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Biomedical subjects

B T Grenfell

Publications and source records attributed to B T Grenfell.

At least 19 recordsLinked to original sources
PubMed2003

Ecological interference between fatal diseases.

An important issue in population biology is the dynamic interaction between pathogens. Interest has focused mainly on the indirect interaction of pathogen strains, mediated by cross immunity. However, a mechanism has recently been proposed for 'ecological interference' between pathogens through the removal of individuals from the susceptible pool after an acute infection. To explore this possibility, we have analysed and modelled historical measles and whooping cough records. Here we show that ecological interference is particularly strong when fatal infections permanently remove susceptibles. Disease interference has substantial dynamical consequences, making multi-annual outbreaks of different infections characteristically out of phase. So, when disease prevalence is high and is associated with significant mortality, it might be impossible to understand epidemic patterns by studying pathogens in isolation. This new ecological null model has important consequences for understanding the multi-strain dynamics of pathogens such as dengue and echoviruses.

Acute Disease↗
PubMed2003

Antibody dynamics in childhood diseases: waning and boosting of immunity and the impact of vaccination.

The introduction of vaccination against acute diseases such as measles induced a dramatic decline in the prevalence of the disease, and a more gradual rise in the proportion of the population whose immunity is derived solely from vaccination. These two factors combine to constitute an important shift in the dynamics of immunity, especially in highly vaccinated populations. We develop a general model to describe both loss of immunity in the absence of disease, and boosting of immunity corresponding to subclinical infection in individuals whose immunity has waned. We consider the interaction between infection and immunity and identify the key parameters that determine the eradication threshold. We explore the dynamics in the years following the introduction of vaccination using a stochastic version of the model, and consider the effect of different assumptions concerning the nature of immunity. A comparison of the model results with recently published data suggests that heterogeneity in host immune response is an important feature of the antibody dynamics.

Antibodies, Viral↗
PubMed2002

Modelling vaccination strategies against foot-and-mouth disease.

Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, 'predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.

Animals↗
PubMed2002

Modelling equine influenza 1: a stochastic model of within-yard epidemics.

This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level implies that less virus will be shed during the infectious period, we identify a high degree of heterogeneity in the response of horses with similar pre-challenge antibody levels. We develop a modified model that incorporates some heterogeneity in levels of infectivity, and compare this with the simpler model.

Animals↗
PubMed2001

An unlikely partnership: parasites, concomitant immunity and host defence.

Concomitant immunity (CI) against macroparasites describes a state of effective anti-larval immunity coupled with persistent adult infection. Experimental studies indicate that immunologically concealed adult worms might promote anti-larval immunity via the release of cross-reactive antigens, thus creating a barrier against continual infection and restricting burden size within the host. CI offers an important potential benefit to established worms by preventing overcrowding within the host. Thus, CI may be interpreted as akin to vaccination; relatively long-lived adult worms 'vaccinate' their host with larval surface antigens and so benefit from reduced conspecific competition. The shared responsibility for host vaccination among adult worms leads to a problem of collective action. Here, we build on earlier analytical findings about the evolutionary forces that shape cooperation among parasites in order to produce a stochastic simulation model of macroparasite social evolution. First, we theoretically investigate a parasite adaptation hypothesis of CI and demonstrate its plausibility under defined conditions, despite the possibility of evolutionary 'cheats'. Then we derive a set of predictions for testing the hypothesis that CI is partly a host-manipulative parasite adaptation. Evidence in support of this model would present an unusual case of adaptive population regulation.

Animals↗
PubMed2001

Travelling waves and spatial hierarchies in measles epidemics.

Spatio-temporal travelling waves are striking manifestations of predator-prey and host-parasite dynamics. However, few systems are well enough documented both to detect repeated waves and to explain their interaction with spatio-temporal variations in population structure and demography. Here, we demonstrate recurrent epidemic travelling waves in an exhaustive spatio-temporal data set for measles in England and Wales. We use wavelet phase analysis, which allows for dynamical non-stationarity--a complication in interpreting spatio-temporal patterns in these and many other ecological time series. In the pre-vaccination era, conspicuous hierarchical waves of infection moved regionally from large cities to small towns; the introduction of measles vaccination restricted but did not eliminate this hierarchical contagion. A mechanistic stochastic model suggests a dynamical explanation for the waves-spread via infective 'sparks' from large 'core' cities to smaller 'satellite' towns. Thus, the spatial hierarchy of host population structure is a prerequisite for these infection waves.

