A review of chronic wasting disease (CWD) spread, surveillance, and control in the United States captive cervid industry.

Chronic wasting disease (CWD) is a fatal prion disease of the family Cervidae that circulates in both wild and captive cervid populations. This disease threatens the health and economic viability of the captive cervid industry, which raises cervids in contained spaces for purposes such as hunting and breeding. Given the high transmissibility and long incubation period of CWD, the introduction and propagation of the infectious prion protein within and between captive cervid farms could be devastating to individual facilities and to the industry as a whole. Despite this risk, there does not yet exist a literature review that summarizes the scientific knowledge, to date, about CWD spread, surveillance, or control measures. Our review, which focused on peer reviewed, primary research conducted in the United States, sought to address this need by searching Google Scholar, Scopus, and Web of Science with a five-term keyword string containing terms related to the (1) location, (2) species affected, (3) disease, (4) captive cervid industry, and (5) topic of focus. Between the three databases, there were 190 articles that were selected for further examination. Those articles were then read to determine if they were about CWD spread, surveillance, and/or control in captive cervid facilities. The 22 articles that met these inclusion criteria were evaluated in detail and discussed, with recommendations for future collaborative work between captive cervid owners, government agencies, and researchers. This work will help to address, inform, and mitigate the rising problem of CWD spread and establishment.

Detection of prions from spiked and free-ranging carnivore feces.

Chronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting wild and captive cervids. Although experimental feeding studies have demonstrated prions in feces of crows (Corvus brachyrhynchos), coyotes (Canis latrans), and cougars (Puma concolor), the role of scavengers and predators in CWD epidemiology remains poorly understood. Here we applied the real-time quaking-induced conversion (RT-QuIC) assay to detect PrPCWD in feces from cervid consumers, to advance surveillance approaches, which could be used to improve disease research and adaptive management of CWD. We assessed recovery and detection of PrPCWD by experimental spiking of PrPCWD into carnivore feces from 9 species sourced from CWD-free populations or captive facilities. We then applied this technique to detect PrPCWD from feces of predators and scavengers in free-ranging populations. Our results demonstrate that spiked PrPCWD is detectable from feces of free-ranging mammalian and avian carnivores using RT-QuIC. Results show that PrPCWD acquired in natural settings is detectable in feces from free-ranging carnivores, and that PrPCWD rates of detection in carnivore feces reflect relative prevalence estimates observed in the corresponding cervid populations. This study adapts an important diagnostic tool for CWD, allowing investigation of the epidemiology of CWD at the community-level.

Ecology and Chronic Wasting Disease Epidemiology Shape Prion Protein Gene Variation in Rocky Mountain Elk (Cervus elaphus nelsoni).

As chronic wasting disease (CWD) continues to spread across North America, the relationship between CWD and host genetics has become of interest. In Rocky Mountain elk (Cervus elaphus nelsoni), one or two copies of a leucine allele at codon 132 of the prion protein gene (132L*) has been shown to prolong the incubation period of CWD. Our study examined the relationship between CWD epidemiology and codon 132 evolution in elk from Wyoming, USA, from 2011 to 2018. Using PCR and Sanger sequencing, we genotyped 997 elk and assessed the relationship between genotype and CWD prevalence estimated from surveillance data. Using logistic regression, we showed that each 1% increase in CWD prevalence is associated with a 9.6% increase in the odds that an elk would have at least one copy of leucine at codon 132. In some regions, however, 132L* variants were found in the absence of CWD, indicating that evolutionary and epidemiologic patterns can be heterogeneous across space and time. We also provide evidence that naturally occurring CWD is not rare in 132L* elk, which merits the study of shedding kinetics in 132L* elk and the influence of genotype on CWD strain diversity. The management implications of cervid adaptations to CWD are difficult to predict. Studies that investigate the degree to which evolutionary outcomes are shaped by host spatial structure can provide useful epidemiologic insight, which can in turn aid management by informing scale and extent of mitigation actions.

Heterogeneity of pathological prion protein accumulation in the brain of moose (Alces alces) from Norway, Sweden and Finland with chronic wasting disease.

Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrPC) into the pathological prion protein (PrPSc). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway. The subsequent intensive CWD surveillance launched in cervids resulted in the detection of CWD in moose (Alces alces), with 11 cases in Norway, 3 in Finland and 4 in Sweden. These moose cases differ considerably from CWD cases in North American and reindeer in Norway, as PrPSc was detectable in the brain but not in lymphoid tissues. These facts suggest the occurrence of a new type of CWD. Here, we show some immunohistochemical features that are clearly different from CWD cases in North American and Norwegian reindeer. Further, the different types of PrPSc deposits found among moose demonstrate strong variations between the cases, supporting the postulation that these cases could carry multiple strains of CWD.

Herd-level risk factors associated with chronic wasting disease-positive herd status in Minnesota, Pennsylvania, and Wisconsin cervid herds.

The objective of this study was to evaluate risks related to introduction of Chronic Wasting Disease (CWD) to farmed cervid herds in Minnesota (MN), Pennsylvania (PA), and Wisconsin (WI). This was the first study to evaluate risk factors related to multiple pathways of CWD transmission to farmed cervid herds. Participating herds in this case-control study included 22 case and 49 control herds identified through participation in the respective mandatory State CWD herd program. Data was voluntarily collected from white-tailed deer (WTD) study herds using a questionnaire and state animal health agency databases. Univariable analyses identified associations between CWD-positive herds and variables representing different transmission pathways, including direct contact with infected farmed cervids (imported from a herd that later tested positive for CWD) odds ratio (OR):7.16, 95 % confidence intervals (CI):1.64-31.21 and indirect contact with infected wild cervids (access of domestic cats to pens or feed storage area) OR:4.07, 95 % CI:1.35-12.26, observed evidence of mammalian scavengers inside or outside of fenceline in the previous 12 months OR:6.55, 95 % CI:1.37-31.32, ≤ 5 km distance to nearest detected CWD-positive wild cervid OR:3.08, 95 % CI:1.01-9.39, forested area crosses the perimeter fenceline OR:3.54, 95 % CI:1.13-11.11, ≤ 0.3 m distance of water source to fenceline OR:4.71, 95 % CI:1.60-13.83, and water source shared with wild cervids (running or standing water) OR:4.17, 95 % CI:1.34-12.92. Three variables from univariable analyses that represented different biological transmission pathways were placed in a Firth's penalized maximum likelihood multivariable logistic regression to evaluate associations between transmission pathway and CWD herd infection status. For the issue of low sample size and overfitting, 95 % CIs for estimated coefficients for the three variables were computed via bootstrapping of 10,000 independent bootstrap samples. The three biological variables were significantly associated with herd CWD infection status: imported cervids from a herd that later tested positive for CWD (OR:5.63; 95 % CI:1.1-28.2), ≤ 0.3 m distance of cervid water source to perimeter fenceline (OR:4.83; 95 % CI:1.5-16.1), and ≤ 5 km distance to nearest detected CWD-positive wild cervid (OR:4.10; 95 % CI:1.1-15.2). The risk factors associated with CWD herd status identified in this study indicated the importance of transmission through direct contact pathways with infected cervid herds (introduction of cervids from herds later identified as CWD-infected) and indirect contact pathways with infected wild cervids that could be related to other animals through the perimeter fence. Further studies are needed to confirm and clarify understanding of indirect pathways to allow development of improved biosecurity practices to prevent CWD introduction to cervid herds.

Canine detection of chronic wasting disease (CWD) in laboratory and field settings.

Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy that affects both free-ranging and farmed cervid species, including mule deer, white-tailed deer, and elk (Odocoileus hemionus, Odocoileus virginianus, and Cervus canadensis). Due to the long incubation period and variability of clinical signs, CWD can expand and spread to new areas before they reach diagnostically detectable levels. Antemortem testing methods currently available can be difficult to obtain and to be applied to the large numbers required for adequate surveillance. However, key volatile biomarkers could be harnessed for non-invasive antemortem surveillance. Detection dogs are the most effective tool currently available for volatile detection; dogs can effectively complete wildlife surveys at rates surpassing that of humans. This study is the first to demonstrate that trained detection dogs can be used as an antemortem test for CWD. First, we trained three dogs to differentiate between CWD-positive and CWD-negative white-tailed deer faeces in a laboratory setting. Dogs spent significantly more time at the positive sample than the negative samples, suggesting that they differentiated between the positive and negative volatile signatures. We then trained the same dogs to search for CWD-positive faecal samples in a more naturalistic field setting. In the field, dogs found 8/11 CWD-positive samples and had an average false detection rate of 13%. These results suggest that dogs can be trained to differentiate CWD-positive faeces from CWD-negative faeces in both laboratory and field settings. Future studies will compare canine accuracy to other antemortem methods, as well as improved canine training methods.

Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland.

Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investigate the properties of prions causing newly emergent CWD in moose in Finland. Although CWD prions from Finland and Norway moose had comparable responses to primary structural differences at residue 226, other distinctive criteria, including transmission kinetics, patterns of neuronal degeneration, and conformational features of prions generated in the brains of diseased mice, demonstrated that the strain properties of Finland moose CWD prions are different from those previously characterized in Norway CWD. Our findings add to a growing body of evidence for a diverse portfolio of emergent strains in Nordic countries that are etiologically distinct from the comparatively consistent strain profile of North America CWD.

The economic costs of chronic wasting disease in the United States.

Cervids are economically important to a wide range of stakeholders and rights holders in the United States. The continued expansion of chronic wasting disease (CWD), a fatal neurodegenerative disease affecting wild and farmed cervids, poses a direct and indirect threat to state and federal government agency operations and cervid related economic activity. However, the scale of this disease's direct economic costs is largely unknown. I synthesized existing publicly available data and stakeholder-provided data to estimate CWD's costs within the continental United States. Federal government agencies collectively spent over $284.1 million on CWD-related efforts between 2000 and 2021, with $203.6 million of this total being spent by the U.S. Department of Agriculture's Animal and Plant Health Inspection Service. In fiscal year 2020, state natural resources agencies and state agriculture/animal health agencies spent over $25.5 million and $2.9 million, respectively, on CWD-related work. Natural resources agencies in states with known CWD cases spent over 8 times as much on CWD as agencies from states with no known cases. The farmed cervid industry spent at least $307,950 on CWD sampling in 2020, though a lack of available data prevented a complete assessment of costs to this industry. Based on limited data, CWD's economic effects on the hunting industry (i.e., outfitters and guides, companies leasing land to cervid hunters), may be negligible at this time. Overall, however, the realized economic costs of CWD appear considerable, and it is likely that the number of stakeholders financially affected by this disease and regulations meant to stem its spread will continue to grow. By understanding the current economic impacts of CWD, we are better positioned to assess the costs and benefits of investments in management and research and to understand the magnitude of this disease's broader societal impacts.

Impact of landcover composition and density of localized deer culling sites on chronic wasting disease prevalence.

Chronic Wasting Disease (CWD), the prion disease of the Cervidae family, has been managed in Illinois deer since it was first detected in the Fall of 2002. Management uses a state-sponsored localized focus culling (LFC) program, implemented as close as possible to previously identified CWD-infected locations (TRSs (township/range/section)). We used hunter-harvest and LFC deer from 4621 and 435 unique TRSs, respectively, over 16 years of surveillance and management (2003-2017). We divided the study area into groups of TRSs with similar landcover types (SPLT) to assess CWD hunter-harvest prevalence at LFC and non-LFC sites by landcover composition. We also evaluate the importance of the month when LFC was implemented and determine whether the density of LFC sites or the total number of deer removed by LFC predicts hunter-harvest CWD prevalence. The percentage of CWD positive samples from hunters was lower than for LFC samples (for the study area and SPLTs). The probability of CWD increased by 5.24% for all the SPLT groups combined in the study area, by 4.6% from areas without an LFC nearby, and by 1.21% for areas with a prior LFC nearby. For all the TRS in the study area, low CWD odds (<1) in hunter-harvest deer were found in three SPLTs, in two SPLTs within TRSs with non-LFC, and five in five SPLTs within TRSs with LFC. The results suggest the importance of accounting for landcover composition to implement and sustain management in habitats with a higher risk of CWD. Our findings support that hunter-harvest alone cannot control CWD and the critical need for continued LFC intervention. For the whole study area-regardless of landcover composition-LFC in January was more important in decreasing hunter-harvest CWD prevalence than when LFC was conducted in March. However, the LFC conducted in January, February, and March were equally important when evaluating the month per habitat. Furthermore, the density of LFC sites in proximity to known infected areas is a better predictor of CWD than the number of deer removed by LFC, suggesting that increasing the density of LFC sites has a greater impact on CWD. The proximity of LFC to infected areas helps control CWD. Ultimately, landowners' and hunters' collaborations with the CWD surveillance and management programs are critical to protecting the Illinois wild deer herd; this study demonstrates their ongoing and valuable contributions to protecting this natural and public resource.

