Processes Underlying Rabies Virus Incursions across US-Canada Border as Revealed by Whole-Genome Phylogeography.

Disease control programs aim to constrain and reduce the spread of infection. Human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. Over the past few decades, a raccoon-specific variant of rabies virus (RRV) has invaded large areas of eastern North America.

INTEGRATING PARASITES AND PATHOGENS INTO THE STUDY OF GEOGRAPHIC RANGE LIMITS.

The geographic distributions of all species are limited, and the determining factors that set these limits are of fundamental importance to the fields of ecology and evolutionary biology. Plant and animal ranges have been of primary concern, while those of parasites, which represent much of the Earth's biodiversity, have been neglected. Here, we review the determinants of the geographic ranges of parasites and pathogens, and explore how parasites provide novel systems with which to investigate the ecological and evolutionary processes governing host/parasite spatial distributions.

The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal Influenza in the United States.

Recent studies have demonstrated the importance of accounting for human mobility networks when modeling epidemics in order to accurately predict spatial dynamics. However, little is known about the impact these movement networks have on the genetic structure of pathogen populations and whether these effects are scale-dependent. We investigated how human movement along the aviation and commuter networks contributed to intra-seasonal genetic structure of influenza A epidemics in the continental United States using spatially-referenced hemagglutinin nucleotide sequences collected from 2003-2013 for both the H3N2 and H1N1 subtypes.

Structuring targeted surveillance for monitoring disease emergence by mapping observational data onto ecological process.

An efficient surveillance system is a crucial factor in identifying, monitoring and tackling outbreaks of infectious diseases. Scarcity of data and limited amounts of economic resources require a targeted effort from public health authorities. In this paper, we propose a mathematical method to identify areas where surveillance is critical and low reporting rates might leave epidemics undetected.

Molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread.

RNA viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. The ecological dynamics of most emerging RNA viruses are still poorly understood and difficult to ascertain. The availability of genome sequence data for many RNA viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution.

Mathematical models for rabies.

Rabies virus and its associated host-pathogen population dynamics have proven a remarkable model system for developing mathematical models of infectious disease emergence and spread. Beginning with simple susceptible-infectious-removed (SIR) compartment models of fox rabies emergence and spread across Western Europe, mathematical models have now been developed to incorporate dynamics across heterogeneous landscapes, host demographic variation, and environmental stochasticity. Model structures range from systems of ordinary differential equations (ODEs) to stochastic agent-based computational simulations.

Molecular phylogenetics of the lyssaviruses--insights from a coalescent approach.

Technical improvements over the past 2 decades have enormously facilitated the generation of nucleotide sequence data for lyssavirus collections. These databases are amenable to methods of phylogenetic analysis, which attempt to define the taxonomic structure of this genus and predict the evolutionary relationships of current circulating strains. Coupled with a range of mathematical tools to explore the appropriateness of nucleotide substitution models and test for positive selection, the evolutionary process is being explored in detail.

Strong seasonality produces spatial asynchrony in the outbreak of infectious diseases.

Models for infectious diseases usually assume a fixed demographic structure. Yet, a disease can spread over a region encountering different local demographic variations that may significantly alter local dynamics. Spatial heterogeneity in the resulting dynamics can lead to important differences in the design of surveillance and control strategies.

The landscape genetics of infectious disease emergence and spread.

The spread of parasites is inherently a spatial process often embedded in physically complex landscapes. It is therefore not surprising that infectious disease researchers are increasingly taking a landscape genetics perspective to elucidate mechanisms underlying basic ecological processes driving infectious disease dynamics and to understand the linkage between spatially dependent population processes and the geographic distribution of genetic variation within both hosts and parasites. The increasing availability of genetic information on hosts and parasites when coupled to their ecological interactions can lead to insights for predicting patterns of disease emergence, spread and control.

Optimal control of a rabies epidemic model with a birth pulse.

A system of ordinary differential equations describes the population dynamics of a rabies epidemic in raccoons. The model accounts for the dynamics of a vaccine, including loss of vaccine due to animal consumption and loss from factors other than racoon uptake. A control method to reduce the spread of disease is introduced through temporal distribution of vaccine packets.

Optimal control of vaccine distribution in a rabies metapopulation model.

We consider an SIR metapopulation model for the spread of rabies in raccoons. This system of ordinary differential equations considers subpopulations connected by movement. Vaccine for raccoons is distributed through food baits.

Rabies virus in raccoons, Ohio, 2004.

