Wildlife Immune Responses to Mycobacterium bovis and to Bacille of Calmette-Guerin.

Bovine tuberculosis (bTB) is a zoonotic bacterial disease presenting public health, veterinary, and economic threats around the globe. Although cattle producers rely on regular testing and management practices to minimize domestic herd exposure, wildlife species around the world continue to be the main reservoirs for disease. Wildlife reservoirs for bTB include the Eurasian badger (Meles meles) in Great Britain and Ireland, the brushtail possum (Trichosurus vulpecula) in New Zealand, wild boar (Sus scrofa) in Spain, as well as white-tailed deer (Odocoileus virginianus) in the United States and red deer (Cervus elaphus) in Spain. Although all reservoir species share the ability to infect cattle, they differ in transmission capability, disease pathogenesis, diagnostic detection, and vaccination strategies. In this review, bTB interactions with these wildlife reservoirs are discussed, illustrating the need to address bTB disease in wildlife hosts to achieve eradication in domestic livestock.

From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic and wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus), the most widely distributed cervid species in the Americas, were shown to be highly susceptible to SARS-CoV-2 in challenge studies and reported natural infection/exposure rates approaching 30-40% in free-ranging WTD in the U.S. Thus, understanding the infection and transmission dynamics of SARS-CoV-2 in WTD is critical to prevent future zoonotic transmission to humans, at the human-WTD interface during hunting or venison farming, and for implementation of effective disease control measures. Here, we demonstrated that following intranasal inoculation with SARS-CoV-2 B.1 lineage, WTD fawns (~8-month-old) shed infectious virus up to day 5 post-inoculation (pi), with high viral loads shed in nasal and oral secretions. This resulted in efficient deer-to-deer transmission on day 3 pi. Consistent a with lack of infectious SARS-CoV-2 shedding after day 5 pi, no transmission was observed to contact animals added on days 6 and 9 pi. We have also investigated the tropism and sites of SARS-CoV-2 replication in adult WTD (3-4 years of age). Infectious virus was detected up to day 6 pi in nasal secretions, and from various respiratory-, lymphoid-, and central nervous system tissues, indicating broad tissue tropism and multiple sites of virus replication. The study provides important insights on the infection and transmission dynamics of SARS-CoV-2 in WTD, a wild animal species that is highly susceptible to infection and with the potential to become a reservoir for the virus in the field.

Quantification of Brucella abortus population structure in a natural host.

Cattle are natural hosts of the intracellular pathogen Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of uniquely barcoded B. abortus strains to temporally and spatially quantify population structure during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a 1-wk time point. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached a parotid lymph node. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present at 1 wk postinfection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.

Coincidence cloning recovery of Brucella melitensis RNA from goat tissues: advancing the in vivo analysis of pathogen gene expression in brucellosis.

BACKGROUND: Brucella melitensis bacteria cause persistent, intracellular infections in small ruminants as well as in humans, leading to significant morbidity and economic loss worldwide. The majority of experiments on the transcriptional responses of Brucella to conditions inside the host have been performed following invasion of cultured mammalian cells, and do not address gene expression patterns during long-term infection. RESULTS: Here, we examine the application of the previously developed coincidence cloning methodology to recover and characterize B. melitensis RNA from the supramammary lymph node of experimentally-infected goats. Using coincidence cloning, we successfully recovered Brucella RNA from supramammary lymph nodes of B. melitensis-infected goats at both short-term (4 weeks) and long-term (38 weeks) infection time points. Amplified nucleic acid levels were sufficient for analysis of Brucella gene expression patterns by RNA-sequencing, providing evidence of metabolic activity in both the short-term and the long-term samples. We developed a workflow for the use of sequence polymorphism analysis to confirm recovery of the inoculated strain in the recovered reads, and utilized clustering analysis to demonstrate a distinct transcriptional profile present in samples recovered in long-term infection. In this first look at B. melitensis gene expression patterns in vivo, the subset of Brucella genes that was highly upregulated in long-term as compared to short-term infection included genes linked to roles in murine infection, such as genes involved in proline utilization and signal transduction. Finally, we demonstrated the challenges of qPCR validation of samples with very low ratios of pathogen:host RNA, as is the case during in vivo brucellosis, and alternatively characterized intermediate products of the coincidence cloning reaction. CONCLUSIONS: Overall, this study provides the first example of recovery plus characterization of B. melitensis RNA from in vivo lymph node infection, and demonstrates that the coincidence cloning technique is a useful tool for characterizing in vivo transcriptional changes in Brucella species. Genes upregulated in long-term infection in this data set, including many genes not previously demonstrated to be virulence factors in mice or macrophage experiments, are candidates of future interest for potential roles in Brucella persistence in natural host systems.

