Biomedical subjects

D Clancy

Publications and source records attributed to D Clancy.

12 recordsLinked to original sources

PubMed2006

A semi-stochastic model for Salmonella infection in a multi-group herd.

A multi-group semi-stochastic model is formulated to identify possible causes of why different strains of Salmonella develop so much variation in their infection dynamics in UK dairy herds. The model includes demography (managed populations) and various types of transmission: direct, pseudovertical and indirect (via free-living infectious units in the environment). The effects of herd size and epidemiological parameters on mean prevalence of infection and mean time until fade out are investigated. Numerical simulation shows that higher pathogen-induced mortality, shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower mean prevalence of infection, a shorter mean time until fade out, and a greater probability of fade out of infection within 600 days. Combining these results and those for the deterministic counterpart could explain differences in observed epidemiological patterns and help to identify the factors inducing the decline in reported cases of epidemic strains such as DT104 in cattle. We further investigate the effect of group structure on the probability of a major outbreak by using the stochastic threshold theory in homogeneous populations and that in heterogeneous populations. Numerical studies suggest that group structure makes major outbreaks less likely than would be the case in a homogeneous population with the same basic reproduction number. Moreover, some control strategies are suggested by investigating the effect of epidemiological parameters on the probability of an epidemic.

Animals↗

PubMed2005

Infection in social networks: using network analysis to identify high-risk individuals.

Simulation studies using susceptible-infectious-recovered models were conducted to estimate individuals' risk of infection and time to infection in small-world and randomly mixing networks. Infection transmitted more rapidly but ultimately resulted in fewer infected individuals in the small-world, compared with the random, network. The ability of measures of network centrality to identify high-risk individuals was also assessed. "Centrality" describes an individual's position in a population; numerous parameters are available to assess this attribute. Here, the authors use the centrality measures degree (number of contacts), random-walk betweenness (a measure of the proportion of times an individual lies on the path between other individuals), shortest-path betweenness (the proportion of times an individual lies on the shortest path between other individuals), and farness (the sum of the number of steps between an individual and all other individuals). Each was associated with time to infection and risk of infection in the simulated outbreaks. In the networks examined, degree (which is the most readily measured) was at least as good as other network parameters in predicting risk of infection. Identification of more central individuals in populations may be used to inform surveillance and infection control strategies.

Community-Acquired Infections↗

PubMed2005

Quantifying uncertainty associated with microbial count data: a Bayesian approach.

We consider the problem of estimating bacterial concentration in a substance, given microbial count data. A Bayesian approach is proposed which naturally allows the incorporation of both plate-count data and extra information from confirmatory tests such as genotyping by polymerase chain reaction (PCR). The estimation methods yield posterior credible regions for bacterial concentration, in contrast to the previous methods, which generally only produce point estimates. The approach is illustrated with specific reference to the enumeration of the food-borne pathogen Escherichia coli O157 by spiral plating, although the methodology can be applied to any bacterium or counting method of interest. The results obtained provide guidance to the experimenter as to the number of confirmatory tests which should be performed, and also suggest that in the initial plate count one should err on the side of including rather than excluding colonies whose genotype seems unclear.

Bayes Theorem↗

PubMed2003

Bayesian methods for estimating pathogen prevalence within groups of animals from faecal-pat sampling.

