Effects of residential acaricide treatments on patterns of pathogen coinfection in blacklegged ticks.

Medically important ixodid ticks often carry multiple pathogens, with individual ticks frequently coinfected and capable of transmitting multiple infections to hosts, including humans. Acquisition of multiple zoonotic pathogens by immature blacklegged ticks (Ixodes scapularis) is facilitated when they feed on small mammals, which are the most competent reservoir hosts for Anaplasma phagocytophilum (which causes anaplasmosis in humans), Babesia microti (babesiosis) and Borrelia burgdorferi (Lyme disease). Here, we used data from a large-scale, long-term experiment to ask whether patterns of single and multiple infections in questing nymphal I. scapularis ticks from residential neighbourhoods differed from those predicted by independent assortment of pathogens, and whether patterns of coinfection were affected by residential application of commercial acaricidal products. Quantitative polymerase chain reaction was used for pathogen detection in multiplex reactions. In control neighbourhoods and those treated with a fungus-based biopesticide deployed against host-seeking ticks (Met52), ticks having only single infections of either B. microti or B. burgdorferi were significantly less common than expected, whereas coinfections with these 2 pathogens were significantly more common. However, use of tick control system bait boxes, which kill ticks attempting to feed on small mammals, eliminated the bias towards coinfection. Although aimed at reducing the abundance of host-seeking ticks, control methods directed at ticks attached to small mammals may influence human exposure to coinfected ticks and the probability of exposure to multiple tick-borne infections.

The more, the healthier: Tree diversity reduces forest pests and pathogens.

How frequently, and under what conditions, biodiversity reduces disease through "dilution effects" has been a subject of ongoing research. A new study of forest pests in PLOS Biology provides strong evidence for their generality.

Spatial variation in risk for tick-borne diseases in residential areas of Dutchess County, New York.

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.

Does Experimental Reduction of Blacklegged Tick (Ixodes scapularis) Abundance Reduce Lyme Disease Incidence?

Controlling the abundance of blacklegged ticks is considered the foundation for the prevention of human exposure to pathogens transmitted by these vectors in eastern North America. The use of broadcast or host-targeted acaricides is generally found to be effective at reducing the local abundance of ticks. However, studies that incorporate randomization, placebo controls, and masking, i.e., "blinding", generally find lower efficacy. The few studies that include measurements of human-tick encounters and cases of tickborne disease have not shown impacts of acaricidal treatments. We compile literature on relevant studies from northeastern North America to address possible causes for discrepancies in study outcomes and suggest possible mechanisms that could underlie the diminished efficacy of tick control in reducing cases of tickborne disease in people.

Effects of Neighborhood-Scale Acaricidal Treatments on Infection Prevalence of Blacklegged Ticks (Ixodes scapularis) with Three Zoonotic Pathogens.

Acaricides are hypothesized to reduce human risk of exposure to tick-borne pathogens by decreasing the abundance and/or infection prevalence of the ticks that serve as vectors for the pathogens. Acaricides targeted at reservoir hosts such as small mammals are expected to reduce infection prevalence in ticks by preventing their acquisition of zoonotic pathogens. By reducing tick abundance, reservoir-targeted or broadcast acaricides could reduce tick infection prevalence by interrupting transmission cycles between ticks and their hosts. Using an acaricide targeted at small-mammal hosts (TCS bait boxes) and one sprayed on low vegetation (Met52 fungal biocide), we tested the hypotheses that infection prevalence of blacklegged ticks with zoonotic pathogens would be more strongly diminished by TCS bait boxes, and that any effects of both acaricidal treatments would increase during the four years of deployment. We used a masked, placebo-controlled design in 24 residential neighborhoods in Dutchess County, New York. Analyzing prevalence of infection with Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti in 5380 nymphal Ixodes scapularis ticks, we found little support for either hypothesis. TCS bait boxes did not reduce infection prevalence with any of the three pathogens compared to placebo controls. Met52 was associated with lower infection prevalence with B. burgdorferi compared to placebo controls but had no effect on prevalence of infection with the other two pathogens. Although significant effects of year on infection prevalence of all three pathogens were detected, hypothesized cumulative reductions in prevalence were observed only for B. burgdorferi. We conclude that reservoir-targeted and broadcast acaricides might not generally disrupt pathogen transmission between reservoir hosts and tick vectors or reduce human risk of exposure to tick-borne pathogens.

