@article{schreeg_cullen_robertson_gookin_2023, title={Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats}, volume={8}, ISSN={["1544-2217"]}, DOI={10.1177/03009858231189450}, abstractNote={Conjoining of the major pancreatic duct and common bile duct at the major duodenal papilla (MDP) is suspected to predispose cats to the clinical syndrome of "triaditis." However, microanatomy of the MDP or presence of lesions at the MDP has not been assessed in cats with or without triaditis. The aims of this study were to characterize feline MDP histomorphology and to identify associations between MDP anatomy/disease and the presence of biliary, pancreatic, or intestinal inflammation or neoplasia. Histologic assessment was prospectively performed on the MDP, duodenum, jejunum, ileum, liver, and pancreas from 124 client-owned cats undergoing postmortem examination. The majority of cats (104/124, 84%) had a complex ductular network at the MDP, with no distinction between pancreatic and common bile ducts. Lymphoid aggregates at the MDP were common (63/124, 51%). Inflammation of the MDP (MDPitis) was present in 35 of 124 cats (28%) and was often concurrent with cholangitis, pancreatitis, or enteritis (32/35, 91%), but was only associated with enteritis (19/35, 54%, P < .05). Triaditis was less common (19/124, 15%), but was associated with both conjoined MDP anatomy (19/19, 100%, P < .05) and MDPitis (12/19, 63%, P < .05). Neoplasia was present in 37 of 124 cats (29%), with lymphoma (28/37, 78%) predominating. Enteropathy-associated T-cell lymphoma type 2 (EATL2) was most common (n = 16/37, 43%) and was associated with triaditis and MDPitis (P < .05). These findings suggest that anatomy, immune activation, and/or inflammation of the MDP may play a role in the pathogenesis of triaditis. Further studies are needed to elucidate the relationships between triaditis, MDPitis, and EATL2.}, journal={VETERINARY PATHOLOGY}, author={Schreeg, Megan E. and Cullen, John M. and Robertson, James and Gookin, Jody L.}, year={2023}, month={Aug} }
 @article{linn-peirano_hepworth-warren_kinsella_diaz-campos_brenseke_cianciolo_schroeder_schreeg_2023, title={Ingesta-associated choledocholithiasis in horses: 2 cases and literature review}, volume={5}, ISSN={["1943-4936"]}, DOI={10.1177/10406387231177251}, abstractNote={Equine ingesta-associated choledocholithiasis is a rare cause of morbidity and mortality. We describe here the clinical, gross, histologic, and microbiologic features of this condition in 2 horses and compare the features to 2 previous cases. Case 1 was a 4-y-old Thoroughbred mare with colic. Case 2 was an 18-y-old American Paint Horse mare with colic, chronic weight loss, and inappropriate mentation. Both had elevated biochemical markers of hepatocellular injury and cholestasis and were euthanized given a poor prognosis. Case 1 had a well-formed 5-cm choledocholith surrounding a piece of hay, and had chronic neutrophilic cholangiohepatitis, bridging fibrosis, and extrahepatic obstruction. Case 2 had an ill-formed choledocholith with occasional hay fragments, wood stick, and twigs, and had regionally extensive hepatocellular necrosis with mild neutrophilic cholangiohepatitis and bridging fibrosis. Enterococcus casseliflavus and Escherichia coli were isolated in both cases; Clostridium spp. were also isolated from case 2. All 4 reported cases had increased activity of cholestatic enzymes, hyperbilirubinemia, portal inflammation, and bridging fibrosis. Colic, pyrexia, leukocytosis with neutrophilia, and elevated hepatocellular enzyme activity were documented in 3 cases. Foreign material in all 4 cases was plant origin (choledochophytolithiasis), including hay (n = 2), sticks/twigs (n = 2), and grass awns (n = 1). Ingesta-associated choledocholithiasis may be considered as a cause of colic, pyrexia, and elevated cholestatic biomarkers in horses.}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Linn-Peirano, Sarah C. C. and Hepworth-Warren, Kate and Kinsella, Hannah and Diaz-Campos, Dubraska and Brenseke, Bonnie M. M. and Cianciolo, Rachel E. E. and Schroeder, Eric and Schreeg, Megan E. E.}, year={2023}, month={May} }
