Perspectives on the Changing Landscape of Epizootic Hemorrhagic Disease Virus Control

Epizootic hemorrhagic disease (EHD) is an insect-transmitted viral disease of wild and domestic ruminants. It was first described following a 1955 epizootic in North American white-tailed deer (Odocoileus virginianus), a species which is highly susceptible to the causative agent of EHD, epizootic hemorrhagic disease virus (EHDV). EHDV has been detected globally across tropical and temperate regions, largely corresponding to the presence of Culicoides spp. biting midges which transmit the virus between ruminant hosts. It regularly causes high morbidity and mortality in wild and captive deer populations in endemic areas during epizootics. Although cattle historically have been less susceptible to EHDV, reports of clinical disease in cattle have increased in the past two decades. There is a pressing need to identify new methods to prevent and mitigate outbreaks and reduce the considerable impacts of EHDV on livestock and wildlife. This review discusses recent research advancements towards the control of EHDV, including the development of new investigative tools and progress in basic and applied research focused on virus detection, disease mitigation, and vector control. The potential impacts and implications of these advancements on EHD management are also discussed.

A Mortality-Based Description of EHDV and BTV Prevalence in Farmed White-Tailed Deer (Odocoileus virginianus) in Florida, USA

Hemorrhagic disease (HD) caused by bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) is the most important viral disease of farmed and wild white-tailed deer (WTD; Odocoileus virginianus) and can cause substantial mortality in susceptible hosts. Captive cervid farming is an emerging industry in Florida, an HD-enzootic region. Morbidity and mortality due to HD are major concerns among deer farmers, but the impact of HD on Florida’s cervid farming industry is unknown. Our primary objective was to determine the prevalence of epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV) among WTD submitted to the University of Florida Institute of Food and Agricultural Sciences Cervidae Health Research Initiative (CHeRI) for post-mortem diagnostics. Our secondary objectives were to identify the predominant circulating EHDV serotypes during each sampling year and to determine the age class with the greatest proportion of EHDV- and BTV-positive post-mortem specimens. From 2016 to 2020, spleen samples from 539 farmed WTD with unexplained mortality were tested for the presence of EHDV and BTV by RT-qPCR. Overall, the prevalence of EHDV, BTV, or EHDV/BTV coinfection was 26%, 16%, and 10%, respectively, and 44% of deer (237/539) were diagnosed with HD by RT-qPCR. The predominant circulating EHDV serotype varied by year. Overall, EHDV-2 was the most commonly identified serotype (55% of PCR-positive cases), and EHDV-1 was the least frequently identified serotype (16% of PCR-positive cases). The greatest proportion of EHDV/BTV positives among mortality cases was observed in young WTD aged 3–6 months (50%–82% positive). There was a significant difference in the prevalence of EHDV/BTV by age when comparing specimens from WTD over 1 year old (p = 0.029, n = 527). Among these samples, the number of reported mortalities and the prevalence of EHDV/BTV were highest in yearling animals (56%). These data provide the first estimate of EHDV and BTV prevalence and virus serotypes among farmed WTD in Florida, identify the WTD age groups with the greatest proportions of EHDV- and BTV-positive specimens, and suggest that HD caused by these two viruses may be a major source of mortality challenging the captive cervid farming industry in Florida.

Bluetongue and Epizootic Hemorrhagic Disease in the United States of America at the Wildlife–Livestock Interface

Bluetongue (BT) and epizootic hemorrhagic disease (EHD) cases have increased worldwide, causing significant economic loss to ruminant livestock production and detrimental effects to susceptible wildlife populations. In recent decades, hemorrhagic disease cases have been reported over expanding geographic areas in the United States. Effective BT and EHD prevention and control strategies for livestock and monitoring of these diseases in wildlife populations depend on an accurate understanding of the distribution of BT and EHD viruses in domestic and wild ruminants and their vectors, the Culicoides biting midges that transmit them. However, national maps showing the distribution of BT and EHD viruses and the presence of Culicoides vectors are incomplete or not available at all. Thus, efforts to accurately describe the potential risk of these viruses on ruminant populations are obstructed by the lack of systematic and routine surveillance of their hosts and vectors. In this review, we: (1) outline animal health impacts of BT and EHD in the USA; (2) describe current knowledge of the distribution and abundance of BT and EHD and their vectors in the USA; and (3) highlight the importance of disease (BT and EHD) and vector surveillance for ruminant populations.

