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West Nile virus (WNV; Flaviviridae: Flavivirus) is a widely distributed arthropod-borne virus that has negatively affected human health and animal populations. WNV infection rates of mosquitoes and human cases have been shown to be correlated with climate. However, previous studies have been conducted at a variety of spatial and temporal scales, and the scale-dependence of these relationships has been understudied. We tested the hypothesis that climate variables are important to understand these relationships at all spatial scales. We analyzed the influence of climate on WNV infection rate of mosquitoes and number of human cases in New York and Connecticut using Random Forests, a machine learning technique. During model development, 66 climate-related variables based on temperature, precipitation and soil moisture were tested for predictive skill. We also included 20-21 non-climatic variables to account for known environmental effects (e.g., land cover and human population), surveillance related information (e.g., relative mosquito abundance), and to assess the potential explanatory power of other relevant factors (e.g., presence of wastewater treatment plants). Random forest models were used to identify the most important climate variables for explaining spatial-temporal variation in mosquito infection rates (abbreviated as MLE). The results of the cross-validation support our hypothesis that climate variables improve the predictive skill for MLE at county- and trap-scales and for human cases at the county-scale. Of the climate-related variables selected, mean minimum temperature from July-September was selected in all analyses, and soil moisture was selected for the mosquito county-scale analysis. Models demonstrated predictive skill, but still over- and under-estimated WNV MLE and numbers of human cases. Models at fine spatial scales had lower absolute errors but had greater errors relative to the mean infection rates., Competing Interests: The authors have declared that no competing interests exist.

Lyme disease is a spatially heterogeneous tick-borne infection, with approximately 85% of US cases concentrated in the mid-Atlantic and northeastern states. Surveillance for Lyme disease and its causative agent, including public health case reporting and entomologic surveillance, is necessary to understand its endemic range, but currently used case detection methods have limitations. To evaluate an alternative approach to Lyme disease surveillance, we have performed a geospatial analysis of Lyme disease cases from the Johns Hopkins Health System in Maryland. We used two sources of cases: a) individuals with both a positive test for Lyme disease and a contemporaneous diagnostic code consistent with a Lyme disease-related syndrome; and b) individuals referred for a Lyme disease evaluation who were adjudicated to have Lyme disease. Controls were individuals from the referral cohort judged not to have Lyme disease. Residential address data were available for all cases and controls. We used a hierarchical Bayesian model with a smoothing function for a coordinate location to evaluate the probability of Lyme disease within 100 km of Johns Hopkins Hospital. We found that the probability of Lyme disease was greatest in the north and west of Baltimore, and the local probability that a subject would have Lyme disease varied by as much as 30-fold. Adjustment for demographic and ecological variables partially attenuated the spatial gradient. Our study supports the suitability of electronic medical record data for the retrospective surveillance of Lyme disease. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV), a flavivirus transmitted by mosquito bites, causes primarily mild symptoms but can also be fatal. Therefore, predicting and controlling the spread of West Nile virus is essential for public health in endemic areas. We hypothesized that socioeconomic factors may influence human risk from WNV. We analyzed a list of weather, land use, mosquito surveillance, and socioeconomic variables for predicting WNV cases in 1-km hexagonal grids across the Chicago metropolitan area. We used a two-stage lightGBM approach to perform the analysis and found that hexagons with incomes above and below the median are influenced by the same top characteristics. We found that weather factors and mosquito infection rates were the strongest common factors. Land use and socioeconomic variables had relatively small contributions in predicting WNV cases. The Light GBM handles unbalanced data sets well and provides meaningful predictions of the risk of epidemic disease outbreaks. [ABSTRACT FROM AUTHOR]

Although human exposure to the ticks that transmit Lyme-disease bacteria is widely considered to occur around people's homes, most studies of variation in tick abundance and infection are undertaken outside residential areas. Consequently, the patterns of variation in risk of human exposure to tick-borne infections in these human-dominated landscapes are poorly understood. Here, we report the results of four years of sampling for tick abundance, tick infection, tick encounters, and tick-borne disease reports on residential properties nested within six neighborhoods in Dutchess County, New York, USA, an area of high incidence for Lyme and other tick-borne diseases. All properties were within neighborhoods that had been randomly assigned as placebo controls in The Tick Project; hence, none were treated to reduce tick abundance during the period of investigation, providing a unique dataset of natural variation within and between neighborhoods. We estimated the abundance of host-seeking blacklegged ticks (Ixodes scapularis) in three types of habitats on residential properties–forests, lawns, and gardens. In forest and lawn habitats, some neighborhoods had consistently higher tick abundance. Properties within neighborhoods also varied consistently between years, suggesting hot spots and cold spots occurring at a small (~ 1-hectare) spatial scale. Across neighborhoods, the abundance of nymphal ticks was explained by neither the amount of forest in that neighborhood, nor by the degree of forest fragmentation. The proportion of ticks infected with three common tick-borne pathogens did not differ significantly between neighborhoods. We observed no effect of tick abundance on human encounters with ticks, nor on either human or pet cases of tick-borne diseases. However, the number of encounters between ticks and outdoor pets in a neighborhood was negatively correlated with the abundance of questing ticks in that neighborhood. Our results reinforce the need to understand how human behavior and neglected ecological factors affect variation in human encounters with ticks and cases of tick-borne disease in residential settings. [ABSTRACT FROM AUTHOR]

