Predicting chronic wasting disease in white-tailed deer at the county scale using machine learning.

Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .

Predicting the odds of chronic wasting disease with Habitat Risk software.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that was first detected in captive cervids in Colorado, United States (US) in 1967, but has since spread into free-ranging white-tailed deer (Odocoileus virginianus) across the US and Canada as well as to Scandinavia and South Korea. In some areas, the disease is considered endemic in wild deer populations, and governmental wildlife agencies have employed epidemiological models to understand long-term environmental risk. However, continued rapid spread of CWD into new regions of the continent has underscored the need for extension of these models into broader tools applicable for wide use by wildlife agencies. Additionally, efforts to semi-automate models will facilitate access of technical scientific methods to broader users. We introduce software (Habitat Risk) designed to link a previously published epidemiological model with spatially referenced environmental and disease testing data to enable agency personnel to make up-to-date, localized, data-driven predictions regarding the odds of CWD detection in surrounding areas after an outbreak is discovered. Habitat Risk requires pre-processing publicly available environmental datasets and standardization of disease testing (surveillance) data, after which an autonomous computational workflow terminates in a user interface that displays an interactive map of disease risk. We demonstrated the use of the Habitat Risk software with surveillance data of white-tailed deer from Tennessee, USA.

Distal toxic acral erythema and mucositis secondary to 6-mercaptopurine in a thiopurine methyltransferase "super shunter".

Toxic erythema of chemotherapy is a broad but useful diagnosis used to summate the non-infectious, non-allergic, and reproducible reaction of certain chemotherapeutics. Due to overlapping chemotherapy side effects and often multiple drug exposures, identification of a singular culprit drug is challenging for dermatologists. Herein, we report a patient with 6-mercaptopurine (6-MP) toxic erythema confirmed via toxic metabolite markers secondary to increased levels of thiopurine methyltransferase activity, or so called "super shunting." Consulting dermatologists should be aware of "super shunting" in pediatric patients and consider testing for metabolites in patients with toxic acral erythema and mucositis in the setting of 6-MP.

A PRELIMINARY INVESTIGATION OF PATHOGEN EXPOSURE OF ADULT FEMALE WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) AND SURVIVAL OF ASSOCIATED FAWNS IN THE WESTERN DAKOTAS, USA.

Exposure of a dam to pathogens may potentially affect her fawns positively or negatively. Mammalian females transfer immunologic protection to their offspring via colostrum obtained while nursing. Conversely, chronic diseases in dams may potentially result in small and weak neonates, reduced milk production or quality, or infection. Little is known about how pathogen exposure in adult female white-tailed deer (Odocoileus virginianus) affects offspring survival. Our objective was to assess pathogen exposure for female white-tailed deer and subsequent survival rates of fawns in Dunn and Grant counties, North Dakota, and Perkins County, South Dakota, USA. We collected blood serum from 150 adult female deer during 2014. We compared survival of 49 fawns to maternal exposure to 10 pathogens from 37 of 150 adult females. There was no difference in fawn mass between dams based on antibody status and no difference in fawn survival for nine pathogens. The 12-wk survival for fawns born to mothers with antibodies against bovine herpesvirus 1 (BoHV-1, causing infectious bovine rhinotracheitis) was lower than for fawns born from mothers without antibodies against BoHV-1; however, the indirect or direct impacts of BoHV-1 exposure in mothers on fawn survival are unclear. Although our findings suggest that the cost of exposure to previous diseases may have minimal impact on short-term fawn survival for most pathogens, additional research with increased sample sizes is needed to confirm our findings.

A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis.

A 4-year-old female with a history of atopic dermatitis developed herpes simplex virus (HSV) encephalitis while being treated with dupilumab and concomitant topical steroids. There was no prior history of HSV infections or immunodeficiency. To our knowledge, this is the first case of HSV encephalitis in a patient receiving dupilumab.

Rapid Discovery and Detection of Haemaphysalis longicornis through the Use of Passive Surveillance and Collaboration: Building a State Tick-Surveillance Network.

Between March 2019 and February 2020, Asian long-horned ticks (Haemaphysalis longicornis Neumann, 1901) were discovered and collected for the first time in one middle and seven eastern Tennessee counties, facilitated by a newly developed passive and collaborative tick-surveillance network. Network collaborators included federal, state, county, university, and private resource personnel working with companion animals, livestock, and wildlife. Specimens were collected primarily from dogs and cattle, with initial detections of female adult stage ticks by stakeholders associated with parasitology positions (e.g., entomologists and veterinary parasitologists). Initial county tick detections were confirmed with morphological and molecular identifications, and then screened for the presence of animal-associated pathogens (Anaplasma marginale, Babesia species, Ehrlichia species, and Theileria orientalis), for which all tests were negative. Herein, we describe the identification and confirmation of these tick specimens as well as other results of the surveillance collaboration.

