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Babesia microti and Borrelia burgdorferi, the respective causative agents of human babesiosis and Lyme disease, are maintained in their enzootic cycles by the blacklegged tick (Ixodes scapularis) and use the white-footed mouse (Peromyscus leucopus) as primary reservoir host. The geographic range of both pathogens has expanded in the United States, but the spread of babesiosis has lagged behind that of Lyme disease. Several studies have estimated the basic reproduction number (R0) for B. microti to be below the threshold for persistence (<1), a finding that is inconsistent with the persistence and geographic expansion of this pathogen. We tested the hypothesis that host coinfection with B. burgdorferi increases the likelihood of B. microti transmission and establishment in new areas. We fed I. scapularis larva on P. leucopus mice that had been infected in the laboratory with B. microti and/or B. burgdorferi. We observed that coinfection in mice increases the frequency of B. microti infected ticks. To identify the ecological variables that would increase the probability of B. microti establishment in the field, we integrated our laboratory data with field data on tick burden and feeding activity in an R0 model. Our model predicts that high prevalence of B. burgdorferi infected mice lowers the ecological threshold for B. microti establishment, especially at sites where larval burden on P. leucopus is lower and where larvae feed simultaneously or soon after nymphs infect mice, when most of the transmission enhancement due to coinfection occurs. Our studies suggest that B. burgdorferi contributes to the emergence and expansion of B. microti and provides a model to predict the ecological factors that are sufficient for emergence of B. microti in the wild.

Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all Lyme disease-endemic areas of the United States. To determine the seroprevalence of IgG against B. miyamotoi sensu lato in the northeastern United States and assess whether serum from B. miyamotoi sensu lato-infected persons is reactive to B. burgdorferi antigens, we tested archived serum samples from area residents during 1991-2012. Of 639 samples from healthy persons, 25 were positive for B. miyamotoi sensu lato and 60 for B. burgdorferi. Samples from ≈10% of B. miyamotoi sensu lato-seropositive persons without a recent history of Lyme disease were seropositive for B. burgdorferi. Our results suggest that human B. miyamotoi sensu lato infection may be common in southern New England and that B. burgdorferi antibody testing is not an effective surrogate for detecting B. miyamotoi sensu lato infection.

Human babesiosis is an emerging tick-borne disease caused by the intraerythrocytic protozoan Babesia microti. Its geographic distribution is more limited than that of Lyme disease, despite sharing the same tick vector and reservoir hosts. The geographic range of babesiosis is expanding, but knowledge of its range is incomplete and relies exclusively on reports of human cases. We evaluated the utility of tick-based surveillance for monitoring disease expansion by comparing the ratios of the 2 infections in humans and ticks in areas with varying B. microti endemicity. We found a close association between human disease and tick infection ratios in long-established babesiosis-endemic areas but a lower than expected incidence of human babesiosis on the basis of tick infection rates in new disease-endemic areas. This finding suggests that babesiosis at emerging sites is underreported. Vector-based surveillance can provide an early warning system for the emergence of human babesiosis.

Babesia microti, the primary cause of human babesiosis in the United States, is transmitted by Ixodes scapularis ticks; transmission may also occur through blood transfusion and transplacentally. Most infected people experience a viral-like illness that resolves without complication, but those who are immunocompromised may develop a serious and prolonged illness that is sometimes fatal. The geographic expansion and increasing incidence of human babesiosis in the northeastern and midwestern United States highlight the need for high-throughput sensitive and specific assays to detect parasites in both ticks and humans with the goals of improving epidemiological surveillance, diagnosis of acute infections, and screening of the blood supply. Accordingly, we developed a B. microti-specific quantitative PCR (qPCR) assay (named BabMq18) designed to detect B. microti DNA in tick and human blood samples using a primer and probe combination that targets the 18S rRNA gene of B. microti. This qPCR assay was compared with two nonquantitative B. microti PCR assays by testing tick samples and was found to exhibit higher sensitivity for detection of B. microti DNA. The BabMq18 assay has a detection threshold of 10 copies per reaction and does not amplify DNA in I. scapularis ticks infected with Babesia odocoilei, Borrelia burgdorferi, Borrelia miyamotoi, or Anaplasma phagocytophilum. This highly sensitive and specific qPCR assay can be used for detection of B. microti DNA in both tick and human samples. Finally, we report the prevalence of B. microti infection in field-collected I. scapularis nymphs from three locations in southern New England that present disparate incidences of human babesiosis.

