Safety and efficacy of foscarnet for the management of ganciclovir-resistant or refractory cytomegalovirus infections: A single-center study.

BACKGROUND: Infection with cytomegalovirus (CMV) is an important cause of morbidity and mortality following solid organ transplantation. Resistance to ganciclovir can rarely develop via mutations in UL97 or UL54. There are limited published studies assessing the safety and efficacy of foscarnet for the management of ganciclovir-resistant or refractory cytomegalovirus infection and many centers are reluctant to utilize this important therapy because of concerns about toxicity. METHODS: Solid organ recipients transplanted between January 1, 2006 and December 31, 2014 who received at least 1 dose of foscarnet were retrospectively reviewed to assess treatment outcomes, tolerability, and safety of foscarnet. RESULTS: Ten of 31 (32.3%) patients who received foscarnet during the study period died during treatment with foscarnet, whereas all 21 surviving recipients successfully cleared infection. Of these surviving patients, 3 (14.3%) developed significant renal dysfunction, defined as >25% decline in estimated glomerular filtration rate during treatment; one-third had definitive renal biopsy results consistent with foscarnet-induced toxicity. CONCLUSION: Although mortality was high in this population, foscarnet use, with proper precautions, was generally safe and significant renal dysfunction was lower than previously reported in other sources, even with extended use.

Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype.

The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands. Cellular responses were analysed by quantitative PCR (Q-PCR), immunoblotting and radiolabelling, including [3H]cholesterol efflux to (apo)lipoprotein A-I (apoA-I), high-density lipoprotein (HDL) and human serum. Induction of macrophage cholesterol deposition by acetylated low-density lipoprotein (AcLDL) increased expression of TSPO mRNA and protein, reflecting findings in human carotid atherosclerosis. Transient overexpression of TSPO enhanced efflux (E%) of [3H]cholesterol to apoA-I, HDL and human serum compared with empty vector (EV) controls, whereas gene knockdown of TSPO achieved the converse. Ligation of TSPO (using PK11195, FGIN-1-27 and flunitrazepam) triggered increases in [3H]cholesterol efflux, an effect that was amplified in TSPO-overexpressing macrophages. Overexpression of TSPO induced the expression of genes [PPARA (peroxisome-proliferator-activated receptor α), NR1H3 (nuclear receptor 1H3/liver X receptor α), ABCA1 (ATP-binding cassette A1), ABCG4 (ATP-binding cassette G4) and APOE (apolipoprotein E)] and proteins (ABCA1 and PPARα) involved in cholesterol efflux, reduced macrophage neutral lipid mass and lipogenesis and limited cholesterol esterification following exposure to AcLDL. Thus, targeting TSPO reduces macrophage lipid content and prevents macrophage foam cell formation, via enhanced cholesterol efflux to (apo)lipoprotein acceptors.

Inhibition of α4ß1 integrin increases ovarian cancer response to carboplatin.

OBJECTIVE: The inability to successfully treat women with ovarian cancer is due to the presence of metastatic disease at diagnosis and the development of platinum resistance. Ovarian cancer metastasizes throughout the peritoneal cavity by attaching to and invading through the mesothelium lining the peritoneum using a mechanism that involves α4ß1 integrin and its ligand (vascular cell adhesion molecule) VCAM-1. Integrin α4ß1 expression on tumor cells is known to confer protection from therapy in other cancers, notably multiple myeloma. We evaluated the role of α4ß1 integrin in response to platinum-based therapy in a mouse model of peritoneal ovarian cancer metastasis by treatment with a humanized anti-α4ß1 integrin function-blocking antibody. METHODS: Integrin α4ß1 expression on primary human ovarian cancer cells, fallopian tube and ovarian surface epithelia and fresh tumor was assessed by flow-cytometry. The therapeutic impact of anti-α4ß1 treatment was assessed in murine models of platinum-resistant peritoneal disease and in vitro using the platinum resistant ovarian cancer cell lines. RESULTS: Treatment of tumor-bearing mice with human-specific α4ß1 integrin function-blocking antibodies, anti-VCAM-1 antibody or carboplatin alone had no effect on tumor burden compared to the IgG control group. However, the combined treatment of anti-α4ß1 integrin or anti-VCAM-1 with carboplatin significantly reduced tumor burden. In vitro, the combination of carboplatin and anti-α4ß1 integrin antibodies resulted in increased cell death and doubling time. CONCLUSIONS: Our findings support a role for α4ß1 integrin in regulating treatment response to carboplatin, implicating α4ß1 integrin as a potential therapeutic target to influence platinum responsiveness in otherwise resistant disease.

