Transboundary determinants of avian zoonotic infectious diseases: challenges for strengthening research capacity and connecting surveillance networks.

As the climate changes, global systems have become increasingly unstable and unpredictable. This is particularly true for many disease systems, including subtypes of highly pathogenic avian influenzas (HPAIs) that are circulating the world. Ecological patterns once thought stable are changing, bringing new populations and organisms into contact with one another. Wild birds continue to be hosts and reservoirs for numerous zoonotic pathogens, and strains of HPAI and other pathogens have been introduced into new regions via migrating birds and transboundary trade of wild birds. With these expanding environmental changes, it is even more crucial that regions or counties that previously did not have surveillance programs develop the appropriate skills to sample wild birds and add to the understanding of pathogens in migratory and breeding birds through research. For example, little is known about wild bird infectious diseases and migration along the Mediterranean and Black Sea Flyway (MBSF), which connects Europe, Asia, and Africa. Focusing on avian influenza and the microbiome in migratory wild birds along the MBSF, this project seeks to understand the determinants of transboundary disease propagation and coinfection in regions that are connected by this flyway. Through the creation of a threat reduction network for avian diseases (Avian Zoonotic Disease Network, AZDN) in three countries along the MBSF (Georgia, Ukraine, and Jordan), this project is strengthening capacities for disease diagnostics; microbiomes; ecoimmunology; field biosafety; proper wildlife capture and handling; experimental design; statistical analysis; and vector sampling and biology. Here, we cover what is required to build a wild bird infectious disease research and surveillance program, which includes learning skills in proper bird capture and handling; biosafety and biosecurity; permits; next generation sequencing; leading-edge bioinformatics and statistical analyses; and vector and environmental sampling. Creating connected networks for avian influenzas and other pathogen surveillance will increase coordination and strengthen biosurveillance globally in wild birds.

Phylogeography of the blacklegged tick (Ixodes scapularis) throughout the USA identifies candidate loci for differences in vectorial capacity.

The blacklegged tick (Ixodes scapularis (Journal of the Academy of Natural Sciences of Philadelphia, 1821, 2, 59)) is a vector of Borrelia burgdorferi sensu stricto (s.s.) (International Journal of Systematic Bacteriology, 1984, 34, 496), the causative bacterial agent of Lyme disease, part of a slow-moving epidemic of Lyme borreliosis spreading across the northern hemisphere. Well-known geographical differences in the vectorial capacity of these ticks are associated with genetic variation. Despite the need for detailed genetic information in this disease system, previous phylogeographical studies of these ticks have been restricted to relatively few populations or few genetic loci. Here we present the most comprehensive phylogeographical study of genome-wide markers in I. scapularis, conducted by using 3RAD (triple-enzyme restriction-site associated sequencing) and surveying 353 ticks from 33 counties throughout the species' range. We found limited genetic variation among populations from the Northeast and Upper Midwest, where Lyme disease is most common, and higher genetic variation among populations from the South. We identify five spatially associated genetic clusters of I. scapularis. In regions where Lyme disease is increasing in frequency, the I. scapularis populations genetically group with ticks from historically highly Lyme-endemic regions. Finally, we identify 10 variable DNA sites that contribute the most to population differentiation. These variable sites cluster on one of the chromosome-scale scaffolds for I. scapularis and are within identified genes. Our findings illuminate the need for additional research to identify loci causing variation in the vectorial capacity of I. scapularis and where additional tick sampling would be most valuable to further understand disease trends caused by pathogens transmitted by I. scapularis.

Evaluating spatial and temporal patterns of tick exposure in the United States using community science data submitted through a smartphone application.