 @article{slead_callahan_schreeg_seiler_stowe_azcarate-peril_jacob_gookin_2023, title={Microbiome analysis of bile from apparently healthy cats and cats with suspected hepatobiliary disease}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16852}, DOI={10.1111/jvim.16852}, abstractNote={Abstract Background Bacterial infection of bile is a common cause of hepatobiliary disease in cats. Whether bile harbors a core microbiota in health or in cases of suspected hepatobiliary disease in cats is unknown. Objectives Establish if gallbladder bile in apparently healthy cats harbors a core microbiota composed of bacterial taxa common to many individuals. Compare results of bile cytology, bile culture, and 16S rRNA gene amplicon sequencing in apparently healthy cats and cats with suspected hepatobiliary disease. Animals Forty‐three client‐owned cats with suspected hepatobiliary disease and 17 control cats. Methods Bile was collected by ultrasound guided cholecystocentesis (cats with suspected hepatobiliary disease) or laparotomy after euthanasia (controls). Bile samples underwent cytologic examination, aerobic and anaerobic culture, and DNA was extracted for 16S rRNA gene amplification and sequencing. Results Microbiome sequencing did not identify a core microbiota in control cats or cats having bile sampled because of clinical suspicion for hepatobiliary disease. Microbiome profiles from control cats were indistinguishable from profiles obtained from sampling instruments and reagents that were not exposed to bile (technical controls). Bacterial taxa that could not be explained by contamination or off‐target amplification were identified only in samples from cats with bactibilia and positive bile culture results for Escherichia coli. In several E. coli positive samples, microbiome sequencing also identified a small number of potentially co‐infecting bacterial genera not identified by culture. Conclusions and Clinical Importance Cat bile does not harbor a core microbiota. Uncultured bacteria may contribute to pathogenesis of hepatobiliary disease in cats with bile E. coli infection.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Slead, Tanner S. and Callahan, Benjamin J. and Schreeg, Megan E. and Seiler, Gabriela S. and Stowe, Devorah M. and Azcarate-Peril, Maria Andrea and Jacob, Megan E. and Gookin, Jody L.}, year={2023}, month={Sep} }
 @article{gaudette_ladouceur_troan_whitehurst_dombrowski_lewbart_linder_passingham_christian_schreeg_2023, title={Retrospective analysis of histologic lesions in captive arachnids}, volume={4}, ISSN={["1544-2217"]}, DOI={10.1177/03009858231162948}, abstractNote={Invertebrates, including arachnids, are a common taxon in zoological collections. Invertebrate medicine and pathology are emerging subspecialties, but there is limited reference material or published resources describing histologic lesions in arachnids. Histopathology of 26 captive arachnids (20 spiders and 6 scorpions) from institutional collections was reviewed. Most animals were found dead with limited clinical signs. Tissues evaluated included body wall (cuticle and epidermis), skeletal muscle, book lungs, digestive tract (pharynx, esophagus, sucking stomach, midgut tube, midgut diverticula, and stercoral pocket), central and peripheral nervous system, heart, hemolymph vessels and sinuses, Malpighian tubules, coxal glands, and gonads. Inflammation was frequent (24/26, 92%), and seen in multiple organs (18/24, 75%) with the midgut diverticulum most commonly affected (14/24, 58%) followed by the book lungs (13/24 arachnids, 54%), and body wall (8/24 arachnids, 33%). Inflammation comprised hemocyte accumulation, hemocytic coagula, melanization, and nodulation. Infectious agents, including bacteria (11/26, 42%), fungi (10/26, 38%), and parasites (2/26, 8%), were seen within inflammatory aggregates. Coinfection with multiple infectious agents was common (6/24, 25%). No etiologic agent was identified in 7/24 (29%) cases with inflammatory lesions. Lesions suggestive of decreased nutritional status or increased metabolic rate included midgut diverticula atrophy in 11/26 (42%) animals and skeletal muscle atrophy in 6/26 (23%) animals. Atrophic lesions were seen in combination with infection (8/11, 73%), pregnancy (2/11, 18%), male sex (2/11, 18%), or without other lesions (1/11, 9%). Other suspected contributors to death included dysecdysis-associated trauma (2/26, 8%) and uterine intussusception (1/26, 4%). No animals had neoplasia.}, journal={VETERINARY PATHOLOGY}, author={Gaudette, Chris and LaDouceur, Elise E. B. and Troan, Brigid V. and Whitehurst, Nathan and Dombrowski, Daniel S. and Lewbart, Gregory A. and Linder, Keith E. and Passingham, Kent and Christian, Larry S. and Schreeg, Megan E.}, year={2023}, month={Apr} }
