Geography but not alternative host species explain the spread of raccoon rabies virus in Vermont.

In North America, the raccoon-associated variant of rabies virus (RRV) is of special concern, given its relatively rapid spread throughout the eastern USA and its potential public health impact due to high raccoon host densities in urban areas. Northward expansion of this epizootic included an outbreak in the Canadian province of Quebec in 2006-2009 due to trans-border spread from the State of Vermont. To inform a more proactive approach to future control efforts, this study uses phylogenetic analyses to explore the role of geography and alternative carnivore hosts in the dynamics of RRV spread within Vermont. Specifically, we sought to examine whether striped skunks, a species frequently infected by RRV, could be part of the maintenance host community. Whole genome sequencing of 160 RRV samples from Vermont and neighbouring US states were used for fine-scale phylogeographic analyses. Results, together with the complete surveillance record of raccoon rabies since its entry into Vermont in 1994, document incursions by two distinct viral lineages and identify topographical features of the landscape which have significantly influenced viral spread, resulting in a complex distribution pattern of viral variants throughout the state. Results of phylogenetic cluster analysis and discrete state reconstruction contained some evidence of skunk-to-skunk and skunk-to-raccoon transmission but overall failed to support a role for skunks as alternative maintenance hosts.

Genomic sequencing, evolution and molecular epidemiology of rabies virus.

Advances in sequencing techniques, improved computational methods of sequence interrogation and more accurate collection of epidemiological data through Global Positioning System (GPS) technology are improving our ability to monitor rabies outbreaks and better understand the processes that affect viral spread, evolution and host restriction. Whole-genome sequencing of rabies viruses (RABVs), using a range of different methodological approaches, is becoming more widespread and permits evolutionary and epidemiological studies at an unprecedented rate. Such studies are yielding insights into the fundamental processes of viral evolution, including molecular mechanisms of host adaptation and viral emergence in novel hosts. In addition, sequence data are revealing the importance of both landscape features and anthropomorphic activities as drivers of rabies spread; knowledge that is crucial for disease control efforts. This review summarises the state of the RABV genomics field and suggests how the above-mentioned approaches can be used to further understand and develop intervention strategies for rabies in the future.

Les avancées enregistrées dans les techniques de séquençage, l'amélioration des logiciels d'interrogation des banques de séquences et la collecte plus précise de données épidémiologiques grâce aux systèmes de géolocalisation par satellite (GPS) renforcent nos capacités de surveillance des foyers de rage et nous aident à mieux comprendre les processus qui influent sur la propagation du virus, sur son évolution et sur les contraintes liées aux hôtes. Le séquençage du génome entier des virus de la rage au moyen d'approches méthodologiques diverses se généralise de plus en plus, permettant d'étudier à un rythme jamais atteint auparavant l'évolution et l'épidémiologie de ces virus. Ces études apportent de nouveaux éclairages sur les processus fondamentaux de l'évolution des virus, y compris les mécanismes moléculaires sous-jacents à l'adaptation des hôtes et à l'émergence virale chez de nouveaux hôtes. En outre, les données de séquençage mettent en lumière le rôle de l'environnement et des activités humaines sur la propagation de la rage, rôle dont la connaissance est déterminante pour lutter efficacement contre la maladie. Les auteurs font le point sur l'état des connaissances dans le domaine de la génomique des virus de la rage et proposent quelques pistes afin d'utiliser ces approches pour approfondir et développer davantage les futures stratégies d'intervention contre la rage.

Gracias al progreso de las técnicas de secuenciación, a la mejora de los métodos informáticos para estudiar las secuencias y a una obtención más exacta de datos epidemiológicos mediante la tecnología del sistema de posicionamiento mundial (GPS), hoy estamos en mejores condiciones para seguir de cerca los brotes de rabia y conocer más a fondo los procesos que inciden en la propagación y evolución del virus y en los factores de restricción de los anfitriones. La secuenciación del genoma entero de virus rábicos con muy diversos enfoques metodológicos, cada vez más extendida, permite hoy realizar estudios evolutivos y epidemiológicos a un ritmo sin precedentes. Estos estudios están arrojando luz sobre los procesos fundamentales de la evolución vírica, incluidos los mecanismos moleculares de la adaptación al anfitrión y la aparición del virus en nuevos anfitriones. Además, los datos de secuenciación están revelando la importancia de las características del paisaje y de las actividades antrópicas como factores de propagación de la rabia, un conocimiento crucial para la labor de lucha contra la enfermedad. Los autores resumen la situación de la genómica aplicada a los virus rábicos y explican cómo utilizar estos métodos para entender mejor la enfermedad y perfeccionar las estrategias de intervención contra ella en el futuro.