Impacts Over Time of Neighborhood-Scale Interventions to Control Ticks and Tick-Borne Disease Incidence.

Background: Controlling populations of ticks with biological or chemical acaricides is often advocated as a means of reducing human exposure to tick-borne diseases. Reducing tick abundance is expected to decrease immediate risk of tick encounters and disrupt pathogen transmission cycles, potentially reducing future exposure risk. Materials and Methods: We designed a placebo-controlled, randomized multiyear study to assess whether two methods of controlling ticks-tick control system (TCS) bait boxes and Met52 spray-reduced tick abundance, tick encounters with people and outdoor pets, and reported cases of tick-borne diseases. The study was conducted in 24 residential neighborhoods in a Lyme disease endemic zone in New York State. We tested the hypotheses that TCS bait boxes and Met52, alone or together, would be associated with increasing reductions in tick abundance, tick encounters, and cases of tick-borne disease over the 4-5 years of the study. Results: In neighborhoods with active TCS bait boxes, populations of blacklegged ticks (Ixodes scapularis) were not reduced over time in any of the three habitat types tested (forest, lawn, shrub/garden). There was no significant effect of Met52 on tick abundance overall, and there was no evidence for a compounding effect over time. Similarly, we observed no significant effect of either of the two tick control methods, used singly or together, on tick encounters or on reported cases of tick-borne diseases in humans overall, and there was no compounding effect over time. Thus, our hypothesis that effects of interventions would accumulate through time was not supported. Conclusions: The apparent inability of the selected tick control methods to reduce risk and incidence of tick-borne diseases after years of use requires further consideration.

Effects of Tick-Control Interventions on Tick Abundance, Human Encounters with Ticks, and Incidence of Tickborne Diseases in Residential Neighborhoods, New York, USA.

Tickborne diseases (TBDs) such as Lyme disease result in ≈500,000 diagnoses annually in the United States. Various methods can reduce the abundance of ticks at small spatial scales, but whether these methods lower incidence of TBDs is poorly understood. We conducted a randomized, replicated, fully crossed, placebo-controlled, masked experiment to test whether 2 environmentally safe interventions, the Tick Control System (TCS) and Met52 fungal spray, used separately or together, affected risk for and incidence of TBDs in humans and pets in 24 residential neighborhoods. All participating properties in a neighborhood received the same treatment. TCS was associated with fewer questing ticks and fewer ticks feeding on rodents. The interventions did not result in a significant difference in incidence of human TBDs but did significantly reduce incidence in pets. Our study is consistent with previous evidence suggesting that reducing tick abundance in residential areas might not reduce incidence of TBDs in humans.

Dilution effects in disease ecology.

For decades, people have reduced the transmission of pathogens by adding low-quality hosts to managed environments like agricultural fields. More recently, there has been interest in whether similar 'dilution effects' occur in natural disease systems, and whether these effects are eroded as diversity declines. For some pathogens of plants, humans and other animals, the highest-quality hosts persist when diversity is lost, so that high-quality hosts dominate low-diversity communities, resulting in greater pathogen transmission. Meta-analyses reveal that these natural dilution effects are common. However, studying them remains challenging due to limitations on the ability of researchers to manipulate many disease systems experimentally, difficulties of acquiring data on host quality and confusion about what should and should not be considered a dilution effect. Because dilution effects are widely used in managed disease systems and have been documented in a variety of natural disease systems, their existence should not be considered controversial. Important questions remain about how frequently they occur and under what conditions to expect them. There is also ongoing confusion about their relationships to both pathogen spillover and general biogeographical correlations between diversity and disease, which has resulted in an inconsistent and confusing literature. Progress will require rigorous and creative research.

Recent Progress in Lyme Disease and Remaining Challenges.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

Modeling COVID-19 spread in small colleges.

We develop an agent-based model on a network meant to capture features unique to COVID-19 spread through a small residential college. We find that a safe reopening requires strong policy from administrators combined with cautious behavior from students. Strong policy includes weekly screening tests with quick turnaround and halving the campus population. Cautious behavior from students means wearing facemasks, socializing less, and showing up for COVID-19 testing. We also find that comprehensive testing and facemasks are the most effective single interventions, building closures can lead to infection spikes in other areas depending on student behavior, and faster return of test results significantly reduces total infections.

Impacts of biodiversity and biodiversity loss on zoonotic diseases.