Algorithms↗
PubMed2001

Dynamics of the 2001 UK foot and mouth epidemic: stochastic dispersal in a heterogeneous landscape.

Foot-and-mouth is one of the world's most economically important livestock diseases. We developed an individual farm-based stochastic model of the current UK epidemic. The fine grain of the epidemiological data reveals the infection dynamics at an unusually high spatiotemporal resolution. We show that the spatial distribution, size, and species composition of farms all influence the observed pattern and regional variability of outbreaks. The other key dynamical component is long-tailed stochastic dispersal of infection, combining frequent local movements with occasional long jumps. We assess the history and possible duration of the epidemic, the performance of control strategies, and general implications for disease dynamics in space and time.

Animal Husbandry↗
PubMed2001

Noisy clockwork: time series analysis of population fluctuations in animals.

Both biotic interactions and abiotic random forcing are crucial influences on population dynamics. This frequently leads to roughly equal importance of deterministic and stochastic forces. The resulting tension between noise and determinism makes ecological dynamics unique, with conceptual and methodological challenges distinctive from those in other dynamical systems. The theory for stochastic, nonlinear ecological dynamics has been developed alongside methods to test models. A range of dynamical components has been considered-density dependence, environmental and demographic stochasticity, and climatic forcing-as well as their often complex interactions. We discuss recent advances in understanding ecological dynamics and testing theory using long-term data and review how dynamical forces interact to generate some central field and laboratory time series.

Animals↗
PubMed2001

Age, sex, density, winter weather, and population crashes in Soay sheep.

Quantifying the impact of density, extrinsic climatic fluctuations, and demography on population fluctuations is a persistent challenge in ecology. We analyzed the effect of these processes on the irregular pattern of population crashes of Soay sheep on the St. Kilda archipelago, United Kingdom. Because the age and sex structure of the population fluctuates independently of population size, and because animals of different age and sex respond in different ways to density and weather, identical weather conditions can result in different dynamics in populations of equal size. In addition, the strength of density-dependent processes is a function of the distribution of weather events. Incorporating demographic heterogeneities into population models can influence dynamics and their response to climate change.

Aging↗
PubMed2001

Host manipulation by Ligula intestinalis: accident or adaptation?

Numerous studies have demonstrated that parasites with complex life-cycles can cause phenotypic modifications in their hosts that lead to an increased rate of transmission, and suggest that these modifications are the result of parasitic adaptations to manipulate the host. Little attention is paid, however, to separating the possibility of adaptive host manipulation from incidental (if fortuitous) side-effects of infection. In this study we combine statistical and analytical tools to interpret the impact of the macroparasite Ligula intestinalis L. (Cestoda, Pseudophyllidea) on the behaviour of its intermediate fish host (the roach, Rutilus rutilus L.), using field data on a natural system. Two distinct sets of generalized linear models agree that both the presence and the intensity of infection contribute to a modified behavioural response in the host. This was illustrated by a preference for the lake-edge in infected fish during autumn. Furthermore, the effect of parasites upon their host is heterogeneous with respect to parasite size, with larger parasite individuals having a disproportionate impact. A series of game-theoretic models of adaptive host manipulation illustrate a potential rationale for a size-dependent manipulation strategy in parasites. These findings illustrate the potential complexity and functionality of the impact of L. intestinalis upon its fish host, which together reduce the parsimony of the alternative 'incidental effect' hypothesis.

Adaptation, Physiological↗
PubMed2001

Quantifying mosquito biting patterns on humans by DNA fingerprinting of bloodmeals.

A major debate in infectious disease epidemiology concerns the relative importance of exposure and host factors, such as sex and acquired immunity, in determining observed age patterns of parasitic infection in endemic communities. Nonhomogeneous contact between hosts and vectors is also expected to increase the reproductive rate, and hence transmission, of mosquito-borne infections. Resolution of these questions for human parasitic diseases has been frustrated by the lack of a quantitative tool for quantifying the exposure rate of people in communities. Here, we show that the polymerase chain reaction (PCR) technique for amplifying and fingerprinting human DNA from mosquito bloodmeals can address this problem for mosquito-borne diseases. Analysis of parallel human and mosquito (resting Culex quinquefasciatus) samples from the same households in an urban endemic focus for bancroftian filariasis in South India demonstrates that a 9-locus radioactive short-tandem repeat system is able to identify the source of human DNA within the bloodmeals of nearly 80% of mosquitoes. The results show that a person's exposure rate, and hence the age and sex patterns of exposure to bites in an endemic community, can be successfully quantified by this method. Out of 276 bloodmeal PCR fingerprints, we also found that on average, 27% of the mosquitoes caught resting within individual households had fed on people outside the household. Additionally, 13% of mosquitoes biting within households contained blood from at least 2 people, with the rate of multiple feeding depending on the density of humans in the household. These complex vector feeding behaviors may partly account for the discrepancies in estimates of the infection rates of mosquito-borne diseases calculated parasitologically and entomologically, and they underline the potential of this tool for investigating the transmission dynamics of infection.