The Northeast Area-wide Tick Control Project (NEATCP) was funded by the United States Department of Agriculture (USDA) as a large-scale cooperative demonstration project of the USDA-Agricultural Research Service (ARS)-patented 4-Poster tick control technology (Pound et al. 1994) involving the USDA-ARS and a consortium of universities, state agencies, and a consulting firm at research locations in the five states of Connecticut (CT), Maryland (MD), New Jersey (NJ), New York (NY), and Rhode Island (RI). The stated objective of the project was "A community-based field trial of ARS-patented tick control technology designed to reduce the risk of Lyme disease in northeastern states." Here we relate the rationale and history of the technology, a chronological listing of events leading to implementation of the project, the original protocol for selecting treatment, and control sites, and protocols for deployment of treatments, sampling, assays, data analyses, and estimates of efficacy.

This series of articles describes the first large-scale experiment designed to explore the efficacy of reducing the risk of tick-borne disease in highly endemic communities of the northeastern and Mid-Atlantic United States through deployment of a self-application device that treats white-tailed deer with acaricide to prevent feeding by adult Ixodes scapularis ticks and all stages of Amblyomma americanum ticks where both species occur. The results of the multicenter study are reported in the accompanying articles in this issue. This article describes the background and rationale for this experiment by reviewing relevant literature on current tick-borne disease epidemics and previous efforts to reduce the public health burden of Lyme disease and other tick-borne diseases.

We evaluated the effects of tick control by acaricide self-treatment of white-tailed deer on the infection prevalence and entomologic risk for three Ixodes scapularis-borne bacteria in host-seeking ticks. Ticks were collected from vegetation in areas treated with the "4-Poster" device and from control areas over a 6-year period in five geographically diverse study locations in the Northeastern United States and tested for infection with two known agents of human disease, Borrelia burgdorferi and Anaplasma phagocytophilum, and for a novel relapsing fever-group spirochete related to Borrelia miyamotoi. Overall, 38.2% of adults and 12.5% of nymphs were infected with B. burgdorferi; 8.5% of adults and 4.2% of nymphs were infected with A. phagocytophilum; and 1.9% of adults and 0.8% of nymphs were infected with B. miyamotoi. In most cases, treatment with the 4-Poster device was not associated with changes in the prevalence of infection with any of these three microorganisms among nymphal or adult ticks. However, the density of nymphs infected with B. burgdorferi, and consequently the entomologic risk for Lyme disease, was reduced overall by 68% in treated areas compared to control areas among the five study sites at the end of the study. The frequency of bacterial coinfections in ticks was generally equal to the product of the proportion of ticks infected with a single bacterium, indicating that enzootic maintenance of these pathogens is independent. We conclude that controlling ticks on deer by self-application of acaricide results in an overall decrease in the human risk for exposure to these three bacterial agents, which is due solely to a reduction in tick density.

As part of the Northeast Area-wide Tick Control Project (NEATCP), meta-analyses were performed using pooled data on the extent of tick-vector control achieved through seven concurrent studies, conducted within five states, using U.S. Department of Agriculture "4-Poster" devices to deliver targeted-acaricide to white-tailed deer. Although reductions in the abundance of all life-stages of Ixodes scapularis were the measured outcomes, this study focused on metrics associated with I. scapularis nymphal tick densities as this measure has consistently proven to directly correlate with human risk of acquiring Lyme disease. Since independent tick sampling schemes were undertaken at each of the five environmentally distinct study locations, a meta-analytic approach permitted estimation of a single true control-effect size for each treatment year of the NEATCP. The control-effect is expressed as the annual percent I. scapularis nymphal control most consistent with meta-analysis data for each treatment year. Our meta-analyses indicate that by the sixth treatment year, the NEATCP effectively reduced the relative density of I. scapularis nymphs by 71% on the 5.14 km(2) treatment sites, corresponding to a 71% lower relative entomologic risk index for acquiring Lyme disease.