In 2004, the raccoon rabies virus variant emerged in Ohio beyond an area where oral rabies vaccine had been distributed to prevent westward spread of this variant. Our genetic investigation indicates that this outbreak may have begun several years before 2004 and may have originated within the vaccination zone.

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants.

Over the last 30 years, Zaire ebolavirus (ZEBOV), a virus highly pathogenic for humans and wild apes, has emerged repeatedly in Central Africa. Thus far, only a few virus isolates have been characterized genetically, all belonging to a single genetic lineage and originating exclusively from infected human patients. Here, we describe the first ZEBOV sequences isolated from great ape carcasses in the Gabon/Congo region that belong to a previously unrecognized genetic lineage.

Rabies in raccoons: optimal control for a discrete time model on a spatial grid.

An epidemic model for rabies in raccoons is formulated with discrete time and spatial features. The goal is to analyze the strategies for optimal distribution of vaccine baits to minimize the spread of the disease and the cost of implementing the control. Discrete optimal control techniques are used to derive the optimality system, which is then solved numerically to illustrate various scenarios.

Spatial dynamics and genetics of infectious diseases on heterogeneous landscapes.

Explicit spatial analysis of infectious disease processes recognizes that host-pathogen interactions occur in specific locations at specific times and that often the nature, direction, intensity and outcome of these interactions depend upon the particular location and identity of both host and pathogen. Spatial context and geographical landscape contribute to the probability of initial disease establishment, direction and velocity of disease spread, the genetic organization of resistance and susceptibility, and the design of appropriate control and management strategies. In this paper, we review the manner in which the physical organization of the landscape has been shown to influence the population dynamics and spatial genetic structure of host-pathogen interactions, and how we might incorporate landscape architecture into spatially explicit population models of the infectious disease process to increase our ability to predict patterns of disease occurrence and optimally design vaccination and control policies.

A high-resolution genetic signature of demographic and spatial expansion in epizootic rabies virus.

Emerging pathogens potentially undergo rapid evolution while expanding in population size and geographic range during the course of invasion, yet it is generally difficult to demonstrate how these processes interact. Our analysis of a 30-yr data set covering a large-scale rabies virus outbreak among North American raccoons reveals the long lasting effect of the initial infection wave in determining how viral populations are genetically structured in space. We further find that coalescent-based estimates derived from the genetic data yielded an amazingly accurate reconstruction of the known spatial and demographic dynamics of the virus over time.

Spatial control of rabies on heterogeneous landscapes.

Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models.

Inferring the population structure and demographic history of the tick, Amblyomma americanum Linnaeus.

A hierarchial population genetic study was conducted on 703 individual Amblyomma americanum from nine populations in Georgia, U.S.A.

Wave-like spread of Ebola Zaire.

In the past decade the Zaire strain of Ebola virus (ZEBOV) has emerged repeatedly into human populations in central Africa and caused massive die-offs of gorillas and chimpanzees. We tested the view that emergence events are independent and caused by ZEBOV variants that have been long resident at each locality. Phylogenetic analyses place the earliest known outbreak at Yambuku, Democratic Republic of Congo, very near to the root of the ZEBOV tree, suggesting that viruses causing all other known outbreaks evolved from a Yambuku-like virus after 1976.

Unifying the spatial population dynamics and molecular evolution of epidemic rabies virus.

Infectious disease emergence is under the simultaneous influence of both genetic and ecological factors. Yet, we lack a general framework for linking ecological dynamics of infectious disease with underlying molecular and evolutionary change. As a model, we illustrate the linkage between ecological and evolutionary dynamics in rabies virus during its epidemic expansion into eastern and southern Ontario.

On the importance of incentives in hospital infection control spending.

Extract: Each year, nosocomial (acquired in hospital) infections affect nearly 2 million patients and cause over 90,000 deaths in the United States alone. According to the Centers for Disease Control and Prevention (CDC), seventy percent of all nosocomial pathogens are resistant to one or more classes of antibiotics. Antibiotic-resistant bacteria such as vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) are leading causes of hospital acquired infections, and they have proven difficult to eradicate and control.

Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio.

Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia.

Ecological theory to enhance infectious disease control and public health policy.

Through the work of international public health organizations and advancements in the biological and technological sciences, substantial progress has been made in our ability to prevent, control, locally eliminate, and in one case eradicate infectious diseases. Yet each successful control or local elimination has been met with the emergence of new pathogens, the evolution of novel strains, or different epidemiological circumstances that have limited or reversed control methods. To respond to the increasing threat of emerging infectious diseases and bioterrorism it is vital that we design and implement efficient programs that prevent and control infectious pathogen transmission.