final output of the model is a distribution curve of the probable vanadium intake based on the variability within the inputs over the 5-year period of the study. The model is adaptable enough for application to other transition metals and species (including man), and could be used as an alternative to plume-dispersion modelling.

Air Pollutants↗

PubMed2006

The type-reproduction number T in models for infectious disease control.

A ubiquitous quantity in epidemic modelling is the basic reproduction number R(0). This became so popular in the 1990s that 'All you need know is R(0)!' became a familiar catch-phrase. The value of R(0) defines, among other things, the control effort needed to eliminate the infection from a homogeneous host population, but can be misleading when applied to a heterogeneous population for the same purpose. We have defined the type-reproduction number T for an infectious disease, and shown that this not only has the required threshold behaviour, but also correctly determines the critical control effort for heterogeneous populations. The two quantities coincide for homogeneous populations. In this paper we further develop the new threshold quantity as an indicator of control effort required in a system where multiple types of individuals are recognised when control targets a specific type.

Algorithms↗

PubMed2006

The assessment of biomarkers in sentinel cattle for monitoring vanadium exposure.

Various potential biomarkers were sampled for vanadium every 3-4 months from Bos indicus beef cattle farmed extensively immediately adjacent (high exposure (HE) group) and two km away (low exposure (LE) group) from a vanadium processing plant, respectively. Vanadium intake (mg vanadium kg(-1) bwt d(-1)) was modelled using environmental and physiological data as inputs. The vanadium intake ranged from 0.57 to 5.44 mg vanadium kg(-1) bwt d(-1) in the HE group and 0.41 to 2.61 mg vanadium kg(-1) bwt d(-1) in the LE group over a five-year period of monitoring. Samples collected from live sentinel animals over the five-year period included caudal coccygeal vertebrae, tail-switch hair, milk, urine, faeces, rib-bone biopsies and a wide range of blood clinical pathology and haematological parameters. The data was analysed for differences in response between the HE and LE groups. Where differences were found, a linear mixed-effects regression model was fitted to model the relationship between the exposure dose and the response variable. The model included the effects of age, duration of exposure and response, and allowed the prediction of the exposure dose given these inputs. Moreover, forty-two adult cattle were slaughtered over the five years. A wide range of tissue samples, rumen content and whole blood were taken from the cattle at slaughter for vanadium determination. In live animals, a difference in response was found between the HE group and LE group with respect to serum albumin (n = 36), monocyte (n = 36) and thrombocyte (n = 36) counts, and hair (n = 2) and faeces (n = 34) vanadium concentrations. No difference in vanadium concentrations could be shown for urine (n = 36), the traditional occupational health biomarker. Regression models are described for serum albumin, monocyte counts, faeces and hair, which showed the most promise as biomarkers. Average concentrations of vanadium in the tissues of slaughtered cattle ranged from 0.08 to 2.94 mg kg(-1) (wet-weight basis) and rumen content contained 16.67 mg kg(-1). Significant correlations were found between the exposure dose (end-dose) just prior to slaughter and the concentrations of vanadium in the coccygeal vertebrae, liver, diaphragm and rib-bone in descending order of magnitude. Other tissues showed poor correlation to the end-dose. Tissue levels of vanadium in healthy cattle include a much wider range than is currently reflected in the literature. The best tissue from slaughter animals for assessing chronic vanadium exposure is probably the liver.

Animals↗

PubMed2006

Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control.

Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: approximately 80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R(0), could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R(0) by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.

Animals↗

PubMed2006

Changes in disease gene frequency over time with differential genotypic fitness and various control strategies.

A spreadsheet model was constructed to describe the change in allelic frequency over time for a lethal recessive mutation in an animal population. The model allowed relative fitness to differ between genotypes, between sexes, and over time. Whereas a lethal recessive allele is naturally eliminated very slowly from a population, a small selective disadvantage of the heterozygote results in a large increase in the rate of elimination. With selective advantage of the heterozygote through linkage with a production trait or pleiotropy, the allele is never naturally eliminated but tends toward a stable equilibrium frequency. The model was used to investigate various alternative control programs based on the detection of heterozygotes by genotyping and their exclusion from breeding. The programs (genotyping males only, genotyping males and 50% of females, and genotyping all breeding animals) were modeled for various initial heterozygote frequencies, and the results were described in terms of the number of generations, number of tests, and number of culls required to reduce the heterozygote frequency to a predefined level. The model can be used to compare the feasibility and cost of various control strategies and to illustrate clearly to breeders the expected outcomes, as well as the danger of prematurely terminating a control program when there is a selective advantage of the heterozygote.

