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2.
J Wildl Dis ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38685759

RESUMEN

Wildlife translocation and cross-species transmission can impede control and elimination of emerging zoonotic diseases. Tracking the geographic origin of both host and virus (i.e., translocation versus local infection) may help determine the most effective response when high-risk cases of emerging pathogens are identified in wildlife. In May 2022, a coyote (Canis latrans) infected with the raccoon (Procyon lotor) rabies virus variant (RRV) was collected in Lewis County, West Virginia, US, an area free from RRV. We applied host population genomics and RRV phylogenetic analyses to determine the most likely geographic origin of the rabid coyote. Coyote genomic analyses included animals from multiple eastern states bordering West Virginia, with the probable origin of the rabid coyote being the county of collection. The RRV phylogenetic analyses included cases detected from West Virginia and neighboring states, with most similar RRV sequences collected in a county 80 km to the northeast, within the oral rabies vaccination zone. The combined results suggest that the coyote was infected in an RRV management area and carried the RRV to Lewis County, a pattern consistent with coyote local movement ecology. Distant cross-species transmission and subsequent host movement presents a low risk for onward transmission in raccoon populations. This information helped with emergency response decision-making, thereby saving time and resources.

3.
Prev Vet Med ; 225: 106145, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38354432

RESUMEN

The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency "contingency" actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017-2019 and 2018-2021) and one in Virginia (2017-2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km2 grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (>0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2-3 years of each contingency action.


Asunto(s)
Vacunas Antirrábicas , Rabia , Animales , Estados Unidos , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , Mapaches , Ohio/epidemiología , Virginia/epidemiología , Animales Salvajes , Administración Oral , Vacunas Antirrábicas/uso terapéutico
4.
J Wildl Dis ; 60(1): 1-13, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37972639

RESUMEN

Management of the raccoon rabies virus variant in North America is conducted primarily using oral rabies vaccination (ORV). When a sufficient proportion of the population is vaccinated (∼60%), rabies transmission can be eliminated. To date, ORV programs have successfully controlled and eliminated raccoon rabies in rural areas, but there has been less success in urban areas. We studied the proportions of rabies virus neutralizing antibodies (RVNA) in a raccoon (Procyon lotor) population during a 3-yr ORV trial in developed areas of Burlington, Vermont, US. We used a modified N-mixture model to estimate raccoon abundance, RVNA seroprevalence, and capture rates jointly to examine factors that relate to ORV success to better inform management. We found that raccoon abundance was lower in less-developed areas compared to urban centers. Raccoon RVNA seroprevalence decreased as population abundance increased; it increased as the average age of the population increased. Nontarget opossum (Didelphis virginiana) captures correlated with a decrease in raccoon RVNA seroprevalence in low-development areas, suggesting that they may be competing for baits. The target bait density across the entire study area was 150 baits/km2, but a hand baiting strategy was heavily concentrated on roads, resulting in uneven bait densities within sampling sites (0-484 baits/km2). Uneven bait distribution across the study area may explain low RVNA seroprevalence in some locations. Our results suggest that increases in bait density across the study area may improve RVNA seroprevalence and support annual ORV to account for raccoon population turnover.


Asunto(s)
Didelphis , Vacunas Antirrábicas , Rabia , Animales , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , Mapaches , Vermont/epidemiología , Estudios Seroepidemiológicos , Administración Oral , Anticuerpos Antivirales , Vacunación/veterinaria , Vacunación/métodos
5.
J Wildl Dis ; 60(1): 95-104, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37924235

RESUMEN

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint.


Asunto(s)
Ketamina , Nalbufina , Animales , Medetomidina/farmacología , Azaperona/farmacología , Butorfanol/farmacología , Mapaches , Nalbufina/farmacología , Xilazina/farmacología , Hipnóticos y Sedantes/farmacología , Ketamina/farmacología , Inmovilización/veterinaria , Inmovilización/métodos , Oxígeno
6.
J Wildl Dis ; 60(1): 26-38, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37924240

