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Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 are not phylogenetically closely related; however, both use the angiotensin-converting enzyme 2 (ACE2) receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda that are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario, and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2 and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

Presents a study that inquired into the question of geographic population genetic structure for microsatellite DNA loci. Chromosomal forms of the genetic structure of Anopheles gambiae sensu stricto in Mali, West Africa; Correlation between the distances of suitable habitat and differences in microsatellite allele frequencies; Differences in microsatellite allele frequencies between populations of Anopheles gambiae in Kenya and Senegal.

Background: Lyme disease continues to expand in Canada and the USA and no single intervention is likely to curb the epidemic., Methods: We propose a platform to quantitatively assess the effectiveness of a subset of Ixodes scapularis tick management approaches. The platform allows us to assess the impact of different control treatments, conducted either individually (single interventions) or in combination (combined efforts), with varying timings and durations. Interventions include three low environmental toxicity measures in differing combinations, namely reductions in white-tailed deer (Odocoileus virginianus) populations, broadcast area-application of the entomopathogenic fungus Metarhizium anisopliae, and fipronil-based rodent-targeted bait boxes. To assess the impact of these control efforts, we calibrated a process-based mathematical model to data collected from residential properties in the town of Redding, southwestern Connecticut, where an integrated tick management program to reduce I.xodes scapularis nymphs was conducted from 2013 through 2016. We estimated parameters mechanistically for each of the three treatments, simulated multiple combinations and timings of interventions, and computed the resulting percent reduction of the nymphal peak and of the area under the phenology curve., Results: Simulation outputs suggest that the three-treatment combination and the bait boxes-deer reduction combination had the overall highest impacts on suppressing I. scapularis nymphs. All (single or combined) interventions were more efficacious when implemented for a higher number of years. When implemented for at least 4 years, most interventions (except the single application of the entomopathogenic fungus) were predicted to strongly reduce the nymphal peak compared with the no intervention scenario. Finally, we determined the optimal period to apply the entomopathogenic fungus in residential yards, depending on the number of applications., Conclusions: Computer simulation is a powerful tool to identify the optimal deployment of individual and combined tick management approaches, which can synergistically contribute to short-to-long-term, costeffective, and sustainable control of tick-borne diseases in integrated tick management (ITM) interventions., (© 2024. The Author(s).)

Lyme disease transmission dynamics in the northeastern United States vary by context. Periurban regions, including Block Island, RI, have experienced decades of endemic transmission. In urban areas, including Staten Island, a borough in New York City, NY, Lyme disease is an emerging issue. Knowledge, attitudes, and practices around Lyme disease evolve as an area progresses from emergent to endemic. We conducted focus group discussions and household surveys within Staten Island, NY and Block Island, RI to compare knowledge, attitudes, and practices surrounding Lyme disease and other tick-borne diseases. Qualitative data were coded into themes, and survey data were used to provide more general context of the focus group discussions. Using item response theory, we developed an index of knowledge from relevant factors within the household survey. We identified a significant difference in knowledge scores between the two study areas. Additionally, we identified key differences across multiple domains. Participants from Block Island were more likely to report prior tick exposure and Lyme disease in themselves or household members and were more likely to express concerns about the environmental impact of mitigation strategies. Individuals on Staten Island were more likely to assign responsibility of prevention and control to local, state, and federal government than to take personal prevention measures. Prevention of Lyme disease and other tick-borne diseases must be tailored to the community context and monitored over time as perceptions and priorities may evolve as transmission dynamics transition from emergent to endemic.

Importance: Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions., Competing Interests: The authors declare no conflict of interest.

Small to mid-sized carnivores, or meso-carnivores, comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues, feces, and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher ( Pekania pennanti ), bobcat ( Lynx rufus ), red fox ( Vulpes vulpes ), and domestic cat (Felis catus) . Next-generation sequencing revealed that all these viruses belonged to the Luchacovirus subgenus ( Alphacoronavirus genus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3'-end of the genome (~12,000bp) revealed that although the viruses detected group with, and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those from rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring.

Background: Public green spaces are important for human health, but they may expose visitors to ticks and tick-borne pathogens. We sought to understand, for the first time, visitors' exposure risk and drivers of tick-preventative behavior in three popular parks on Staten Island, New York City, NY, USA, by integrating tick hazard and park visitors' behaviors, risk perceptions and knowledge., Methods: We conducted tick sampling in three parks, across three site types (open spaces, the edge of open spaces, and trails) and three within-park habitats (maintained grass, unmaintained herbaceous, and leaf litter) to estimate tick density during May-August 2019. Human behavior was assessed by observations of time spent and activity type in each site. We integrated the time spent in each location by park visitors and the tick density to estimate the probability of human-tick encounter. To assess visitors' tick prevention behaviors, a knowledge, attitude, and practices (KAP) survey was administered., Results: Three tick species (Ixodes scapularis, Amblyomma americanum and Haemaphysalis longicornis) were collected. For all species, the density of nymphs was greatest in unmaintained herbaceous habitats and trails, however, the fewest people entered these hazardous locations. The KAP survey revealed that most respondents (N = 190) identified parks as the main location for tick exposure, but most believed they had minimal risk for tick encounter. Consequently, many visitors did not conduct tick checks. People were most likely to practice tick checks if they knew multiple prevention methods and perceived a high likelihood of tick encounter., Conclusions: By integrating acarological indices with park visitor behaviors, we found a mismatch between areas with higher tick densities and areas more frequently used by park visitors. However, this exposure risk varied among demographic groups, the type of activities and parks, with a higher probability of human-tick encounters in trails compared to open spaces. Furthermore, we showed that people's KAP did not change across parks even if parks represented different exposure risks. Our research is a first step towards identifying visitor risk, attitudes, and practices that could be targeted by optimized messaging strategies for tick bite prevention among park visitors., (© 2022. The Author(s).)

Background: The incidence of tick-borne disease has increased dramatically in recent decades, with urban areas increasingly recognized as high-risk environments for exposure to infected ticks. Green spaces may play a key role in facilitating the invasion of ticks, hosts and pathogens into residential areas, particularly where they connect residential yards with larger natural areas (e.g. parks). However, the factors mediating tick distribution across heterogeneous urban landscapes remain poorly characterized., Methods: Using generalized linear models in a multimodel inference framework, we determined the residential yard- and local landscape-level features associated with the presence of three tick species of current and growing public health importance in residential yards across Staten Island, a borough of New York City, in the state of New York, USA., Results: The amount and configuration of canopy cover immediately surrounding residential yards was found to strongly predict the presence of Ixodes scapularis and Amblyomma americanum, but not that of Haemaphysalis longicornis. Within yards, we found a protective effect of fencing against I. scapularis and A. americanum, but not against H. longicornis. For all species, the presence of log and brush piles strongly increased the odds of finding ticks in yards., Conclusions: The results highlight a considerable risk of tick exposure in residential yards in Staten Island and identify both yard- and landscape-level features associated with their distribution. In particular, the significance of log and brush piles for all three species supports recommendations for yard management as a means of reducing contact with ticks., (© 2022. The Author(s).)

Haemaphysalis longicornis, the Asian longhorned tick, is an invasive ixodid tick that has rapidly spread across the northeastern and southeastern regions of the United States since first reported in 2017. The emergence of H. longicornis presents a potential threat for livestock, wildlife, and human health as the host associations and vector potential of this invasive pest in the United States are poorly understood. Previous field data from the United States has shown that H. longicornis was not associated with natural populations of small mammals or birds, but they show a preference for medium sized mammals in laboratory experiments. Therefore, medium and large sized mammals were sampled on Staten Island, New York, United States, to determine H. longicornis host associations and vector potential for a range of human and veterinary pathogens. A total of 97 hosts were sampled and five species of tick (Amblyomma americanum, Dermacentor variabilis, H. longicornis, Ixodes scapularis, Ixodes cookei) were found feeding concurrently on these hosts. Haemaphysalis longicornis was found in the highest proportions compared with other native tick species on raccoons (55.4%), Virginia opossums (28.9%), and white-tailed deer (11.5%). Tissue, blood, and engorged larvae were tested for 17 different pathogens using a nanoscale PCR platform. Infection with five pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, Rickettsia spp., Mycoplasma haemocanis, and Bartonella spp.) was detected in host samples, but no pathogens were found in any larval samples. These results suggest that although large and medium sized mammals feed large numbers of H. longicornis ticks in the environment, there is presently a low potential for H. longicornis to acquire pathogens from these wildlife hosts., (Copyright © 2020 Australian Society for Parasitology. All rights reserved.)

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

The cricetine rodent Peromyscus leucopus is an important reservoir for several human zoonoses, including Lyme disease, in North America. Akin to hamsters, the white-footed deermouse has been unevenly characterized in comparison to the murid Mus musculus. To further understanding of P. leucopus' total genomic content, we investigated gut microbiomes of an outbred colony of P. leucopus, inbred M. musculus, and a natural population of P. leucopus. Metagenome and whole genome sequencing were combined with microbiology and microscopy approaches. A focus was the genus Lactobacillus, four diverse species of which were isolated from forestomach and feces of colony P. leucopus. Three of the species-L. animalis, L. reuteri, and provisionally-named species "L. peromysci"-were identified in fecal metagenomes of wild P. leucopus but not discernibly in samples from M. musculus. L. johnsonii, the fourth species, was common in M. musculus but absent or sparse in wild P. leucopus. Also identified in both colony and natural populations were a Helicobacter sp. in feces but not stomach, and a Tritrichomonas sp. protozoan in cecum or feces. The gut metagenomes of colony P. leucopus were similar to those of colony M. musculus at the family or higher level and for major subsystems. But there were multiple differences between species and sexes within each species in their gut metagenomes at orthologous gene level. These findings provide a foundation for hypothesis-testing of functions of individual microbial species and for interventions, such as bait vaccines based on an autochthonous bacterium and targeting P. leucopus for transmission-blocking., Competing Interests: The authors have declared that no competing interests exist.

Lyme disease, caused by some Borrelia burgdorferi sensu lato, is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic spread, continue to grow. Previously identified B. burgdorferi proteins, lipid immunogens, and live mutants lead the design of canonical vaccines aimed at disrupting infection in the host. Discovery of the mechanism of action of the first vaccine catalyzed the development of new strategies to control Lyme disease that bypassed direct vaccination of the human host. Thus, novel prevention concepts center on proteins produced by B. burgdorferi during tick transit and on tick proteins that mediate feeding and pathogen transmission. A burgeoning area of research is tick immunity as it can unlock mechanistic pathways that could be targeted for disruption. Studies that shed light on the mammalian immune pathways engaged during tick-transmitted B. burgdorferi infection would further development of vaccination strategies against Lyme disease., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

The mammalian meat allergy known as the "α-Gal syndrome" relates to IgE specific for galactose-α-1,3-galactose (α-Gal), an oligosaccharide that is present in cells and tissues of nonprimate mammals. The recognition of delayed reactions to food derived from mammals in patients with IgE to α-Gal and also the association with tick bites have been increasing worldwide. In 2018, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop on this emerging tick-related disease. International experts from the fields of tick biology, allergy, immunology, infectious disease, and dermatology discussed the current state of our understanding of this emerging medical condition. The participants provided suggestions for specific research priorities and for the development of resources to advance our knowledge of the mechanisms, diagnosis, management, and prevention of this allergic disease. This publication is a summary of the workshop and the panel's recommendations are presented herein., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host's skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts., Competing Interests: The authors have declared no competing interests exist.

Lyme disease (LD) is a commonly cited model for the link between habitat loss and/or fragmentation and disease emergence, based in part on studies showing that forest patch size is negatively related to LD entomological risk. An equivalent relationship has not, however, been shown between patch size and LD incidence (LDI). Because entomological risk is measured at the patch scale, while LDI is generally assessed in relation to aggregate landscape statistics such as forest cover, we posit that the contribution of individual patches to human LD risk has not yet been directly evaluated. We design a model that directly links theoretical entomological risk at the patch scale to larger-scale epidemiological data. We evaluate its predictions for relative LD risk in artificial landscapes with varying composition and configuration, and test its ability to predict countywide LDI in a 12-county region of New York. On simulated landscapes, we find that the model predicts a unimodal relationship between LD incidence and forest cover, mean patch size, and mean minimum distance (a measure of isolation), and a protective effect for percolation probability (a measure of connectivity). In New York, risk indices generated by this model are significantly related to countywide LDI. The results suggest that the lack of concordance between entomological risk and LDI may be partially resolved by this style of model.

Ticks carry a wide range of known human and animal pathogens and are postulated to carry others with the potential to cause disease. Here we report a discovery effort wherein unbiased high-throughput sequencing was used to characterize the virome of 2,021 ticks, including Ixodes scapularis ( n = 1,138), Amblyomma americanum ( n = 720), and Dermacentor variabilis ( n = 163), collected in New York, Connecticut, and Virginia in 2015 and 2016. We identified 33 viruses, including 24 putative novel viral species. The most frequently detected viruses were phylogenetically related to members of the Bunyaviridae and Rhabdoviridae families, as well as the recently proposed Chuviridae . Our work expands our understanding of tick viromes and underscores the high viral diversity that is present in ticks. IMPORTANCE The incidence of tick-borne disease is increasing, driven by rapid geographical expansion of ticks and the discovery of new tick-associated pathogens. The examination of the tick microbiome is essential in order to understand the relationship between microbes and their tick hosts and to facilitate the identification of new tick-borne pathogens. Genomic analyses using unbiased high-throughput sequencing platforms have proven valuable for investigations of tick bacterial diversity, but the examination of tick viromes has historically not been well explored. By performing a comprehensive virome analysis of the three primary tick species associated with human disease in the United States, we gained substantial insight into tick virome diversity and can begin to assess a potential role of these viruses in the tick life cycle.

Background: Birds play a major role in the maintenance of enzootic cycles of pathogens transmitted by ticks. Due to their mobility, they affect the spatial distribution and abundance of both ticks and pathogens. In the present study, we aim to identify members of a pathogen community [Borrelia burgdorferi (s.l.), B. miyamotoi, 'Ca. Neoehrlichia mikurensis', Anaplasma phagocytophilum and Rickettsia helvetica] in songbird-derived ticks from 11 locations in the Netherlands and Belgium (2012-2014)., Results: Overall, 375 infested songbird individuals were captured, belonging to 35 species. Thrushes (Turdus iliacus, T. merula and T. philomelos) were trapped most often and had the highest mean infestation intensity for both Ixodes ricinus and I. frontalis. Of the 671 bird-derived ticks, 51% contained DNA of at least one pathogenic agent and 13% showed co-infections with two or more pathogens. Borrelia burgdorferi (s.l.) DNA was found in 34% of the ticks of which majority belong to so-called avian Borrelia species (distribution in Borrelia-infected ticks: 47% B. garinii, 34% B. valaisiana, 3% B. turdi), but also the mammal-associated B. afzelii (16%) was detected. The occurrence of B. miyamotoi was low (1%). Prevalence of R. helvetica in ticks was high (22%), while A. phagocytophilum and 'Ca. N. mikurensis' prevalences were 5% and 4%, respectively. The occurrence of B. burgdorferi (s.l.) was positively correlated with the occurrence of 'Ca. N. mikurensis', reflecting variation in susceptibility among birds and/or suggesting transmission facilitation due to interactions between pathogens., Conclusions: Our findings highlight the contribution of European songbirds to co-infections in tick individuals and consequently to the exposure of humans to multiple pathogens during a tick bite. Although poorly studied, exposure to and possibly also infection with multiple tick-borne pathogens in humans seems to be the rule rather than the exception.

As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win-win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model. With this model, we show that declining habitat, and thus declining biodiversity, can lead to either increasing or decreasing infectious-disease risk, measured as endemic prevalence. Whether larger habitats, and thus greater biodiversity, lead to a decrease (dilution effect) or increase (amplification effect) in infection prevalence depends upon the pathogen transmission mode and how host competence scales with body size. Dilution effects were detected for most frequency-transmitted pathogens and amplification effects were detected for density-dependent pathogens. Amplification effects were also observed over a particular range of habitat loss in frequency-dependent pathogens when we assumed that host competence was greatest in large-bodied species. By contrast, only amplification effects were observed for density-dependent pathogens; host competency only affected the magnitude of the effect. These models can be used to guide future empirical studies of biodiversity-disease relationships across gradients of habitat loss. The type of transmission, the relationship between host competence and community assembly, the identity of hosts contributing to transmission, and how transmission scales with area are essential factors to consider when elucidating the mechanisms driving disease risk in shrinking habitat.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'., (© 2017 The Author(s).)

Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R 0 , the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding - such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. However, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen DNA., Results: We addressed this challenge by using custom probes for multiplexed hybrid capture to enrich for and sequence 30 Borrelia burgdorferi genomes from field samples of its arthropod vector. Hybrid capture enabled sequencing of nearly the complete genome (~99.5 %) of the Borrelia burgdorferi pathogen with 132-fold coverage, and identification of up to 12,291 single nucleotide polymorphisms per genome., Conclusions: The proprosed culture-independent method enables efficient whole genome capture and sequencing of pathogens directly from arthropod vectors, thus making population genomic study of vector-borne and zoonotic infectious diseases economically feasible and scalable. Furthermore, given the similarities of invertebrate field specimens to other mixed DNA templates characterized by a high ratio of host to pathogen DNA, we discuss the potential applicabilty of hybrid capture for genomic study across diverse study systems.

The effect of biodiversity declines on human health is currently debated, but empirical assessments are lacking. Lyme disease provides a model system to assess relationships between biodiversity and human disease because the etiologic agent, Borrelia burgdorferi, is transmitted in the United States by the generalist black-legged tick (Ixodes scapularis) among a wide range of mammalian and avian hosts. The 'dilution effect' hypothesis predicts that species-poor host communities dominated by white-footed mice (Peromyscus leucopus) will pose the greatest human risk because P. leucopus infects the largest numbers of ticks, resulting in higher human exposure to infected I. scapularis ticks. P. leucopus-dominated communities are also expected to maintain a higher frequency of those B. burgdorferi outer surface protein C (ospC) genotypes that this host species more efficiently transmits ('multiple niche polymorphism' hypothesis). Because some of these genotypes are human invasive, an additive increase in human disease risk is expected in species-poor settings. We assessed these theoretical predictions by comparing I. scapularis nymphal infection prevalence, density of infected nymphs and B. burgdorferi genotype diversity at sites on Block Island, RI, where P. leucopus dominates the mammalian host community, to species-diverse sites in northeastern Connecticut. We found no support for the dilution effect hypothesis; B. burgdorferi nymphal infection prevalence was similar between island and mainland and the density of B. burgdorferi infected nymphs was higher on the mainland, contrary to what is predicted by the dilution effect hypothesis. Evidence for the multiple niche polymorphism hypothesis was mixed: there was lower ospC genotype diversity at island than mainland sites, but no overrepresentation of genotypes with higher fitness in P. leucopus or that are more invasive in humans. We conclude that other mechanisms explain similar nymphal infection prevalence in both communities and that high ospC genotype diversity can be maintained in both species-poor and species-rich communities., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

The basic reproduction number of a pathogen, R0, determines whether a pathogen will spread (R0>1), when introduced into a fully susceptible population or fade out (R0<1), because infected hosts do not, on average, replace themselves. In this paper we develop a simple mechanistic model for the basic reproduction number for a group of tick-borne pathogens that wholly, or almost wholly, depend on horizontal transmission to and from vertebrate hosts. This group includes the causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of human babesiosis, Babesia microti, for which transmission between co-feeding ticks and vertical transmission from adult female ticks are both negligible. The model has only 19 parameters, all of which have a clear biological interpretation and can be estimated from laboratory or field data. The model takes into account the transmission efficiency from the vertebrate host as a function of the days since infection, in part because of the potential for this dynamic to interact with tick phenology, which is also included in the model. This sets the model apart from previous, similar models for R0 for tick-borne pathogens. We then define parameter ranges for the 19 parameters using estimates from the literature, as well as laboratory and field data, and perform a global sensitivity analysis of the model. This enables us to rank the importance of the parameters in terms of their contribution to the observed variation in R0. We conclude that the transmission efficiency from the vertebrate host to Ixodes scapularis ticks, the survival rate of Ixodes scapularis from fed larva to feeding nymph, and the fraction of nymphs finding a competent host, are the most influential factors for R0. This contrasts with other vector borne pathogens where it is usually the abundance of the vector or host, or the vector-to-host ratio, that determine conditions for emergence. These results are a step towards a better understanding of the geographical expansion of currently emerging horizontally transmitted tick-borne pathogens such as Babesia microti, as well as providing a firmer scientific basis for targeted use of acaricide or the application of wildlife vaccines that are currently in development., (© 2013 Elsevier Ltd. All rights reserved.)

Background: A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling., Methodology/principal Findings: Using data from seven censuses of A. aegypti pupae (2007-2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban 'patches' (1-3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R(0)) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R(0), and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities., Significance/conclusions: These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person's home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy.

Aedes aegypti is implicated in dengue transmission in tropical and subtropical urban areas around the world. Ae. aegypti populations are controlled through integrative vector management. However, the efficacy of vector control may be undermined by the presence of alternative, competent species. In Puerto Rico, a native mosquito, Ae. mediovittatus, is a competent dengue vector in laboratory settings and spatially overlaps with Ae. aegypti. It has been proposed that Ae. mediovittatus may act as a dengue reservoir during inter-epidemic periods, perpetuating endemic dengue transmission in rural Puerto Rico. Dengue transmission dynamics may therefore be influenced by the spatial overlap of Ae. mediovittatus, Ae. aegypti, dengue viruses, and humans. We take a landscape epidemiology approach to examine the association between landscape composition and configuration and the distribution of each of these Aedes species and their co-occurrence. We used remotely sensed imagery from a newly launched satellite to map landscape features at very high spatial resolution. We found that the distribution of Ae. aegypti is positively predicted by urban density and by the number of tree patches, Ae. mediovittatus is positively predicted by the number of tree patches, but negatively predicted by large contiguous urban areas, and both species are predicted by urban density and the number of tree patches. This analysis provides evidence that landscape composition and configuration is a surrogate for mosquito community composition, and suggests that mapping landscape structure can be used to inform vector control efforts as well as to inform urban planning.

Background: The optimal method for early prediction of human West Nile virus (WNV) infection risk remains controversial. We analyzed the predictive utility of risk factor data for human WNV over a six-year period in Connecticut., Results and Discussion: Using only environmental variables or animal sentinel data was less predictive than a model that considered all variables. In the final parsimonious model, population density, growing degree-days, temperature, WNV positive mosquitoes, dead birds and WNV positive birds were significant predictors of human infection risk, with an ROC value of 0.75., Conclusion: A real-time model using climate, land use, and animal surveillance data to predict WNV risk appears feasible. The dynamic patterns of WNV infection suggest a need to periodically refine such prediction systems., Methods: Using multiple logistic regression, the 30-day risk of human WNV infection by town was modeled using environmental variables as well as mosquito and wild bird surveillance.

We evaluated the blood-feeding patterns in several mosquito species that may serve as vectors of disease agents in the northeastern United States. Blood-fed mosquitoes were collected from 91 different sites throughout Connecticut over a 6-yr period (June-October 2002-2007), and the host-feeding patterns of 23 mosquito species representing six genera were examined by using a polymerase chain reaction-based assay and sequencing portions of the cytochrome b gene of mitochondrial DNA. This study was part of a statewide surveillance program and for some of the mosquito species a limited number of specimens were examined [e.g., Aedes communis (De Geer) (1), Anopheles barberi Coquillett (1), Uranotaenia sapphirina (Osten Sacken) (5)]. With the exception of Culex territans Walker that acquired bloodmeals from all four classes of vertebrates--birds, reptiles, amphibians, and mammals--all species of Aedes, Anopheles, Coquillettidia, Psorophora, and to a lesser degree, Uranotaenia, were found to feed predominately upon mammalian hosts. Fourteen mammalian species were identified as sources of blood, but the majority of feedings were taken from the white-tailed deer, Odocoileus virginianus. Human-derived bloodmeals were identified from 13 of the 23 mosquito species. Limited avian-derived bloodmeals were detected in Aedes canadensis (Theobald), Aedes cantator (Coquillett), Aedes cinereus Meigen, Aedes triseriatus (Coquillett), Aedes trivittatus (Coquillett), Coquillettidia perturbans (Walker) Cx. territans, Psorophoraferox (von Humboldt), and Ur. sapphirina. American robin, Turdus migratorius, was the most common source of avian blood, followed by a few other mostly Passeriformes birds. We conclude that the white-tailed deer serve as the main vertebrate host for these mammalophilic mosquitoes in this region of the United States. This feeding pattern supports enzootic amplification of arboviruses, including Jamestown Canyon, Cache Valley, and Potosi viruses that perpetuate in cervid hosts. Occasional feeding on avian hosts suggests that some of these mosquito species, such as Cq. perturbans, also could facilitate transmission of West Nile and eastern equine encephalitis viruses from viremic birds to mammalian hosts.

Lyme borreliosis in North America is caused by the tick-borne spirochete Borrelia burgdorferi, a zoonotic bacterium that is able to persistently infect a wide range of vertebrate species. Given the pronounced strain structure of B. burgdorferi in the northeastern United States, we asked whether the fitness of the different genotypes varies among susceptible vertebrate hosts. The transmission dynamics of two genetically divergent human isolates of B. burgdorferi, BL206 and B348, were analyzed experimentally in white-footed mice and in C3H/HeNCrl mice over a time period of almost 3 months. We found that the initially high transmission efficiency from white-footed mice to ticks declined sharply for isolate B348 but remained considerably high for isolate BL206. In contrast, in C3H/HeNCrl mice, high transmission efficiency persisted for both isolates. Our findings provide proof-of-principle evidence for intrinsic fitness variation of B. burgdorferi strains in vertebrate host species, perhaps indicating the beginnings of adaptive radiation.

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.