Patrick Foley

Urban habituation, ecological connectivity and epidemic dampening: the emergence of Hendra virus from flying foxes (Pteropus spp.)

Anthropogenic environmental change is often implicated in the emergence of new zoonoses from wildlife; however, there is little mechanistic understanding of these causal links. Here, we examine the transmission dynamics of an emerging zoonotic paramyxovirus, Hendra virus (HeV), in its endemic host, Australian Pteropus bats (fruit bats or flying foxes). HeV is a biosecurity level 4 (BSL-4) pathogen, with a high case-fatality rate in humans and horses. With models parametrized from field and laboratory data, we explore a set of probable contributory mechanisms that explain the spatial and temporal pattern of HeV emergence; including urban habituation and decreased migration—two widely observed changes in flying fox ecology that result from anthropogenic transformation of bat habitat in Australia. Urban habituation increases the number of flying foxes in contact with human and domestic animal populations, and our models suggest that, in addition, decreased bat migratory behaviour could lead to a decline in population immunity, giving rise to more intense outbreaks after local viral reintroduction. Ten of the 14 known HeV outbreaks occurred near urbanized or sedentary flying fox populations, supporting these predictions. We also demonstrate that by incorporating waning maternal immunity into our models, the peak modelled prevalence coincides with the peak annual spill-over hazard for HeV. These results provide the first detailed mechanistic framework for understanding the sporadic temporal pattern of HeV emergence, and of the urban/peri-urban distribution of HeV outbreaks in horses and people.

Extinction Models for Local Populations

Publisher Summary This chapter reviews stochastic models of extinction within a local population. The main thread of the chapter is an analytic model of environmental stochasticity, in which populations fluctuate between a ceiling and extinction. A diffusion analysis of environmental and demographic stochasticity is complemented by analytic and numerical investigations into the robustness of the analysis. The environmental stochasticity model presented in this chapter generates simple analytic predictions of extinction rates and population densities. These can be used in metapopulation models to improve analysis of the fundamental processes of extinction and colonization. The environmental stochasticity model has many largely unexplored implications for metapopulation dynamics. Emigration rates are influenced by local fluctuations; extinction rates become correlated across populations; and the time scales of local growth and extinction may overlap. Simulations in discrete time, used in the study, show that the diffusion analysis works. The robustness investigations show that the model can be extended to deal with many biological details.

GRANULOCYTIC EHRLICHIOSIS AND TICK INFESTATION IN MOUNTAIN LIONS IN CALIFORNIA

Forty-seven mountain lions (Puma concolor) collected year-round in 1996 to 1998 from the Sierra Nevada foothills, the northern coast ranges, and in Monterey County (California, USA) were examined for infestation with Ixodes pacificus and Dermacentor variabilis ticks. Ticks were found predominantly in winter and spring. The seroprevalence of granulocytic ehrlichiae (GE) antibodies (Ehrlichia equi or the agent of human granulocytic ehrlichiosis) was 17% and the PCR-prevalence of DNA characteristic of GE in blood was 16%. There were eight polymerase chain reaction (PCR)-positive but seronegative mountain lions, one that was PCR-positive and seropositive, and eight that were PCR-negative and seropositive. Nineteen percent of engorged tick pools from mountain lions were PCR-positive. Because mountain lions inhabit tick-infested habitat and are frequently bitten by I. pacificus, surveillance for GE antibodies and DNA in mountain lions and other vertebrate hosts may be useful as indicators for geographical regions in which humans are at risk of GE infection.

Zoonotic Bartonella Species in Fleas Collected on Gray Foxes (Urocyon cinereoargenteus)