RESUMEN

Raccoon rabies virus (RRV) has been managed using multiple vaccination strategies, including oral rabies vaccination and trap-vaccinate-release (TVR). Identifying a rabies vaccination strategy for an area is a nontrivial task. Vaccination strategies differ in the amount of effort and monetary costs required to achieve a particular level of vaccine seroprevalence (efficiency). Simulating host movement relative to different vaccination strategies in silico can provide a useful tool for exploring the efficiency of different vaccination strategies. We refined a previously developed individual-based model of raccoon movement to evaluate vaccination strategies for urban Hamilton, Ontario, Canada. We combined different oral rabies vaccination baiting (hand baiting, helicopter, and bait stations) with TVR strategies and used GPS data to parameterize and simulate raccoon movement in Hamilton. We developed a total of 560 vaccination strategies, in consultation with the Ontario Ministry of Natural Resources and Forestry, for RRV control in Hamilton. We documented the monetary costs of each vaccination strategy and estimated the population seroprevalence. Intervention costs and seroprevalence estimates were used to calculate the efficiency of each strategy to meet targets set for the purpose of RRV control. Estimated seroprevalence across different strategies varied widely, ranging from less than 5% to more than 70%. Increasing bait densities (distributed using by hand or helicopter) led to negligible increase in seroprevalence. Helicopter baiting was the most efficient and TVR was the least efficient, but helicopter-based strategies led to lower levels of seroprevalence (6-12%) than did TVR-based strategies (17-70%). Our simulations indicated that a mixed strategy including at least some TVR may be the most efficient strategy for a local urban RRV control program when seroprevalence levels >30% may be required. Our simulations provide information regarding the efficiency of different vaccination strategies for raccoon populations, to guide local RRV control in urban settings.


Asunto(s)
Vacunas Antirrábicas , Virus de la Rabia , Rabia , Animales , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , Mapaches , Estudios Seroepidemiológicos , Administración Oral , Vacunación/veterinaria , Ontario/epidemiología
7.
Sci Rep ; 13(1): 22944, 2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-38135706

RESUMEN

The small Indian mongoose (Urva auropunctata) is the primary terrestrial wildlife rabies reservoir on at least four Caribbean islands, including Puerto Rico. In Puerto Rico, mongooses represent a risk to public health, based on direct human exposure and indirectly through the transmission of rabies virus to domestic animals. To date, the fundamental ecological relationships of space use among mongooses and between mongooses and domestic animals remain poorly understood. This study is the first to report mongoose home range estimates based on GPS telemetry, as well as concurrent space use among mongooses and free roaming domestic dogs (FRDD; Canis lupus familiaris). Mean (± SE) home range estimates from 19 mongooses in this study (145 ± 21 ha and 60 ± 14 ha for males and females, respectively) were greater than those reported in prior radiotelemetry studies in Puerto Rico. At the scale of their home range, mongooses preferentially used dry forest and shrubland areas, but tended to avoid brackish water vegetation, salt marshes, barren lands and developed areas. Home ranges from five FRDDs were highly variable in size (range 13-285 ha) and may be influenced by availability of reliable anthropogenic resources. Mongooses displayed high home range overlap (general overlap index, GOI = 82%). Home range overlap among mongooses and FRDDs was intermediate (GOI = 50%) and greater than home range overlap by FRDDs (GOI = 10%). Our results provide evidence that space use by both species presents opportunities for interspecific interaction and contact and suggests that human provisioning of dogs may play a role in limiting interactions between stray dogs and mongooses.


Asunto(s)
Herpestidae , Rabia , Femenino , Masculino , Animales , Perros , Humanos , Rabia/epidemiología , Rabia/veterinaria , Puerto Rico/epidemiología , Fenómenos de Retorno al Lugar Habitual , Animales Domésticos
8.
Evol Appl ; 16(12): 1937-1955, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38143904

RESUMEN

North America is recognized for the exceptional richness of rabies virus (RV) wildlife reservoir species. Management of RV is accomplished through vaccination targeting mesocarnivore reservoir populations, such as the raccoon (Procyon lotor) in Eastern North America. Raccoons are a common generalist species, and populations may reach high densities in developed areas, which can result in contact with humans and pets with potential exposures to the raccoon variant of RV throughout the eastern United States. Understanding the spatial movement of RV by raccoon populations is important for monitoring and refining strategies supporting the landscape-level control and local elimination of this lethal zoonosis. We developed a high-throughput genotyping panel for raccoons based on hundreds of microhaplotypes to identify population structure and genetic diversity relevant to rabies management programs. Throughout the eastern United States, we identified hierarchical population genetic structure with clusters that were connected through isolation-by-distance. We also illustrate that this genotyping approach can be used to support real-time management priorities by identifying the geographic origin of a rabid raccoon that was collected in an area of the United States that had been raccoon RV-free for 8 years. The results from this study and the utility of the microhaplotype panel and genotyping method will provide managers with information on raccoon ecology that can be incorporated into future management decisions.