CAUSE OF DEATH, PATHOLOGY, AND CHRONIC WASTING DISEASE STATUS OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) MORTALITIES IN WISCONSIN, USA.

White-tailed deer (WTD; Odocoileus virginianus) are a critical species for ecosystem function and wildlife management. As such, studies of cause-specific mortality among WTD have long been used to understand population dynamics. However, detailed pathological information is rarely documented for free-ranging WTD, especially in regions with a high prevalence of chronic wasting disease (CWD). This leaves a significant gap in understanding how CWD is associated with disease processes or comorbidities that may subsequently alter broader population dynamics. We investigated unknown mortalities among collared WTD in southwestern Wisconsin, USA, an area of high CWD prevalence. We tested for associations between CWD and other disease processes and used a network approach to test for co-occurring disease processes. Predation and infectious disease were leading suspected causes of death, with high prevalence of CWD (42.4%; of 245 evaluated) and pneumonia (51.2%; of 168 evaluated) in our sample. CWD prevalence increased with age, before decreasing among older individuals, with more older females than males in our sample. Females were more likely to be CWD positive, and although this was not statistically significant when accounting for age, females were significantly more likely to die with end-stage CWD than males and may consequently be an underrecognized source of CWD transmission. Presence of CWD was associated with emaciation, atrophy of marrow fat and hematopoietic cells, and ectoparasitism (lice and ticks). Occurrences of severe infectious disease processes clustered together (e.g., pneumonia, CWD), as compared to noninfectious or low-severity processes (e.g., sarcocystosis), although pneumonia cases were not fully explained by CWD status. With the prevalence of CWD increasing across North America, our results highlight the critical importance of understanding the potential role of CWD in favoring or maintaining disease processes of importance for deer population health and dynamics.

Transmission, Strain Diversity, and Zoonotic Potential of Chronic Wasting Disease.

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, its spillover and zoonotic potential and strategies to minimize the CWD threat.

No evidence of uptake or propagation of reindeer CWD prions in environmentally exposed sheep.

BACKGROUND: Chronic wasting disease (CWD) is a prion disease of cervids first reported in North America in the 1960s. In Europe, CWD was first diagnosed in 2016 in a wild reindeer in Norway. Detection of two more cases in the same mountain area led to the complete culling of this partially confined reindeer population of about 2400 animals. A total of 19 CWD positive animals were identified. The affected area is extensively used for the grazing of sheep during summers. There are many mineral licks intended for sheep in the area, but these have also been used by reindeer. This overlap in area use raised concerns for cross-species prion transmission between reindeer and sheep. In this study, we have used global positioning system (GPS) data from sheep and reindeer, including tracking one of the CWD positive reindeer, to investigate spatial and time-relevant overlaps between these two species. Since prions can accumulate in lymphoid follicles following oral uptake, samples of gut-associated lymphoid tissue (GALT) from 425 lambs and 78 adult sheep, which had grazed in the region during the relevant timeframe, were analyzed for the presence of prions. The recto-anal mucosa associated lymphoid tissue (RAMALT) from all the animals were examined by histology, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), and the ileal Peyer's patch (IPP) from a subsample of 37 lambs were examined by histology and IHC, for the detection of prions. RESULTS: GPS data showed an overlap in area use between the infected reindeer herd and the sheep. In addition, the GPS positions of an infected reindeer and some of the sampled sheep showed temporospatial overlap. No prions were detected in the GALT of the investigated sheep even though the mean lymphoid follicle number in RAMALT and IPP samples were high. CONCLUSION: The absence of prions in the GALT of sheep that have shared pasture with CWD-infected reindeer, may suggest that transmission of this novel CWD strain to sheep does not easily occur under the conditions found in these mountains. We document that the lymphoid follicle rich RAMALT could be a useful tool to screen for prions in sheep.

Spreading speed of chronic wasting disease across deer groups with overlapping home ranges.

