Models of foot-and-mouth disease.

During the 2001 foot-and-mouth disease outbreak in the UK, three very different models were used in an attempt to predict the disease dynamics and inform control measures. This was one of the first times that models had been used during an epidemic to support the decision-making process. It is probable that models will play a pivotal role in any future livestock epidemics, and it is therefore important that decision makers, veterinarians and farmers understand the uses and limitations of models.

Appropriate models for the management of infectious diseases.

Background: Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models.

Methods And Findings: First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data.

Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype.

Raising insulin acutely in the periphery and in brain improves verbal memory. Intranasal insulin administration, which raises insulin acutely in the CNS without raising plasma insulin levels, provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes. Based on prior research with intravenous insulin, we predicted that the treatment response would differ between subjects with (epsilon4+) and without (epsilon4-) the APOE-epsilon4 allele.

The implications of network structure for epidemic dynamics.

It has long been realised that the standard assumptions of mass-action mixing are a crude approximation of the true mechanistic processes that govern the transmission of infection. In particular, many infections can be considered to be spread through a limited network of contacts. Yet, despite the underlying discrepancies, mass-action models continue to be used and provide a remarkably accurate description of epidemic behaviour.

Using conservation of pattern to estimate spatial parameters from a single snapshot.

Rapid reaction in the face of an epidemic is a key element in effective and efficient control; this is especially important when the disease has severe public health or economic consequences. Determining an appropriate level of response requires rapid estimation of the rate of spread of infection from limited disease distribution data. Generally, the techniques used to estimate such spatial parameters require detailed spatial data at multiple time points; such data are often time-consuming and expensive to collect.

Monogamous networks and the spread of sexually transmitted diseases.

Patterns of sexual mixing and heterogeneity in the number of sexual partners can have a huge effect on the spread of a sexually transmitted disease (STD). The sexual mixing network identifies all partnerships within a population over a given period and is a powerful tool in the study of such infections. Previous models assumed all links within the network to be concurrent active partnerships.

The colour of noise in short ecological time series data.

The statistical properties of ecological time series data and general trends therein have historically been of great interest to ecologists. In recent years, there has been a focus on establishing the relative importance of 'memory' in these data. The classic study by Pimm & Redfearn (1988 Nature, 334, 613-614) has been extremely important in establishing within the ecological community the idea that population time series are generally 'red-shifted' (dominated by long-term trends).

Contact tracing and disease control.

Contact tracing, followed by treatment or isolation, is a key control measure in the battle against infectious diseases. It is an extreme form of locally targeted control, and as such has the potential to be highly efficient when dealing with low numbers of cases. For this reason it is frequently used to combat sexually transmitted diseases and new invading pathogens.

Planning for smallpox outbreaks.

Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979.

The invasion and coexistence of competing Wolbachia strains.

Cytoplasmic incompatibility between arthropods infected with different strains of Wolbachia has been proposed as an important mechanism for speciation. However, a basic requirement for this mechanism is the coexistence of different strains in neighbouring populations. Here we test whether this required coexistence is possible in a spatial context.

Neighbourhood control policies and the spread of infectious diseases.

We present a model of a control programme for a disease outbreak in a population of livestock holdings. Control is achieved by culling infectious holdings when they are discovered and by the pre-emptive culling of livestock on holdings deemed to be at enhanced risk of infection. Because the pre-emptive control programme cannot directly identify exposed holdings, its implementation will result in the removal of both infected and uninfected holdings.

Disease evolution on networks: the role of contact structure.

Owing to their rapid reproductive rate and the severe penalties for reduced fitness, diseases are under immense evolutionary pressure. Understanding the evolutionary response of diseases in new situations has clear public-health consequences, given the changes in social and movement patterns over recent decades and the increased use of antibiotics. This paper investigates how a disease may adapt in response to the routes of transmission available between infected and susceptible individuals.

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.

Modeling dynamic and network heterogeneities in the spread of sexually transmitted diseases.

A wide range of communicable human diseases can be considered as spreading through a network of possible transmission routes. The implied network structure is vital in determining disease dynamics, especially when the average number of connections per individual is small as is the case for many sexually transmitted diseases (STDs). Here we develop an intuitive mathematical framework to deal with the heterogeneities implicit within contact networks and those that arise because of the infection process.

Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge.

Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free SHIV-vpu+ by passive immunization with synergistic human neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000).

Surgical technique for ambulatory management of airsacculitis in a chimpanzee (Pan troglodytes).

Purpose: Bacterial infections of the air sac have been reported in many nonhuman primates. Approaches to the management of airsacculitis have included combinations of medical and surgical therapies. These strategies have often required repeated attempts to drain exudate from the affected air sac, as well as necessitating that the animal endure isolation or undergo intensive postoperative care before returning to its social group.

Hematologic and serum biochemical reference intervals for the chimpanzee (Pan troglodytes) categorized by age and sex.

Normal reference range intervals for hematologic and serum biochemical values in the chimpanzee (Pan troglodytes) have seldom been reported. The few studies that have been conducted either report values on the basis of a small number of animals, report values for all age groups or both sexes combined, or were designed specifically to document the effect of a particular condition on the normal range of hematologic and serum biochemical values. On the basis of data collected from 133 chimpanzees over a 17-year period, empirically based clinical reference ranges were derived to provide a guide for basic diagnostic and clinical care of chimpanzees.

Understanding the persistence of measles: reconciling theory, simulation and observation.

Ever since the pattern of localized extinction associated with measles was discovered by Bartlett in 1957, many models have been developed in an attempt to reproduce this phenomenon. Recently, the use of constant infectious and incubation periods, rather than the more convenient exponential forms, has been presented as a simple means of obtaining realistic persistence levels. However, this result appears at odds with rigorous mathematical theory; here we reconcile these differences.

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.

Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.

Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely.

Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?

To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J.

Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge.

To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et al.

Bubonic plague: a metapopulation model of a zoonosis.

Bubonic plague (Yersinia pestis) is generally thought of as a historical disease; however, it is still responsible for around 1000-3000 deaths each year worldwide. This paper expands the analysis of a model for bubonic plague that encompasses the disease dynamics in rat, flea and human populations. Some key variables of the deterministic model, including the force of infection to humans, are shown to be robust to changes in the basic parameters, although variation in the flea searching efficiency, and the movement rates of rats and fleas will be considered throughout the paper.