 @article{kang_womble_cullen_harrison_premanandan_schreeg_2023, title={Severe bronchiectasis resulting from chronic bacterial bronchitis and bronchopneumonia in a jungle cat}, volume={11}, ISSN={["1943-4936"]}, DOI={10.1177/10406387231216181}, abstractNote={Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat (Felis chaus) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli. There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids.}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Kang, Danyue and Womble, Mandy and Cullen, John M. and Harrison, Tara M. and Premanandan, Christopher and Schreeg, Megan E.}, year={2023}, month={Nov} }
 @article{schreeg_radkin_haugland_murphy_rushton_linder_2022, title={Ameloblastic carcinoma in horses: case report and literature review}, ISSN={["1943-4936"]}, DOI={10.1177/10406387211068459}, abstractNote={Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin–vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin–vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin–vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Schreeg, Megan E. and Radkin, Megan and Haugland, Jennifer and Murphy, Brian G. and Rushton, Steve and Linder, Keith E.}, year={2022}, month={Jan} }
 @article{bauer_murillo_schreeg_borst_watanabe_2022, title={Pathology in Practice}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.03.0119}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bauer, Katherine and Murillo, Daniel Felipe Barrantes and Schreeg, Megan E. and Borst, Luke B. and Watanabe, Tatiane Terumi Negrao}, year={2022}, month={Sep}, pages={1466–1468} }
 @article{schreeg_miller_cullen_2021, title={Choledochal cyst with secondary cholangitis, choledochitis, duodenal papillitis, and pancreatitis in a young domestic shorthair cat}, ISSN={["1943-4936"]}, DOI={10.1177/10406387211017107}, abstractNote={Choledochal cysts, congenital segmental dilations of the common bile duct, have been reported in few cats, and histologic characterization is lacking. A 20-mo-old spayed female domestic shorthair cat was presented because of vomiting and weight loss. There was progressive elevation of liver enzyme activity (ALT > ALP, GGT) and hyperbilirubinemia. Diagnostic imaging identified focal cystic dilation of the common bile duct, dilation and tortuosity of adjacent hepatic ducts, and a prominent duodenal papilla. A choledochal cyst was suspected, and the animal was euthanized. On postmortem examination, there was a 2-cm, firm, thickened, cystic dilation of the common bile duct, patent with adjacent ducts. Histologically, the cyst wall was expanded by fibroblasts, collagen, and lymphoplasmacytic inflammation. Adjacent bile ducts were markedly dilated and tortuous, with lymphoplasmacytic inflammation and papillary mucosal hyperplasia that extended to the major duodenal papilla. There was chronic neutrophilic cholangitis, suggesting bacterial infection and/or disturbed bile drainage, extrahepatic obstruction, and lymphoplasmacytic pancreatitis with ductular metaplasia. Prominent lymphoid follicles within biliary ducts and duodenum suggested chronic antigenic stimulation. Choledochal cysts can be associated with chronic neutrophilic cholangitis, extrahepatic obstruction, choledochitis, duodenal papillitis, and pancreatitis, and should be a differential for increased hepatic enzymes and hyperbilirubinemia in young cats.}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Schreeg, Megan E. and Miller, Sybille A. and Cullen, John M.}, year={2021}, month={May} }