Zoonotic diseases are infectious diseases of humans caused by pathogens that are shared between humans and other vertebrate animals. Previously, pristine natural areas with high biodiversity were seen as likely sources of new zoonotic pathogens, suggesting that biodiversity could have negative impacts on human health. At the same time, biodiversity has been recognized as potentially benefiting human health by reducing the transmission of some pathogens that have already established themselves in human populations. These apparently opposing effects of biodiversity in human health may now be reconcilable. Recent research demonstrates that some taxa are much more likely to be zoonotic hosts than others are, and that these animals often proliferate in human-dominated landscapes, increasing the likelihood of spillover. In less-disturbed areas, however, these zoonotic reservoir hosts are less abundant and nonreservoirs predominate. Thus, biodiversity loss appears to increase the risk of human exposure to both new and established zoonotic pathogens. This new synthesis of the effects of biodiversity on zoonotic diseases presents an opportunity to articulate the next generation of research questions that can inform management and policy. Future studies should focus on collecting and analyzing data on the diversity, abundance, and capacity to transmit of the taxa that actually share zoonotic pathogens with us. To predict and prevent future epidemics, researchers should also focus on how these metrics change in response to human impacts on the environment, and how human behaviors can mitigate these effects. Restoration of biodiversity is an important frontier in the management of zoonotic disease risk.

A new genetic approach to distinguish strains of Anaplasma phagocytophilum that appear not to cause human disease.

Genetic diversity of Anaplasma phagocytophilum was assessed in specimens from 16 infected patients and 16 infected Ixodes scapularis ticks. A region immediately downstream of the 16S rRNA gene, which included the gene encoding SdhC, was sequenced. For the A. phagocytophilum strains from patients no sequence differences were detected in this region. In contrast, significantly fewer ticks had a sequence encoding SdhC that was identical to that of the human strains (11/16 vs. 16/16, p = 0.04). This variation is consistent with the premise that not all A. phagocytophilum strains present in nature are able to cause clinical illness in humans. A strain referred to as A. phagocytophilumVariant-1 that is regarded as non-pathogenic for humans was previously described using a different typing method. Data from the current study suggest that both typing methods are identifying the same non-pathogenic strains.

Correction to: Systematic review and meta-analysis of tick-borne disease risk factors in residential yards, neighborhoods, and beyond.

Following publication of the original article [1], one of the authors, Dr. Sarah E. Bowden reported that at the time of the study she wasn't working for the Division of Global Migration and Quarantine, Centers for Disease Control, 1600 Clifton Road, Atlanta, GA 30329-4027, USA.

Systematic review and meta-analysis of tick-borne disease risk factors in residential yards, neighborhoods, and beyond.

BACKGROUND: Exposure to blacklegged ticks Ixodes scapularis that transmit pathogens is thought to occur peri-domestically. However, the locations where people most frequently encounter infected ticks are not well characterized, leading to mixed messages from public health officials about where risk is highest. METHODS: We conducted a systematic review and meta-analysis on spatial risk factors for tick-borne disease and tick bites in eastern North America. We examined three scales: the residential yard, the neighborhood surrounding (but not including) the yard, and outside the neighborhood. Nineteen eligible studies represented 2741 cases of tick-borne illness and 1447 tick bites. Using random effects models, we derived pooled odds ratio (OR) estimates. RESULTS: The meta-analysis revealed significant disease risk factors at the scale of the yard (OR 2.60 95% CI 1.96 - 3.46), the neighborhood (OR 4.08 95% CI 2.49 - 6.68), and outside the neighborhood (OR 2.03 95% CI 1.59 - 2.59). Although significant risk exists at each scale, neighborhood scale risk factors best explained disease exposure. Analysis of variance revealed risk at the neighborhood scale was 57% greater than risk at the yard scale and 101% greater than risk outside the neighborhood. CONCLUSIONS: This analysis emphasizes the importance of understanding and reducing tick-borne disease risk at the neighborhood scale. Risk-reducing interventions applied at each scale could be effective, but interventions applied at the neighborhood scale are most likely to protect human health. TRIAL REGISTRATION: The study was registered with PROSPERO: CRD42017079169 .

Risk Factors for Bites and Diseases Associated With Black-Legged Ticks: A Meta-Analysis.