Comparative genomic analysis identifies potential adaptive variation in Mycoplasma ovipneumoniae.

Mycoplasma ovipneumoniae is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared M. ovipneumoniae genomes for 99 samples from 6 countries (Australia, Bosnia and Herzegovina, Brazil, China, France and USA) and 4 host species (domestic sheep, domestic goats, bighorn sheep and caribou). Core genome sequences of M. ovipneumoniae assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species. Genome assemblies from bighorn sheep and caribou also fell within these two clades, indicating multiple spillover events, most commonly from domestic sheep. Pangenome analysis indicated a high percentage (91.4 %) of accessory genes (i.e. genes found only in a subset of assemblies) compared to core genes (i.e. genes found in all assemblies), potentially indicating a propensity for this pathogen to adapt to within-host conditions. In addition, many genes related to carbon metabolism, which is a virulence factor for Mycoplasmas, showed evidence for homologous recombination, a potential signature of adaptation. The presence or absence of annotated genes was very similar between sheep and goat clades, with only two annotated genes significantly clade-associated. However, three M. ovipneumoniae genome assemblies from asymptomatic caribou in Alaska formed a highly divergent subclade within the sheep clade that lacked 23 annotated genes compared to other assemblies, and many of these genes had functions related to carbon metabolism. Overall, our results suggest that adaptation of M. ovipneumoniae has involved evolution of carbon metabolism pathways and virulence mechanisms related to those pathways. The genes involved in these pathways, along with other genes identified as potentially involved in virulence in this study, are potential targets for future investigation into a possible genomic basis for the high variation observed in disease outcomes within and between wild and domestic host species.

Mitochondrial (dys)function and regulation of macrophage cholesterol efflux.

Cholesterol trafficking from the outer to the cholesterol-poor inner mitochondrial membrane requires energized, polarized and actively respiring mitochondria, mediated by a highly regulated multimeric (140-200 kDa) protein complex comprising StAR (steroidogenic acute regulatory protein), mitochondrial TSPO (translocator protein), VDAC (voltage-dependent anion channel), ANT (adenine nucleotide transporter) and associated regulatory proteins. Mitochondrial cholesterol transport is rate-limiting in the CYP27A1 (sterol 27-hydroxylase)-dependent generation of oxysterol ligands for LXR (liver X receptor) transcription factors that regulate the expression of genes encoding proteins in the cholesterol efflux pathway, such as ABC transporters (ATP-binding cassette transporters) ABCA1 and ABCG1. These transporters transfer cholesterol and/or phospholipids across the plasma membrane to (apo)lipoprotein acceptors, generating nascent HDLs (high-density lipoproteins), which can safely transport excess cholesterol through the bloodstream to the liver for excretion in bile. Utilizing information from steroidogenic tissues, we propose that perturbations in mitochondrial function may reduce the efficiency of the cholesterol efflux pathway, favouring accumulation of cholesteryl ester 'foam cells' and allowing the toxic accumulation of free cholesterol at the interface between the endoplasmic reticulum and the mitochondrial membrane. In turn, this will trigger opening of the permeability transition pore, allowing unregulated production of oxysterols via CYP27A1, allowing the accumulation of esterified forms of this oxysterol within human atherosclerotic lesions. Defective cholesterol efflux also induces endoplasmic reticulum stress, proteasomal degradation of ABCA1 and Fas-dependent apoptosis, replicating findings in macrophages in advanced atherosclerotic lesions. Small molecules targeted to mitochondria, capable of sustaining mitochondrial function or improving cholesterol trafficking may aid cholesterol efflux from macrophage 'foam' cells, regressing and stabilizing the atherosclerotic plaque.

Optimal risk-based allocation of disease surveillance effort for clustered disease outbreaks.