Adolescent↗
PubMed2000

Individual-based perspectives on R(0).

Without doubt the basic reproductive ratio, R(0), is the most widely used quantity in epidemic theory. Standard compartmental models show how R(0)is related to the average age of infection, vaccination thresholds for eradication and equilibrium solutions. However, many of the basic formulae for R(0)break down when we consider transmission of infection to be a stochastic process involving discrete individuals. This paper clarifies why and when these differences arise and predicts when individual-based considerations are likely to be important in modelling infection dynamics.

Disease Outbreaks↗
PubMed2000

A simple model for complex dynamical transitions in epidemics.

Dramatic changes in patterns of epidemics have been observed throughout this century. For childhood infectious diseases such as measles, the major transitions are between regular cycles and irregular, possibly chaotic epidemics, and from regionally synchronized oscillations to complex, spatially incoherent epidemics. A simple model can explain both kinds of transitions as the consequences of changes in birth and vaccination rates. Measles is a natural ecological system that exhibits different dynamical transitions at different times and places, yet all of these transitions can be predicted as bifurcations of a single nonlinear model.

Baltimore↗
PubMed1999

Opposite patterns of synchrony in sympatric disease metapopulations.

Measles epidemics in UK cities, which were regular and highly synchronous before vaccination, are known to have become irregular and spatially uncorrelated in the vaccine era. Whooping cough shows the reverse pattern, namely a shift from spatial incoherence and irregularity before vaccination to regular, synchronous epidemics afterward. Models show that these patterns can arise from disease-specific responses to dynamical noise. This analysis has implications for vaccination strategies and illustrates the power of comparative dynamical studies of sympatric metapopulations.

Bordetella pertussis↗
PubMed1999

Anthelmintic resistance revisited: under-dosing, chemoprophylactic strategies, and mating probabilities.

Deterministic and stochastic models are used to examine the evolution of anthelmintic resistance among trichostrongylid parasites of domestic ruminants. We find that the relative selection pressures exerted by chemoprophylactic (preventive) control strategies, chemotherapeutic (salvage) control strategies, and regimens involving "under-dosing" are critically dependent on a variety of host and parasite parameters (particularly host immunity and grazing behaviour, parasite fecundity, and the survival of the free-living stages on the pasture). Chemoprophylactic strategies are not necessarily more likely to exert a stronger selection pressure than chemotherapeutic strategies. Similarly, as one reduces dosage levels, there is a range of dose levels where under-dosing promotes resistance and a range of dose levels where under-dosing impedes resistance. The most dangerous dose is either that necessary to kill all the susceptible homozygotes, or that necessary to kill all the susceptible homozygotes and all the heterozygotes. Which one prevails depends upon model parameters. The stochastic formulation indicates that spatial heterogeneity in transmission may be a significant force in promoting the spread of resistant genotypes--at least when infection is at low levels.

Animals↗
PubMed1999

The effect of pregnancy on Wuchereria bancrofti microfilarial load in humans.

As part of a drug trial against bancroftian filariasis in the East Sepik Province of Papua New Guinea we measured the pre-treatment microfilarial densities of 2219 individuals. Mean levels generally increased with age in both sexes, with a tendency to plateau at the highest ages. However, there was a reduction among women of approximately reproductive age. Allowing for the tendency for aggregation to decrease with age, this reduction was statistically significant. However, a comparison of pregnant women and controls showed no evidence that the reduction is specifically related to pregnancy. Moreover, a simple differential equation model of microfilarial acquisition and loss suggests that age-specific patterns of exposure are also unlikely to be solely responsible. Therefore, we suggest that the observed reduction in microfilarial intensity may result from hormonal changes associated with female reproduction, possibly in combination with other factors.

Age Factors↗