A. Marm Kilpatrick

Predicting the global spread of H5N1 avian influenza

The spread of highly pathogenic H5N1 avian influenza into Asia, Europe, and Africa has resulted in enormous impacts on the poultry industry and presents an important threat to human health. The pathways by which the virus has and will spread between countries have been debated extensively, but have yet to be analyzed comprehensively and quantitatively. We integrated data on phylogenetic relationships of virus isolates, migratory bird movements, and trade in poultry and wild birds to determine the pathway for 52 individual introduction events into countries and predict future spread. We show that 9 of 21 of H5N1 introductions to countries in Asia were most likely through poultry, and 3 of 21 were most likely through migrating birds. In contrast, spread to most (20/23) countries in Europe was most likely through migratory birds. Spread in Africa was likely partly by poultry (2/8 introductions) and partly by migrating birds (3/8). Our analyses predict that H5N1 is more likely to be introduced into the Western Hemisphere through infected poultry and into the mainland United States by subsequent movement of migrating birds from neighboring countries, rather than from eastern Siberia. These results highlight the potential synergism between trade and wild animal movement in the emergence and pandemic spread of pathogens and demonstrate the value of predictive models for disease control.

West Nile Virus Epidemics in North America Are Driven by Shifts in Mosquito Feeding Behavior

West Nile virus (WNV) has caused repeated large-scale human epidemics in North America since it was first detected in 1999 and is now the dominant vector-borne disease in this continent. Understanding the factors that determine the intensity of the spillover of this zoonotic pathogen from birds to humans (via mosquitoes) is a prerequisite for predicting and preventing human epidemics. We integrated mosquito feeding behavior with data on the population dynamics and WNV epidemiology of mosquitoes, birds, and humans. We show that Culex pipiens, the dominant enzootic (bird-to-bird) and bridge (bird-to-human) vector of WNV in urbanized areas in the northeast and north-central United States, shifted its feeding preferences from birds to humans by 7-fold during late summer and early fall, coinciding with the dispersal of its preferred host (American robins, Turdus migratorius) and the rise in human WNV infections. We also show that feeding shifts in Cx. tarsalis amplify human WNV epidemics in Colorado and California and occur during periods of robin dispersal and migration. Our results provide a direct explanation for the timing and intensity of human WNV epidemics. Shifts in feeding from competent avian hosts early in an epidemic to incompetent humans after mosquito infection prevalences are high result in synergistic effects that greatly amplify the number of human infections of this and other pathogens. Our results underscore the dramatic effects of vector behavior in driving the transmission of zoonotic pathogens to humans.

West Nile virus emergence and large-scale declines of North American bird populations

Emerging infectious diseases present a formidable challenge to the conservation of native species in the twenty-first century. Diseases caused by introduced pathogens have had large impacts on species abundances, including the American chestnut, Hawaiian bird species and many amphibians. Changes in host population sizes can lead to marked shifts in community composition and ecosystem functioning. However, identifying the impacts of an introduced disease and distinguishing it from other forces that influence population dynamics (for example, climate) is challenging and requires abundance data that extend before and after the introduction. Here we use 26 yr of Breeding Bird Survey (BBS) data to determine the impact of West Nile virus (WNV) on 20 potential avian hosts across North America. We demonstrate significant changes in population trajectories for seven species from four families that concur with a priori predictions and the spatio-temporal intensity of pathogen transmission. The American crow population declined by up to 45% since WNV arrival, and only two of the seven species with documented impact recovered to pre-WNV levels by 2005. Our findings demonstrate the potential impacts of an invasive species on a diverse faunal assemblage across broad geographical scales, and underscore the complexity of subsequent community response.

Host heterogeneity dominates West Nile virus transmission

Heterogeneity in host populations and communities can have large effects on the transmission and control of a pathogen. In extreme cases, a few individuals give rise to the majority of secondary infections, which have been termed super spreading events. Here, we show that transmission of West Nile virus (WNV) is dominated by extreme heterogeneity in the host community, resulting in highly inflated reproductive ratios. A single relatively uncommon avian species, American robin (Turdus migratorius), appeared to be responsible for the majority of WNV-infectious mosquitoes and acted as the species equivalent of a super spreader for this multi-host pathogen. Crows were also highly preferred by mosquitoes at some sites, while house sparrows were significantly avoided. Nonetheless, due to their relative rarity, corvids (crows and jays) were relatively unimportant in WNV amplification. These results challenge current beliefs about the role of certain avian species in WNV amplification and demonstrate the importance of determining contact rates between vectors and host species to understand pathogen transmission dynamics.