A Duplex Fluorescent Microsphere Immunoassay for Detection of Bluetongue and Epizootic Hemorrhagic Disease Virus Antibodies in Cattle Sera

Bluetongue virus (BTV) causes internationally reportable hemorrhagic disease in cattle, sheep, and white-tailed deer. The closely related, and often co-circulating, epizootic hemorrhagic disease virus causes a clinically similar devastating disease in white-tailed deer, with increasing levels of disease in cattle in the past 10 years. Transmitted by Culicoides biting midges, together, they constitute constant disease threats to the livelihood of livestock owners. In cattle, serious economic impacts result from decreased animal production, but most significantly from trade regulations. For effective disease surveillance and accurate trade regulation implementation, rapid, sensitive assays that can detect exposure of cattle to BTV and/or EHDV are needed. We describe the development and validation of a duplex fluorescent microsphere immunoassay (FMIA) to simultaneously detect and differentiate antibodies to BTV and EHDV in a single bovine serum sample. Performance of the duplex FMIA for detection and differentiation of BTV and EHDV serogroup antibodies was comparable, with higher sensitivity than commercially available single-plex competitive enzyme-linked immunosorbent assays (cELISA) for detection of each virus antibody separately. The FMIA adds to the currently available diagnostic tools for hemorrhagic orbiviral diseases in cattle as a sensitive, specific assay, with the benefits of serogroup differentiation in a single serum sample, and multiplexing flexibility in a high-throughput platform.

Vector Competence of Florida Culicoides insignis (Diptera: Ceratopogonidae) for Epizootic Hemorrhagic Disease Virus Serotype-2

Epizootic hemorrhagic disease virus (EHDV; family Reoviridae, genus Orbivirus) is an arthropod-borne virus of ungulates, primarily white-tailed deer in North America. Culicoides sonorensis, the only confirmed North American vector of EHDV, is rarely collected from Florida despite annual virus outbreaks. Culicoides insignis is an abundant species in Florida and is also a confirmed vector of the closely related Bluetongue virus. In this study, oral challenge of C. insignis was performed to determine vector competence for EHDV serotype-2. Field-collected female midges were provided bovine blood spiked with three different titers of EHDV-2 (5.05, 4.00, or 2.94 log10PFUe/mL). After an incubation period of 10 days or after death, bodies and legs were collected. Saliva was collected daily from all females from 3 days post feeding until their death using honey card assays. All samples were tested for EHDV RNA using RT-qPCR. Our results suggest that C. insignis is a weakly competent vector of EHDV-2 that can support a transmissible infection when it ingests a high virus titer (29% of midges had virus positive saliva when infected at 5.05 log10PFUe/mL), but not lower virus titers. Nevertheless, due to the high density of this species, particularly in peninsular Florida, it is likely that C. insignis plays a role in the transmission of EHDV-2.

Resource Selection by Wild and Ranched White-Tailed Deer (Odocoileus virginianus) during the Epizootic Hemorrhagic Disease Virus (EHDV) Transmission Season in Florida

Epizootic hemorrhagic disease virus (EHDV) causes serious disease in wild and privately ranched white-tailed deer (Odocoileusvirginianus) in the United States. In Florida, there is high EHDV prevalence, yet no treatments. There are few management strategies for the disease due to limited knowledge of virus–vector–host interactions. We conducted a telemetry study on white-tailed deer to examine resource use by wild and ranched animals in the Florida panhandle during the 2016 transmission risk period. We built generalized linear mixed models (GLMMs) to estimate resource selection and map habitat preferences for wild and ranched deer in the study area to reveal how second-order selection may relate to higher disease prevalence in ranched deer. Wild deer preferred areas closer to tertiary roads and supplementary food sources but farther from permanent water. Ranched deer selected bottomland mixed forest and areas closer to tertiary roads, supplementary food sources, and permanent water. Ranched deer behaviors may increase the likelihood of EHDV vector encounters, as these deer selected preferred habitats of several putative vector species, which may increase vector blood meal success and viral transmission risk. Disparate resource selection behaviors may be a factor in observed differential EHDV exposure risk between ranched and wild white-tailed deer in Florida.