Designing a disease surveillance program to detect a disease is challenging when animals are organized into herds, in part because disease cases are likely to be clustered. Clustered diseases are often surveilled using two-stage sampling, which allocates tests both among herds and within herds. Finding the optimal allocation of tests is computationally difficult, so some surveillance programs simply seek an approximate solution. We developed a search algorithm to find the optimal allocation of tests by iteratively searching for adjustments to the test allocation that yielded marginal improvements in system sensitivity. We digitally generated 21 herds of various sizes, evenly divided among three regions that differed in relative risk. We then analyzed 29 scenarios that differed in disease and testing characteristics. We also analyzed a Chronic Wasting Disease (CWD) surveillance effort for 23 elk game management units of various sizes that were spread across three regions in Arizona, USA. We compared our marginal sensitivity approach to two other strategies for approximating the optimal distribution of tests: allocating the same number of tests to all herds selected for testing, and allocating tests so that all herds selected for testing achieve the same sensitivity. Across analysis scenarios, we found that low prevalence, high relative risk, a small budget, or high overhead costs were best addressed by concentrating tests in large, high-risk herds. When we expect multiple herds to be infected, the optimal allocation of tests depended on how we expected the cases to be distributed. Across the analyzed scenarios, our marginal sensitivity approach was most efficient, with alternative strategies requiring 0-228 % more tests to achieve the same sensitivity. For CWD in Arizona, we found the potential to double system sensitivity, given a population design prevalence of 0.16 %, from 35.8 % to 70.5 %, although social and budgetary considerations would likely constrain changes to the current allocation of tests. The marginal sensitivity approach we developed has the potential to improve disease surveillance, especially when a population includes a limited number of herds that differ in size. An important limitation of our approach is that computer runtimes could become unacceptably long for a population with many herds.

Convenience Sampling Yields No Evidence of SARS-CoV-2 Infection in Free-Ranging Mammalian Wildlife in Arizona, USA, 2021-23.

Susceptibility of free-ranging US wildlife to SARS-CoV-2 infection has been documented. Nasal or oral swabs and blood from 337 wild mammals (31 species) in Arizona USA, tested for antibodies and by reverse-transcription PCR, did not reveal evidence of SARS-CoV-2. Broader surveillance efforts are necessary to understand the role of wildlife.

Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apo)A-I from murine RAW 264.7 macrophages.

BACKGROUND: Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. METHODS: Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo) A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett's or Bonferroni post t-tests, as appropriate. RESULTS: The positive control, resveratrol (24 h), significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 µM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; p<0.01) and oligomycin (55%; p<0.01), under conditions (10 µM, 3 h) which did not induce cellular toxicity or deplete total cellular ATP content. Levels of ATP binding cassette transporter A1 (ABCA1) protein were repressed by oligomycin under optimal efflux conditions, despite paradoxical increases in Abca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 µM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1) and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2), indicating profound dysregulation of cholesterol homeostasis. CONCLUSIONS: Acute loss of mitochondrial function, and in particular Δψm, reduces cholesterol efflux to apoA-I and dysregulates macrophage cholesterol homeostasis mechanisms. Bioavailable antioxidants, targeted to mitochondria and capable of sustaining effective mitochondrial function, may therefore prove effective in maintenance of arterial health.

Overexpression of STARD3 in human monocyte/macrophages induces an anti-atherogenic lipid phenotype.

Dysregulated macrophage cholesterol homoeostasis lies at the heart of early and developing atheroma, and removal of excess cholesterol from macrophage foam cells, by efficient transport mechanisms, is central to stabilization and regression of atherosclerotic lesions. The present study demonstrates that transient overexpression of STARD3 {START [StAR (steroidogenic acute regulatory protein)-related lipid transfer] domain 3; also known as MLN64 (metastatic lymph node 64)}, an endosomal cholesterol transporter and member of the 'START' family of lipid trafficking proteins, induces significant increases in macrophage ABCA1 (ATP-binding cassette transporter A1) mRNA and protein, enhances [(3)H]cholesterol efflux to apo (apolipoprotein) AI, and reduces biosynthesis of cholesterol, cholesteryl ester, fatty acids, triacylglycerol and phospholipids from [(14)C]acetate, compared with controls. Notably, overexpression of STARD3 prevents increases in cholesterol esterification in response to acetylated LDL (low-density lipoprotein), blocking cholesteryl ester deposition. Thus enhanced endosomal trafficking via STARD3 induces an anti-atherogenic macrophage lipid phenotype, positing a potentially therapeutic strategy.

Herd-level prevalence of Mycoplasma spp mastitis and characteristics of infected dairy herds in Utah as determined by a statewide survey.