Bartonella spp. are fastidious, gram-negative, rod-shaped bacteria and are usually vector-borne. However, the vector has not been definitively identified for many recently described species. In northern California, gray foxes (Urocyon cinereoargenteus) are infected with two zoonotic Bartonella species, B. rochalimae and B. vinsonii subsp. berkhoffii. Fleas (range 1-8 fleas per fox) were collected from 22 (41.5%) of 54 gray foxes from urban and backcountry zones near Hoopa, California. The flea species were determined, and DNA was individually extracted to establish the Bartonella species harbored by these fleas. Of the 108 fleas collected, 99 (92%) were identified as Pulex simulans. Overall, 39% (42/108) of the fleas were polymerase chain reaction (PCR)-positive for Bartonella, with B. rochalimae and B. vinsonii subsp. berkhoffii identified in 34 (81%) and 8 (19%) of the PCR-positive fleas, respectively. There was no difference between the prevalence of Bartonella spp. in P. simulans for the urban and backcountry zones. Fourteen (64%) of the 22 foxes were Bartonella bacteremic at one or more of the capture dates. In 10 instances, both the foxes and the fleas collected from them at the same blood collection were Bartonella-positive. B. rochalimae was the predominant species identified in both foxes and fleas. The competency of Pulex fleas as a vector of B. rochalimae has not been confirmed and will need to be demonstrated experimentally. Pulex spp. fleas readily feed on humans and may represent a source of human exposure to zoonotic species of Bartonella.

Diversity of Anaplasma phagocytophilum strains, USA.

We analyzed the structure of the expression site encoding the immunoprotective protein MSP2/P44 from multiple Anaplasma phagocytophilum strains in the United States. The sequence of p44ESup1 had diverged in Ap-variant 1 strains infecting ruminants. In contrast, no differences were detected between A. phagocytophilum strains infecting humans and domestic dogs.

Ectoparasite diversity and exposure to vector-borne disease agents in wild rodents in central coastal California

Abstract A survey of wild rodents was performed in the Morro Bay area of central coastal California to determine serological and polymerase chain reaction (PCR) prevalence of Anaplasma phagocytophilum Dumler, Barbet, Bekker, Dasch, Palmer, Ray, Rikihisa, and Rurangirwa, Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt, and Brenner, Francisella tularensis McCoy, and Yersinia pestis Yersin; to describe the ectoparasitic fauna on important vector-borne disease hosts; and to determine whether pathogen exposure was associated with infestation by ectoparasites. We trapped 411 rodents from 10 species in 2004 and 2005. Anaplasma phagocytophilum exposure was detected in 11% of all wild rodents tested, with seropositive animals in eight species. Anaplasma phagocytophilum DNA was detected by PCR amplification in Neotoma fuscipes Baird and Reithrodontomys megalotis Baird (0.6% of all rodents). Yersinia spp. exposure was identified in 3.2% of all rodents tested, with highest detected exposure in peridomestic rodents, Mus musculus L. (20%), and Rattus rattus L. (50%). No individuals tested positive for the Y. pestis pla gene by PCR. In total, 338 fleas were identified from each of 10 rodent species examined. The most abundant flea was Malareus telchinus Rothschild. Relative density of flea infestation was highest on Spermophilus beecheyi Richardson and Microtus californicus Peale. Ticks recovered from trapped animals included Ixodes angustus Neumann, Ixodes pacificus Cooley & Kohls, Ixodes spinipalpis Hadwen & Nuttall, and Dermacentor occidentalis Marx. Given the moderate climate and diversity of rodents and arthropods in the Morro Bay area, ongoing investigation of this region will be helpful in understanding disease maintenance cycles.

Antigen Diversity in the Parasitic Bacterium Anaplasma phagocytophilum Arises from Selectively-Represented, Spatially Clustered Functional Pseudogenes

Anaplasma phagocytophilum is a tick-transmitted bacterial pathogen of humans and other animals, and is an obligate intracellular parasite. Throughout the course of infection, hosts acquire temporary resistance to granulocytic anaplasmosis as they develop immunity specific for the major antigen, major surface protein 2 (Msp2). However, the bacterium then utilizes a novel recombination mechanism shuffling functional pseudogenes sequentially into an expression cassette with conserved 5′ and 3′ ends, bypassing host immunity. Approximately 100 pseudogenes are present in the only fully sequenced human-origin HZ genome, representing the possibility for almost unlimited antigenic diversity. In the present study, we identified a select group of 20% of the A. phagocytophilum HZ msp2 pseudogenes that have matched preferentially to human, canine, and equine expression cassettes. Pseudogenes cluster predominantly in one spatial run limited to a single genomic island in less than 50% of the genome but phylogenetically related pseudogenes are neither necessarily located in close proximity on the genome nor share similar percent identity with expression cassettes. Pseudogenes near the expression cassette (and the origin) are more likely to be expressed than those farther away. Taken together, these findings suggest that there may be natural selection pressure to retain pseudogenes in one cluster near the putative origin of replication, even though global recombination shuffles pseudogenes around the genome, separating pseudogenes that share genetic origins as well as those with similar identities.

