RESUMO
To understand susceptibility of wild California sea lions and Northern elephant seals to influenza A virus (IAV), we developed an ex vivo respiratory explant model and used it to compare infection kinetics for multiple IAV subtypes. We first established the approach using explants from colonized rhesus macaques, a model for human IAV. Trachea, bronchi, and lungs from 11 California sea lions, 2 Northern elephant seals, and 10 rhesus macaques were inoculated within 24 h postmortem with 6 strains representing 4 IAV subtypes. Explants from the 3 species showed similar IAV infection kinetics, with peak viral titers 48 to 72 h post-inoculation that increased by 2 to 4 log10 PFU/explant relative to the inoculum. Immunohistochemistry localized IAV infection to apical epithelial cells. These results demonstrate that respiratory tissue explants from wild marine mammals support IAV infection. In the absence of the ability to perform experimental infections of marine mammals, this ex vivo culture of respiratory tissues mirrors the in vivo environment and serves as a tool to study IAV susceptibility, host range, and tissue tropism. IMPORTANCE Although influenza A virus can infect marine mammals, a dearth of marine mammal cell lines and ethical and logistical challenges prohibiting experimental infections of living marine mammals mean that little is known about IAV infection kinetics in these species. We circumvented these limitations by adapting a respiratory tract explant model first to establish the approach with rhesus macaques and then for use with explants from wild marine mammals euthanized for nonrespiratory medical conditions. We observed that multiple strains representing 4 IAV subtypes infected trachea, bronchi, and lungs of macaques and marine mammals with variable peak titers and kinetics. This ex vivo model can define infection dynamics for IAV in marine mammals. Further, use of explants from animals euthanized for other reasons reduces use of animals in research.
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Vírus da Influenza A/fisiologia , Infecções por Orthomyxoviridae/virologia , Infecções Respiratórias/virologia , Animais , Cães , Especificidade de Hospedeiro , Vírus da Influenza A/classificação , Cinética , Macaca mulatta , Células Madin Darby de Rim Canino , Modelos Biológicos , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Leões-Marinhos , Focas Verdadeiras , Especificidade da Espécie , Carga Viral , Tropismo ViralRESUMO
The majority of vector-borne disease cases reported annually in the United States are caused by pathogens spread by the blacklegged tick, Ixodes scapularis. The number and geographic distribution of cases have increased as the geographic range and abundance of the tick have expanded in recent decades. A large proportion of Lyme disease and other I. scapularis-borne diseases are associated with nymphal tick bites; likelihood of such bites generally increases with increasing nymphal densities. National tick surveillance was initiated in 2018 to track changes in the distribution and abundance of medically important ticks at the county spatial scale throughout the United States. Tick surveillance records, including historical data collected prior to the initiation of the national program, are collated in the ArboNET Tick Module database. Through exploration of ArboNET Tick Module data, we found that efforts to quantify the density of host-seeking I. scapularis nymphs (DON) were unevenly distributed among geographic regions with the greatest proportion of counties sampled in the Northeast and Upper Midwest. Submissions covering tick collections from 2004 through 2022 revealed extensive variation in DON estimates at collection site, county, state, and regional spatial scales. Throughout the entire study period, county DON estimates ranged from 0.0 to 488.5 nymphs/1,000 m2 . Although substantial variation was recorded within regions, DON estimates were greatest in the Northeast, Upper Midwest, and northern states within the Southeast regions (Virginia and North Carolina); densities were intermediate in the Ohio Valley and very low in the South and Northern Rockies and Plains regions. The proportion of counties classified as moderate or high DON was lower in the Northeast, Ohio Valley, and Southeast regions during the 2004 through 2017 time period (prior to initiation of the national tick surveillance program) compared to 2018 through 2022; DON estimates remained similarly low between these time periods in the South and the Northern Rockies and Plains regions. Despite the limitations described herein, the ArboNET Tick Module provides useful data for tracking changes in acarological risk across multiple geographic scales and long periods of time.
Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Picadas de Carrapatos , Estados Unidos/epidemiologia , Animais , Doença de Lyme/epidemiologia , Meio Ambiente , NinfaRESUMO
Vector-borne disease incidence and burden are on the rise. Weather events and climate patterns are known to influence vector populations and disease distribution and incidence. Changes in weather trends and climatic factors can shift seasonal vector activity and host behavior, thus altering pathogen distribution and introducing diseases to new geographic regions. With the upward trend in global temperature, changes in the incidence and distribution of disease vectors possibly linked to climate change have been documented. Forecasting and modeling efforts are valuable for incorporating climate into predicting changes in vector and vector-borne disease distribution. These predictions serve to optimize disease outbreak preparedness and response. The purpose of this scoping review was to describe the use of climate data in vector-borne disease prediction in North America between 2000 and 2022. The most investigated diseases were West Nile virus infection, Lyme disease, and dengue. The uneven geographical distribution of publications could suggest regional differences in the availability of surveillance data required for vector-borne disease predictions and forecasts across the United States, Canada, and Mexico. Studies incorporated environmental data from ground-based sources, satellite data, previously existing data, and field-collected data. While environmental data such as meteorological and topographic factors were well-represented, further research is warranted to ascertain if relationships with less common variables, such as oceanographic characteristics and drought, hold among various vector populations and throughout wider geographical areas. This review provides a catalogue of recently used climatic data that can inform future assessments of the value of such data in vector-borne disease models.