Cache Valley virus (CVV) disease is a mosquito-borne zoonosis endemic to North America. CVV disease is reported most often in sheep, causing lethal congenital deformities. There are limited data on CVV in Ontario, which is the largest sheep producing province in Canada. This study aimed to determine CVV seroprevalence in Ontario sheep flocks and investigate farm management factors associated with CVV exposure. A cross-sectional study was performed including 364 mature ewes across 18 farms selected from the five largest sheep districts in the province. A questionnaire was administered at each farm to determine farm management practices pertinent to the flock and ewes specifically sampled. Mixed multivariable logistic regression with a random effect for farm was conducted to assess associations between CVV seropositivity (outcome variable) and farm management risk factors (predictor variables). CVV seroprevalence was 33.2% in individual ewes (95% CI: 28.4%-38.1%) as determined by a virus neutralization assay with a titre > 4. Sixteen of the eighteen flocks (88.9%) had at least one CVV seropositive ewe. Increased age, smaller flock size, and sheep housing near wetlands, lakes, or ponds were found to be significantly associated with higher odds of CVV seropositivity. These findings are valuable in guiding breeding practices and housing during mosquito season to minimize infection and, ultimately, CVV disease in the flock. [ABSTRACT FROM AUTHOR]

Ticks are the most important vectors of zoonotic disease-causing pathogens in North America and Europe. Many tick species are expanding their geographic range. Although correlational evidence suggests that climate change is driving the range expansion of ticks, experimental evidence is necessary to develop a mechanistic understanding of ticks' response to a range of climatic conditions. Previous experiments used simulated microclimates, but these protocols require hazardous salts or expensive laboratory equipment to manipulate humidity. We developed a novel, safe, stable, convenient, and economical method to isolate individual ticks and manipulate their microclimates. The protocol involves placing individual ticks in plastic tubes, and placing six tubes along with a commercial two-way humidity control pack in an airtight container. We successfully used this method to investigate how humidity affects survival and host-seeking (questing) behavior of three tick species: the lone star tick (Amblyomma americanum), American dog tick (Dermacentor variabilis), and black-legged tick (Ixodes scapularis). We placed 72 adult females of each species individually into plastic tubes and separated them into three experimental relative humidity (RH) treatments representing distinct climates: 32% RH, 58% RH, and 84% RH. We assessed the survival and questing behavior of each tick for 30 days. In all three species, survivorship significantly declined in drier conditions. Questing height was negatively associated with RH in Amblyomma, positively associated with RH in Dermacentor, and not associated with RH in Ixodes. The frequency of questing behavior increased significantly with drier conditions for Dermacentor but not for Amblyomma or Ixodes. This report demonstrates an effective method for assessing the viability and host-seeking behavior of tick vectors of zoonotic diseases under different climatic conditions. [ABSTRACT FROM AUTHOR]

The mosquito Culex erythrothorax Dyar is a West Nile virus (WNV) vector that breeds in wetlands with emergent vegetation. Urbanization and recreational activities near wetlands place humans, birds and mosquitoes in close proximity, increasing the risk of WNV transmission. Adult Cx. erythrothorax abundance peaked in a wetland bordering the San Francisco Bay of California (USA) during the first 3 hours after sunset (5527 ± 4070 mosquitoes / trap night) while peak adult Culex tarsalis Coquillett abundance occurred during the subsequent 3 h period (83 ± 30 Cx. tarsalis). When insecticide resistance was assessed using bottle bioassay, Cx. erythrothorax was highly sensitive to permethrin, naled, and etofenprox insecticides compared to a strain of Culex pipiens that is susceptible to insecticides (LC50 = 0.35, 0.71, and 4.1 μg/bottle, respectively). The Cx. erythrothorax were 2.8-fold more resistant to resmethrin, however, the LC50 value was low (0.68 μg/bottle). Piperonyl butoxide increased the toxicity of permethrin (0.5 μg/bottle) and reduced knock down time, but a higher permethrin concentration (2.0 μg/bottle) did not have similar effects. Bulk mixed-function oxidase, alpha-esterase, or beta-esterase activities in mosquito homogenates were higher in Cx. erythrothorax relative to the Cx. pipiens susceptible strain. There was no difference in the activity of glutathione S-transferase between the two mosquito species and insensitive acetylcholine esterase was not detected. Larvicides that were applied to the site had limited impact on reducing mosquito abundance. Subsequent removal of emergent vegetation in concert with larvicide applications and reduced daily environmental temperature substantially reduced mosquito abundance. To control Cx. erythrothorax in wetlands, land managers should consider vegetation removal so that larvicide can efficiently enter the water. Vector control agencies may more successfully control adult viremic Cx. erythrothorax that enter nearby neighborhoods by applying adulticides during the 3 h that follow sunset. [ABSTRACT FROM AUTHOR]