Animal Husbandry↗

PubMed2005

A model of contagious bovine pleuropneumonia transmission dynamics in East Africa.

The dynamics of contagious bovine pleuropneumonia (CBPP) transmission vary widely between livestock production systems. This paper describes the development of a homogeneous, stochastic, compartmental model for CBPP transmission in pastoral herds of East Africa. The model was built using parameter estimates based on data published in the literature and on observations of livestock owners obtained through participatory research. The basic reproduction number for CBPP in southern Sudan was estimated to range from 3.2 to 4.6. The homogeneous model indicates that the critical community size for the persistence of CBPP falls within the typical herd sizes for pastoral communities in East Africa suggesting that individual isolated herds are capable of maintaining infection indefinitely. Vaccination alone with currently available vaccines was unlikely to eradicate the disease.

Africa, Eastern↗

PubMed2005

A heterogeneous population model for contagious bovine pleuropneumonia transmission and control in pastoral communities of East Africa.

Pastoral cattle live in highly structured communities characterized by complex contact patterns. The present paper describes a spatially heterogeneous model for the transmission of contagious bovine pleuropneumonia (CBPP) developed specifically for pastoral communities of East Africa. The model is validated against serological data on the prevalence of CBPP infection in several communities of southern Sudan and against livestock owner information on community structure, livestock contact and cattle exchange. The model is used to assess the impact of alternative control strategies including mass and elective vaccination programmes, potential treatment regimes and the combination of vaccination and treatment in a single unified strategy. The results indicate that the eradication of CBPP using mass vaccination with currently available vaccines is unlikely to succeed. On the other hand, elective control programmes based on herd level vaccination, treatment of clinical cases or a combination of both vaccination and treatment enabled individual livestock owners to capture a large benefit in terms of reduced animal-level prevalence and mortality experience. The most promising intervention scenario was a programme which combined the vaccination of healthy animals with treatment of clinical cases.

Africa, Eastern↗

PubMed2005

The public health implications of farming cattle in areas with high background concentrations of vanadium.

Forty-two adult Brahman-cross cattle farmed extensively in two groups, immediately adjacent to and 2 km from a vanadium processing plant respectively, were slaughtered over a 5 year period at a nearby abattoir. Cattle were being exposed to vanadium at close to no-adverse-effect levels. The dose of vanadium that cattle were taking in prior to slaughter was calculated for each animal from environmental and physiological data using a stochastic risk assessment model. The median exposure doses in the month prior to slaughter ranged from 0.55 to 2.73 mg vanadium/kg body weight/day. A range of tissues was taken from the cattle at slaughter for vanadium determination and tissue levels of vanadium in muscle, liver and kidney are reported. The concentrations of vanadium in the milk of cattle from the same farm sampled over 5 years are also reported. Concentrations were further modelled using a lognormal distribution function to look at possible extreme values that are likely to occur. The concentrations of vanadium in commonly consumed tissues ranged from <0.05 to 11.51 mg/kg (wet-mass basis). The median concentration of vanadium in milk was 0.23 mg vanadium/kg. People drinking milk were at highest risk. The potential oral daily intake of vanadium for people consuming these foodstuffs was modelled using a stochastic model. The model predicted that there is less than a 5% chance that the potential daily intake of vanadium from milk will be >0.44 microg/kg/day for adults. Based on this upper limit it was concluded from current knowledge of toxicity in humans that the tissue and milk residues from cattle should pose no health risk to the consumer.

Agriculture↗

PubMed2005

A model of lineage-1 and lineage-2 rinderpest virus transmission in pastoral areas of East Africa.

The development of a stochastic, state-transition model of rinderpest transmission dynamics is described using parameter estimates obtained from both laboratory and participatory research. Using serological data, the basic reproduction numbers for lineage-1 rinderpest virus in southern Sudan and for lineage-2 rinderpest virus in Somali livestock were estimated as 4.4 and between 1.2 and 1.9, respectively. The model predictions for the inter-epidemic period in Sudan and Somalia (1.2 and 4.2 years, respectively) were in agreement with analysis of livestock-owner reports (1-2 years and 5 years, respectively).