From 1997 to 2002, the U.S. Department of Agriculture's Northeast Area-wide Tick Control Project used acaricide-treated 4-Poster Deer Treatment Bait Stations in five eastern states to control ticks feeding on white-tailed deer. The objectives of this host-targeted technology were to reduce free-living blacklegged (Ixodes scapularis Say) and lone star (Amblyomma americanum [L.]) tick populations and thereby to reduce the risk of tick-borne disease. During 2002 to 2004, treatments were suspended, and tick population recovery rates were assayed. Subsequently, the major factors that influenced variations in efficacy were extrapolated to better understand and improve this technology. Treatments resulted in significant reductions in free-living populations of nymphal blacklegged ticks at six of the seven sites, and lone star ticks were significantly reduced at all three sites where they were present. During the study, maximal significant (p < or = 0.05) efficacies against nymphal blacklegged and lone star ticks at individual sites ranged from 60.0 to 81.7 and 90.9 to 99.5%, respectively. The major environmental factor that reduced efficacy was the occurrence of heavy acorn masts, which provided an alternative food resource for deer. Although the 4-Poster technology requires 1 or more years to show efficacy, this host-targeted intervention was demonstrated to be an efficacious, economical, safe, and environment-friendly alternative to area-wide spraying of acaricide to control free-living populations of these tick species.

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.

Since 1999, West Nile virus (WNV) disease has affected the northeastern United States. To describe the spatial epidemiology and identify risk factors for disease incidence, we analyzed 8 years (1999-2006) of county-based human WNV disease surveillance data. Among the 56.6 million residents in 8 northeastern states sharing primary enzootic vectors, we found 977 cases. We controlled for population density and potential bias from surveillance and spatial proximity. Analyses demonstrated significant spatial spreading from 1999 through 2004 (p<0.01, r2 = 0.16). A significant trend was apparent among increasingly urban counties; county quartiles with the least (<38%) forest cover had 4.4-fold greater odds (95% confidence interval [CI] 1.4-13.2, p = 0.01) of having above-median disease incidence (>0.75 cases/100,000 residents) than counties with the most (>70%) forest cover. These results quantify urbanization as a risk factor for WNV disease incidence and are consistent with knowledge of vector species in this area.

We examined the degree of host specialization of different strains of Borrelia burgdorferi, the tickborne pathogen that causes Lyme borreliosis in the northeastern United States. We first assessed the genetic population structures of B. burgdorferi in ticks obtained from different mammalian host species and in questing ticks sampled in a woodland ecosystem in Connecticut. By comparing the patterns found in our study with data from another cross-sectional study, we demonstrate that B. burgdorferi is a generalist microparasite and conclude that efficient cross-species transmission of B. burgdorferi is a key feature that has allowed the rapid spread of Lyme borreliosis across the northeastern United States.

Surveillance programs that identify areas where both the vector (Ixodes dammini) and etiologic agent (Borrelia burgdorferi) are present may identify the risk of Lyme disease and its spread earlier and more accurately than do programs relying on any single method, particularly human case reports. Hunter-killed deer (n = 1,204) from 22 counties in Maryland, Massachusetts, New Hampshire, New York, and Pennsylvania were examined in fall 1989 and all ectoparasites were identified. The following spring, canine sera (n = 884) were obtained from these sites, which included known endemic areas and those where Lyme disease is uncommon, and tested by enzyme-linked immunosorbent assay. Regression analysis of canine seroprevalence versus tick prevalence on deer from the same counties demonstrate a significant positive linear relationship. Sites were designated as low-, moderate-, or high-risk counties based upon their position on the regression curve. The geographic distribution of the sites correlated well with the distribution of known Lyme disease endemic and nonendemic areas. Locations were also identified where Lyme disease may be emerging. The positive relationship between measures of vector and pathogen abundance determined in this study permits public health workers to identify endemic and potentially endemic areas independently of human case reports.