Chronic wasting disease (CWD) is a fatal disease of cervid species that continues to spread across North America and now in Europe. It poses a threat to cervid populations and the local ecological and economic communities that depend on them. Although empirical studies have shown that host home range overlap and male dispersal are important in the spread of disease, there are few mechanistic models explicitly considering those factors. We built a spatio-temporal, differential equation model for CWD spreading with restricted movement of hosts within home ranges. The model incorporates both direct and environmental transmission within and between groups as well as male dispersal. We compared the relative influence of host density, sex ratio, home range size, and male dispersal distance on the spreading speed using sensitivity analysis. We also assessed the effect of landscape heterogeneity, quantified as edge density, on the spreading speed of CWD because it jointly alters the host density and home range size. Our model binds the theoretical study of CWD spreading speed together with empirical studies on deer home ranges and sets a base for models in 2D space to evaluate management and control strategies.

Increased Attack Rates and Decreased Incubation Periods in Raccoons with Chronic Wasting Disease Passaged through Meadow Voles.

Chronic wasting disease (CWD) is a naturally-occurring neurodegenerative disease of cervids. Raccoons (Procyon lotor) and meadow voles (Microtus pennsylvanicus) have previously been shown to be susceptible to the CWD agent. To investigate the potential for transmission of the agent of CWD from white-tailed deer to voles and subsequently to raccoons, we intracranially inoculated raccoons with brain homogenate from a CWD-affected white-tailed deer (CWDWtd) or derivatives of this isolate after it had been passaged through voles 1 or 5 times. We found that passage of the CWDWtd isolate through voles led to a change in the biologic behavior of the CWD agent, including increased attack rates and decreased incubation periods in raccoons. A better understanding of the dynamics of cross-species transmission of CWD prions can provide insights into how these infectious proteins evolve in new hosts.

Extended application of the rapid post-mortem test kit for bovine spongiform encephalopathy to chronic wasting disease.

Chronic wasting disease (CWD) is a prion disease affecting cervid species primarily in the United States of America and Canada; however, it is now emerging in Scandinavian countries. Although CWD cases have not been reported in Japan, in case of a CWD outbreak occuring, it is critical to prepare for testing a large number of specimens. The present study showed that a rapid post-mortem test kit, which is used for bovine spongiform encephalopathy surveillance in Japan, is valid for the detection of CWD prion.

Apparent stability masks underlying change in a mule deer herd with unmanaged chronic wasting disease.

The contagious prion disease "chronic wasting disease" (CWD) infects mule deer (Odocoileus hemionus) and related species. Unchecked epidemics raise ecological, socioeconomic, and public health concerns. Prion infection shortens a deer's lifespan, and when prevalence (proportion of adults infected) becomes sufficiently high CWD can affect herd dynamics. Understanding population responses over time is key to forecasting long-term impacts. Here we describe unexpected stability in prevalence and abundance in a mule deer herd where CWD has been left unmanaged. High apparent prevalence (~30%) since at least 2005 likely drove observed changes in the proportion and age distribution of wild-type native prion protein (PRNP) gene homozygotes among deer sampled. Predation by mountain lions (Puma concolor) may be helping keep CWD in check. Despite stable appearances, prion disease nonetheless impairs adult survival and likely resilience in this deer herd, limiting its potential for growth despite refuge from hunter harvest and favorable habitat and winter conditions.

COMPARISON OF CHRONIC WASTING DISEASE DETECTION METHODS AND PROCEDURES: IMPLICATIONS FOR FREE-RANGING WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) SURVEILLANCE AND MANAGEMENT.