OBJECTIVE: To determine herd-level prevalence of Mycoplasma spp mastitis in Utah dairy herds and characterize farms and management practices for positive herds. DESIGN: Epidemiologic study. SAMPLE POPULATION: Bulk tank milk samples from 222 of 285 (78%) dairy farms in Utah. PROCEDURES: Milk haulers or dairy producers collected 5 milk samples from all bulk tanks at 3- to 4-day intervals for mycoplasmal culture. Owners of all positive herds were offered follow-up visits. RESULTS: Milk samples from 16 of 222 (7%) herds had positive mycoplasmal culture results. Follow-up information was obtained from 14 of 16 herds; 12 provided complete data. Some characteristics of mycoplasma-positive herds included the following: 8 of 14 herds had > 750 lactating cows, 9 of 11 had bulk tank milk somatic cell count of 140,000 to 240,000 cells/mL, 7 of 11 had actual milk production of 9,535 to 11,622 kg (21,000 to 25,600 lb)/305 d, 11 of 12 had cows with clinical mastitis that was nonresponsive to treatment and involved >or= 2 mammary gland quarters, 9 of 12 had cows with clinical mastitis that spread from 1 mammary gland quarter to another, 8 of 12 had cows with droopy ears, 7 of 12 had cows with a head tilt, 7 of 12 used common milking towels, 2 of 12 were closed to replacement cattle for > 1 year, and 2 of 12 purchased bulls only. CONCLUSIONS AND CLINICAL RELEVANCE: Herd-level prevalence of mycoplasma mastitis in Utah was relatively high, compared with other areas of the United States.

Effect of Canine Parvovirus and Canine Distemper Virus on the Mexican Wolf (Canis lupus baileyi) Population in the USA.

Mexican wolves (Canis lupus baileyi), classified as probably extinct in the wild in Mexico and endangered in the US, were reintroduced into Arizona in 1998. We combined annual serologic testing results from samples collected between 2003 and 2016 from 108 wolves and known survival data from 118 wolves born in the recovery area from 2003 to 2014 to evaluate whether exposure to canine distemper virus (CDV) or canine parvovirus (CPV) was associated with a greater risk of mortality before 2 yr of age. We used mixed-effects logistic regression to estimate the effect of CDV and CPV on the probability of mortality. Annual seroprevalence rates for CDV and CPV ranged from 0% to 62% and from 33% to 100%, respectively (median, 14.2% and 90.3%, respectively). The covariate, age at testing, had a negative effect on mortality, indicating that younger animals had lower survival, whereas sex had little effect on mortality. The best-supported model excluded any effect of CPV or CDV on death before 2 yr old at both the pack and individual level. Although our analysis did not detect an effect of these viruses on mortality before 2 yr old, CDV was later identified as the cause of mortality in two individuals in 2017. Additional information is needed to assess the impact of these diseases on Mexican wolves.

CHLAMYDIA PSITTACI IN FERAL ROSY-FACED LOVEBIRDS ( AGAPORNIS ROSEICOLLIS) AND OTHER BACKYARD BIRDS IN MARICOPA COUNTY, ARIZONA, USA.

In 2013, a mortality event of nonnative, feral Rosy-faced Lovebirds ( Agapornis roseicollis) in residential backyards in Maricopa County, Arizona, US was attributed to infection with Chlamydia psittaci. In June 2014, additional mortality occurred in the same region. Accordingly, in August 2014 we sampled live lovebirds and sympatric bird species visiting backyard bird feeders to determine the prevalence of DNA and the seroprevalence of antibodies to C. psittaci using real-time PCR-based testing and elementary body agglutination, respectively. Chlamydia psittaci DNA was present in conjunctival-choanal or cloacal swabs in 93% (43/46) of lovebirds and 10% (14/142) of sympatric birds. Antibodies to C. psittaci were detected in 76% (31/41) of lovebirds and 7% (7/102) of sympatric birds. Among the sympatric birds, Rock Doves ( Columba livia) had the highest prevalence of C. psittaci DNA (75%; 6/8) and seroprevalence (25%; 2/8). Psittacine circovirus 1 DNA was also identified, using real-time PCR-based testing, from the same swab samples in 69% (11/16) of species sampled, with a prevalence of 80% (37/46) in lovebirds and 27% (38/142) in sympatric species. The presence of either Rosy-faced Lovebirds or Rock Doves at residential bird feeders may be cause for concern for epizootic and zoonotic transmission of C. psittaci in this region.

Mortality of Western Burrowing Owls ( Athene cunicularia hypugaea) Associated with Brodifacoum Exposure.

Western Burrowing Owls ( Athene cunicularia hypugaea) frequently occupy periurban areas, where they may be exposed to pest control agents. This short communication describes necropsy findings and detected brodifacoum rodenticide levels for four Western Burrowing Owls in Lake Havasu City, Arizona, US, 2013-15. Levels detected ranged from 0.077 mg/kg to 0.497 mg/kg. Brodifacoum, one of several second-generation anticoagulant rodenticides recently removed from the general consumer market, is still available for use by licensed pesticide applicators. Despite recent regulatory actions, second-generation anticoagulant pesticides continue to threaten predatory species in periurban areas.

Bald Eagle Nestling Mortality Associated with Argas radiatus and Argas ricei Tick Infestation and Successful Management with Nest Removal in Arizona, USA.