 @article{womble_schreeg_hoch_meira_foster_premanandan_watanabe_2021, title={Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)}, volume={189}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2021.09.007}, abstractNote={An adult alpaca (Vicugna pacos) with a history of colic and anorexia was euthanized because of failure to respond to treatment. Macroscopically, pale-tan, multifocal to coalescing, firm nodules and plaques markedly expanded the omentum, mesentery and the parietal and visceral peritoneum of multiple abdominal organs, especially the right oviduct and associated mesosalpinx. Abundant dark-red watery digesta were present in the duodenum and jejunum. Histological evaluation of the right oviduct, abdominal visceral nodules and plaques and mesenteric lymph nodes revealed transmural expansion and replacement by an epithelial malignant neoplasm, comprised of tubules and acini of ciliated columnar cells supported by abundant fibrous connective tissue. Both ovaries were histologically normal. On the basis of the ciliated morphology of the neoplastic cells, the focus on the proximal reproductive tract and the unremarkable ovaries, a reproductive tubal adenocarcinoma with carcinomatosis was diagnosed, with both the endometrium and oviduct considered as the tissues of origin. The prominent ciliated morphology of the neoplastic cells and the classification of human fallopian tube (oviduct) neoplasia lead us to propose oviductal adenocarcinoma with widespread carcinomatosis as the definitive diagnosis. The lamina propria of the small intestine was infiltrated segmentally by lymphocytes, plasma cells and neutrophils, and Clostridium perfringens with beta2 toxin production was identified by polymerase chain reaction in the small intestinal contents. To our knowledge, this is the first report of these two distinct diseases in an alpaca.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Womble, Mandy and Schreeg, Megan E. and Hoch, Allison and Meira, Enoch B. de Souza, Jr. and Foster, Derek and Premanandan, Christopher and Watanabe, Tatiane T. Negrao}, year={2021}, month={Nov}, pages={52–58} }
 @article{mones_schreeg_sommer_linder_lewbart_2021, title={Surgical management and histopathology of wen overgrowth and neoplasia in four oranda goldfish (Carassius auratus)}, volume={9}, ISSN={["2052-6121"]}, DOI={10.1002/vrc2.27}, abstractNote={Abstract The wen is a cap of gelatinous soft tissue that extends over the head and face of many varieties of fancy goldfish ( Carassius auratus ). Here, we describe the surgical management and histopathology of four fish with proliferative wen lesions. All fish were anesthetized for debulking or biopsy of the affected wen. One fish was diagnosed with wen hyperplasia, one fish was diagnosed with wen hyperplasia with a concurrent spindle cell neoplasm, and two fish were diagnosed with epithelial neoplasms of the wen, including a carcinoma arising within a papilloma and an epidermal papilloma with spindle cell and hyalinized matrix proliferation. This is the first published report of neoplasia in the wen of fancy goldfish. Regular evaluation of the wen during routine physical examinations may allow for biopsy of wen lesions, leading to early diagnosis and treatment interventions.}, number={1}, journal={VETERINARY RECORD CASE REPORTS}, author={Mones, Alissa and Schreeg, Megan and Sommer, Samantha and Linder, Keith and Lewbart, Gregory}, year={2021}, month={Mar} }
 @article{baneth_nachum-biala_birkenheuer_schreeg_prince_florin-christensen_schnittger_aroch_2020, title={A new piroplasmid species infecting dogs: morphological and molecular characterization and pathogeny of Babesia negevi n. sp.}, volume={13}, ISSN={["1756-3305"]}, DOI={10.1186/s13071-020-3995-5}, abstractNote={Abstract Introduction Babesiosis is a protozoan tick-borne infection associated with anemia and life-threatening disease in humans, domestic and wildlife animals. Dogs are infected by at least six well-characterized Babesia spp. that cause clinical disease. Infection with a piroplasmid species was detected by light microscopy of stained blood smears from five sick dogs from Israel and prompted an investigation on the parasite’s identity. Methods Genetic characterization of the piroplasmid was performed by PCR amplification of the 18S rRNA and the cytochrome c oxidase subunit 1 ( cox 1) genes, DNA sequencing and phylogenetic analysis. Four of the dogs were