Evidence of Multiple Zoonotic Agents in a Wild Rodent Community in the Eastern Sierra Nevada

This study aimed to describe the occurrence of Yersinia pestis, Rickettsia rickettsii, Anaplasma phagocytophilum, and ectoparasites in a wild rodent community in the eastern Sierra Nevada. From May to September 2006, rodents were live-trapped, examined for ectoparasites, and blood was collected. All rodents were serologically tested for antibodies to Y. pestis, R. rickettsii, and A. phagocytophilum; in addition, blood samples and ectoparasites were tested by PCR to detect the presence of these zoonotic agents. Overall, 89 rodents, 46 fleas, and four ticks were collected. Antibody prevalence rates observed for rodents were 14% for R. rickettsii or antigenically related spotted-fever group rickettsiae, and 8% for A. phagocytophilum. No samples were positive for antibodies to Y. pestis. Positive PCR results included one yellow-pine chipmunk for Y. pestis (CT=32.8), one golden-mantled ground squirrel for R. rickettsii (CT=33), and one flea found to be co-infected with both R. rickettsii (CT=17) and A. phagocytophilum (CT=36). The results of this study provide evidence of multiple zoonoses overlapping within a single, located rodent community.

Emergence of Tick-Borne Granulocytic Anaplasmosis Associated with Habitat Type and Forest Change in Northern California

An important ecosystem service of intact forests is protection from some emerging infectious diseases. Tick-transmitted disease granulocytic anaplasmosis increasingly occupies second-growth forest. We hypothesized that areas of second growth would have increases in tick and rodent abundance, facilitating emergence of anaplasmosis. We predicted Anaplasma phagocytophilum presence as a function of biocomplexity and forest structure, including vegetation, ticks, and rodents in four sites in California. Significant risk factors for exposure included host species (woodrats with 13% seroprevalence, odds ratio [OR] = 8.3 and chipmunks with 27% seroprevalence, OR = 20.7), and park location (northern parks, OR 25.5-27.7). Exposure to A. phagocytophilum was more likely among chipmunks in redwood sites at one park, but with woodrats and oaks at another. Overall, transects on which small mammals showed greatest A. phagocytophilum exposure had high biodiversity in ticks, rodents, and vegetation, as well as intermediate-sized trees with a high mean and variance in diameter at breast height, findings which suggest that a dilution effect, where increased biodiversity reduces disease risk, does not necessarily apply in this system. Thus, enzootic and potentially emerging anaplasmosis were linked to high biodiversity and mature second-growth forest.

MODELING PLAGUE PERSISTENCE IN HOST-VECTOR COMMUNITIES IN CALIFORNIA

Plague is an enzootic disease in the western United States, even though long-term persistent infections do not seem to occur. Enzootic persistence may occur as a function of dynamic interactions between flea vectors and transiently infected hosts, but the specific levels of vector competence, host competence, and transmission and recovery rates that would promote persistence and emergence among wild hosts and vectors are not known. We developed a mathematical model of enzootic plague in the western United States and implemented the model with the following objectives: 1) to use matrix manipulation within a classic susceptible→infective→resistant→susceptible (SIRS) model framework to describe transmission of the plague bacterium Yersinia pestis among rodents and fleas in California, 2) to perform sensitivity analysis with model parameters and variables to indicate which values tended to dominate model output, and 3) to determine whether enzootic maintenance would be predicted with realistic parameter values obtained from the literature for Y. pestis in California rodents and fleas. The model PlagueSIRS was implemented in discrete time as a computer simulation incorporating environmental stochasticity and seasonality, by using matrix functions in the computer language R, allowing any number of rodent and flea species to interact through parasitism and disease transmission. Sensitivity analysis indicated that the model was sensitive to flea attack rate, host recovery rate, and rodent host carrying capacity but relatively insensitive to changes in the duration of latent infection in the flea, host and vector competence, flea recovery from infection, and host mortality attributable to plague. Realistic parameters and variable values did allow for the model to predict enzootic plague in some combinations, specifically when rodent species that were susceptible to infection but resistant to morbidity were parasitized by multiple poorly competent flea species, including some that were present year-round. This model could be extended to similar vectorborne disease systems and could be used iteratively with data collection in sylvatic plague studies to better understand plague persistence and emergence in nature.