Research initiatives that engage the public (i.e., community science or citizen science) increasingly provide insights into tick exposures in the United States. However, these data have important caveats, particularly with respect to reported travel history and tick identification. Here, we assessed whether a smartphone application, The Tick App, provides reliable and novel insights into tick exposures across three domains - travel history, broad spatial and temporal patterns of species-specific encounters, and tick identification. During 2019-2021, we received 11,424 tick encounter submissions from across the United States, with nearly all generated in the Midwest and Northeast regions. Encounters were predominantly with human hosts (71%); although one-fourth of ticks were found on animals. Half of the encounters (51%) consisted of self-reported peri­domestic exposures, while 37% consisted of self-reported recreational exposures. Using phone-based location services, we detected differences in travel history outside of the users' county of residence along an urbanicity gradient. Approximately 75% of users from large metropolitan and rural counties had travel out-of-county in the four days prior to tick detection, whereas an estimated 50-60% of users from smaller metropolitan areas did. Furthermore, we generated tick encounter maps for Dermacentor variabilis and Ixodes scapularis that partially accounted for travel history and overall mirrored previously published species distributions. Finally, we evaluated whether a streamlined three-question sequence (on tick size, feeding status, and color) would inform a simple algorithm to optimize image-based tick identification. Visual aides of tick coloration and size engaged and guided users towards species and life stage classification moderately well, with 56% of one-time submitters correctly selecting photos of D. variabilis adults and 76% of frequent-submitters correctly selecting photos of D. variabilis adults. Together, these results indicate the importance of bolstering the use of smartphone applications to engage community scientists and complement other active and passive tick surveillance systems.

Knowledge, attitudes, and behaviors regarding tick-borne disease prevention in Lyme disease-endemic areas of the Upper Midwest, United States.

Lyme disease and other tick-borne diseases are a major public health threat in the Upper Midwestern United States, including Michigan, Minnesota, and Wisconsin. To prevent tick bites and tick-borne diseases, public health officials commonly recommend personal protective measures and property management techniques. Adoption of tick-borne disease prevention behaviors and practices by individuals are, however, highly variable. We aimed to characterize current tick-borne disease knowledge, attitudes, and prevention behaviors (KAB) practiced by the public in these states, as well as their willingness to use specific tick control methods. We conducted a population-based survey in summer 2019 in 48 high-risk counties (those having a five-year average (2013-2017) Lyme disease incidence of ≥ 10 cases per 100,000 persons per year), in Michigan, Minnesota, and Wisconsin. A total of 2713 surveys were analyzed; survey weights were used to account for household selection probability and post-stratified to match county-level joint age and sex population distributions in population-level inference. An estimated 98% of the population had heard of Lyme disease, with most perceiving it as very or extremely serious (91%); however, only an estimated 25% perceived tick-borne diseases as very or extremely common in their community. Among those who spent time in places with ticks from April through October, an estimated 68% check themselves thoroughly for ticks most of the time or always and 43% use bug repellent on skin or clothing most of the time or always. An estimated 13% of the population had ever treated their property with a pesticide to kill ticks, and 3% had ever used devices that apply pesticide to rodents to kill ticks on their property. Willingness to practice tick bite prevention behaviors, however, was estimated to be much higher; with 82% being willing to perform tick checks at least once a day, and more than 60% willing to use bug repellent, tick control products on pets, or to bathe within two hours of being outdoors. We found that residents would likely be willing to support a county-wide tick control program to reduce the risk of tick-borne disease in their community (81%) or to apply tick control products to their property to reduce the risk of tick-borne disease in their household (79%). Tick checks were more likely to be practiced among participants who perceived tick-borne diseases to be highly prevalent in their community, if they or a household member had been previously diagnosed with a tick-borne disease?, or if they perceived tick exposure to be likely around their home, cabin, or vacation home. In addition, property-based tick control methods were associated with perceived risk of encountering ticks around the home, cabin, or vacation home. Participants who had seen information from state health departments were also more likely to practice preventive measures. The most common reported barriers to using any of these methods were forgetfulness, safety concerns, and lack of awareness. Our survey findings shed light on how residents from these Upper Midwest states may adopt tick control and tick bite prevention measures and how public health outreach may be most effective for this population.

Inter-annual variation in prevalence of Borrelia burgdorferi sensu stricto and Anaplasma phagocytophilum in host-seeking Ixodes scapularis (Acari: Ixodidae) at long-term surveillance sites in the upper midwestern United States: Implications for public health practice.