9.
PLoS One ; 18(11): e0293133, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37943745

RESUMEN

The movement ecology of raccoons varies widely across habitats with important implications for the management of zoonotic diseases such as rabies. However, the spatial ecology of raccoons remains poorly understood in many regions of the United States, particularly in the southeast. To better understand the spatial ecology of raccoons in the southeastern US, we investigated the role of sex, season, and habitat on monthly raccoon home range and core area sizes in three common rural habitats (bottomland hardwood, upland pine, and riparian forest) in South Carolina, USA. From 2018-2022, we obtained 264 monthly home ranges from 46 raccoons. Mean monthly 95% utilization distribution (UD) sizes ranged from 1.05 ± 0.48 km2 (breeding bottomland females) to 5.69 ± 3.37 km2 (fall riparian males) and mean monthly 60% UD sizes ranged from 0.25 ± 0.15 km2 (breeding bottomland females) to 1.59 ± 1.02 km2 (summer riparian males). Males maintained home range and core areas ~2-5 times larger than females in upland pine and riparian habitat throughout the year, whereas those of bottomland males were only larger than females during the breeding season. Home ranges and core areas of females did not vary across habitats, whereas male raccoons had home ranges and core areas ~2-3 times larger in upland pine and riparian compared to bottomland hardwood throughout much of the year. The home ranges of males in upland pine and riparian are among the largest recorded for raccoons in the United States. Such large and variable home ranges likely contribute to elevated risk of zoonotic disease spread by males in these habitats. These results can be used to inform disease mitigation strategies in the southeastern United States.


Asunto(s)
Rabia , Mapaches , Animales , Masculino , Femenino , Estados Unidos , Fitomejoramiento , Sudeste de Estados Unidos , Ecología , Zoonosis
10.
J Wildl Dis ; 59(4): 673-683, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37846907

RESUMEN

Chagas disease, a significant public health concern in the Americas, is caused by a protozoan parasite, Trypanosoma cruzi. The life cycle of T. cruzi involves kissing bugs (Triatoma spp.) functioning as vectors and mammalian species serving as hosts. Raccoons (Procyon lotor) and opossums (Didelphis virginiana) have been identified as important reservoir species in the life cycle of T. cruzi, but prevalence in both species in the southeastern US is currently understudied. We quantified T. cruzi prevalence in these two key reservoir species across our study area in South Carolina, US, and identified factors that may influence parasite detection. We collected whole blood from 183 raccoons and 126 opossums and used PCR to detect the presence of T. cruzi. We then used generalized linear models with parasite detection status as a binary response variable and predictor variables of land cover, distance to water, sex, season, and species. Our analysis indicated that raccoons experienced significantly higher parasite detection rates than Virginia opossums, with T. cruzi prevalence found to be 26.5% (95% confidence interval [CI], 20.0-33.8) in raccoons and 10.5% (95% CI, 5.51-17.5) in opossums. Overall, our results concur with previous studies, in that T. cruzi is established in reservoir host populations in natural areas of the southeastern US.


Asunto(s)
Enfermedad de Chagas , Didelphis , Triatoma , Trypanosoma cruzi , Animales , Didelphis/parasitología , Mapaches/parasitología , South Carolina/epidemiología , Virginia , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/veterinaria , Zarigüeyas/parasitología
11.
JAMA Health Forum ; 4(10): e233535, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37831461

RESUMEN

Importance: There is a paucity of systematically captured data on the costs incurred by society-individuals, families, and communities-from untreated mental illnesses in the US. However, these data are necessary for decision-making on actions and allocation of societal resources and should be considered by policymakers, clinicians, and employers. Objective: To estimate the economic burden associated with untreated mental illness at the societal level. Design, Setting, and Participants: This cross-sectional study used multiple data sources to tabulate the annual cost of untreated mental illness among residents (≥5 years old) in Indiana in 2019: the US National Survey on Drug Use and Health, the National Survey of Children's Health, Indiana government sources, and Indiana Medicaid enrollment and claims data. Data analyses were conducted from January to May 2022. Main Outcomes and Measures: Direct nonhealth care costs (eg, criminal justice system, homeless shelters), indirect costs (unemployment, workplace productivity losses due to absenteeism and presenteeism, all-cause mortality, suicide, caregiver direct health care, caregiver productivity losses, and missed primary education), and direct health care costs (disease-related health care expenditures). Results: The study population consisted of 6 179 105 individuals (median [SD] age, 38.0 [0.2] years; 3 132 806 [50.7%] were women) of whom an estimated 429 407 (95% CI, 349 526-528 171) had untreated mental illness in 2019. The economic burden of untreated mental illness in Indiana was estimated to be $4.2 billion annually (range of uncertainty [RoU], $2.1 billion-$7.0 billion). The cost of untreated mental illness included $3.3 billion (RoU, $1.7 billion-$5.4 billion) in indirect costs, $708.5 million (RoU, $335 million-$1.2 billion) in direct health care costs, and $185.4 million (RoU, $29.9 million-$471.5 million) in nonhealth care costs. Conclusion and Relevance: This cross-sectional study found that untreated mental illness may have significant financial consequences for society. These findings put into perspective the case for action and should be considered by policymakers, clinicians, and employers when allocating societal resources and funding. States can replicate this comprehensive framework as they prioritize key areas for action regarding mental health services and treatments.


