Jean I. Tsao

Fundamental processes in the evolutionary ecology of Lyme borreliosis.

The evolutionary ecology of many emerging infectious diseases, particularly vector-borne zoonoses, is poorly understood. Here, we aim to develop a biological, process-based framework for vector-borne zoonoses, using Borrelia burgdorferi sensu lato (s.l.), the causative agent of Lyme borreliosis in humans, as an example. We explore the fundamental biological processes that operate in this zoonosis and put forward hypotheses on how extrinsic cues and intrinsic dynamics shape B. burgdorferi s.l. populations. Additionally, we highlight possible epidemiological parallels between B. burgdorferi s.l. and other vector-borne zoonotic pathogens, including West Nile virus.

An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccines effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.

Niche Partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the Same Tick Vector and Mammalian Reservoir Species

The Lyme borreliosis agent Borrelia burgdorferi and the relapsing fever group species Borrelia miyamotoi co-occur in the United States. We used species-specific, quantitative polymerase chain reaction to study both species in the blood and skin of Peromyscus leucopus mice and host-seeking Ixodes scapularis nymphs at a Connecticut site. Bacteremias with B. burgdorferi or B. miyamotoi were most prevalent during periods of greatest activity for nymphs or larvae, respectively. Whereas B. burgdorferi was 30-fold more frequent than B. miyamotoi in skin biopsies and mice had higher densities of B. burgdorferi densities in the skin than in the blood, B. miyamotoi densities were higher in blood than skin. In a survey of host-seeking nymphs in 11 northern states, infection prevalences for B. burgdorferi and B. miyamotoi averaged approximately 0.20 and approximately 0.02, respectively. Co-infections of P. leucopus or I. scapularis with both B. burgdorferi and B. miyamotoi were neither more nor less common than random expectations.

Spatiotemporal Patterns of Host-Seeking Ixodes scapularis Nymphs (Acari: Ixodidae) in the United States

Abstract The risk of Lyme disease for humans in the eastern United States is dependent on the density of host-seeking Ixodes scapularis Say nymphal stage ticks infected with Borrelia burgdorferi. Although many local and regional studies have estimated Lyme disease risk using these parameters, this is the first large-scale study using a standardized methodology. Density of host-seeking I. scapularis nymphs was measured by drag sampling of closed canopy deciduous forest habitats in 95 locations spaced among 2° quadrants covering the entire United States east of the 100th meridian. Sampling was done in five standardized transects at each site and repeated three to six times during the summer of 2004. The total number of adults and nymphs of the seven tick species collected was 17,972, with 1,405 nymphal I. scapularis collected in 31 of the 95 sites. Peak global spatial autocorrelation values were found at the smallest lag distance (300 km) and decreased significantly after 1,000 km. Local autocorrelation statistics identified two significant high-density clusters around endemic areas in the northeast and upper Midwest and a low-density cluster in sites south of the 39th parallel, where only 21 nymphs were collected. Peak nymphal host-seeking density occurred earlier in the southern than in the most northern sites. Spatiotemporal density patterns will be combined with Borrelia prevalence data as part of a 4-yr survey to generate a nationwide spatial risk model for I. scapularis-borne Borrelia, which will improve targeting of disease prevention efforts.

Human risk of infection with Borrelia burgdorferi, the Lyme disease agent, in eastern United States.

The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection.

Climate and tick seasonality are predictors of Borrelia burgdorferi genotype distribution.

ABSTRACT The blacklegged tick, Ixodes scapularis, is of significant public health importance as a vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The timing of seasonal activity of each immature I. scapularis life stage relative to the next is critical for the maintenance of B. burgdorferi because larvae must feed after an infected nymph to efficiently acquire the infection from reservoir hosts. Recent studies have shown that some strains of B. burgdorferi do not persist in the primary reservoir host for more than a few weeks, thereby shortening the window of opportunity between nymphal and larval feeding that sustains their enzootic maintenance. We tested the hypothesis that climate is predictive of geographic variation in the seasonal activity of I. scapularis, which in turn differentially influences the distribution of B. burgdorferi genotypes within the geographic range of I. scapularis. We analyzed the relationships between climate, seasonal activity of I. scapularis, and B. burgdorferi genotype frequency in 30 geographically diverse sites in the northeastern and midwestern United States. We found that the magnitude of the difference between summer and winter daily temperature maximums was positively correlated with the degree of seasonal synchrony of the two immature stages of I. scapularis. Genotyping revealed an enrichment of 16S-23S rRNA intergenic spacer restriction fragment length polymorphism sequence type 1 strains relative to others at sites with lower seasonal synchrony. We conclude that climate-associated variability in the timing of I. scapularis host seeking contributes to geographic heterogeneities in the frequencies of B. burgdorferi genotypes, with potential consequences for Lyme borreliosis morbidity.