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

The effect of DNA repair defects on reproductive performance in nucleotide excision repair (NER) mouse models: an epidemiological approach.

In this study, we used an epidemiological approach to analyze an animal database of DNA repair deficient mice on reproductive performance in five Nucleotide Excision Repair (NER) mutant mouse models on a C57BL/6 genetic background, namely CSA, CSB, XPA, XPC [models for the human DNA repair disorders Cockayne Syndrome (CS) and xeroderma pigmentosum (XP), respectively] and mHR23B (not associated with human disease). This approach allowed us to detect and quantify reproductive effects based on a relatively small number of matings. We measured and quantified the scale of the effect between factors that might influence reproductive performance (i.e. age at co-housing, seasons) and reproductive parameters (i.e. litter size and pairing-to-birth interval -'pbi'). Besides, we detected and quantified the differences in reproductive performance between wild type mice and heterozygous/homozygous NER mutant mice. From our analyses, we found impaired reproduction in heterozygous and homozygous knock out mice; in particular, reduced litter size and lengthened pbi was related to the NER mutation-mHR23B, in heterozygous couples, even if they were otherwise phenotypically normal. Heterozygous mHR23B couples produced a 6.6-fold lower number of mHR23B(-/-) pups than indicated by Mendelian expectation; other genetic deficiencies studied were not statistically significant from each other or wild type controls. We concluded that careful epidemiological evaluations by analysis of animal database could provide reliable information on reproductive performance and detect deviations that would remain unnoticed without this. Also, some managerial aspects of mouse breeding could be evaluated.

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↗

PubMed2003

A new method for estimating the effort required to control an infectious disease.

We propose a new threshold quantity for the analysis of the epidemiology of infectious diseases. The quantity is similar in concept to the familiar basic reproduction ratio, R0, but it singles out particular host types instead of providing a criterion that is uniform for all host types. Using this methodology we are able to identify the long-term effects of disease-control strategies for particular subgroups of the population, to estimate the level of control necessary when targeting control effort at a subset of host types, and to identify host types that constitute a reservoir of infection. These insights cannot be obtained by using R0 alone.

Animals↗

PubMed2002

The metapopulation dynamics of an infectious disease: tuberculosis in possums.

An SEI metapopulation model is developed for the spread of an infectious agent by migration. The model portrays two age classes on a number of patches connected by migration routes which are used as host animals mature. A feature of this model is that the basic reproduction ratio may be computed directly, using a scheme that separates topography, demography, and epidemiology. We also provide formulas for individual patch basic reproduction numbers and discuss their connection with the basic reproduction ratio for the system. The model is applied to the problem of spatial spread of bovine tuberculosis in a possum population. The temporal dynamics of infection are investigated for some generic networks of migration links, and the basic reproduction ratio is computed-its value is not greatly different from that for a homogeneous model. Three scenarios are considered for the control of bovine tuberculosis in possums where the spatial aspect is shown to be crucial for the design of disease management operations.

Animal Migration↗

PubMed2002

A brief history of R0 and a recipe for its calculation.

In this paper I present the genesis of R0 in demography, ecology and epidemiology, from embryo to its current adult form. I argue on why it has taken so long for the concept to mature in epidemiology when there were ample opportunities for cross-fertilisation from demography and ecology from where it reached adulthood fifty years earlier. Today, R0 is a more fully developed adult in epidemiology than in demography. In the final section I give an algorithm for its calculation in heterogeneous populations.

Animals↗

PubMedDate not supplied

Daniel Bernoulli's epidemiological model revisited.

The seminal paper by Daniel Bernoulli published in 1766 is put into a new perspective. After a short account of smallpox inoculation and of Bernoulli's life, the motivation for that paper and its impact are described. It determines the age-specific equilibrium prevalence of immune individuals in an endemic potentially lethal infectious disease. The gain in life expectancy after elimination of this cause of death can be explicitly expressed in terms of the case fatality and the endemic prevalence of susceptibles. D'Alembert developed in 1761 an alternative method for dealing with competing risks of death, which is also applicable to non-infectious diseases. Bernoulli's formula for the endemic prevalence of susceptibles has so far escaped attention. It involves the lifetime risk of the infection, the force of infection and the life expectancy at birth. A new formula for the basic reproduction number is derived which involves the average force of infection, the average case fatality and the life expectancy at the time of infection. One can use this estimate to assess the gain in life expectancy if only a fraction of the population is immunized.

Age Factors↗