Because of the increasing threat that Zika virus (ZIKV) poses to more sub-tropical area due to increased global travel, there is a need for better understanding of the effect(s) of temperature on the establishment potential of ZIKV within these subtropical, temperate, and/or seasonal Ae. aegypti populations. The first step to determining risk establishment of ZIKV in these regions is to assess ZIKV's ability to infect mosquitoes at less tropical temperatures, and thus be detected through common surveillance programs. To that end, the effect of two rearing temperatures (RT) and extrinsic incubation temperatures (EIT) on infection and dissemination rates was evaluated, as well as the interactions of such. Total, there were four combinations (RT24-EIT24, RT24-EIT28, RT28-EIT24, RT28-EIT28). Further, a stochastic SEIR framework was adapted to determine whether observed data could lead to differential success of establishment of ZIKV in naive mosquito populations. There was no consistent pattern in significant differences found across treatments for either infection or dissemination rates (p>0.05), where only a significant difference was found in infection rates between RT24-EIT24 (44%) and RT28-EIT24 (82.6%). Across all temperature conditions, the model predicted between a 76.4% and 95.4% chance of successful establishment of ZIKV in naive mosquito populations under model assumptions. We further show that excluding the maximum observed infection and dissemination rates likely overestimates the probability of local establishment of ZIKV. These results indicate that 1) there is no straightforward relationship between RT, EIT, and infection/dissemination rates, 2) in more temperate climates, ZIKV may still have the ability to establish in populations of Aedes aegypti, 3) despite an overall lack of significant differences in infection/dissemination rates, temperature may still alter the kinetics of ZIKV within the mosquito enough to affect the likelihood of infection establishment and detection within the context of mosquito surveillance programs, and 4) both the temporal and magnitude qualities of vector competence are necessary for parameterization of within-mosquito virus kinetics. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi, the causative agent of Lyme disease, is a vector-borne bacterial infection that is transmitted through the bite of an infected tick. If not treated with antibiotics during the early stages of infection, disseminated infection can spread to the central nervous system (CNS). In non-human primates (NHPs) it has been demonstrated that the leptomeninges are among the tissues colonized by B. burgdorferi spirochetes. Although the NHP model parallels aspects of human borreliosis, a small rodent model would be ideal to study the trafficking of spirochetes and immune cells into the CNS. Here we show that during early and late disseminated infection, B. burgdorferi infects the meninges of intradermally infected mice, and is associated with concurrent increases in meningeal T cells. We found that the dura mater was consistently culture positive for spirochetes in transcardially perfused mice, independent of the strain of B. burgdorferi used. Within the dura mater, spirochetes were preferentially located in vascular regions, but were also present in perivascular, and extravascular regions, as late as 75 days post-infection. At the same end-point, we observed significant increases in the number of CD3+ T cells within the pia and dura mater, as compared to controls. Flow cytometric analysis of leukocytes isolated from the dura mater revealed that CD3+ cell populations were comprised of both CD4 and CD8 T cells. Overall, our data demonstrate that similarly to infection in peripheral tissues, spirochetes adhere to the dura mater during disseminated infection, and are associated with increases in the number of meningeal T cells. Collectively, our results demonstrate that there are aspects of B. burgdorferi meningeal infection that can be modelled in laboratory mice, suggesting that mice may be useful for elucidating mechanisms of meningeal pathogenesis by B. burgdorferi. [ABSTRACT FROM AUTHOR]