Local adaptation with high gene flow: temperature parameters drive adaptation to altitude in the common frog (Rana temporaria).

Both environmental and genetic influences can result in phenotypic variation. Quantifying the relative contributions of local adaptation and phenotypic plasticity to phenotypes is key to understanding the effect of environmental variation on populations. Identifying the selective pressures that drive divergence is an important, but often lacking, next step. High gene flow between high- and low-altitude common frog (Rana temporaria) breeding sites has previously been demonstrated in Scotland. The aim of this study was to assess whether local adaptation occurs in the face of high gene flow and to identify potential environmental selection pressures that drive adaptation. Phenotypic variation in larval traits was quantified in R. temporaria from paired high- and low-altitude sites using three common temperature treatments. Local adaptation was assessed using Q(ST)-F(ST) analyses, and quantitative phenotypic divergence was related to environmental parameters using Mantel tests. Although evidence of local adaptation was found for all traits measured, only variation in larval period and growth rate was consistent with adaptation to altitude. Moreover, this was only evident in the three mountains with the highest high-altitude sites. This variation was correlated with mean summer and winter temperatures, suggesting that temperature parameters are potentially strong selective pressures maintaining local adaptation, despite high gene flow.

Using genetic variation to infer associations with climate in the common frog, Rana temporaria.

Recent and historical species' associations with climate can be inferred using molecular markers. This knowledge of population and species-level responses to climatic variables can then be used to predict the potential consequences of ongoing climate change. The aim of this study was to predict responses of Rana temporaria to environmental change in Scotland by inferring historical and contemporary patterns of gene flow in relation to current variation in local thermal conditions. We first inferred colonization patterns within Europe following the last glacial maximum by combining new and previously published mitochondrial DNA sequences. We found that sequences from our Scottish samples were identical to (92%), or clustered with, the common haplotype previously identified from Western Europe. This clade showed very low mitochondrial variation, which did not allow inference of historical colonization routes but did allow interpretation of patterns of current fine-scale population structure without consideration of confounding historical variation. Second, we assessed fine-scale microsatellite-based patterns of genetic variation in relation to current altitudinal temperature gradients. No population structure was found within altitudinal gradients (average FST=0.02), despite a mean annual temperature difference of 4.5 °C between low- and high-altitude sites. Levels of genetic diversity were considerable and did not vary between sites. The panmictic population structure observed, even along temperature gradients, is a potentially positive sign for R. temporaria persistence in Scotland in the face of a changing climate. This study demonstrates that within taxonomic groups, thought to be at high risk from environmental change, levels of vulnerability can vary, even within species.

Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model.

Landscape epidemiology and landscape genetics combine advances in molecular techniques, spatial analyses and epidemiological models to generate a more real-world understanding of infectious disease dynamics and provide powerful new tools for the study of RNA viruses. Using dog rabies as a model we have identified how key questions regarding viral spread and persistence can be addressed using a combination of these techniques. In contrast to wildlife rabies, investigations into the landscape epidemiology of domestic dog rabies requires more detailed assessment of the role of humans in disease spread, including the incorporation of anthropogenic landscape features, human movements and socio-cultural factors into spatial models. In particular, identifying and quantifying the influence of anthropogenic features on pathogen spread and measuring the permeability of dispersal barriers are important considerations for planning control strategies, and may differ according to cultural, social and geographical variation across countries or continents. Challenges for dog rabies research include the development of metapopulation models and transmission networks using genetic information to uncover potential source/sink dynamics and identify the main routes of viral dissemination. Information generated from a landscape genetics approach will facilitate spatially strategic control programmes that accommodate for heterogeneities in the landscape and therefore utilise resources in the most cost-effective way. This can include the efficient placement of vaccine barriers, surveillance points and adaptive management for large-scale control programmes.

Phylogenetic characterisation of naturally occurring feline immunodeficiency virus in the United Kingdom.

Feline immunodeficiency virus (FIV) is a significant pathogen of domestic and non-domestic felids worldwide. In domestic cats, FIV is classified into five distinct subtypes (A-E) with subtypes A and B distributed most widely. However, little is known about the degree of intrasubtype viral diversity and this may prove critical in determining whether monovalent vaccines are likely to protect against FIV strains within a single subtype. Here, we characterise novel env sequences from 47 FIV strains recovered from infected cats in the United Kingdom and its environs. Phylogenetic analyses revealed that all bar one sequence belonged to subtype A, the predominant subtype in Western Europe. A single sequence was identified as a likely subtype A/C recombinant, intriguing given that subtype C does not appear to exist in either the UK or North Western Europe and suggestive of a recombination event predating its introduction into the UK. Subtype A strains from the UK were not significantly differentiated from representative subtype A isolates found elsewhere suggesting multiple introductions of FIV into the country. Divergence among isolates was comparable to that observed for subtype A isolates worldwide, indicating that FIV in the UK covers the full spectrum of subtype A diversity seen globally. This study demonstrates that while subtype A is predominant in the UK, novel introductions may result in the emergence of novel subtypes or intersubtype recombinants, potentially circumventing vaccine strategies. However, the dominance of subtype A suggests that the development of a regional or subtype-specific protective vaccine for the UK could be achievable.