Persistence of viral RNA in North American elk experimentally infected with an ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

White-tailed deer (Odocoileus virginianus) have emerged as a reservoir host for SARS-CoV-2 given their susceptibility to infection and demonstrated high rates of seroprevalence and infection across the United States. As SARS-CoV-2 circulates within free-ranging white-tailed deer populations, there is the risk of transmission to other wildlife species and even back to the human population. The goal of this study was to determine the susceptibility, shedding, and immune response of North American elk (Cervus elaphus canadensis) to experimental infection with SARS-CoV-2, to determine if another wide-ranging cervid species could potentially serve as a reservoir host for the virus. Here we demonstrate that while North American elk do not develop clinical signs of disease, they do develop a neutralizing antibody response to infection, suggesting the virus is capable of replicating in this mammalian host. Additionally, we demonstrate SARS-CoV-2 RNA presence in the medial retropharyngeal lymph nodes of infected elk three weeks after experimental infection. Consistent with previous observations in humans, these data may highlight a mechanism of viral persistence for SARS-CoV-2 in elk.

Corrigendum: Fecal and vaginal microbiota of vaccinated and non-vaccinated pregnant elk challenged with Brucella abortus.

[This corrects the article DOI: 10.3389/fvets.2024.1334858.].

Fecal and vaginal microbiota of vaccinated and non-vaccinated pregnant elk challenged with Brucella abortus.

Introduction: Brucella abortus is the causative agent of brucellosis in cattle and in humans, resulting in economic losses in the agricultural sector and representing a major threat to public health. Elk populations in the American Northwest are reservoirs for this bacterium and transmit the agent to domestic cattle herds. One potential strategy to mitigate the transmission of brucellosis by elk is vaccination of elk populations against B. abortus; however, elk appear to be immunologically distinct from cattle in their responses to current vaccination strategies. The differences in host response to B. abortus between cattle and elk could be attributed to differences between the cattle and elk innate and adaptive immune responses. Because species-specific interactions between the host microbiome and the immune system are also known to affect immunity, we sought to investigate interactions between the elk microbiome and B. abortus infection and vaccination. Methods: We analyzed the fecal and vaginal microbial communities of B. abortus-vaccinated and unvaccinated elk which were challenged with B. abortus during the periparturient period. Results: We observed that the elk fecal and vaginal microbiota are similar to those of other ruminants, and these microbial communities were affected both by time of sampling and by vaccination status. Notably, we observed that taxa representing ruminant reproductive tract pathogens tended to increase in abundance in the elk vaginal microbiome following parturition. Furthermore, many of these taxa differed significantly in abundance depending on vaccination status, indicating that vaccination against B. abortus affects the elk vaginal microbiota with potential implications for animal reproductive health. Discussion: This study is the first to analyze the vaginal microbiota of any species of the genus Cervus and is also the first to assess the effects of B. abortus vaccination and challenge on the vaginal microbiome.

Promotion of a functional B cell germinal center response after Leishmania species co-infection is associated with lesion resolution.

Co-infection of C3HeB/FeJ (C3H) mice with both Leishmania major and Leishmania amazonensis leads to a healed footpad lesion, whereas co-infection of C57BL/6 (B6) mice leads to non-healing lesions. This inability to heal corresponds to a deficiency in B cell stimulation of the macrophage-mediated killing of L. amazonensis in vitro and a less robust antibody response. The mechanism that leads to healing of these lesions is not completely known, although our studies implicate the B cell response as having an important effector function in killing L. amazonensis. To understand more completely this disparate clinical outcome to the same infection, we analyzed the draining lymph node germinal center B cell response between co-infected C3H and B6 mice. There were more germinal center B cells, more antibody isotype-switched germinal center B cells, more memory B cells, and more antigen-specific antibody-producing cells in co-infected C3H mice compared to B6 mice as early as 2 weeks postinfection. Interleukin (IL)-21 production and IL-21 receptor expression in both mouse strains, however, were similar at 2 weeks, suggesting that the difference in the anti-Leishmania response in these mouse strains may be due to differences in T follicular cell commitment or intrinsic B cell differences. These data support the idea that functional B cells are important for healing L. amazonensis in this infectious disease model.

Pulmonary hamartoma in an elk calf.