Asunto(s)
Estrés Financiero , Trastornos Mentales , Niño , Estados Unidos/epidemiología , Humanos , Femenino , Adulto , Preescolar , Masculino , Indiana/epidemiología , Estudios Transversales , Costo de Enfermedad , Trastornos Mentales/epidemiología
12.
PLoS One ; 18(8): e0285852, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37607164

RESUMEN

Wildlife disease surveillance and monitoring poses unique challenges when assessing rates of population vaccination, immunity, or infection prevalence. Non-invasively detected biomarkers can help reduce risk to both animal and field personnel during wildlife disease management activities. In this study, we investigated the utility of fecal microbiome data collected from captive striped skunks (Mephitis mephitis) in predicting rabies virus vaccination and infection status. We sequenced the hypervariable region 4 (V4) of the bacterial 16S gene and estimated alpha and beta diversity across timepoints in three groups of skunks: vaccination then rabies virus infection, sham vaccination then rabies virus infection, and rabies virus infected without vaccination. Alpha diversity did not differ among treatment groups but beta diversity between treatments was statistically significant. The phyla Firmicutes and Proteobacteria were dominant among all samples. Using Random Forests, we identified operational taxonomic units (OTUs) that greatly influenced classification of fecal samples into treatment groups. Each of these OTUs was correlated with fecal volatile organic compounds detected from the samples for companion treatment groups in another study. This research is the first to highlight striped skunk microbiome biodiversity as a vaccination biomarker which pushes the frontier on alternative methods for surveillance and monitoring of vaccination and disease in wildlife populations.


Asunto(s)
Microbiota , Virus de la Rabia , Rabia , Animales , Mephitidae , Bosques Aleatorios , Animales Salvajes , Biodiversidad , Biomarcadores , Complicaciones Posoperatorias
13.
Cell Chem Biol ; 30(11): 1377-1389.e8, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37586370

RESUMEN

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation. The exceptionally diverse antibodies included RBD-binders with broad neutralizing activity against SARS-CoV-2 variants, and S2-binders with broad specificity against betacoronaviruses and the ability to block membrane fusion. A subset of these RBD- and S2-binding antibodies demonstrated robust protection against challenge in hamster and mouse models. This high-throughput approach can accelerate discovery of diverse, multifunctional antibodies against any target of interest.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Ratones , Humanos , Anticuerpos Neutralizantes , Anticuerpos ampliamente neutralizantes , Anticuerpos Antivirales
14.
J Wildl Dis ; 59(4): 577-589, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37486871

RESUMEN

The small Indian mongoose (Urva auropuncata) is a rabies reservoir in Puerto Rico and accounts for over 70% of reported animal rabies cases annually. The presence of rabies virus-neutralizing antibodies (RVNA) is often used as a tool to measure exposure to rabies virus in wildlife populations. We conducted a serosurvey of mongooses at 11 sites representing six habitat types across Puerto Rico. We collected a serum sample from 464 individual mongooses during 2014-21. Overall, 80/464 (17.0%; 95% confidence interval, 14.1-20.9%; 55 male, 23 female, and two sexes not recorded) of individual mongooses sampled across all habitats were RVNA positive. The geometric mean (SD) RVNA titer for 80 unique seropositive animals was 0.58 (2.92) IU/mL. Our models indicated that the probability of mongooses being RVNA seropositive mostly varied by habitat, with some influence of sex in the individual-level analyses. Population-level RVNA seroprevalence is dynamic in mongoose populations, but these data may shed light on rabies virus transmission across regions to help inform rabies management activities in Puerto Rico.