The recent range expansion of human babesiosis in the northeastern United States, once found only in restricted coastal sites, is not well understood. This study sought to utilize a large number of samples to examine the population structure of the parasites on a fine scale to provide insights into the mode of emergence across the region. 228 B. microti samples collected in endemic northeastern U.S. sites were genotyped using published Variable number tandem repeat (VNTR) markers. The genetic diversity and population structure were analysed on a geographic scale using Phyloviz and TESS, programs that utilize two different methods to identify population membership without predefined population data. Three distinct populations were detected in northeastern US, each dominated by a single ancestral type. In contrast to the limited range of the Nantucket and Cape Cod populations, the mainland population dominated from New Jersey eastward to Boston. Ancestral populations of B. microti were sufficiently isolated to differentiate into distinct populations. Despite this, a single population was detected across a large geographic area of the northeast that historically had at least 3 distinct foci of transmission, central New Jersey, Long Island and southeastern Connecticut. We conclude that a single B. microti genotype has expanded across the northeastern U.S. The biological attributes associated with this parasite genotype that have contributed to such a selective sweep remain to be identified. [ABSTRACT FROM AUTHOR]

The epidemiology and ecology of West Nile virus (WNV) have not yet been completely described. In particular, the specific roles of climate and water in the landscape in the occurrence of human WNV cases remain unknown. This study used Poisson regression to describe the relationships between WNV cases and temperature, precipitation, and the hydrogeography of the landscape in New York State from 2000 to 2010. Fully adjusted models showed that hydrogeographic area was significantly inversely associated with WNV cases (incidence rate ratio (IRR) = 0.99; 95% C.I. = 0.98-0.997< p = 0.04), such that each one square kilometer increase in hydrogeographic area was associated with a 1% decrease in WNV incidence. This association was independent of both temperature, which was also associated with WNV incidence (IRR = 2.06; 95% C.I. = 1.84-2.31, p<0.001), and precipitation, which was not (IRR = 1.0; 95% C.I. = 0.99-1.01, p = 0.16). While the results are only suggestive due to the county-level aggregated data, these findings do identify a potentially important surveillance signal in the landscape epidemiology of WNV infection. [ABSTRACT FROM AUTHOR]

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Tolllike receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. IL-10 inhibits TLR induced B-1P cell activation by blocking the classical NF-κB pathway. Co-stimulation with CD40 or BAFF abrogated the IL-10 inhibitory effect on B-1P cells during TLR stimulation. Finally, B-1P cells adoptively transferred from the peritoneal cavity of IL-10-/- mice showed better clearance of Borrelia hermsii than wild-type B-1P cells. This study described a novel autoregulatory property of B-1P cells mediated by B- 1P cell derived IL-10, which may affect the function of B-1P cells in infection and autoimmunity. [ABSTRACT FROM AUTHOR]

The article offers information on the avian host-selection by culex pipiens in experimental trial. It states that heterogeneities in contact rates between arthropod vectors and hosts are important to vector-borne disease dynamics, because they can result in increased disease transmission if vector blood meals occur more commonly on pathogen-competent hosts. In contrast, transmission may be reduced if blood meals are 'diluted' by feeding on non-competent hosts. It mentions that to control for environmental confounders influencing contact rates, host-choice experiments using traps baited with whole-host odors have been conducted to determine innate host preferences of a vector.

Recent infectious disease models illustrate a suite of mechanisms that can result in lower incidence of disease in areas of higher disease host diversity-the 'dilution effect'. These models are particularly applicable to human zoonoses, which are infectious diseases of wildlife that spill over into human populations. As many recent emerging infectious diseases are zoonoses, the mechanisms that underlie the 'dilution effect' are potentially widely applicable and could contribute greatly to our understanding of a suite of diseases. The dilution effect has largely been observed in the context of Lyme disease and the predictions of the underlying models have rarely been examined for other infectious diseases on a broad geographic scale. Here, we explored whether the dilution effect can be observed in the relationship between the incidence of human West Nile virus (WNV) infection and bird (host) diversity in the eastern US. We constructed a novel geospatial contrasts analysis that compares the small differences in avian diversity of neighboring US counties (where one county reported human cases of WNV and the other reported no cases) with associated between-county differences in human disease. We also controlled for confounding factors of climate, regional variation in mosquito vector type, urbanization, and human socioeconomic factors that are all likely to affect human disease incidence. We found there is lower incidence of human WNV in eastern US counties that have greater avian (viral host) diversity. This pattern exists when examining diversitydisease relationships both before WNV reached the US (in 1998) and once the epidemic was underway (in 2002). The robust disease-diversity relationships confirm that the dilution effect can be observed in another emerging infectious disease and illustrate an important ecosystem service provided by biodiversity, further supporting the growing view that protecting biodiversity should be considered in public health and safety plans. [ABSTRACT FROM AUTHOR]