Pathogens such as Escherichia coli O157:H7 and Campylobacter spp. have been implicated in outbreaks of food poisoning in the UK and elsewhere. Domestic animals and wildlife are important reservoirs for both of these agents, and cross-contamination from faeces is believed to be responsible for many human outbreaks. Appropriate parameterisation of quantitative microbial-risk models requires representative data at all levels of the food chain. Our focus in this paper is on the early stages of the food chain-specifically, sampling issues which arise at the farm level. We estimated animal-pathogen prevalence from faecal-pat samples using a Bayesian method which reflected the uncertainties inherent in the animal-level prevalence estimates. (Note that prevalence here refers to the percentage of animals shedding the bacteria of interest). The method offers more flexibility than traditional, classical approaches: it allows the incorporation of prior belief, and permits the computation of a variety of distributional and numerical summaries, analogues of which often are not available through a classical framework. The Bayesian technique is illustrated with a number of examples reflecting the effects of a diversity of assumptions about the underlying processes. The technique appears to be both robust and flexible, and is useful when defecation rates in infected and uninfected groups are unequal, where population size is uncertain, and also where the microbiological-test sensitivity is imperfect. We also investigated the determination of the sample size necessary for determining animal-level prevalence from pat samples to within a pre-specified degree of accuracy.

Agriculture↗

PubMed2003

Two sets of HLA Class II DRB and DQB1 alleles co-segregate among family members in a single maternal haplotype.

HLA class II typing by sequence specific oligonucleotide probes (SSOP) on the family of a Burkit's Lymphoma patient produced hybridization patterns indicating the presence of two DRB1, and two linked DQB1 genes on the same maternal chromosome. DRB and DQB1 exon 2 amplification products associated with the novel maternal haplotype were identified by DNA typing techniques: These products corresponded to DRB1*0101, DRB1*1501, DRB5*01, DQB1*0501 and DQB1*0602 alleles. These alleles were seen to co-segregate among siblings sharing the same maternal haplotype. The patient, his mother and two of his siblings each appeared to possess elements of three DRB1, DQA1 and DQB1 genes. HLA DNA typing results indicated that a DNA sequence of approximately 100 Kb, spanning the region between, and including, DRB1 and DQB1 genes was inserted into the maternal haplotype. Serological typing on EBV transformed B lymphocytes obtained from the patient's mother showed three expressed DRB1 antigens. Serology on EBV transformed patient's cells also indicated multiple DRB1 antigen expression. The expression of three DRB1 and DQB1 genes on the cells of this patient would make it virtually impossible to obtain a suitably matched unrelated stem cell donor.

Alleles↗

PubMed2002

Dose-response relationships for foot and mouth disease in cattle and sheep.

The relationships between the inhaled dose of foot and mouth disease virus and the outcomes of infection and disease were examined by fitting dose-response models to experimental data. The parameters for both the exponential and beta-poisson models were estimated using maximum likelihood and Bayesian methods. The median probability of infection given a single inhaled TCID50 was estimated to be 0.031 with 95% Bayesian credibility intervals (CI) of 0.018-0.052 for cattle, and 0.045 (CI = 0.024-0.080) for sheep. These estimates were used to construct dose-response curves and uncertainty distributions for use in quantitative risk assessments.

Animals↗

PubMed2001

A stochastic model for disease transmission in a managed herd, motivated by Neospora caninum amongst dairy cattle.

A stochastic model for the spread of Neospora caninum infection within a herd of dairy cattle is studied, in particular the long-term (equilibrium) behaviour of the model. The model incorporates the interesting feature that total herd size is constrained to lie within a fairly small interval, but not held exactly constant. Approximations for the joint distribution of numbers of susceptible and infected individuals present in equilibrium are derived based upon a diffusion approximation to the infection process. The effect of both 'typical herd size' and 'the amount of permitted variation in herd size' upon disease prevalence in equilibrium are considered using both the exact equilibrium distribution of the process and our approximations.

Animals↗

PubMed2000

Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response.

The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30-700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-gamma, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction. The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression. Strategies aimed at maintaining IFN-gamma induction, such as the addition of IL-2, may further augment the response rate to this schedule of rhIL-12.

Adult↗

PubMed1999

Optimal intervention for epidemic models with general infection and removal rate functions.