Exposure to Select Pathogens in an Expanding Moose (Alces alces) Population in North Dakota, USA.

Forty female moose (Alces alces) captured in North Dakota, US, in March 2014 were tested for antibodies to a variety of pathogens. Antibodies to West Nile virus (WNV) were detected in 39 (98%) moose following a year with a high number of human cases, suggesting the population accurately reflects WNV activity. Fifteen percent of moose (6/40) had antibodies to Borrelia burgdorferi, implying expansion of the tick vector into the area. Antibodies to Anaplasma spp. were detected in 55% of moose (22/40), a higher rate than previously detected in cattle from the region. Low titers (100-400) to one or more serovars of Leptospira spp. were detected in 23% of moose (9/40), a common finding in wild ruminants. Exposure to other pathogens was uncommon (<8%; <3/40) or not documented. Survival and recruitment were high during the study period, suggesting a limited population-level impact at current levels of exposure and environmental co-stressors.

Development of Bronchopleural Fistula Complicated by Empyema Fifteen Years After Right Lower Lobe Lobectomy: A Case Report.

BACKGROUND Bronchopleural fistula formation is a rare complication of lobectomy surgery, with a frequency reported ranging from 0.5% to 1%. A post-lobectomy bronchopleural fistula usually presents within 14 days of surgery. To our knowledge, it is extremely rare for a bronchopleural fistula to develop many years after an operation. CASE REPORT We present the case of a 55-year-old male smoker with history of a right lower lobe lobectomy 15 years prior who presented to the Emergency Department with complaints of worsening back pain, shortness of breath, and cough productive of sputum. He was found to have a right bronchopleural fistula with right-sided empyema. He was taken to the operating room a few days after initial admission for right thoracoscopic chest exploration, right chest debridement, right chest wall resection, and window procedure with creation of pleurocutaneous fistula. Ultimately, he required a right completion pneumonectomy and buttress of bronchial stump with transdiaphragmatic omental flap. CONCLUSIONS We diagnosed a rare case of post-lobectomy bronchopleural fistula complicated by an empyema that demonstrates bronchopleural fistulas can appear 15 years postoperatively and present with subacute clinical signs and symptoms.

Takotsubo cardiomyopathy triggered by SARS-CoV-2 infection in a critically ill patient.

COVID-19 became a global pandemic in early 2020. While well known for its pulmonary manifestations, the virus also has a number of cardiac manifestations as well. Takotsubo syndrome has scarcely been reported in patients with COVID-19, but it is possible that the cytokine storm associated with the infection can trigger Takotsubo syndrome in patients with underlying risk factors for Takotsubo (emotional distress, physical distress, history of psychiatric disorders).

Seborrhea herpeticum: cutaneous herpes simplex virus infection within infantile seborrheic dermatitis.

Eczema herpeticum has been well described in the setting of atopic dermatitis (AD) and other dermatoses. We present the case of a 2-month-old infant boy with cutaneous herpes simplex virus (HSV) infection within existing diffuse infantile seborrheic dermatitis. Providers should be aware that cutaneous HSV can be confined to a seborrheic distribution and may represent underlying epidermal dysfunction secondary to seborrheic dermatitis.

Effects of Neonicotinoid Insecticides on Physiology and Reproductive Characteristics of Captive Female and Fawn White-tailed Deer.

Over the past decade, abnormalities have been documented in white-tailed deer (Odocoileus virginianus) in west-central Montana. Hypotheses proposed to explain these anomalies included contact with endocrine disrupting pesticides, such as imidacloprid. We evaluated the effects of imidacloprid experimentally at the South Dakota State University Wildlife and Fisheries Captive Facility where adult white-tailed deer females and their fawns were administered aqueous imidacloprid (an untreated control, 1,500 ng/L, 3,000 ng/L, and 15,000 ng/L). Water consumption, thyroid hormone function, behavioral responses, and skull and jawbone measurements were compared among treatments. Additionally, liver, spleen, genital, and brain imidacloprid concentrations were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicated that 1) control deer consumed more water than treatment groups, 2) imidacloprid was present in the organs of our control group, indicating environmental contamination, 3) as imidacloprid increased in the spleen, fawn survival, thyroxine levels, jawbone lengths, body weight, and organ weights decreased, 4) adult female imidacloprid levels in the genitals were negatively correlated with genital organ weight and, 5) behavioral observations indicated that imidacloprid levels in spleens were negatively correlated with activity levels in adult females and fawns. Results demonstrate that imidacloprid has direct effects on white-tailed deer when administered at field-relevant doses.

Host-specific parvovirus evolution in nature is recapitulated by in vitro adaptation to different carnivore species.

Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats and related carnivores. Although both viruses have wide host ranges, analysis of viral sequences recovered from different wild carnivore species, as shown here, demonstrated that>95% were derived from CPV-like viruses, suggesting that CPV is dominant in sylvatic cycles. Many viral sequences showed host-specific mutations in their capsid proteins, which were often close to sites known to control binding to the transferrin receptor (TfR), the host receptor for these carnivore parvoviruses, and which exhibited frequent parallel evolution. To further examine the process of host adaptation, we passaged parvoviruses with alternative backgrounds in cells from different carnivore hosts. Specific mutations were selected in several viruses and these differed depending on both the background of the virus and the host cells in which they were passaged. Strikingly, these in vitro mutations recapitulated many specific changes seen in viruses from natural populations, strongly suggesting they are host adaptive, and which were shown to result in fitness advantages over their parental virus. Comparison of the sequences of the transferrin receptors of the different carnivore species demonstrated that many mutations occurred in and around the apical domain where the virus binds, indicating that viral variants were likely selected through their fit to receptor structures. Some of the viruses accumulated high levels of variation upon passage in alternative hosts, while others could infect multiple different hosts with no or only a few additional mutations. Overall, these studies demonstrate that the evolutionary history of a virus, including how long it has been circulating and in which hosts, as well as its phylogenetic background, has a profound effect on determining viral host range.

Comparative cost analysis of endobronchial ultrasound-guided and blind TBNA in the evaluation of hilar and mediastinal lymphadenopathy.

BACKGROUND: The superior accuracy of endobronchial ultrasound (EBUS) averts many diagnostic surgical procedures. This likely leads to significant cost savings despite an increased per procedure cost. We sought to compare the true costs of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) compared with "blind" fiberoptic bronchoscopy-transbronchial needle aspiration (FB-TBNA) factoring in the impact of diagnostic surgical procedures in the diagnosis of mediastinal lymphadenopathy. METHODS: In this retrospective case study, we selected 294 patients with thoracic lymphadenopathy as diagnosed by computed tomography at a university hospital. Information was extracted from the electronic record. Costs were determined from the Centers for Medicare and Medicaid Services resource-based relative value scale. We defined a positive diagnosis as one where benign or malignant disease was found. A negative biopsy was one where lymph node sampling was confirmed, but no pathology (benign or malignant) was seen. A nondiagnostic biopsy was one where no pathology was seen and lymph node sampling could not be confirmed. The total cost of endoscopic and surgical diagnostic procedures was tallied for each patient to obtain mean costs per patient. RESULTS: Thirty-seven patients underwent FB-TBNA and 257 underwent EBUS-TBNA. A diagnosis was found in 90% of patients in the EBUS group and 62.2% of patients in the FB-TBNA group (P<0.001). More patients in the FB-TBNA group underwent a diagnostic surgical procedure (HR= -0.1573, 95% confidence interval, -0.30 to -0.15; P<0.001). After accounting for all diagnostic procedures, the mean savings with EBUS was $1071.09 (P=0.09) per patient. CONCLUSIONS: EBUS-TBNA is less expensive than blind FB-TBNA in the evaluation of thoracic lymphadenopathy when accounting for diagnostic surgical procedures.

Variation in the ITS-1 and ITS-2 rRNA genomic regions of Cytauxzoon felis from bobcats and pumas in the eastern United States and comparison with sequences from domestic cats.

Cytauxzoon felis, a tick-borne protozoan parasite, is the causative agent of cytauxzoonosis in domestic cats in the United States. The natural reservoir for this parasite is the bobcat (Lynx rufus), which typically does not develop clinical signs. Although not likely important reservoirs, C. felis has also been detected in pumas (Puma concolor) in Florida and Louisiana. Recent studies suggest that specific genotypes of C. felis that circulate in domestic cats may be associated with variable clinical outcomes and specific spatial locations. In the current study, we investigated the intraspecific variation of the C. felis internal transcribed spacer (ITS)-1 and ITS-2 rRNA regions from 145 wild felids (139 bobcats and six pumas) from 11 states (Florida, Georgia, Kansas, Kentucky, Louisiana, Missouri, North Carolina, North Dakota, South Carolina, Oklahoma, and Pennsylvania). Unambiguous ITS-1 and ITS-2 data were obtained for 144 and 112 samples, respectively, and both ITS-1 and ITS-2 sequences were obtained for 111 (77%) samples. For the ITS-1 region, sequences from 65 samples collected from wild felids were identical to those previously reported in domestic cats, while the other 79 sequences were unique. C. felis from 45 bobcats and one puma had ITS-1 sequences identical to the most common sequence reported from domestic cats. Within the ITS-2 region, sequences from 49 bobcats were identical to those previously reported in domestic cats and 63 sequences were unique (with some occurring in more than one bobcat). The most common ITS-2 sequence from domestic cats was also common in wild felids (31 bobcats and a puma). Samples from three pumas from Florida and two bobcats from Missouri had a 40- or 41-bp insert in the ITS-2 similar to one described previously in a domestic cat from Arkansas. Additionally, a previously undescribed 198- or 199-bp insert was detected in the ITS-2 sequence from four bobcats. Collectively, based on combined ITS-1 and ITS-2 sequences, five different genotypes were detected in the wild felids. Genotype ITSa was the most common genotype (11 bobcats and one puma) and fewer numbers of ITSb, ITSe, ITSg, and ITSi were detected in bobcats. These data indicate that, based on ITS-1 and ITS-2 sequences, numerous C. felis strains may circulate in wild felids.