Hamartomas are benign tumor-like lesions composed of disorganized growth of mature mesenchymal or epithelial tissues indigenous to the organ involved. Sporadically observed in ruminants, vascular, fibrous, nasal, and pulmonary hamartomas have been reported in calves; pulmonary and cutaneous forms have been reported in sheep. A full-term elk calf found dead had a large intrathoracic mass replacing the left caudal lung lobe and compressing other thoracic organs. Histologically, cross- and tangential sections of bronchi were separated by collagenous mesenchyme and irregularly shaped canaliculi and saccules resembling terminal bronchioles. Rarely present were regions in which saccules, lined by simple cuboidal epithelium, transitioned into attenuated epithelium lining fully developed alveoli. These findings are consistent with a pulmonary hamartoma. To our knowledge, pulmonary hamartoma has not been reported previously in a non-domestic ruminant.

Effects of concurrent administration of modified live viral vaccines with RB51 on immune responses to RB51.

Brucella abortus is a gram negative, zoonotic pathogen that can cause abortions and stillbirths in the cattle industry and has contributed to significant economic losses to cow-calf producers. Cell mediated immunity (CMI) is an important component of the immune response associated with protection against Brucella abortus and other intracellular pathogens. Brucellosis and viral modified live vaccines (vMLV) are licensed individually but may be used concurrently under field conditions. Peripheral blood mononuclear cells (PBMC) from non-vaccinated cattle and cattle vaccinated with either Brucella abortus strain RB51, a vMLV or both RB51 and a vMLV vaccine were isolated. The frequency of CD4+, CD8+ and γδ+ T cell populations within PBMC, and the frequency of interferon gamma (IFN-γ) production within these cell types was characterized via flow-cytometry. The goal of this study was to characterize immune responses to RB51 vaccination and determine the effect of concurrent vaccine administration. Although immune responses were greatest in PBMC from cattle vaccinated with only RB51, cattle vaccinated with both RB51 and vMLV demonstrated measurable T cell responses associated with protective immunity. Data suggests a lack of significant biological differences between the groups in protective immune responses. Collectively, our data demonstrated a lack of vaccine interference following concurrent administration of vMLV and RB51. Although concurrent administration of individually licensed vaccines may influence immune responses and contribute to vaccine interference, potential vaccine combinations should be evaluated for biological effects.

Vaccination of White-Tailed Deer with Mycobacterium bovis Bacillus Calmette-Guérin (BCG): Effect of Mycobacterium avium ssp. paratuberculosis Infection.

In many parts of the world, bovine tuberculosis eradication efforts are hampered by wildlife reservoirs of Mycobacterium bovis, which serve as a constant source of M. bovis for nearby cattle. The human tuberculosis vaccine, M. bovis BCG has been investigated for use in several wildlife species, including deer. In the US, white-tailed deer in Michigan have been the source of infection for over 82 cattle herds since M. bovis was discovered in free-ranging deer in 1995. The efficacy of BCG may be influenced by many factors, including prior exposure or infection with non-tuberculous mycobacteria, that is, species other than members of the M. tuberculosis complex. M. avium subspecies paratuberculosis (Map) infection is not uncommon in ruminants such as deer. Using natural exposure to Map and experimental infection with M. bovis, we demonstrate that Map infection increased BCG vaccine efficacy as measured by lesion severity scores.

Genomic regions associated with pseudorabies virus infection status in naturally infected feral swine (Sus scrofa).

Pseudorabies virus (PRV)-the causative agent of Aujeszky's disease-was eliminated from commercial pig production herds in the United States (US) in 2004; however, PRV remains endemic among invasive feral swine (Sus scrofa). The circulation of PRV among abundant, widespread feral swine populations poses a sustained risk for disease spillover to production herds. Risk-based surveillance has been successfully implemented for PRV in feral swine populations in the US. However, understanding the role of host genetics in infection status may offer new insights into the epidemiology and disease dynamics of PRV that can be applied to management strategies. Genetic mechanisms underlying host susceptibility to PRV are relatively unknown; therefore, we sought to identify genomic regions associated with PRV infection status among naturally infected feral swine using genome-wide association studies (GWAS) and gene set enrichment analysis of single nucleotide polymorphism data (GSEA-SNP). Paired serological and genotypic data were collected from 6,081 feral swine distributed across the invaded range within the contiguous US. Three complementary study populations were developed for GWAS: 1) comprehensive population consisting of feral swine throughout the invaded range within the contiguous US; 2) population of feral swine under high, but temporally variable PRV infection pressure; and 3) population of feral swine under temporally stable, high PRV infection pressure. We identified one intronic SNP associated with PRV infection status within candidate gene AKAP6 on autosome 7. Various gene sets linked to metabolic pathways were enriched in the GSEA-SNP. Ultimately, improving disease surveillance efforts in feral swine will be critical to further understanding of the role host genetics play in PRV infection status, helping secure the health of commercial pork production.