In this paper, known results on optimal intervention policies for the general stochastic epidemic model are extended to epidemic models with more general infection and removal rate functions. We consider first policies allowing for the isolation of any number of infectives from the susceptible population at any time, secondly policies allowing for the immunisation of the entire susceptible population at any time, and finally policies allowing for either of these interventions. In each case the costs of infection, isolation and immunisation are assumed to have a particular, rather simple, form. Sufficient conditions are given on the infection and removal rate functions of the model for the optimal policies to take the same simple form as in the case of the general stochastic epidemic model. More general costs are briefly discussed, and some numerical examples given. Finally, we discuss possible directions for further work.

Animals↗

PubMed1999

Mathematical models of Neospora caninum infection in dairy cattle: transmission and options for control.

The transmission and control of Neospora caninum infection in dairy cattle was examined using deterministic and stochastic models. Parameter estimates were derived from recent studies conducted in the UK and from the published literature. Three routes of transmission were considered: maternal vertical transmission with a high probability (0.95), horizontal transmission from infected cattle within the herd, and horizontal transmission from an independent external source. Putative infection via pooled colostrum was used as an example of within-herd horizontal transmission, and the recent finding that the dog is a definitive host of N. caninum supported the inclusion of an external independent source of infection. The predicted amount of horizontal transmission required to maintain infection at levels commonly observed in field studies in the UK and elsewhere, was consistent with that observed in studies of post-natal seroconversion (0.85-9.0 per 100 cow-years). A stochastic version of the model was used to simulate the spread of infection in herds of 100 cattle, with a mean infection prevalence similar to that observed in UK studies (around 20%). The distributions of infected and uninfected cattle corresponded closely to Normal distributions, with S.D.s of 6.3 and 7.0, respectively. Control measures were considered by altering birth, death and horizontal transmission parameters. A policy of annual culling of infected cattle very rapidly reduced the prevalence of infection, and was shown to be the most effective method of control in the short term. Not breeding replacements from infected cattle was also effective in the short term, particularly in herds with a higher turnover of cattle. However, the long-term effectiveness of these measures depended on the amount and source of horizontal infection. If the level of within-herd transmission was above a critical threshold, then a combination of reducing within-herd, and blocking external sources of transmission was required to permanently eliminate infection.

Animals↗

PubMed1996

Carrier-borne epidemic models incorporating population mobility.

A study was made of multigroup epidemic models in which individuals are able to move between groups, infectious contact occurring only between an infective and a susceptible in the same group. Because of the mathematical intractability of such models; we look mainly at the number of susceptibles directly contacted by the infectives that are initially introduced into the population, ignoring subsequent infections caused by these newly infected individuals. We thus have a generalization of the carrier-borne epidemic model of Weiss [Biometrics 21:481-491 (1965)]. We consider first a model in which only infectives are able to move, then one in which both infectives and susceptibles move between groups. In each case we study both deterministic and stochastic versions of the model, concentrating mainly on the effect of varying the speed at which individuals move between groups on the number of initial susceptibles contacted. For the case in which only infectives move, the model is compared with a suitably matched model in which there is no movement between groups but infectives are able to infect outside their own group. The paper concludes with remarks on the behavior of the epidemic process if initially susceptible individuals that become infected are able to contribute to the further spread of the disease.

Carrier State↗

PubMed1996

Naturally-occurring Wolbachia infection in Drosophila simulans that does not cause cytoplasmic incompatibility.

Microbes of the genus Wolbachia are transmitted by their hosts via the maternal parent and are responsible for cytoplasmic incompatibility among insect populations. This phenomenon can result in Wolbachia spreading through natural populations as previously demonstrated in Drosophila simulans. Here we describe another Wolbachia infection in D. simulans that does not cause cytoplasmic incompatibility. This is a property of the Wolbachia rather than the nuclear background. The infection occurs at a low frequency in natural populations from eastern Australia. The infection shows perfect maternal transmission in the field and does not cause any detectable deleterious effects on its host. These findings suggest that the Wolbachia infection behaves like a neutral variant in populations. The infection may represent an evolutionary outcome of interactions between Wolbachia infections and their hosts.

Animals↗