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Mudança Climática , Doenças Transmitidas por Vetores , Doenças Transmitidas por Vetores/epidemiologia , Doenças Transmitidas por Vetores/transmissão , América do Norte/epidemiologia , Animais , Humanos , Modelos Biológicos , PrevisõesRESUMO
BACKGROUND: Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens. The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs). DISCUSSION: Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets. This could partly explain why transmission in poultry populations has not been eliminated more broadly. We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004-2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission. We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets. SUMMARY: Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public. These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence. These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission.
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Vírus da Influenza A/fisiologia , Influenza Aviária/virologia , Influenza Humana/prevenção & controle , Animais , China , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Aviária/prevenção & controle , Influenza Aviária/transmissão , Influenza Humana/virologia , Pandemias , Aves DomésticasRESUMO
The majority of vector-borne disease cases reported in the United States (U.S.) are caused by pathogens spread by the blacklegged tick, Ixodes scapularis. In recent decades, the geographic ranges of the tick and its associated human pathogens have expanded, putting an increasing number of communities at risk for tick-borne infections. In 2018, the U.S. Centers for Disease Control and Prevention (CDC) initiated a national tick surveillance program to monitor changes in the distribution and abundance of ticks and the presence and prevalence of human pathogens in them. We assessed the geographical representativeness of prevalence data submitted to CDC as part of the national tick surveillance effort. We describe county, state, and regional variation in the prevalence of five human pathogens (Borrelia burgdorferi sensu stricto (s.s.), Borrelia mayonii, Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia microti) in host-seeking I. scapularis and I. pacificus nymphs and adults. Although I. scapularis and I. pacificus are widely distributed in the eastern and western U.S., respectively, pathogen prevalence was estimated predominantly in ticks collected in the Northeast, Ohio Valley, and Upper Midwest regions, where human Lyme disease cases are most commonly reported. Within these regions, we found that state and regional estimates of pathogen prevalence generally reached predictable and stable levels, but variation in prevalence estimates at the sub-state level was considerable. Borrelia burgdorferi s.s. was the most prevalent and widespread pathogen detected. Borrelia miyamotoi and A. phagocytophilum shared a similarly broad geographic range, but were consistently detected at much lower prevalence compared with B. burgdorferi s.s. Babesia microti was detected at similar prevalence to A. phagocytophilum, where both pathogens co-occurred, but was reported over a much more limited geographic range compared with A. phagocytophilum or B. burgdorferi s.s. Borrelia mayonii was identified at very low prevalence with a focal distribution within the Upper Midwest. National assessments of risk for tick-borne diseases need to be improved through collection and testing of ticks in currently under-represented regions, including the West, South, Southeast, and eastern Plains states.
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Babesia microti , Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Borrelia , Ixodes , Adulto , Animais , Humanos , Estados Unidos/epidemiologia , PrevalênciaRESUMO
Ivermectin (IVM)-treated birds provide the potential for targeted control of Culex mosquitoes to reduce West Nile virus (WNV) transmission. Ingestion of IVM increases mosquito mortality, which could reduce WNV transmission from birds to humans and in enzootic maintenance cycles affecting predominantly bird-feeding mosquitoes and from birds to humans. This strategy might also provide an alternative method for WNV control that is less hampered by insecticide resistance and the logistics of large-scale pesticide applications. Through a combination of field studies and modeling, we assessed the feasibility and impact of deploying IVM-treated birdfeed in residential neighborhoods to reduce WNV transmission. We first tracked 105 birds using radio telemetry and radio frequency identification to monitor their feeder usage and locations of nocturnal roosts in relation to five feeder sites in a neighborhood in Fort Collins, Colorado. Using these results, we then modified a compartmental model of WNV transmission to account for the impact of IVM on mosquito mortality and spatial movement of birds and mosquitoes on the neighborhood level. We found that, while the number of treated lots in a neighborhood strongly influenced the total transmission potential, the arrangement of treated lots in a neighborhood had little effect. Increasing the proportion of treated birds, regardless of the WNV competency status, resulted in a larger reduction in infection dynamics than only treating competent birds. Taken together, model results indicate that deployment of IVM-treated feeders could reduce local transmission throughout the WNV season, including reducing the enzootic transmission prior to the onset of human infections, with high spatial coverage and rates of IVM-induced mortality in mosquitoes. To improve predictions, more work is needed to refine estimates of daily mosquito movement in urban areas and rates of IVM-induced mortality. Our results can guide future field trials of this control strategy.