A FUNDAMENTAL TRADE-OFF IN RESOURCE EXPLOITATION BY DAPHNIA AND CONSEQUENCES TO PLANKTON COMMUNITIES

The genus Daphnia (Crustacea: Branchipoda) includes a diversity of species that are generalist grazers on plankton in freshwater lakes. Despite substantial intraspecific variation in body size, explanations of functional differences among Daphnia species con- tinue to emphasize body size. In this study, we ask whether Daphnia in a relatively narrow range of body sizes differ in ability to exploit the array of resources commonly encountered in lakes. We compared juvenile growth rates of several clones and species of Daphnia fed natural planktonic resources that differed in overall dietary richness. We observed, both among and within species, a trade-off between growth rates in rich and poor resource conditions. We compared the ability of different species and clones to exploit natural resources in a lake mesocosm experiment, testing the prediction that clones displaying the greatest growth rates in rich resource conditions would have the highest minimum resource requirements. Using 8000-L whole water column enclosures, replicate populations of D. rosea and two different morphs of D. pulicaria were established separately in monoculture in a thermally stratified lake. An additional treatment without crustacean zooplankton was also established. We quantified resources in the enclosures using multiple indirect measures (e.g., chlorophyll a) and a growth bioassay. Results supported predictions; rankings of resource levels achieved in the different treatments suggest that Daphnia trade off high maximum growth rates for low minimum resource requirements. This field experiment also documented large differences among the species and clones of Daphnia in their impact on phytoplankton resources, water clarity, and formation of calcite particles (whiting). We suggest that these large ecological effects stem from the trade-off in abilities to use rich vs. poor resources and constitute an important aspect of grazer-resource interactions. We review the literature on growth and reproductive responses of zooplankton species to resource level and find general agreement with the concept of a trade-off between abilities to exploit rich and poor resource conditions. A reanalysis of data from a comprehensive study on Daphniidae growth confirms our results and suggests that the breadth of species in this family conforms to the trade-off. Furthermore, the trade-off is only weakly, and not significantly, associated with body size. Our study presents a new framework for under- standing the functional significance of daphniid diversity to plankton food webs and illus- trates how an ecological trade-off provides a means of linking species diversity to ecosystem function.

Typing of Borrelia Relapsing Fever Group Strains

Partial sequencing of the 16S-23S rDNA intergenic spacer showed two to four genotypes each for Borrelia hermsii and B. turicatae, both relapsing fever agents transmitted by argasid ticks, and for B. miyamotoi and B. lonestari, transmitted by ixodid ticks. Field surveys of Ixodes ticks in Connecticut and Sweden showed limited local diversity for B. miyamotoi.

Borrelia burgdorferi Infection in a Natural Population of Peromyscus Leucopus Mice: A Longitudinal Study in an Area Where Lyme Borreliosis Is Highly Endemic

Blood samples from Peromyscus leucopus mice captured at an enzootic site in Connecticut were examined for antibodies to and DNA of Borrelia burgdorferi, to characterize the dynamics of infection in this reservoir population. From trappings conducted over the course of 2 transmission seasons, 598 (75%) of 801 serum samples from 514 mice were found to be positive by enzyme immunoassay. Seropositivity correlated with date of capture and mouse age, was similar among locations within the site, increased from 57% to 93% over the course of the transmission season, and was associated with antibodies to outer surface protein (Osp) C, but not to OspA. Longitudinal samples from 184 mice revealed an incidence of 0.2 cases/mouse/week. Nineteen (10%) of 187 samples were found by polymerase chain reaction to be positive for B. burgdorferi, and, of those, 14 (74%) were found to be seropositive. Nearly the entire population of P. leucopus mice became infected with B. burgdorferi by late August, coinciding with the peak activity period of host-seeking larvae uninfected with the spirochete Ixodes scapularis, thereby perpetuating the agent through succeeding generations of ticks.

A Dispersal Model for the Range Expansion of Blacklegged Tick (Acari: Ixodidae)

Abstract The blacklegged tick, Ixodes scapularis Say, a vector for the agents of Lyme borreliosis and other diseases, has expanded its range dramatically over the past 20 yr. However, the relative contributions of different vertebrate host species to this expansion have remained largely unexplored. To address this issue, we simulated the expansion of a theoretical tick population across a simple landscape by using a deterministic, spatially explicit, cellular automata model. The model incorporates the ecology of ticks and three vertebrate hosts: white-tailed deer, Odocoileus virginianus Zimmermann; white-footed mouse, Peromyscus leucopus Rafinesque; and American robin, Turdus migratorius L. Host contribution to tick dispersal is modeled as a function of tick burden, home range size, and population density. These parameters were determined using published and unpublished data. Our results suggest that 1) hosts with high tick burdens and large home ranges (e.g., deer) play a critical role in I. scapularis range expansion; 2) hosts with small home ranges (e.g., mice) can limit range expansion if they divert a sufficient number of ticks from feeding on more mobile hosts; and (3) birds that migrate annually (e.g., robins) can play a crucial role in tick range expansion.