The Bovine Tuberculoid Granuloma.

The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.

Enhanced Detection of Mycobacterium bovis-Specific T Cells in Experimentally-Infected Cattle.

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferation provides a deeper understanding of the functional nature of these cells. The work presented here, analyzes the T cell response following experimental M. bovis infection in cattle via in vitro antigenic expansion and re-stimulation to characterize antigen-specific CD4, CD8, and γδ T cells and their functional phenotype, shedding light on the variable functional ability of these cells. Data gathered from these studies can help us better understand the cellular response to M. bovis infection and develop improved vaccines and diagnostic tools.

Heterogeneity of Pulmonary Granulomas in Cattle Experimentally Infected With Mycobacterium bovis.

Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-γ, TNF-α, TGF-ß, granuloma stage, or lung lesion score, although there was a modest positive correlation with IL-10 expression. Granuloma stage did have modest positive and negative correlations with TNF-α and IL-10, respectively. Heterogeneity and mean expression of IFN-γ, IL-10 and TNF-α did not differ significantly over time, however, expression of TGF-ß at 90 days was significantly greater than that seen at 30 days after infection.

Immune Responses and Efficacy of Brucella Abortus Strain RB51 in Bison After Delivery in a Dry Dart Formulation or by Parenteral Inoculation.

Bison (Bison bison) heifer calves (n = 32) were randomly assigned to control or vaccination with 1010 colony-forming units of Brucella abortus strain RB51 (RB51) vaccine by single or boostered parenteral delivery, or by surgical implantation of a dry dart formulation (n = 8/trt). Serum and/or peripheral blood mononuclear cells (PBMC) were obtained at 0, 4, 8, 13, 16, 21, and 24 wks after initial vaccination and at 0, 4, 8, 12, 15, 22, and 27 wks after booster vaccination to characterize humoral and cellular immune responses to RB51. Bison in both RB51 vaccination treatments demonstrated greater (P < 0.0001) serum humoral responses when compared to non-vaccinates, with parenteral vaccinates demonstrating greater (P < 0.01) responses when compared to mean responses of bison inoculated with the dry dart. Only the booster vaccinated treatment demonstrated greater (P < 0.0001) humoral responses than control bison in samples collected after re-inoculation. At 4, 8, 12, 16, and 24 wks after initial vaccination, PBMC from parenteral RB51 vaccinates demonstrated greater proliferative responses to RB51 when compared to responses of control animals. In comparison, bison inoculated with the RB51 dry dart did not demonstrate greater (P > 0.05) proliferative responses when compared to responses of non-vaccinates. Bison were pasture bred and pregnant animals experimentally challenged in mid-gestation with 107 CFU of B. abortus strain 2,308. Bison in parenteral vaccination treatments had reduced (P < 0.05) abortions and infection in uterine and fetal samples as compared to non-vaccinated bison, with booster vaccinates tending to have the lowest colonization (CFU/gm) in tissues. In comparison, the dry dart formulation did reduce abortion (P < 0.05) but not infection (P > 0.05) in most tissues when compared to non-vaccinated bison. The results of this study reaffirm the efficacy of boostered parenteral vaccination of bison with RB51 in preventing brucellosis. Our data also suggests that the novel dry dart RB51 formulation does not induce sufficient efficacy in bison after a single inoculation.

Influence of species of negative control sera on results of a brucellosis fluorescence polarization assay.

We evaluated serologic responses of cattle, bison, elk, and swine representing negative control, early vaccination (4-8 wk), late vaccination (21-28 wk) or booster vaccination, early after-experimental challenge (2-4 wk), and late after-experimental challenge (8-21 wk), in a brucellosis fluorescence polarization assay (FPA; n = 10 sera per species per treatment) using negative control sera from cattle, bison, elk, and swine (n = 5 per species). Sera from cattle shedding Brucella abortus strain RB51 in milk were also evaluated against the 20 negative control sera. The species of negative control sera used in the FPA could increase (p < 0.05) delta millipolarization (mP; delta mP = sample mP - negative control mP) results. In general, the species of negative control sera did not alter the interpretation of FPA results in control, vaccinated, or infected animals. Even after repeated RB51 vaccinations in bison, cattle, or elk, or in cattle shedding RB51 in milk, serologic results from the FPA remained negative. Species differences in FPA results were noted; elk developed robust humoral responses very quickly after infection that resulted in strong positive FPA results. In cattle and bison, humoral responses appeared to develop over a longer period of time, and greater delta mP values were detected at later times after infection. Sensitivity of the FPA for detecting infected animals was greatest for elk in early challenge samples and bison in late challenge samples. Our data suggest that species of origin of negative control sera does not influence interpretation of the FPA in natural hosts of Brucella abortus.