co-infected with Borrelia persica (Dschunkowsky, 1913), a relapsing fever spirochete transmitted by the argasid tick Ornithodoros tholozani Laboulbène & Mégnin. Co-infection of dogs with B. persica raised the possibility of transmission by O. tholozani and therefore, a piroplasmid PCR survey of ticks from this species was performed. Results The infected dogs presented with fever (4/5), anemia, thrombocytopenia (4/5) and icterus (3/5). Comparison of the 18S rRNA and cox 1 piroplasmid gene sequences revealed 99–100% identity between sequences amplified from different dogs and ticks. Phylogenetic trees demonstrated a previously undescribed species of Babesia belonging to the western group of Babesia ( sensu lato ) and closely related to the human pathogen Babesia duncani Conrad, Kjemtrup, Carreno, Thomford, Wainwright, Eberhard, Quick, Telfrom & Herwalt, 2006 while more moderately related to Babesia conradae Kjemtrup, Wainwright, Miller, Penzhorn & Carreno, 2006 which infects dogs. The piroplasm forms detected included tetrads (Maltese cross), merozoite and trophozoite stages whose average size was larger than stages of other canine Babesia spp. belonging to the Babesia ( s.l .) and B. gibsoni Patton, 1910, and smaller than other canine Babesia ( sensu stricto ) spp. Of 212 O. tholozani ticks surveyed, 11 (5.2%) harbored DNA of the new species of Babesia . Conclusions Babesia negevi n. sp. is described based on morphological and genetic characterization and phylogenetic analyses. The species is named after the Negev desert of southern Israel, where the first infected dog originated from. Despite co-infection in four dogs, the fifth dog had fatal disease attesting that B. negevi n. sp. infection requires clinical attention. Incriminating O. tholozani or another tick species as the vector of Babesia negevi n. sp., would require additional studies.}, number={1}, journal={PARASITES & VECTORS}, author={Baneth, Gad and Nachum-Biala, Yaarit and Birkenheuer, Adam Joseph and Schreeg, Megan Elizabeth and Prince, Hagar and Florin-Christensen, Monica and Schnittger, Leonhard and Aroch, Itamar}, year={2020}, month={Apr} }
 @article{schreeg_evans_allen_lewis_luckring_evola_richard_piner_thompson_adin_et al._2019, title={Cardiac Leiomyosarcoma in a Cat Presenting for Bilateral Renal Neoplasia}, volume={168}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2019.02.005}, abstractNote={A 10-year-old neutered female domestic longhair cat was presented to a tertiary care veterinary hospital for evaluation of a right renal mass that was identified incidentally on abdominal radiographs and classified further as a sarcoma based on fine needle aspiration cytology. Further diagnostic workup, including ultrasound and cytology, identified a sarcoma in the left kidney. After approximately 1 month of conservative medical management, the clinical condition deteriorated and the cat was humanely destroyed. Post-mortem examination confirmed bilateral renal masses with multifocal infarction and extensive necrosis, and further identified a large mass at the apex of the heart as well as multiple pulmonary nodules. Microscopical examination of the masses identified a population of poorly-differentiated neoplastic spindle cells, consistent with sarcoma. Immunohistochemically, the neoplastic cells expressed smooth muscle actin and muscle-specific actin, but were negative for myoglobin and factor VIII. Phosphotungstic acid–haematoxylin staining was unable to identify cross-striations in the neoplastic cells. Based on these results and the pattern of lesion distribution, the cat was diagnosed with cardiac leiomyosarcoma with pulmonary and bilateral renal metastasis.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Schreeg, M. E. and Evans, B. J. and Allen, J. and Lewis, M. C. and Luckring, E. and Evola, M. and Richard, D. K. and Piner, K. and Thompson, E. M. and Adin, D. B. and et al.}, year={2019}, month={Apr}, pages={19–24} }