The ecology and impact of chytridiomycosis: an emerging disease of amphibians

Emerging infectious diseases are increasingly recognized as key threats to wildlife. Batrachochytrium dendrobatidis (Bd), the causative agent of chytridiomycosis, has been implicated in widespread amphibian declines and is currently the largest infectious disease threat to biodiversity. Here, we review the causes of Bd emergence, its impact on amphibian populations and the ecology of Bd transmission. We describe studies to answer outstanding issues, including the origin of the pathogen, the effect of Bd relative to other causes of population declines, the modes of Bd dispersal, and factors influencing the intensity of its transmission. Chytridiomycosis is an archetypal emerging disease, with a broad host range and significant impacts on host populations and, as such, poses a crucial challenge for wildlife managers and an urgent conservation concern.

West Nile Virus Risk Assessment and the Bridge Vector Paradigm

In the northeast United States, control of West Nile virus (WNV) vectors has been unfocused because of a lack of accurate knowledge about the roles different mosquitoes play in WNV transmission. We analyzed the risk posed by 10 species of mosquitoes for transmitting WNV to humans by using a novel risk-assessment measure that combines information on the abundance, infection prevalence, vector competence, and biting behavior of vectors. This analysis suggests that 2 species (Culex pipiens L. and Cx. restuans Theobald [Diptera: Cilicidae]) not previously considered important in transmitting WNV to humans may be responsible for up to 80% of human WNV infections in this region. This finding suggests that control efforts should be focused on these species which may reduce effects on nontarget wetland organisms. Our risk measure has broad applicability to other regions and diseases and can be adapted for use as a predictive tool of future human WNV infections.

Globalization, Land Use, and the Invasion of West Nile Virus

Many invasive species that have been spread through the globalization of trade and travel are pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future pathogen introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. This research provides a framework for predicting and preventing the emergence of foreign vector-borne pathogens.

Temperature, Viral Genetics, and the Transmission of West Nile Virus by Culex pipiens Mosquitoes

The distribution and intensity of transmission of vector-borne pathogens can be strongly influenced by the competence of vectors. Vector competence, in turn, can be influenced by temperature and viral genetics. West Nile virus (WNV) was introduced into the United States of America in 1999 and subsequently spread throughout much of the Americas. Previously, we have shown that a novel genotype of WNV, WN02, first detected in 2001, spread across the US and was more efficient than the introduced genotype, NY99, at infecting, disseminating, and being transmitted by Culex mosquitoes. In the current study, we determined the relationship between temperature and time since feeding on the probability of transmitting each genotype of WNV. We found that the advantage of the WN02 genotype increases with the product of time and temperature. Thus, warmer temperatures would have facilitated the invasion of the WN02 genotype. In addition, we found that transmission of WNV accelerated sharply with increasing temperature, T, (best fit by a function of T4) showing that traditional degree-day models underestimate the impact of temperature on WNV transmission. This laboratory study suggests that both viral evolution and temperature help shape the distribution and intensity of transmission of WNV, and provides a model for predicting the impact of temperature and global warming on WNV transmission.

''Bird biting'' mosquitoes and human disease: A review of the role of Culex pipiens complex mosquitoes in epidemiology

The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Culex pipiens pipiens with two forms, pipiens and molestus, Culex pipiens pallens, Culex quinquefasciatus, Culex australicus, and Culex globocoxitus. While several members of the complex have limited geographic distributions, Cx. pipienspipiens and Cx. quinquefasciatus are found in all known urban and sub-urban temperate and tropical regions, respectively, across the world, where they are often principal disease vectors. In addition, hybrids are common in areas of overlap. Although gaps in our knowledge still remain, the advent of genetic tools has greatly enhanced our understanding of the history of speciation, domestication, dispersal, and hybridization. We review the taxonomy, genetics, evolution, behavior, and ecology of members of the Cx. pipiens complex and their role in the transmission of medically important pathogens. The adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to their global distribution through dispersal via humans and, combined with their mixed feeding patterns on birds and mammals (including humans), increased the transmission of several avian pathogens to humans. We highlight several unanswered questions that will increase our ability to control diseases transmitted by these mosquitoes.

Drivers, dynamics, and control of emerging vector-borne zoonotic diseases.

Emerging vector-borne diseases are an important issue in global health. Many vector-borne pathogens have appeared in new regions in the past two decades, while many endemic diseases have increased in incidence. Although introductions and emergence of endemic pathogens are often considered to be distinct processes, many endemic pathogens are actually spreading at a local scale coincident with habitat change. We draw attention to key differences between dynamics and disease burden that result from increased pathogen transmission after habitat change and after introduction into new regions. Local emergence is commonly driven by changes in human factors as much as by enhanced enzootic cycles, whereas pathogen invasion results from anthropogenic trade and travel where and when conditions (eg, hosts, vectors, and climate) are suitable for a pathogen. Once a pathogen is established, ecological factors related to vector characteristics can shape the evolutionary selective pressure and result in increased use of people as transmission hosts. We describe challenges inherent in the control of vector-borne zoonotic diseases and some emerging non-traditional strategies that could be effective in the long term.