Asunto(s)
Herpestidae , Vacunas Antirrábicas , Virus de la Rabia , Rabia , Animales , Masculino , Femenino , Rabia/epidemiología , Rabia/veterinaria , Puerto Rico/epidemiología , Estudios Seroepidemiológicos , Anticuerpos Antivirales
15.
Sci Rep ; 13(1): 10447, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37369730

RESUMEN

Raccoons (Procyon lotor) are routinely translocated both legally and illegally to mitigate conflicts with humans, which has contributed to the spread of rabies virus across eastern North America. The movement behavior of translocated raccoons has important ramifications for disease transmission yet remains understudied and poorly quantified. To examine the spatial ecology of raccoons following experimental translocation, we performed reciprocal 16 km-distance translocations of 30 raccoons between habitats of high and low raccoon density (bottomland hardwood and upland pine, respectively) across the Savannah River Site (SRS) in Aiken, South Carolina, USA (2018-2019). Translocation influenced patterns of raccoon space use, with translocated animals exhibiting a 13-fold increase in 95% utilization distributions (UDs) post- compared to pre-translocation (mean 95% UD 35.8 ± 36.1 km2 vs 1.96 ± 1.17 km2). Raccoons originating from upland pine habitats consistently had greater space use and larger nightly movement distances post-translocation compared to raccoons moved from bottomland hardwood habitats, whereas these differences were generally not observed prior to translocation. Estimated home ranges of male raccoons were twice the area as estimated for female raccoons, on average, and this pattern was not affected by translocation. After a transient period lasting on average 36.5 days (SD = 30.0, range = 3.25-92.8), raccoons often resumed pre-experiment movement behavior, with 95% UD sizes not different from those prior to translocation (mean = 2.27 ± 1.63km2). Most animals established new home ranges after translocation, whereas three raccoons moved > 16 km from their release point back to the original capture location. Four animals crossed a 100-m wide river within the SRS post-translocation, but this behavior was not documented among collared raccoons prior to translocation. Large increases in space use combined with the crossing of geographic barriers such as rivers may lead to elevated contact rates with conspecifics, which can heighten disease transmission risks following translocation. These results provide additional insights regarding the potential impacts of raccoon translocation towards population level risks of rabies outbreaks and underscore the need to discourage mesocarnivore translocations to prevent further spread of wildlife rabies.


Asunto(s)
Vacunas Antirrábicas , Virus de la Rabia , Rabia , Humanos , Animales , Masculino , Femenino , Mapaches , Rabia/epidemiología , Rabia/veterinaria , Rabia/prevención & control , Animales Salvajes , Brotes de Enfermedades/prevención & control
16.
Nat Commun ; 14(1): 2192, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37185332

RESUMEN

Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.


Asunto(s)
Melanoma , Proteoglicanos , Humanos , Ratones , Animales , Proteoglicanos/metabolismo , Antígenos , Proteoglicanos Tipo Condroitín Sulfato , Melanoma/metabolismo , Anticuerpos Monoclonales/farmacología , Inmunoglobulina E , Microambiente Tumoral
18.
Cell Rep ; 42(1): 112014, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36681898

RESUMEN

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Etnicidad , Epítopos , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Pruebas de Neutralización
19.
Diseases ; 10(4)2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36547207

RESUMEN

The reservoir for zoonotic o'nyong-nyong virus (ONNV) has remained unknown since this virus was first recognized in Uganda in 1959. Building on existing evidence for mosquito blood-feeding on various frugivorous bat species in Uganda, and seroprevalence for arboviruses among bats in Uganda, we sought to assess if serum samples collected from bats in Uganda demonstrated evidence of exposure to ONNV or the closely related zoonotic chikungunya virus (CHIKV). In total, 652 serum samples collected from six bat species were tested by plaque reduction neutralization test (PRNT) for neutralizing antibodies against ONNV and CHIKV. Forty out of 303 (13.2%) Egyptian rousettes from Maramagambo Forest and 1/13 (8%) little free-tailed bats from Banga Nakiwogo, Entebbe contained neutralizing antibodies against ONNV. In addition, 2/303 (0.7%) of these Egyptian rousettes contained neutralizing antibodies to CHIKV, and 8/303 (2.6%) contained neutralizing antibodies that were nonspecifically reactive to alphaviruses. These data support the interepidemic circulation of ONNV and CHIKV in Uganda, although Egyptian rousette bats are unlikely to serve as reservoirs for these viruses given the inconsistent occurrence of antibody-positive bats.

20.
Viruses ; 14(5)2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-35632587

RESUMEN

Rabies is an ancient lethal scourge that has plagued humankind for centuries [...].


Asunto(s)
Virus de la Rabia , Rabia , Humanos , Rabia/prevención & control
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