Infectious disease modeling and the dynamics of transmission.

The dynamics of any infectious disease are heavily dependent on the rate of transmission from infectious to susceptible hosts. In many disease models, this rate is captured in a single compound parameter, the probability of transmission P. However, closer examination reveals how beta can be further decomposed into a number of biologically relevant variables, including contact rates among individuals and the probability that contact events actually result in disease transmission. We start by introducing some of the basic concepts underlying the different approaches to modeling disease transmission and by laying out why a more detailed understanding of the variables involved is usually desirable. We then describe how parameter estimates of these variables can be derived from empirical data, drawing primarily from the existing literature on human diseases. Finally, we discuss how these concepts and approaches may be applied to the study of pathogen transmission in wildlife diseases. In particular, we highlight recent technical innovations that could help to overcome some the logistical challenges commonly associated with empirical disease research in wild populations.

Assessing excess deaths in St. Louis, Missouri: 1980 to 1994.

Excess deaths in the city of St. Louis from 1980 to 1994, their trends over time, and racial death patterns were assessed using the CDC's Wonder mortality database. Death rates in the city were compared with the three lowest statistically valid county death rates in the state of Missouri. The number and percent of preventable deaths in the city population also were estimated. Findings show that approximately 50 percent of city deaths from the nine leading causes may be preventable.

Evaluation of an outbreak of foodborne illness initiated in the emergency department.

STUDY OBJECTIVES: For many foodborne outbreaks, the pathogen and food vehicle never are identified. Delayed collection of epidemiologic and microbiologic information may contribute to this. We postulated that collection of this information from ill persons as they presented to the emergency department during a recent outbreak might contribute to earlier identification of the pathogen and vehicle. DESIGN: At least 690 of 1,900 conventioneers developed gastrointestinal symptoms after attending a banquet. A questionnaire was developed to collect information on specific food histories, incubation periods, symptoms, physical findings, and demographics. These results were compared with results of investigations by the city and state departments of public health. SETTING: The ED of Rush-Presbyterian-St Luke's Medical Center, a tertiary care university hospital in Chicago, Illinois. TYPE OF PARTICIPANTS: Adults (24 men and nine women) presenting to the ED with gastrointestinal symptoms after eating a common meal. MEASUREMENTS AND MAIN RESULTS: The clinical syndrome suggested an invasive pathogen. Based on this, clinical microbiology laboratory procedures were modified (isolation plates were reviewed during the evening shift). This led to early identification of the first isolates (Salmonella enteritidis) from the outbreak. The questionnaire also narrowed the vehicle to one of two foods served. Investigations by the departments of public health subsequently identified one of these, bread pudding with a raw egg based-sauce, as the vehicle. CONCLUSION: Outbreak evaluations can begin in the ED or any other patient care facility. This evaluation need not always add significantly to the expenditure of time, manpower, or laboratory studies. The evaluation of even a small percentage of ill persons from a large outbreak may provide useful epidemiologic information and be particularly important in settings with limited public health resources.

Frequency of Salmonella typhimurium the year after a massive outbreak.

In 1985, Illinois experienced a large milkborne outbreak of Salmonella typhimurium with over 16,000 cases. During this year, 49.4% of United States and 86.4% of Illinois salmonellae were S. typhimurium. In 1986, 1133 microbiologically confirmed and serotyped cases of salmonellosis were reported in the City of Chicago, comprising 37% of the 3034 cases reported for the State of Illinois. The most frequent serotypes were S. typhimurium (21.3%), Salmonella heidelberg (18.2%), Salmonella enteritidis (10.7%), and Salmonella braenderup (7.7%), similar to the state as a whole. Nationally, excluding Illinois, the most frequent serotypes in 1986 were S. typhimurium (26.1%), S. enteritidis (14.7%), and S. heidelberg (13.0%). S. braenderup comprised 0.9% of the non-Illinois total. Regional variations in the epidemiology of salmonellae are probable and may reflect detected or undetected outbreaks. Within a year of the nation's largest Salmonella outbreak, there was no trace of any effect on the frequency of isolation of Salmonella spp.