The emergence and spread of Lyme disease and other infections associated with black-legged ticks is causing a public health crisis. No human vaccines are currently available, and both diagnosis and treatment are sometimes ineffectual, leading to advocacy for self-directed preventative measures. These recommendations are widely communicated to the public, but there is limited evidence for their efficacy. We undertook a systematic review and mixed-effects meta-regression analysis of factors purported to increase or decrease risk of black-legged tick bites and tick-borne disease. Published articles used in the study spanned the years 1984-2018. Variables associated with increased probability of tick-borne disease, with odds ratios significantly greater than 1, included deer abundance, high density of nymph-stage black-legged ticks, landscapes with interspersed herbaceous and forested habitat, low human population density, gardens, cat ownership, and race. Contrary to recommendations, use of landscape-related tick control measures, such as clearing brush, trimming branches, and having a dry barrier between lawn and woods, tended to increase risk. Pet ownership increased bite risk. Bite risk was highest for children aged 5 years or less, with a secondary peak in persons aged 50-70 years. Although some widely disseminated recommendations are supported by the research analyzed, others require further evaluation. Additional research is also needed to understand the mechanisms underlying significant relationships.

Assessing Effectiveness of Recommended Residential Yard Management Measures Against Ticks.

Public health authorities recommend a range of nonchemical measures to control blacklegged ticks Ixodes scapularis Say, 1821 (Ixodida: Ixodidae) in residential yards. Here we enumerate these recommendations and assess their relationship to larval tick abundance in 143 yards in Dutchess County, New York, an area with high Lyme disease incidence. We examined the relationship between larval tick abundance and eight property features related to recommendations from public health agencies: presence or absence of outdoor cats, wood piles, trash, stone walls, wood chip barriers separating lawn from adjacent forest, bird feeders, fencing, and prevalence of Japanese barberry (Berberis thunbergii DC [Ranunculales: Berberidaceae]). We assessed abundance of larval ticks using two methods, flagging for questing ticks and visual examination of ticks on white-footed mice Peromyscus leucopus Rafinesque, 1818 (Rodentia: Cricetidae). More questing larvae were found in yards where trash or stone walls were present. These effects were less pronounced as forest area increased within the yard. Counts of larvae per mouse were lower in properties with >75% of the yard fenced than in properties with less fencing. We find partial support for recommendations regarding trash, stone walls, and fencing. We did not detect effects of outdoor cats, bird feeders, barriers, wood piles, or Japanese barberry. There was low statistical power to detect effects of ground barriers (gravel, mulch, or woodchip), which were present in only two properties.

Potential effects of blood meal host on bacterial community composition in Ixodes scapularis nymphs.

Tick microbiomes may play an important role in pathogen transmission. However, the drivers of microbiome variation are poorly understood, and this limitation has impeded mechanistic understanding of the functions of microbial communities for pathogen acquisition. The goal of this research was to characterize the role of the blood meal host in structuring the microbiome of Ixodes scapularis, the primary vector of Lyme disease in the eastern United States, and to determine if ticks that fed from different host species harbor distinct bacterial communities. We performed high-throughput 16S rDNA amplicon sequencing on I. scapularis nymphs that fed as larvae from known wildlife hosts: raccoon, Virginia opossum, striped skunk, red squirrel or gray squirrel. Using Analysis of Similarity, we found significant differences in the abundance-weighted Unifrac distance matrix among ticks fed from different host species (p = 0.048) and a highly significant difference in the weighted and unweighted Unifrac matrices for individuals within species (p < 0.01). This finding of associations between the blood meal host and I. scapularis microbiome demonstrates that the blood meal host may be a driver of microbiome variation that should be accounted for in studies of pathogen acquisition by ticks.

A coupled forage-grazer model predicts viability of livestock production and wildlife habitat at the regional scale.

Informed management of livestock on rangelands underpins both the livelihoods of communities that depend on livestock for sustenance, and the conservation of wildlife that often depend on livestock-dominated landscapes for habitat. Understanding spatial patterns of rangeland productivity is therefore crucial to designing global development strategies that balance social and environmental benefits. Here we introduce a new rangeland production model that dynamically links the Century ecosystem model with a basic ruminant diet selection and physiology model. With lightweight input data requirements that can be met with global sources, the model estimates the viability of broad livestock management decisions, and suggests possible implications of these management decisions for grazing wildlife. Using minimal field data, the new rangeland production model enables the reliable estimation of cattle stocking density; this is an important predictor of the viability of livestock production and forage available for grazing wildlife.