The geographic range of the blacklegged tick, Ixodes scapularis, and its associated human pathogens have expanded substantially over the past 20 years putting an increasing number of persons at risk for tick-borne diseases, particularly in the upper midwestern and northeastern United States. Prevention and diagnosis of tick-borne diseases rely on an accurate understanding by the public and health care providers of when and where persons may be exposed to infected ticks. While tracking changes in the distribution of ticks and tick-borne pathogens provides fundamental information on risk for tick-borne diseases, metrics that incorporate prevalence of infection in ticks better characterize acarological risk. However, assessments of infection prevalence are more labor intensive and costly than simple measurements of tick or pathogen presence. Our objective was to examine whether data derived from repeated sampling at longitudinal sites substantially influences public health recommendations for Lyme disease and anaplasmosis prevention, or if more constrained sampling is sufficient. Here, we summarize inter-annual variability in prevalence of the agents of Lyme disease (Borrelia burgdorferi s.s.) and anaplasmosis (Anaplasma phagocytophilum) in host-seeking I. scapularis nymphs and adults at 28 longitudinal sampling sites in the Upper Midwestern US (Michigan, Minnesota, and Wisconsin). Infection prevalence was highly variable among sites and among years within sites. We conclude that monitoring infection prevalence in ticks aids in describing coarse acarological risk trends, but setting a fixed prevalence threshold for prevention or diagnostic decisions is not feasible given the observed variability and lack of temporal trends. Reducing repeated sampling of the same sites had minimal impact on regional (Upper Midwest) estimates of average infection prevalence; this information should be useful in allocating scarce public health resources for tick and tick-borne pathogen surveillance, prevention, and control activities.

Selective Host Attachment by Ixodes scapularis (Acari: Ixodidae): Tick-Lizard Associations in the Southeastern United States.

Questing behavior and host associations of immature blacklegged ticks, Ixodes scapularis Say, from the southeastern United States are known to differ from those in the north. To elucidate these relationships we describe host associations of larval and nymphal I. scapularis from 8 lizard species sampled from 5 sites in the southeastern U.S. Larvae and nymphs attached in greater numbers to larger lizards than to smaller lizards, with differential levels of attachment to different lizard species. Blacklegged ticks are generally attached to skinks of the genus Plestiodon in greater numbers per unit lizard weight than to anoles (Anolis) or fence lizards (Sceloporus). The broad-headed skink, Plestiodon laticeps (Schneider), was a particularly important host for immature I. scapularis in our study and in several previous studies of tick-host associations in the southeast. Blacklegged ticks show selective attachment to Plestiodon lizard hosts in the southeast, but whether this results from behavioral host preferences or from ecological factors such as timing or microhabitat distributions of tick questing and host activity remains to be determined.

Correction: Why Lyme disease is common in the northern US, but rare in the south: The roles of host choice, host-seeking behavior, and tick density.

[This corrects the article DOI: 10.1371/journal.pbio.3001066.].

Lake Michigan insights from island studies: the roles of chipmunks and coyotes in maintaining Ixodes scapularis and Borrelia burgdorferi in the absence of white-tailed deer.

Deer management (e.g., reduction) has been proposed as a tool to reduce the acarological risk of Lyme disease. There have been few opportunities to investigate Ixodes scapularis (blacklegged tick) and Borrelia burgdorferi sensu stricto dynamics in the absence of white-tailed deer (Odocoileus virginianus) in midwestern North America. A pair of islands in Lake Michigan presented a unique opportunity to study the role of alternative hosts for the adult stage of the blacklegged tick for maintaining a tick population as a deer herd exists on North Manitou Island but not on South Manitou Island, where coyotes (Canis latrans) and hares (Lepus americanus) are the dominant medium mammals. Additionally, we were able to investigate the maintenance of I. scapularis and B. burgdorferi in small mammal communities on both islands, which were dominated by eastern chipmunks (Tamias striatus). From 2011 to 2015, we surveyed both islands for blacklegged ticks by drag cloth sampling, bird mist netting, and small and medium-sized mammal trapping. We assayed questing ticks, on-host ticks, and mammal biopsies for the Lyme disease pathogen, B. burgdorferi. We detected all three life stages of the blacklegged tick on both islands. Of the medium mammals sampled, no snowshoe hares (Lepus americanus, 0/23) were parasitized by adult blacklegged ticks, but 2/2 coyotes (Canis latrans) sampled on South Manitou Island in 2014 were parasitized by adult blacklegged ticks, suggesting that coyotes played a role in maintaining the tick population in the absence of deer. We also detected I. scapularis ticks on passerine birds from both islands, providing support that birds contribute to maintaining as well as introducing blacklegged ticks and B. burgdorferi to the islands. We observed higher questing adult and nymphal tick densities, and higher B. burgdorferi infection prevalence in small mammals and in adult ticks on the island with deer as compared to the deer-free island. On the islands, we also found that 25% more chipmunks were tick-infested than mice, fed more larvae and nymphs relative to their proportional abundance compared to mice, and thus may play a larger role compared to mice in the maintenance of B. burgdorferi. Our investigation demonstrated that alternative hosts could maintain a local population of blacklegged ticks and an enzootic cycle of the Lyme disease bacterium in the absence of white-tailed deer. Thus, alternative adult blacklegged tick hosts should be considered when investigating deer-targeted management tools for reducing tick-borne disease risk, especially when the alternative host community may be abundant and diverse.