Mucosal IFNγ production and potential role in protection in Escherichia coli O157:H7 vaccinated and challenged cattle.

Shiga-toxin producing Escherichia coli O157:H7 (O157)-based vaccines can provide a potential intervention strategy to limit foodborne zoonotic transmission of O157. While the peripheral antibody response to O157 vaccination has been characterized, O157-specific cellular immunity at the rectoanal junction (RAJ), a preferred site for O157 colonization, remains poorly described. Vaccine induced mucosal O157-specific antibodies likely provide some protection, cellular immune responses at the RAJ may also play a role in protection. Distinct lymphoid follicles were increased in the RAJ of vaccinated/challenged animals. Additionally, increased numbers of interferon (IFN)γ-producing cells and γδ + T cells were detected in the follicular region of the RAJ of vaccinated/challenged animals. Likewise, adjuvanted-vaccine formulation is critical in immunogenicity of the O157 parenteral vaccine. Local T cell produced IFNγ may impact epithelial cells, subsequently limiting O157 adherence, which was demonstrated using in vitro attachment assays with bovine epithelial cells. Thus, distinct immune changes induced at the mucosa of vaccinated and challenged animals provide insight of mechanisms associated with limiting O157 fecal shedding. Enhancing mucosal immunity may be critical in the further development of efficacious vaccines for controlling O157 in ruminants and thus limiting O157 transmission to humans.

Enhancing the Detection of Brucella-Specific CD4+ T Cell Responses in Cattle via in vitro Antigenic Expansion and Restimulation.

Bovine brucellosis, cause by infection with Brucella abortus, causes reproductive failure in cattle, has a major economic impact to producers, and as a zoonoses, it is a disease of public health concern. Characterization of the protective immune response against Brucella infection is important to our understanding of disease pathogenesis and for the development of diagnostic assays and vaccines. Most of the knowledge regarding protection against Brucella comes from studies in the murine model, but less is known about the immune responses in cattle. Assessment of antigen-specific T cell frequency and functional phenotype are critical to understand the immune status of the host, characterize mechanisms of protective immunity and immunopathology, and to predict immune protection. The frequency of circulating T cells specific for a particular pathogen is often very low, making analysis of such responses difficult. Our goal was to develop a flow-cytometry based approach to better track Brucella-specific T cell responses. Using peripheral blood mononuclear cells (PMBC) from Brucella abortus strain RB51-vaccinated cattle, we optimized an in vitro stimulation protocol based on a combination of antigen and pan-T cell stimulation. We then assessed RB51-specific T cell responses by concurrently measuring proliferation and cytokine production using flow-cytometry. This methodology enhances the detection of peripheral, Brucella-specific responses in cattle following RB51 vaccination. This protocol is versatile in that it can be modified to fit other in vitro stimulation systems and additional functional or phenotypic parameters can be added for flow cytometric detection and characterization of antigen-specific T cells.

Case Report: Fading Elk Syndrome in a Herd of Captive Elk (Cervus elaphus) in the North American Midwest.

Fading elk syndrome, or chronic ill-thrift of elk, is a disease associated with abomasal parasitism with Ostertagia species, of which elk appear to be particularly susceptible. While this syndrome has been extensively reported to affect wapiti-type red deer hybrids farmed in New Zealand since the mid 1980's, there is only a single report of this disease in North America. Here, we report a case of fading elk syndrome in a herd of 34 elk (Cervus elaphus) in Ames, Iowa, at the National Animal Disease Center. Analysis of complete blood counts were unremarkable, but blood chemistry demonstrated a severe hypoalbuminemia. Fecal floatations were also unremarkable, and non-diagnostic. Histological examination of tissues collected at necropsy revealed proliferative abomasitis and nematodes consistent with Ostertagia spp. Anthelmintic treatment consisting of a combination of pour-on Cydectin® and injectable Noromectin Plus®, at double the recommended dose for cattle, showed positive results, as all remaining animals in the herd recovered. The work presented here is the first report of naturally-acquired disease in a herd of captive elk used for research and sheds light on this seldomly-reported disease in North America.