 @article{naor_lindemann_schreeg_marr_birkenheuer_carpenter_ryseff_2019, title={Clinical, morphological, and molecular characterization of an undetermined Babesia species in a maned wolf (Chrysocyon brachyurus)}, volume={10}, ISSN={["1877-9603"]}, DOI={10.1016/j.ttbdis.2018.09.005}, abstractNote={A possible novel Babesia species infection of a maned wolf (Chrysocyon brachyurus) was first reported in 2012. The current case details a confirmed report of a maned wolf with infection by an undetermined species of Babesia. As the mortality and morbidity of babesiosis is high, this may become a significant concern to captive maned wolves, which are considered a near-threatened species by the World Association of Zoos and Aquariums. The aim of this study is to report the clinical, morphological and molecular characterization of this Babesia species. A 2.5-year-old, intact female maned wolf was found laterally recumbent with pale mucous membranes and jaundice the morning of presentation. Hematological and serum biochemical data were consistent with babesiosis and showed a regenerative severe anemia, leukocytosis, thrombocytopenia, hyperbilirubinemia, azotemia, increased creatine phosphokinase and increase alanine aminotransferase. On blood film review, inclusion bodies were seen in the red blood cells with cytomorphological features that were most consistent with a small form Babesia species. A blood sample was sent for polymerase chain reaction (PCR) testing and multi-locus sequence analyses. These findings suggested a unique Babesia species that is most closely related to a Babesia species (Babesia sp. AJB-2006) that has been found to infect raccoons (Procyon lotor) in North America. Although the cytomorphological features of the piroplasms and the clinical presentation were similar in both the current and 2012 case, when comparing the 18S melt curve temperature of the two Babesia isolates, the peak temperature was different. Unfortunately, genetic material from the 2012 case was not available so comparison of multi-locus gene sequences could not be performed, excluding the possibility to definitively state if the Babesia spp. from both cases were distinct from each other. The maned wolf was treated with a whole blood transfusion, dexamethazone (0.28 mg/kg IM), azithromycin (10 mg/kg in NaCl SC), atavaquone (1.5 cc PO), and 2 imidocarb (6.6 mg/kg IM) injections, and clinically improved. These findings demonstrate the need to further characterize the molecular and epidemiological differences of the Babesia species in this case report and the Babesia species known to infect raccoons.}, number={1}, journal={TICKS AND TICK-BORNE DISEASES}, author={Naor, Adi Wasserkrug and Lindemann, Dana M. and Schreeg, Megan E. and Marr, Henry S. and Birkenheuer, Adam J. and Carpenter, James W. and Ryseff, Julia K.}, year={2019}, month={Jan}, pages={124–126} }
 @article{khana_peterson_stanton_schreeg_birkenheuer_tarigo_2018, title={Genetic conservation of Cytauxzoon felis antigens and mRNA expression in the schizont life-stage}, volume={263}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2018.10.007}, abstractNote={Cytauxzoonosis is a highly fatal disease of domestic cats caused by the apicomplexan protozoan Cytauxzoon felis, which is most closely related to Theileria spp. The growing prevalence, high morbidity and mortality, and treatment cost of cytauxzoonosis emphasize the need for vaccine development. Traditional approaches for vaccine development, however, have been hindered by the inability to culture C. felis in vitro. Recent availability of the annotated C. felis genome combined with genome-based vaccine design and protein microarray immunoscreening allowed for high-throughput identification of C. felis antigens that could serve as vaccine candidates. This study assessed the suitability of three of these vaccine candidates (cf30, cf63, cf58) in addition to a previously reported vaccine candidate (cf76) based on two criteria: genetic conservation among diverse C. felis geographic isolates and expression in tissues containing the C. felis schizont life stage, which has been previously associated with the development of a protective immune response. A comparison of seventeen C. felis isolates across seven states demonstrated high sequence identity (99-100%) for cf30, cf63, and cf58, similar to the degree of conservation previously reported for cf76. RNAscope® in situ hybridization using acutely infected feline splenic tissue revealed robust levels of all transcripts in the schizont life stage of the parasite. These data support the suitability of these three antigens for further investigation as vaccine candidates against cytauxzoonosis.}, journal={VETERINARY PARASITOLOGY}, author={Khana, Daven B. and Peterson, David S. and Stanton, James B. and Schreeg, Megan E. and Birkenheuer, Adam J. and Tarigo, Jaime L.}, year={2018}, month={Nov}, pages={49–53} }