Throughout North America, chronic wasting disease (CWD) has emerged as perhaps the greatest threat to wild cervid populations, including white-tailed deer (WTD; Odocoileus virginianus). White-tailed deer are the most sought-after big game species across North America with populations of various subspecies in nearly all Canadian provinces, the contiguous US, and Mexico. Documented CWD cases have dramatically increased across the WTD range since the mid-1990s, including in Minnesota, US. CWD surveillance in free-ranging WTD and other cervid populations mainly depends upon immunodetection methods such as immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) on medial retropharyngeal lymph nodes and obex. More recent technologies centered on prion protein amplification methods of detection have shown promise as more sensitive and rapid CWD diagnostic tools. Here, we used blinded samples to test the efficacy of real-time quaking-induced conversion (RT-QuIC) in comparison to ELISA for screening tissues collected in 2019 from WTD in southeastern Minnesota, where CWD has been routinely detected since 2016. Our results support previous findings that RT-QuIC is a more sensitive tool for CWD detection than current antibody-based methods. Additionally, a CWD testing protocol that includes multiple lymphoid tissues (e.g., medial retropharyngeal lymph node, parotid lymph node, and palatine tonsil) per animal can effectively identify a greater number of CWD detections in a WTD population than a single sample type (e.g., medial retropharyngeal lymph nodes). These results show that the variability of CWD pathogenesis, sampling protocol, and testing platform must be considered for the effective detection and management of CWD throughout North America.

Chronic wasting disease in Norway-A survey of prion protein gene variation among cervids.

Susceptibility of cervids to Chronic Wasting Disease (CWD), a prion disease, can be modulated by variations in the prion protein gene (PRNP), encoding the cellular prion protein (PrPC ). In prion diseases, PrPC is conformationally converted to pathogenic conformers (PrPSc ), aggregates of which comprise infectious prions. CWD has recently been observed in its contagious form in Norwegian reindeer (Rangifer tarandus) and in novel, potentially sporadic forms, here called 'atypical CWD', in moose (Alces alces) and red deer (Cervus elaphus). To estimate relative susceptibility of different Norwegian cervid species to CWD, their non-synonymous PRNP variants were analyzed. In reindeer, seven PRNP alleles were observed and in red deer and moose two alleles were present, whereas roe deer (Capreolus capreolus) PRNP was monomorphic. One 'archetypal' PRNP allele associated with susceptibility was common to all four cervid species. The distribution of PRNP alleles differed between wild and semi-domesticated reindeer, with alleles associated with a high susceptibility occurring, on average, above 55% in wild reindeer and below 20% in semi-domesticated reindeer. This difference may reflect the diverse origins of the populations and/or selection processes during domestication and breeding. Overall, PRNP genetic data indicate considerable susceptibility to CWD among Norwegian cervids and suggest that PRNP homozygosity may be a risk factor for the atypical CWD observed in moose. The CWD isolates found in the Norwegian cervid species differ from those previously found in Canada and USA. Our study provides an overview of the PRNP genetics in populations exposed to these emerging strains that will provide a basis for understanding these strains' dynamics in relation to PRNP variability.

Evaluating the ability of a locally focused culling program in removing chronic wasting disease infected free-ranging white-tailed deer in Illinois, USA, 2003-2020.

In northern Illinois, chronic wasting disease (CWD) was first identified in free-ranging white-tailed deer (Odocoileus virginianus; hereafter referred to as "deer") in 2002. To reduce CWD transmission rates in Illinois, wildlife biologists have conducted locally focussed culling of deer since 2003 in areas where CWD has been detected. We used retrospective spatial, temporal and space-time scan statistical models to identify areas and periods where culling removed higher than expected numbers of CWD-positive deer. We included 490 Public Land Survey "sections" (∼2.59 km2 ) from 15 northern Illinois counties in which at least one deer tested positive for CWD between 2003 and 2020. A negative binomial regression model compared the proportion of CWD positive cases removed from sections with at least one CWD case detected in the previous years, "local area 1 (L1)," to the proportion of CWD cases in adjacent sections-L2, L3, and L4-designated by their increasing distance from L1. Of the 14,661 deer removed and tested via culling, 325 (2.22 %) were CWD-positive. A single temporal CWD cluster occurred in 2020. Three spatial clusters were identified, with a primary cluster located at the border of Boone and Winnebago counties. Four space-time clusters were identified with a primary cluster in the northern portion of the study area from 2003 to 2005 that overlapped with the spatial cluster. The proportion of CWD cases removed from L1 (3.92, 95% CI, 2.56-6.01) and L2 (2.32, 95% CI, 1.50-3.59) were significantly higher compared to L3. Focussing culling efforts on accessible properties closest to L1 areas results in more CWD-infected deer being removed, which highlights the value of collaborations among landowners, hunters, and wildlife management agencies to control CWD. Continuous evaluation and updating of the culling and surveillance programs are essential to mitigate the health burden of CWD on deer populations in Illinois.