The Contribution of Wildlife Hosts to the Rise of Ticks and Tick-Borne Diseases in North America.

Wildlife vertebrate hosts are integral to enzootic cycles of tick-borne pathogens, and in some cases have played key roles in the recent rise of ticks and tick-borne diseases in North America. In this forum article, we highlight roles that wildlife hosts play in the maintenance and transmission of zoonotic, companion animal, livestock, and wildlife tick-borne pathogens. We begin by illustrating how wildlife contribute directly and indirectly to the increase and geographic expansion of ticks and their associated pathogens. Wildlife provide blood meals for tick growth and reproduction; serve as pathogen reservoirs; and can disperse ticks and pathogens-either through natural movement (e.g., avian migration) or through human-facilitated movement (e.g., wildlife translocations and trade). We then discuss opportunities to manage tick-borne disease through actions directed at wildlife hosts. To conclude, we highlight key gaps in our understanding of the ecology of tick-host interactions, emphasizing that wildlife host communities are themselves a very dynamic component of tick-pathogen-host systems and therefore complicate management of tick-borne diseases, and should be taken into account when considering host-targeted approaches. Effective management of wildlife to reduce tick-borne disease risk further requires consideration of the 'human dimensions' of wildlife management. This includes understanding the public's diverse views and values about wildlife and wildlife impacts-including the perceived role of wildlife in fostering tick-borne diseases. Public health agencies should capitalize on the expertise of wildlife agencies when developing strategies to reduce tick-borne disease risks.

Environmental Correlates of Lyme Disease Emergence in Southwest Virginia, 2005-2014.

Lyme disease is the most common tick-borne disease in North America. Though human infection is mostly transmitted in a limited geography, the range has expanded in recent years. One notable area of recent expansion is in the mountainous region of southwestern Virginia. The ecological factors that facilitate or constrain the range of human Lyme disease in this region remain uncertain. To evaluate this further, we obtained ecological data, including remotely sensed data on forest structure and vegetation, weather data, and elevation. These data were aggregated within the census block groups of a 9,153 km2 area around the cities of Blacksburg and Roanoke, VA, an area with heterogeneous Lyme disease transmission. In this geographic area, 755 individuals were reported to have Lyme disease in the 10 yr from 2006 to 2015, and these cases were aggregated by block group. A zero-inflated negative binomial model was used to evaluate which environmental variables influenced the abundance of Lyme disease cases. Higher elevation and higher vegetation density had the greatest effect size on the abundance of Lyme disease. Measures of forest edge, forest integrity, temperature, and humidity were not associated with Lyme disease cases. Future southward expansion of Lyme disease into the southeastern states may be most likely in ecologically similar mountainous areas.

Why Lyme disease is common in the northern US, but rare in the south: The roles of host choice, host-seeking behavior, and tick density.

Lyme disease is common in the northeastern United States, but rare in the southeast, even though the tick vector is found in both regions. Infection prevalence of Lyme spirochetes in host-seeking ticks, an important component to the risk of Lyme disease, is also high in the northeast and northern midwest, but declines sharply in the south. As ticks must acquire Lyme spirochetes from infected vertebrate hosts, the role of wildlife species composition on Lyme disease risk has been a topic of lively academic discussion. We compared tick-vertebrate host interactions using standardized sampling methods among 8 sites scattered throughout the eastern US. Geographical trends in diversity of tick hosts are gradual and do not match the sharp decline in prevalence at southern sites, but tick-host associations show a clear shift from mammals in the north to reptiles in the south. Tick infection prevalence declines north to south largely because of high tick infestation of efficient spirochete reservoir hosts (rodents and shrews) in the north but not in the south. Minimal infestation of small mammals in the south results from strong selective attachment to lizards such as skinks (which are inefficient reservoirs for Lyme spirochetes) in the southern states. Selective host choice, along with latitudinal differences in tick host-seeking behavior and variations in tick densities, explains the geographic pattern of Lyme disease in the eastern US.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Seasonality of acarological risk of exposure to Borrelia miyamotoi from questing life stages of Ixodes scapularis collected from Wisconsin and Massachusetts, USA.