 @article{schreeg_marr_tarigo_sherrill_outi_scholl_bird_vigil_hung_nakajima_et al._2018, title={Identification of Cytauxzoon felis antigens via protein microarray and assessment of expression library immunization against cytauxzoonosis}, volume={15}, ISSN={["1559-0275"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85059281263&partnerID=MN8TOARS}, DOI={10.1186/s12014-018-9218-9}, abstractNote={Cytauxzoonosis is a disease of felids in North America caused by the tick-transmitted apicomplexan parasite Cytauxzoon felis. Cytauxzoonosis is particularly virulent for domestic cats, but no vaccine currently exists. The parasite cannot be cultivated in vitro, presenting a significant limitation for vaccine development.Recent sequencing of the C. felis genome has identified over 4300 putative protein-encoding genes. From this pool we constructed a protein microarray containing 673 putative C. felis proteins. This microarray was probed with sera from C. felis-infected and naïve cats to identify differentially reactive antigens which were incorporated into two expression library vaccines, one polyvalent and one monovalent. We assessed the efficacy of these vaccines to prevent of infection and/or disease in a tick-challenge model.Probing of the protein microarray resulted in identification of 30 differentially reactive C. felis antigens that were incorporated into the two expression library vaccines. However, expression library immunization failed to prevent infection or disease in cats challenged with C. felis.Protein microarray facilitated high-throughput identification of novel antigens, substantially increasing the pool of characterized C. felis antigens. These antigens should be considered for development of C. felis vaccines, diagnostics, and therapeutics.}, number={1}, journal={CLINICAL PROTEOMICS}, author={Schreeg, Megan E. and Marr, Henry S. and Tarigo, Jaime L. and Sherrill, Meredith K. and Outi, Hilton K. and Scholl, Elizabeth H. and Bird, David M. and Vigil, Adam and Hung, Chris and Nakajima, Rie and et al.}, year={2018}, month={Dec} }
 @article{mylonakis_schreeg_chatzis_pearce_marr_saridomichelakis_birkenheuer_2018, title={Molecular detection of vector-borne pathogens in Greek cats}, volume={9}, ISSN={["1877-9603"]}, DOI={10.1016/j.ttbdis.2017.08.013}, abstractNote={Infectious diseases have been increasingly recognized in cats worldwide. The objective of this study was the molecular investigation of the prevalence of selected pathogens in healthy and sick cats from Greece, a country highly endemic for several canine vector-borne pathogens. Blood and/or bone marrow samples from 50 clinically healthy and 50 sick adult (>1 year-old) cats were retrospectively examined for the amplification of Bartonella spp., haemoplasmas, Ehrlichia spp., Anaplasma spp., Babesia spp., and Cytauxzoon spp. DNA. Overall, 14.9% of the cats were found to be infected or co-infected by haemoplasmas, including Candidatus Mycoplasma haemominutum and M. haemofelis. In addition, 8.5% of the cats were infected by Bartonella henselae, Bartonella clarridgeiae or Bartonella koehlerae. In contrast, DNA of Ehrlichia spp., Anaplasma spp., Babesia spp. and Cytauxzoon spp. was not amplified from the blood or bone marrow of any cat. There was no significant difference in either haemoplasma or Bartonella infection rates when comparing healthy and sick cats. This study represents the first description of Bartonella koehlerae in Greek cats.}, number={2}, journal={TICKS AND TICK-BORNE DISEASES}, author={Mylonakis, Mathios E. and Schreeg, Megan and Chatzis, Manolis K. and Pearce, Julian and Marr, Henry S. and Saridomichelakis, Manolis N. and Birkenheuer, Adam J.}, year={2018}, month={Feb}, pages={171–175} }