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Culex , Culicidae , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Animais , Humanos , Febre do Nilo Ocidental/prevenção & controle , Febre do Nilo Ocidental/veterinária , Ivermectina/farmacologia , Ivermectina/uso terapêutico , AvesRESUMO
Tick-borne diseases continue to threaten human health across the United States. Both active and passive tick surveillance can complement human case surveillance, providing spatio-temporal information on when and where humans are at risk for encounters with ticks and tick-borne pathogens. However, little work has been done to assess the concordance of the acarological risk metrics from each surveillance method. We used data on Ixodes scapularis and its associated human pathogens from Connecticut (2019-2021) collected through active collections (drag sampling) or passive submissions from the public to compare county estimates of tick and pathogen presence, infection prevalence, and tick abundance by life stage. Between the surveillance strategies, we found complete agreement in estimates of tick and pathogen presence, high concordance in infection prevalence estimates for Anaplasma phagocytophilum, Borrelia burgdorferi sensu stricto, and Babesia microti, but no consistent relationships between actively and passively derived estimates of tick abundance or abundance of infected ticks by life stage. We also compared nymphal metrics (i.e., pathogen prevalence in nymphs, nymphal abundance, and abundance of infected nymphs) with reported incidence of Lyme disease, anaplasmosis, and babesiosis, but did not find any consistent relationships with any of these metrics. The small spatial and temporal scale for which we had consistently collected active and passive data limited our ability to find significant relationships. Findings are likely to differ if examined across a broader spatial or temporal coverage with greater variation in acarological and epidemiological outcomes. Our results indicate similar outcomes between some actively and passively derived tick surveillance metrics (tick and pathogen presence, pathogen prevalence), but comparisons were variable for abundance estimates.
Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Doenças Transmitidas por Carrapatos , Animais , Estados Unidos/epidemiologia , Humanos , Incidência , Doenças Transmitidas por Carrapatos/epidemiologia , Doença de Lyme/epidemiologia , NinfaRESUMO
West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental United States (CONUS). Spatial heterogeneity in historical incidence, environmental factors, and complex ecology make prediction of spatiotemporal variation in WNV transmission challenging. Machine learning provides promising tools for identification of important variables in such situations. To predict annual WNV neuroinvasive disease (WNND) cases in CONUS (2015-2021), we fitted 10 probabilistic models with variation in complexity from naïve to machine learning algorithm and an ensemble. We made predictions in each of nine climate regions on a hexagonal grid and evaluated each model's predictive accuracy. Using the machine learning models (random forest and neural network), we identified the relative importance and variation in ranking of predictors (historical WNND cases, climate anomalies, human demographics, and land use) across regions. We found that historical WNND cases and population density were among the most important factors while anomalies in temperature and precipitation often had relatively low importance. While the relative performance of each model varied across climatic regions, the magnitude of difference between models was small. All models except the naïve model had non-significant differences in performance relative to the baseline model (negative binomial model fit per hexagon). No model, including the ensemble or more complex machine learning models, outperformed models based on historical case counts on the hexagon or region level; these models are good forecasting benchmarks. Further work is needed to assess if predictive capacity can be improved beyond that of these historical baselines.
RESUMO
BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases).
Assuntos
Culicidae , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Animais , Humanos , Febre do Nilo Ocidental/epidemiologia , Saúde Pública , Clima , Surtos de Doenças , PrevisõesRESUMO
BACKGROUND: Vector control strategies typically rely on pesticides to target mosquitoes involved in enzootic and zoonotic transmission of West Nile virus (WNV). Nevertheless, increasing insecticide resistance and a desire to reduce pesticide usage provide the impetus for developing alternative strategies. Ivermectin (IVM), an antiparasitic drug which is widely used in human and veterinary medicine, is a potential alternative for targeted control because Culex mosquitoes experience increased mortality following ingestion of IVM in bloodmeals. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a randomized field trial to investigate the impact of treating backyard chicken flocks with IVM in urban neighborhoods across Davis, California on mosquito populations and WNV transmission dynamics. We observed a significant reduction in WNV seroconversions in treated vs. untreated chickens, suggesting a reduction in WNV transmission intensity around treated flocks. We also detected a reduction in parity rates of Cx. tarsalis near treated vs. untreated flocks and increased mortality in wild mosquitoes following a bloodmeal on treated chickens (IVM serum concentration > 5ng/mL) vs. chickens with IVM serum concentrations < 5 ng/mL. However, we did not find a significant difference in abundance or infection prevalence in mosquitoes between treatment groups associated with the reductions in seroconversions. Mosquito immigration from surrounding larval habitat, relatively low WNV activity in the study area, and variable IVM serum concentrations likely contributed to uncertainty about the impact. CONCLUSIONS/SIGNIFICANCE: Taken together, our results point to a reduction in WNV transmission due to the impact of IVM on Culex mosquito populations and support the ongoing investigation of oral administration of IVM to wild birds for local control of WNV transmission, although further work is needed to optimize dosing and understand effects on entomological endpoints.