Distribution and prevalence of Cytauxzoon felis in bobcats (Lynx rufus), the natural reservoir, and other wild felids in thirteen states.

Cytauxzoon felis, a protozoan parasite of wild and domestic felids, is the causative agent of cytauxzoonosis in domestic and some exotic felids in the United States. The bobcat (Lynx rufus) is the natural reservoir for this parasite, but other felids such as Florida panthers (Puma concolor coryii) and domestic cats may maintain long-term parasitemias and serve as reservoirs. Experimentally, two tick species, Dermacentor variabilis and Amblyomma americanum, have demonstrated the ability to transmit C. felis. These two tick species have overlapping distributions throughout much of the southeastern United States. The objective of the current study was to determine the distribution and prevalence of C. felis in free-ranging bobcat populations from 13 states including California, Colorado, Florida, Georgia, Kansas, Kentucky, Missouri, North Carolina, North Dakota, Ohio, Oklahoma, South Carolina, and West Virginia. These states were selected because of differential vector presence; D. variabilis is present in each of these states except for the region of Colorado sampled and A. americanum is currently known to be present only in a subset of these states. Blood or spleen samples from 696 bobcats were tested for C. felis infection by a polymerase chain reaction (PCR) assay which targeted the first ribosomal internal transcribed spacer region (ITS-1). Significantly higher prevalences of C. felis were detected from Missouri (79%, n=39), North Carolina (63%, n=8), Oklahoma (60%, n=20), South Carolina (57%, n=7), Kentucky (55%, n=74), Florida (44%, n=45), and Kansas (27%, n=41) compared with Georgia (9%, n=159), North Dakota (2.4%, n=124), Ohio (0%, n=19), West Virginia (0%, n=37), California (0%, n=26), and Colorado (0%, n=67). In addition to bobcats, seven cougars (Puma concolor) from Georgia, Louisiana, and North Dakota and one serval (Leptailurus serval) from Louisiana were tested for C. felis. Only one cougar from Louisiana was PCR positive, which represents the first report of an infected cougar outside of the Florida panther population. These data also indicate that C. felis is present in North Dakota where infection has not been reported in domestic cats. Based on a nonparametric analysis, prevalence rates were significantly higher in states where there are established populations of A. americanum, which supports recent data on the experimental transmission of C. felis by A. americanum and the fact that domestic cat clinical cases are temporally associated with A. americanum activity. Collectively, these data confirm that bobcats are a common reservoir for C. felis and that A. americanum is likely an epidemiologically important vector.

Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation.

BACKGROUND: Long-term success in lung transplantation is limited by obliterative bronchiolitis (OB). Presently, complete understanding of the mechanisms of OB has been elusive. Bone marrow-derived mesenchymal stem cells (MSC) have been shown to modulate repair of the injured lung in multiple disease models. We hypothesized that the injection of MSC would prevent development of early airway obstruction (AO) in the heterotopic tracheal transplant model. METHODS: Forty-four tracheas from BALB/c and C57BL/6 donors were transplanted into 22 C57BL/6 recipients. At the time of transplant, 13 of the allogeneic recipient mice were injected with 5 × 10(5) MSC from various murine sources. To confirm the role of the immune response in the generation of AO we used a permeable inhibitor of nuclear factor-kappaB (NF-κB) in 11 recipients after transplantation with 22 BALB/c tracheas. RESULTS: After transplantation, administration of MSC inhibited intraluminal obstruction by collagen in 98% of the mice and transforming factor-beta (TGF-ß) expression decreased to levels similar to those observed in isograft controls. These effects were associated with a significant (p < 0.05) increase in expression of the anti-inflammatory cytokine interleukin-10 (IL-10). NF-κB inhibitor showed decreased expression of transforming growth factor-beta (TGF-ß) in the Day 7 and Day 14 groups, resulting in a 60% reduction of luminal obstruction as well as a decrease in inflammatory cells to the airway. CONCLUSION: Our observations suggest that administration of MSC prevents development of airway occlusion in a mouse model, probably through the modulated immune response altering TGF-ß expression.