Measures of acarological risk of exposure to Ixodes scapularis-borne disease agents typically focus on nymphs; however, the relapsing fever group spirochete Borrelia miyamotoi can be passed transovarially, and I. scapularis larvae are capable of transmitting B. miyamotoi to their hosts. To quantify the larval contribution to acarological risk, relative to nymphs and adults, we collected questing I. scapularis for 3 yr at Fort McCoy, Wisconsin (WI, n = 23,367 ticks), and Cape Cod, Massachusetts (MA, n = 4190) in the United States. Borrelia miyamotoi infection prevalence was estimated for I. scapularis larvae, nymphs, females, and males, respectively, as 0.88, 2.05, 0.63, and 1.22 % from the WI site and 0.33, 2.32, 2.83, and 2.11 % from the MA site. Densities of B. miyamotoi-infected ticks (DIT, per 1000 m2) were estimated for larvae, nymphs, females, and males, respectively, as 0.36, 0.14, 0.01, and 0.03 from the WI site and 0.05, 0.06, 0.03, and 0.02 from the MA site. Thus, although larval infection prevalence with B. miyamotoi was significantly lower than that of nymphs and similar to that of adults, because of their higher abundance, the larval contribution to the overall DIT was similar to that of nymphs and trended towards a greater contribution than adults. Assuming homogenous contact rates with humans, these results suggest that eco-epidemiological investigations of B. miyamotoi disease in North America should include larvae. A fuller appreciation of the epidemiological implications of these results, therefore, requires an examination of the heterogeneity in contact rates with humans among life stages.

Possible Effects of Climate Change on Ixodid Ticks and the Pathogens They Transmit: Predictions and Observations.

The global climate has been changing over the last century due to greenhouse gas emissions and will continue to change over this century, accelerating without effective global efforts to reduce emissions. Ticks and tick-borne diseases (TTBDs) are inherently climate-sensitive due to the sensitivity of tick lifecycles to climate. Key direct climate and weather sensitivities include survival of individual ticks, and the duration of development and host-seeking activity of ticks. These sensitivities mean that in some regions a warming climate may increase tick survival, shorten life-cycles and lengthen the duration of tick activity seasons. Indirect effects of climate change on host communities may, with changes in tick abundance, facilitate enhanced transmission of tick-borne pathogens. High temperatures, and extreme weather events (heat, cold, and flooding) are anticipated with climate change, and these may reduce tick survival and pathogen transmission in some locations. Studies of the possible effects of climate change on TTBDs to date generally project poleward range expansion of geographical ranges (with possible contraction of ranges away from the increasingly hot tropics), upslope elevational range spread in mountainous regions, and increased abundance of ticks in many current endemic regions. However, relatively few studies, using long-term (multi-decade) observations, provide evidence of recent range changes of tick populations that could be attributed to recent climate change. Further integrated 'One Health' observational and modeling studies are needed to detect changes in TTBD occurrence, attribute them to climate change, and to develop predictive models of public- and animal-health needs to plan for TTBD emergence.

Landscape features predict the current and forecast the future geographic spread of Lyme disease.

Lyme disease, the most prevalent vector-borne disease in North America, is increasing in incidence and geographic distribution as the tick vector, Ixodes scapularis, spreads to new regions. We re-construct the spatial-temporal invasion of the tick and human disease in the Midwestern US, a major focus of Lyme disease transmission, from 1967 to 2018, to analyse the influence of spatial factors on the geographic spread. A regression model indicates that three spatial factors-proximity to a previously invaded county, forest cover and adjacency to a river-collectively predict tick occurrence. Validation of the predictive capability of this model correctly predicts counties invaded or uninvaded with 90.6% and 98.5% accuracy, respectively. Reported incidence increases in counties after the first report of the tick; based on this modelled relationship, we identify 31 counties where we suspect I. scapularis already occurs yet remains undetected. Finally, we apply the model to forecast tick establishment by 2021 and predict 42 additional counties where I. scapularis will probably be detected based upon historical drivers of geographic spread. Our findings leverage resources dedicated to tick and human disease reporting and provide the opportunity to take proactive steps (e.g. educational efforts) to prevent and limit transmission in areas of future geographic spread.