Assuntos
Culex , Culicidae , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Animais , Galinhas , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Mosquitos Vetores , Febre do Nilo Ocidental/tratamento farmacológico , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/veterináriaRESUMO
BACKGROUND: Aerial applications of insecticides that target adult mosquitoes are widely used to reduce transmission of West Nile virus to humans during periods of epidemic risk. However, estimates of the reduction in abundance following these treatments typically focus on single events, rely on pre-defined, untreated control sites and can vary widely due to stochastic variation in population dynamics and trapping success unrelated to the treatment. METHODS: To overcome these limitations, we developed generalized additive models fitted to mosquito surveillance data collected from CO2-baited traps in Sacramento and Yolo counties, California from 2006 to 2017. The models accounted for the expected spatial and temporal trends in the abundance of adult female Culex (Cx.) tarsalis and Cx. pipiens in the absence of aerial spraying. Estimates for the magnitude of deviation from baseline abundance following aerial spray events were obtained from the models. RESULTS: At 1-week post-treatment with full spatial coverage of the trapping area by pyrethroid or pyrethrin products, Cx. pipiens abundance was reduced by a mean of 52.4% (95% confidence intrval [CI] - 65.6, - 36.5%) while the use of at least one organophosphate pesticide resulted in a mean reduction of 76.2% (95% CI - 82.8, - 67.9%). For Cx. tarsalis, at 1-week post-treatment with full coverage there was a reduction in abundance of 30.7% (95% CI - 54.5, 2.5%). Pesticide class was not a significant factor contributing to the reduction. In comparison, repetition of spraying over three to four consecutive weeks resulted in similar estimates for Cx. pipiens and estimates of somewhat smaller magnitude for Cx. tarsalis. CONCLUSIONS: Aerial adulticides are effective for achieving a rapid short-term reduction of the abundance of the primary West Nile virus vectors, Cx. tarsalis and Cx. pipiens. A larger magnitude of reduction was estimated in Cx. pipiens, possibly due to the species' focal distribution. Effects of aerial sprays on Cx. tarsalis populations are likely modulated by the species' large dispersal ability, population sizes and vast productive larval habitat present in the study area. Our modeling approach provides a new way to estimate effects of public health pesticides on vector populations using routinely collected observational data and accounting for spatio-temporal trends and contextual factors like weather and habitat. This approach does not require pre-selected control sites and expands upon past studies that have focused on the effects of individual aerial treatment events.
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Culex/efeitos dos fármacos , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Distribuição Animal , Animais , Culex/crescimento & desenvolvimento , Ecossistema , Feminino , Humanos , Masculino , Modelos Biológicos , Controle de Mosquitos/instrumentação , Mosquitos Vetores/crescimento & desenvolvimento , Densidade Demográfica , Dinâmica Populacional , Piretrinas/farmacologia , Estações do Ano , Análise Espaço-Temporal , Febre do Nilo Ocidental/transmissão , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/fisiologiaRESUMO
West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.
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Tomada de Decisões , Modelos Biológicos , Administração em Saúde Pública , Febre do Nilo Ocidental/prevenção & controle , HumanosRESUMO
Bioassays of native cervid hosts have established the presence of infectious chronic wasting disease (CWD) prions in saliva, blood, urine, and feces of clinically diseased and pre-clinical infected deer. The intra-host trafficking of prions from the time of initial infection to shedding has been less well defined. We created a discrete-time compartmentalized model to simulate the misfolding catalysis, trafficking, and shedding of infectious prions throughout the organ systems of CWD-infected cervids. Using parameter values derived from experimental infections of North American deer (Odocoileus spp.), the exponential-based model predicts prion deposition over time with: 1) nervous tissues containing the highest deposition of prions at 20 months post-infection and 2) excreted fluids containing low levels of prions throughout infection with the highest numbers of prions predicted to be shed in saliva and feces (as high as 10 lethal doses (1.34 × 1029 prions) in 11-15 months). These findings are comparable to prion deposition described in literature as assayed by conventional and ultrasensitive amplification assays. The comparison of our model to published data suggests that highly sensitive assays (sPMCA, RT-QuIC, and bioassay) are appropriate for early prion detection in bodily fluids and secretions. The model provides a view of intra-host prion catalysis leading to pre-clinical shedding and provides a framework for continued development of antemortem diagnostic methods.