 @article{qurollo_archer_schreeg_marr_birkenheuer_haney_thomas_breitschwerdt_2017, title={Improved molecular detection of Babesia infections in animals using a novel quantitative real-time PCR diagnostic assay targeting mitochondrial DNA}, volume={10}, ISSN={1756-3305}, url={http://dx.doi.org/10.1186/s13071-017-2064-1}, DOI={10.1186/s13071-017-2064-1}, abstractNote={Babesiosis is a protozoal, tick transmitted disease found worldwide in humans, wildlife and domesticated animals. Commonly used approaches to diagnose babesiosis include microscopic examination of peripheral blood smears, detection of circulating antibodies and PCR. To screen and differentiate canine Babesia infections many PCR assays amplify the 18S rRNA gene. These sequences contain hypervariable regions flanked by highly conserved regions allowing for amplification of a broad-range of Babesia spp. However, differences in the 18S rRNA gene sequence of distantly related clades can make it difficult to design assays that will amplify all Babesia species while excluding the amplification of other eukaryotes. By targeting Babesia mitochondrial genome (mtDNA), we designed a novel three primer qPCR with greater sensitivity and broader screening capabilities to diagnose and differentiate Babesia spp. Using 13 Babesia mtDNA sequences, a region spanning two large subunit rRNA gene fragments (lsu5-lsu4) was aligned to design three primers for use in a qPCR assay (LSU qPCR) capable of amplifying a wide range of Babesia spp. Plasmid clones were generated and used as standards to determine efficiency, linear dynamic range and analytical sensitivity. Animals naturally infected with vector-borne pathogens were tested retrospectively and prospectively to determine relative clinical sensitivity and specificity by comparing the LSU qPCR to an established 18S rDNA qPCR. The LSU qPCR efficiencies ranged between 92 and 100% with the limit of detection at five copies/reaction. The assay did not amplify mammalian host or other vector-borne pathogen gDNA except Cytauxzoon felis (a feline protozoal pathogen). The LSU qPCR assay amplified 12 different Babesia. sp. and C. felis from 31/31 (100%) archived samples, whereas the 18S qPCR amplified only 26/31 (83.9%). By prospective analysis, 19/394 diagnostic accessions (4.8%) were LSU qPCR positive, compared to 11/394 (2.8%) 18S rDNA qPCR positive. We have developed a more sensitive qPCR assay with a more expansive range of Babesia spp. detection by targeting a highly conserved region of mtDNA, when compared to an established 18S qPCR.}, number={1}, journal={Parasites & Vectors}, publisher={Springer Nature}, author={Qurollo, Barbara A. and Archer, Nikole R. and Schreeg, Megan E. and Marr, Henry S. and Birkenheuer, Adam J. and Haney, Kaitlin N. and Thomas, Brittany S. and Breitschwerdt, Edward B.}, year={2017}, month={Mar} }
 @article{schreeg_marr_tarigo_cohn_bird_scholl_levy_wiegmann_birkenheuer_2016, title={Mitochondrial Genome Sequences and Structures Aid in the Resolution of Piroplasmida phylogeny}, volume={11}, ISSN={["1932-6203"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84994744879&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0165702}, abstractNote={The taxonomy of the order Piroplasmida, which includes a number of clinically and economically relevant organisms, is a hotly debated topic amongst parasitologists. Three genera (Babesia, Theileria, and Cytauxzoon) are recognized based on parasite life cycle characteristics, but molecular phylogenetic analyses of 18S sequences have suggested the presence of five or more distinct Piroplasmida lineages. Despite these important advancements, a few studies have been unable to define the taxonomic relationships of some organisms (e.g. C. felis and T. equi) with respect to other Piroplasmida. Additional evidence from mitochondrial genome sequences and synteny should aid in the inference of Piroplasmida phylogeny and resolution of taxonomic uncertainties. In this study, we have amplified, sequenced, and annotated seven previously uncharacterized mitochondrial genomes (Babesia canis, Babesia vogeli, Babesia rossi, Babesia sp. Coco, Babesia conradae, Babesia microti-like sp., and Cytauxzoon felis) and identified additional ribosomal fragments in ten previously characterized mitochondrial genomes. