Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes.

BACKGROUND: Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid (BHBA; the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with BHBA. RESULTS: We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows; the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca2+ mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca2+ responses when HCAR2 was knocked down by siRNA silencing, indicating Ca2+ mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin (NA-1 and NA-5), were tested; monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca2+ mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic AMP. CONCLUSIONS: We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca2+ mobilization in a HCAR2-dependent manner.

Introduction of the ectoparasite Rhipicephalus pulchellus (Ixodida: Ixodidae) into Connecticut with a human traveler from Tanzania, and a review of its importation records into the United States.

Globalization, increased frequency of travel, and a rise in legal and illegal animal trades can introduce exotic ticks into the United States. We herein report the importation of a male Rhipicephalus pulchellus (Gerstäcker) on a human traveler returning to Connecticut from Tanzania, Africa, and review historical importation records of this species into the United States. This common tick is broadly distributed throughout East Africa, from Eritrea to Tanzania, has a wide host range on domestic animals and wildlife, and has been most frequently introduced into the United States on tick-infested wild animal hosts and animal trophies, but documentation of importation on humans has been rare. Archival records at the United States Department of Agriculture's National Veterinary Services Laboratories show R. pulchellus has been introduced into the United States at least 40 times over the last 62 yr. Rhipicephalus pulchellus has been linked to Rickettsia conorii, the agent of boutonneuse fever in humans, Crimean-Congo hemorrhagic fever orthonairovirus, and Nairobi sheep disease orthonairovirus. Given the potential for this exotic tick to introduce animal or human pathogens, proper surveillance, interception, identification, and reporting of these ticks are vital in protecting human and animal health.

Orally delivered fipronil-laced bait reduces juvenile blacklegged tick (Ixodes scapularis) burdens on wild white-footed mice (Peromyscus leucopus).

While the topical acaricidal treatment of rodent pathogen reservoirs has been readily explored over the past several decades, oral systemic acaricidal treatment is only recently gaining traction as an alternative approach to the management of ticks and tick-borne pathogens. Recent laboratory tests have shown promise in the effectiveness of this systemic strategy against the blacklegged tick (Ixodes scapularis) and a Canadian field evaluation was recently published, but no recent field data from the United States yet exist. With this research, we sought to field deploy a commercially available fipronil-laced bait (Kaput® Flea Control Bait, Scimetrics LLC., Wellington, CO, USA; 0.005% fipronil; Environmental Protection Agency Reg. No. 72500-28), in an alternate use targeting white-footed mice (Peromyscus leucopus) to determine bait acceptance and potential impacts to juvenile I. scapularis burdens. Bait was readily accepted by wild P. leucopus and other rodent reservoirs. An ad libitum distribution strategy as well as placing smaller volumes of fipronil-laced bait within individual Sherman traps both resulted in significant reductions (57-94%) in juvenile I. scapularis burdens as compared to control over two years. The oral delivery of systemic acaricides shows promise in reduction of I. scapularis burdens on P. leucopus and should be further explored to determine effectiveness on host-seeking tick abundances, associated pathogen infection, and potentially incorporated into integrated tick management programs.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

BACKGROUND: Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia. This study aimed to clarify whether these three constructs influence clinical and functional outcome of schizophrenia. METHOD: At baseline, 127 first-episode schizophrenia patients completed a behavioural paradigm for emotion-behaviour decoupling, and self-report scales for experiential pleasure and emotion expressivity deficits. Cluster-analysis was applied to characterize schizophrenia subgroups based on these three constructs. At end-point (mean follow-up = 5.37 years, SD = 1.03 years), 85 schizophrenia patients were reassessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and a clinician-rated social functioning scale. RESULTS: Cluster 1 (n = 74) did not show emotion-behaviour decoupling, and had intact experiential pleasure and emotion expressivity. Cluster 2 (n = 29) showed emotion-behaviour decoupling and experiential pleasure deficits. Cluster 3 (n = 24) showed emotion expressivity deficits. At endpoint, the three clusters differed significantly in CAINS MAP factor (p = 0.016) and social functioning (p = 0.019), but not CAINS EXP factor. Specifically, Cluster 2 (n = 18) showed more severe negative symptoms of CAINS MAP factor (p = 0.046) and poorer social functioning (p = 0.022) than Cluster 1 (n = 49). Cluster 3 (n = 18) did not differ from Cluster 1 and Cluster 2 in negative symptoms and social functioning. DISCUSSION: Emotion-behaviour decoupling and experiential pleasure deficits predicted clinical and functional outcome of schizophrenia.

Evaluation of reticuloruminal temperature for the prediction of clinical mastitis in dairy cows challenged with Streptococcus uberis.

Automated monitoring devices have become increasingly utilized in the dairy industry, especially for monitoring or predicting disease status. While multiple automated monitoring devices have been developed for the prediction of clinical mastitis (CM), limitations in performance or applicability remain. The aims of this study were to (1) detect variations in reticuloruminal temperature (RRT) relative to an experimental intramammary challenge with Streptococcus uberis and (2) evaluate alerts generated automatically based on variation in RRT to predict initial signs of CM in the challenged cows based on severity of clinical signs and the concentration of bacteria (cfu/mL) in the infected quarter separately. Clinically healthy Holstein cows without a history of CM in the 60 d before the experiment (n = 37, parity 1 to 5, ≥120 d in milk) were included if they were microbiologically negative and had a somatic cell count under 200,000 cells/mL based on screening of quarter milk samples 1 wk before challenge. Each cow received an intra-reticuloruminal automated monitoring device before the trial and was challenged with 2,000 cfu of Strep. uberis 0140J in 1 rear quarter. Based on interrupted time series analysis, intramammary challenge with Strep. uberis increased RRT by 0.54°C [95% confidence interval (CI): 0.41, 0.66] at 24 h after the challenge, which remained elevated until the end of the study. Alerts based on RRT correctly classified 78.3% (95% CI: 65.8, 87.9) of first occurrences of CM at least 24 h in advance, with a sensitivity of 70.0% (95% CI: 50.6, 85.3) and a specificity of 86.7% (95% CI: 69.3, 96.2). The accuracy of CM for a given severity score was 90.9% (95% CI: 70.8, 98.9) for mild cases, 85.2% (95% CI: 72.9, 93.4) for moderate cases, and 92.9% (95% CI: 66.1, 99.8) for severe cases. Test characteristics of the RRT alerts to predict initial signs of CM improved substantially after bacterial count in the challenged quarter reached 5.0 log10 cfu/mL, reaching a sensitivity of 73.5% (95% CI: 55.6, 87.1) and a specificity of 87.5% (95% CI: 71.0, 96.5). Overall, the results of this study indicated that RRT was affected by the intramammary challenge with Strep. uberis and the RRT-generated alerts had similar accuracy as reported for other sensors and algorithms. Further research that includes natural infections with other pathogens as well as different variations in RRT to determine CM status is warranted.

Anomalous morphologies in Ixodes scapularis feeding on human hosts.

Cases of anomalous morphologies in the blacklegged tick, Ixodes scapularis, have been reported in both field-collected and human-biting specimen in the Northeastern and Midwestern United States, complicating the identification of this medically important tick species. We herein describe four cases of morphological anomalies in I. scapularis females exhibiting nanism and abnormally small genital apertures. We also report a female I. scapularis displaying slight asymmetry in the lower abdomen oriented toward the right side and an abnormal anal groove completely enclosing the anus. The identity of each specimen was confirmed using taxonomic keys, high resolution light and scanning electron microscopy imaging, and DNA sequencing of the 18S rRNA gene. All specimens described in this study were found parasitizing human hosts and were submitted to the Connecticut Agricultural Experiment Station-Tick Testing Laboratory in 2021 for species identification and pathogen screening. Here, we also discuss recent reports of teratological abnormalities in I. scapularis as well as likely causes for such deformities and potential implications.

Oro-Naso-Sino-Orbital-Cutaneous Fistula From Prolonged Cocaine Use.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

Prospective Memory Influences Social Functioning in People With First-Episode Schizophrenia: A Network Analysis and Longitudinal Study.

Background: Prospective memory (PM) impairment is associated with impaired social functioning, but evidence is limited to chronic schizophrenia samples and cross-sectional design. The aim of this study was to utilize network analysis to address the complex interplay between PM, psychopathology, and functional outcome.Methods: This longitudinal study recruited 119 people with first-episode DSM-IV schizophrenia and followed up with them for 2 to 6 years. PM and working memory were assessed at baseline (in 2010-2015) using valid computerized tasks and the Letter-Number Span Test, respectively. Psychopathology and social functioning were assessed at endpoint (in 2016-2017) using the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively. Network analysis examined the effect of baseline PM on SOFAS while accounting for the effects of psychopathology.Results: The resultant network showed that social functioning, PANSS positive symptoms, and PANSS general symptoms clustered together, whereas time-based and event-based PM and working memory formed another cluster. Time-based PM linked event-based PM and working memory with social functioning. Time-based PM (expected influence [EI] = 0.69), event-based PM (EI = 0.65), and working memory (EI = 0.83) demonstrated high values of expected influence, but social functioning (variance explained = 0.685) and PANSS negative (variance explained = 0.657) and general (variance explained = 0.583) subscales demonstrated high values of predictability.Conclusions: Time-based PM is the central node linking neurocognitive functions with social functioning. PM and working memory are "target" nodes for interventions bringing changes to the network, whereas social functioning and psychopathology are "malleable" nodes. PM and working memory are promising intervention targets for functional recovery in schizophrenia.

Rhipicephalus capensis (Acari: Ixodidae), A geographically restricted South African tick, returning with a human traveler to the United States.

Accelerated frequency of recreational travel, globalization of business, and legal and illegal plant and animal trades have contributed to enduring introductions of exotic ticks into the United States. We herein report a new incursion of a female Rhipicephalus capensis on a human traveler returning to Connecticut from South Africa. Natural distribution of R. capensis is restricted to the Western Cape Province and southwestern portion of the Northern Cape Province of South Africa, an area called the Fynbos Biome, and adults of this species primarily parasitize large, wild ungulate hosts. Only one previous international introduction of this tick is documented on imported South African plant material into the United States in 1985. The specimen described here was identified initially by morphological means and subsequently, a partial DNA sequence for the mitochondrial ribosomal RNA gene was generated in a PCR assay, which showed 94.86% identity to an R. capensis sequence in GenBank. We also provide information on several other previously unreported or under-reported incursions by South African ticks into the United States in association with imported Fynbos floricultural materials and speckled Cape tortoises, Chersobius signatus. Documentation of these additional exotic tick species incursions highlights ongoing challenges of the international movement of humans, animals, and other goods carrying ticks of human and veterinary importance.

Integrated Tick Management in Guilford, CT: Fipronil-Based Rodent-Targeted Bait Box Deployment Configuration and Peromyscus leucopus (Rodentia: Cricetidae) Abundance Drive Reduction in Tick Burdens.

Integrated tick management (ITM) is a comprehensive strategy used to reduce presence of ticks and their associated pathogens. Such strategies typically employ a combination of host and non-host targeted treatments which often include fipronil-based, rodent-targeted bait boxes. Bait boxes target small-bodied rodents, specifically white-footed mice (Peromyscus leucopus Rafinesque) that not only play a crucial role in the blacklegged tick (Ixodes scapularis Say (Ixodida: Ixodidae)) life cycle, but also in the transmission of numerous pathogens, primarily Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner (Spirochaetales: Spirochaetaceae), the causal agent of Lyme disease. This study aimed to determine the effect of bait box deployment configuration on tick burden reduction while also further exploring bait consumption and P. leucopus abundances as measures of bait box usage and effectiveness. Boxes were deployed on nine properties within each of six neighborhoods (n = 54) in two different configurations: grid and perimeter. Multiple factors were analyzed as potential predictors for reduction in tick burdens using a backward stepwise selection procedure. Results confirmed the perimeter configuration was a more effective deployment strategy. In addition, overall P. leucopus abundance was a significant predictor of tick burden reduction while bait consumption was not. These findings not only further support the recommended perimeter deployment configuration but provide insight into effective utilization in areas of high P. leucopus abundance. The identification of this significant relationship, in addition to configuration, can be utilized by vector control professionals and homeowners to make informed decisions on bait box placement to make sustained impacts on the I. scapularis vector and associated pathogens within an ITM framework.

First Record of Established Populations of the Invasive Pathogen Vector and Ectoparasite Haemaphysalis longicornis (Acari: Ixodidae) in Connecticut, United States.

A number of invasive tick species capable of transmitting pathogens have been accidentally introduced into the U.S. in recent years. The invasion and further range expansion of these exotic ticks have been greatly facilitated by frequent global travel and trade as well as increases in legal and illegal importation of animals. We describe the discovery of the first established populations of Haemaphysalis longicornis Neumann and the first fully engorged human parasitizing specimen documented through passive tick surveillance in Fairfield County, Connecticut, U.S. We also report several individual specimens of this invasive arthropod and vector of multiple pathogens of medical and veterinary importance collected through active tick surveillance from three counties (Fairfield, New Haven, and New London). Considering the potential for invasive ticks to transmit numerous native and emerging pathogens, the implementation of comprehensive surveillance programs will aid in prompt interception of these ticks and reduce the risk of infection in humans and wildlife.

Different trajectories of neurological soft signs progression between treatment-responsive and treatment-resistant schizophrenia patients.

Schizophrenia patients exhibit subtle and non-localizing neurological abnormalities, known as neurological soft signs (NSS). Life-span evidence suggests that NSS vary along the course of schizophrenia. An association between NSS and treatment response has been proposed, suggesting that NSS reflect the underlying neuropathology development in schizophrenia. However, few studies have investigated the relationship between NSS and treatment resistance in first-episode schizophrenia patients. We conducted a longitudinal study on 52 first-episode schizophrenia patients, who were assessed at baseline, the sixth month, and the fifth year using the abridged version of the Cambridge Neurological Inventory. The trajectories of NSS between 29 treatment-responsive patients (with full symptomatic remission) and 23 treatment-resistant patients (who received clozapine) were compared using mixed model ANOVA. We also controlled for the effect of age and estimated IQ, using a mixed ANCOVA model. Although the two schizophrenia groups had comparable NSS at the baseline, their trajectories of NSS differed significantly. Compared with their treatment-responsive counterparts, treatment-resistant schizophrenia patients had worsening of NSS over time. Our findings support the potential utility of NSS in identifying treatment resistance in first-episode schizophrenia. Progressive worsening of NSS in treatment-resistant schizophrenia patients may reflect the development of underlying neuropathology. Further studies using large samples of treatment-resistant schizophrenia patients are needed.

Effective control of the motile stages of Amblyomma americanum and reduced Ehrlichia spp. prevalence in adults via permethrin treatment of white-tailed deer in coastal Connecticut, USA.

The lone star tick, Amblyomma americanum, is a common human-biting species whose range has been largely restricted to the southeastern United States, until recent detections of established populations on Long Island, New York and throughout coastal southern New England. We evaluated the effectiveness of topical treatment of 10 % permethrin delivered via 4-poster devices to white-tailed deer, Odocoileus virginianus, in the management of a newly discovered A. americanum population in Norwalk, Connecticut. Using a high-density deployment of one 4-poster device/12.7 ha, we were successful in significantly reducing densities of host-seeking adults (93 % reduction), nymphs (92 %), and larvae (96 %) from 2018 to 2020. We also documented a significant reduction (87 %) in parasitizing adults and nymphs on white-tailed deer from 2018 to 2019. The prevalence of Ehrlichia chaffeensis and Ehrlichia ewingii combined in host-seeking adults declined significantly from 47 % at the time the A. americanum population was discovered in 2017 to 7% in 2020. However, the prevalence in nymphs remained static (∼9%) throughout the study period. These data demonstrate that, when properly deployed in a density-dependent manner in terms of deer abundance, 4-poster devices can effectively manage parasitizing and host-seeking A. americanum populations and reduce the prevalence of two ehrlichial species of public health importance.

Rabbit Bot Fly Furuncular, Tracheopulmonary, and Human Bot Fly Infestations in Connecticut (Oestridae: Cuterebrinae).

Endemic and tropical human bot infestations are relatively uncommon or unreported in the United States. We report two cases in Connecticut: an unusual furuncular and respiratory myiasis by the rabbit bot Cuterebra buccata (Fab.) (Diptera: Oestridae) in a 74-yr-old male and a case of human bot fly, Dermatobia hominis (L.) (Diptera: Oestridae), myiasis in a 4-yr-old female with a tropical travel history with her family. Identification of C. buccata was based morphologically, in part, on spinal armature and further corroborated by DNA sequencing of the mitochondrial COI gene and comparison to the National Center for Biotechnology Information GenBank DNA sequence database. The resulting annotated sequence data were deposited into the National Center for Biotechnology Information GenBank. The unique medical aspects, and limitations and specifics on bot fly larval habits and identification are discussed.

Barriers to Effective Tick Management and Tick-Bite Prevention in the United States (Acari: Ixodidae).

Lyme and other tick-borne diseases are increasing in the United States. Development of tick control tools have focused primarily on the blacklegged tick, Ixodes scapularis Say. Application of acaricides or entomopathogenic fungal agents to kill host-seeking ticks or ticks on rodents can suppress I. scapularis abundance in residential landscapes, but evidence is lacking for impact on human tick bites or tick-borne disease. Similar studies remain limited for the lone star tick, Amblyomma americanum (L.). Other knowledge gaps include how well homeowners and pest control companies perform in the broadcast application of tick-killing products, relative to high efficacy reported in research studies, and the tick-killing potential of natural product formulations exempt from Environmental Protection Agency registration. Area-wide control based on preventing ticks from feeding on their main reproductive host, the white-tailed deer, can suppress populations of both I. scapularis and A. americanum. Some studies also suggest an impact on Lyme disease cases, but this needs to be further validated in larger-scale intervention studies. The effectiveness, scale, cost, and implementation of various tick management strategies are important considerations in efforts to reduce human tick encounters and tick-borne disease. Additional barriers include weak incentives for industry and academia to develop, test, and register new tick and pathogen control technologies, including vaccines targeting humans, tick reproductive hosts, or wildlife pathogen reservoirs. Solutions will need to be 'two-pronged': improving the tick and pathogen control toolbox and strengthening the public health workforce engaging in tick control at local and state levels.

Enduring Challenge of Invasive Ticks: Introduction of Amblyomma oblongoguttatum (Acari: Ixodidae) into the United States on a Human Traveler Returning from Central America.

Introduction of exotic tick vectors of bacteria, protozoa, viruses, and filarial parasites into the United States has accelerated in recent years, primarily because of globalization, increased frequency of travel, and a rise in legal and illegal animal trades. We herein report introduction of a live specimen of Amblyomma oblongoguttatum on a human into the United States from Central America, and we review 4 previous similar incidents. This tick species occurs widely in the neotropics, from western and southern Mexico, southwards through Central America, to the northern half of South America. It is a potential vector of bacterial agents of spotted fever group rickettsioses, raising concern that if A. oblongoguttatum ticks become established in this country, they might also be able to carry pathogens of human and veterinary concern. Given the potential for exotic ticks as vectors of numerous pathogens, proper surveillance, interception, and identification of these ticks are vital to protecting human and veterinary health. Rigorous governmental inspections of imported livestock and pet animals at ports of entry and educating human travelers and medical practitioners about the risks should be part of an overall national tick program.

Humane Use of Cardiac Puncture for Non-Terminal Phlebotomy of Wild-Caught and Released Peromyscus spp.

The cardiac puncture technique for obtaining relatively large volume (50-150 µL) blood samples from sedated rodents has been used in research for nearly a century. Historically, its use to phlebotomize and then release live rodents was more common. However, recently its use in a non-terminal capacity frequently imparts negative connotations in part because exsanguination of sedated animals via cardiac puncture is now an American Veterinary Medical Association-approved euthanasia technique. This association has resulted in ethical concerns by manuscript reviewers and in a few instances, outright refusal by some peer-reviewed journals to publish research that utilized the technique. To counter the perceived negative associations with its non-terminal use, we summarized nearly two decades (2001-2019) of capture and handling data throughout Connecticut, resulting in over 7000 cardiac punctures performed on nearly 5000 sedated, live-captured and released Peromyscus spp. We show that our total handling mortality rate (3.7%) was comparable, if not lower, than similar field studies that utilized other phlebotomy techniques. Many public health, integrated tick management, and vector-borne disease ecology studies require samples from individual wild-caught Peromyscus spp. over time to determine intervention efficacy and pathogen infection monitoring, and in such field studies, post-operative care is not an option. Proper execution of cardiac puncture does not increase susceptibility of individuals to predation upon release as can potential ocular abnormalities or infections that can occur as the result of use of other techniques. We posit that neither exsanguination nor resulting euthanasia are requirements of cardiac puncture and that its use is entirely appropriate for obtaining blood samples from live-captured and released Peromyscus spp. Properly performed cardiac puncture is an excellent technique to obtain blood samples from sedated, individual Peromyscus spp. on multiple appropriately-spaced occasions over single trapping seasons while keeping animal welfare a top priority.

Administration of an Orally Delivered Substrate Targeting a Mammalian Zoonotic Pathogen Reservoir Population: Novel Application and Biomarker Analysis.

Reservoir-targeted vaccines (RTVs) have the potential to be effective at breaking the transmission cycle of many tick-borne pathogens including, but not limited to, Borrelia burgdorferi, B. miyamotoi, B. mayonii, Babesia microti, and Anaplasma phagocytophilum. To determine what proportion of a wild reservoir species we could effectively target, we distributed an experimental non-RTV Rhodamine B (RhB)-coated pellet formulation devoid of nutrient supplementation using bait boxes with ad libitum access, in battery-operated time-release bait stations, and by hand broadcast. Regardless of distribution method, a total of 208 of 242 (86%) white-footed mouse (Peromyscus leucopus) captures were positive for RhB by either pelage staining or by detecting fluorescent expression in vibrissae under a microscope. In bait box locations, 91% of captured mice were RhB-positive, 89% in hand broadcast locations, and 80% in time-release station locations. Based on results, we are confident that the bait formulation was readily accepted regardless of distribution technique, reached a substantial proportion of the reservoir population, and provides an effective vehicle to deliver a range of RTVs to targeted, wild, pathogen reservoir populations.

Field evaluation of a novel oral reservoir-targeted vaccine against Borrelia burgdorferi utilizing an inactivated whole-cell bacterial antigen expression vehicle.

Blacklegged ticks (Ixodes scapularis) are the principal vector for Borrelia burgdorferi, among other infectious agents, in the northeastern, mid-Atlantic, and upper midwestern USA. White-footed mice (Peromyscus leucopus) are the primary and most competent reservoir host of B. burgdorferi in the Northeast. Live reservoir-targeted vaccines (RTVs) to limit enzootic transmission of B. burgdorferi were previously developed and successfully evaluated in laboratory and controlled field trials. A novel, inactivated RTV was developed to minimize regulatory and market challenges facing previous RTVs based on live bacterial or viral vehicles. Thirty-two residential properties in Redding, Connecticut, participated in a field trial of an orally delivered, inactivated RTV efficacy study (2015-2016). During the two-year vaccination period, a significant decrease in the percentage of B. burgdorferi-infected I. scapularis larvae parasitizing P. leucopus was observed, as was a significant reduction in the percentage of infected P. leucopus on RTV-treated properties when compared to control properties. This novel inactivated RTV was effective in reducing numbers of B. burgdorferi-infected I. scapularis and B. burgdorferi-infected P. leucopus on properties where it was distributed.