Biomedical subjects

B T Grenfell

Publications and source records attributed to B T Grenfell.

At least 19 recordsLinked to original sources

PubMed2006

Estimating transmission intensity for a measles epidemic in Niamey, Niger: lessons for intervention.

The objective of this study is to estimate the effective reproductive ratio for the 2003-2004 measles epidemic in Niamey, Niger. Using the results of a retrospective and prospective study of reported cases within Niamey during the 2003-2004 epidemic, we estimate the basic reproductive ratio, effective reproductive ratio (RE) and minimal vaccination coverage necessary to avert future epidemics using a recent method allowing for estimation based on the epidemic case series. We provide these estimates for geographic areas within Niamey, thereby identifying neighbourhoods at high risk. The estimated citywide RE was 2.8, considerably lower than previous estimates, which may help explain the long duration of the epidemic. Transmission intensity varied during the course of the epidemic and within different neighbourhoods (RE range: 1.4-4.7). Our results indicate that vaccination coverage in currently susceptible children should be increased by at least 67% (vaccine efficacy 90%) to produce a citywide vaccine coverage of 90%. This research highlights the importance of local differences in vaccination coverage on the potential impact of epidemic control measures. The spatial-temporal spread of the epidemic from district to district in Niamey over 30 weeks suggests that targeted interventions within the city could have an impact.

Age Distribution↗

PubMed2004

Waning immunity and subclinical measles infections in England.

Following the introduction of vaccination against measles, levels of clinical infection have dropped markedly. As we move further into the vaccine era, increasingly many individuals owe their measles immunity to vaccination and have had few (if any) exposures to wild virus. A number of recent reports suggest that vaccinated individuals with low levels of immunity may be at risk of subclinical measles infection. We explore the interplay between levels of infection and immunity over time using a mathematical model that simulates infection, waning and boosting of immunity. We focus particularly on the situation in England, where vaccination has been in place since 1966. Simulations of our model demonstrate a rise in the levels of subclinical measles infection over time, and a corresponding rise in clinical measles infections if vaccination levels are too low. We compare the impact of intervention strategies, and find that the rise in cases is most effectively reduced by 'catch-up' vaccination of children. In recent years, vaccination levels in England have dropped from above 90% in the 1990s to 84% in 2001/2002. We discuss the impact of declining vaccination levels on clinical and subclinical infections.

Antibodies, Viral↗

PubMed2004

The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population.

We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross-reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine-induced level of cross-reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring.

Animals↗

PubMed2004

Why large-scale climate indices seem to predict ecological processes better than local weather.

Large-scale climatic indices such as the North Atlantic Oscillation are associated with population dynamics, variation in demographic rates and values of phenotypic traits in many species. Paradoxically, these large-scale indices can seem to be better predictors of ecological processes than local climate. Using detailed data from a population of Soay sheep, we show that high rainfall, high winds or low temperatures at any time during a 3-month period can cause mortality either immediately or lagged by a few days. Most measures of local climate used by ecologists fail to capture such complex associations between weather and ecological process, and this may help to explain why large-scale, seasonal indices of climate spanning several months can outperform local climatic factors. Furthermore, we show why an understanding of the mechanism by which climate influences population ecology is important. Through simulation we demonstrate that the timing of bad weather within a period of mortality can have an important modifying influence on intraspecific competition for food, revealing an interaction between climate and density dependence that the use of large-scale climatic indices or inappropriate local weather variables might obscure.

Aging↗

PubMed2004

The effect of heterogeneity in measles vaccination on population immunity.

High overall vaccination levels sometimes hide pockets of poor coverage. We adopted a meta-population framework to model local aggregation of populations, and used this to investigate the effects of vaccination heterogeneity. A recent survey of antibody levels in a community with low vaccination levels in The Netherlands enabled us to assess the relative importance of local and long-range infective contacts, and thus identify feasible levels of aggregation in the meta-population model. In the aggregated model, we found that heterogeneity in vaccination coverage can lead to a much increased rate of infection among unvaccinated individuals, with a simultaneous drop in the average age at infection.

Humans↗

PubMed2003

Interpreting time-series analyses for continuous-time biological models--measles as a case study.

An increasing number of recent studies involve the fitting of mechanistic models to ecological time-series. In some cases, it is necessary for these models to be discrete-time approximations of continuous-time processes. We test the validity of discretization in the case of measles, where time-series models have recently been developed to estimate ecological parameters directly from data. We find that a non-homogeneous contact function is necessary to capture the host-parasite interaction in a discrete-time model, even in the absence of heterogeneities due to spatial or age structure. We derive a mathematical relationship describing the expected departure from mass-action transmission in terms of the epidemiological parameters in the model, and identify conditions under which the discretization process may fail.

Birth Rate↗

PubMed2003

Optimising vaccination strategies in equine influenza.

A stochastic model of equine influenza (EI) is constructed to assess the risk of an outbreak in a Thoroughbred population at a typical flat race training yard. The model is parameterised using data from equine challenge experiments conducted by the Animal Health Trust (relating to the latent and infectious period of animals) and also published data on previous epidemics (to estimate the transmission rate for equine influenza). Using 89 ponies, an empirical relationship between pre-challenge antibody and the probability of becoming infectious is established using logistic regression. Changes in antibody level over time are quantified using published and unpublished studies comprising 618 ponies and horses. A plausible Thoroughbred population is examined over the course of a year and the model is used to assess the risk of an outbreak of EI in the yard under the current minimum vaccination policy in the UK. The model is adapted to consider an alternative vaccination programme where the frequency of vaccination in older horses (2-year-olds and upwards) is increased. Model results show that this practical alternative would offer a significant increase in protection. Spread of infection between yards is also considered to ascertain the risk of secondary outbreaks.

Age Factors↗

PubMed2003

Spatial parasite transmission, drug resistance, and the spread of rare genes.

The transmission of many parasitic worms involves aggregated movement between hosts of "packets" of infectious larvae. We use a generic metapopulation model to show that this aggregation naturally promotes the preferential spread of rare recessive genes, compared with the expectations of traditional nonspatial models. A more biologically realistic model also demonstrates that this effect could explain the rapid observed spread of recessive or weakly dominant drug-resistant genotypes in nematode parasites of sheep. This promotion of a recessive trait arises from a novel mechanism of inbreeding arising from the metapopulation dynamics of transmission.

Animals↗

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↗