Eight Bald Eagle ( Haliaeetus leucocephalus ) nestlings heavily infested with larval ticks were found in or under a nest near the confluence of the Verde and Salt rivers in Arizona in 2009-11. The 8-12-wk-old nestlings were slow to respond to stimuli and exhibited generalized muscle weakness or paresis of the pelvic limbs. Numerous cutaneous and subcutaneous hemorrhages were associated with sites of tick attachment. Ticks were identified as Argas radiatus and Argas ricei. Treatment with acaricides and infection with West Nile virus (WNV) may have confounded the clinical presentation in 2009 and 2010. However, WNV-negative birds exhibited similar signs in 2011. One nestling recovered from paresis within 36 h after the removal of all adult and larval ticks (>350) and was released within 3 wk. The signs present in the heavily infested Bald Eagle nestlings resembled signs associated with tick paralysis, a neurotoxin-mediated paralytic syndrome described in mammals, reptiles, and wild birds (though not eagles). Removal of the infested nest and construction of a nest platform in a different tree was necessary to break the cycle of infection. The original nesting pair constructed a new nest on the man-made platform and successfully fledged two Bald Eagles in 2012.

Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses.

The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis. Macrophage generation of oxysterol activators of liver X receptors (LXRs), via sterol 27-hydroxylase, is regulated by the rate of flux of cholesterol to the inner mitochondrial membrane, via a complex of cholesterol trafficking proteins. Oxysterols are key signalling molecules, regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production, key features influencing the impact of these cells within atherosclerotic lesions. The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate, but may include steroidogenic acute regulatory protein and translocator protein. There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters (ABCA1, ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages. Thus, molecules which can sustain or improve mitochondrial structure, the function of the electron transport chain, or increase the activity of components of the protein complex involved in cholesterol transfer, may therefore have utility in limiting or regressing atheroma development, reducing the incidence of coronary heart disease and myocardial infarction.

Bighorn sheep pneumonia: sorting out the cause of a polymicrobial disease.

Pneumonia of bighorn sheep (Ovis canadensis) is a dramatic disease of high morbidity and mortality first described more than 80 years ago. The etiology of the disease has been debated since its initial discovery, and at various times lungworms, Mannheimia haemolytica and other Pasteurellaceae, and Mycoplasma ovipneumoniae have been proposed as primary causal agents. A multi-factorial "respiratory disease complex" has also been proposed as confirmation of causation has eluded investigators. In this paper we review the evidence for each of the candidate primary agents with regard to causal criteria including strength of association, temporality, plausibility, experimental evidence, and analogy. While we find some degree of biological plausibility for all agents and strong experimental evidence for M. haemolytica, we demonstrate that of the alternatives considered, M. ovipneumoniae is the best supported by all criteria and is therefore the most parsimonious explanation for the disease. The strong but somewhat controversial experimental evidence implicating disease transmission from domestic sheep is consistent with this finding. Based on epidemiologic and microbiologic data, we propose that healthy bighorn sheep populations are naïve to M. ovipneumoniae, and that its introduction to susceptible bighorn sheep populations results in epizootic polymicrobial bacterial pneumonia often followed by chronic infection in recovered adults. If this hypothesized model is correct, efforts to control this disease by development or application of vectored vaccines to Pasteurellaceae are unlikely to provide significant benefits, whereas efforts to ensure segregation of healthy bighorn sheep populations from M. ovipneumoniae-infected reservoir hosts are crucial to prevention of new disease epizootics. It may also be possible to develop M. ovipneumoniae vaccines or other management strategies that could reduce the impact of this devastating disease in bighorn sheep.

Expansion of an exotic species and concomitant disease outbreaks: pigeon paramyxovirus in free-ranging Eurasian collared doves.

Eurasian collared doves (Streptopelia decaocto) have expanded their range across the United States since their introduction several decades ago. Recent mortality events in Eurasian collared doves in Arizona and Montana, USA, during the winter of 2009-2010 were the result of pigeon paramyxovirus (PPMV), a novel disease agent. The first instance of mortality by this emerging infectious disease in this species occurred in Florida in 2001 with subsequent disease events in 2006 and 2008. Full diagnostic necropsies were performed on carcasses from the three states. PPMV was identified by RT-PCR and virus isolation and was sequenced to the VIb genotype of avian paramyxovirus-1 (APMV). Other APMVs are common in a variety of free-ranging birds, but concern is warranted because of the potential for commingling of this species with native birds, virus evolution, and threats to domestic poultry. Improved surveillance for wildlife mortality events and efforts to prevent introduction of non-native animals could reduce the threat of introducing new pathogens.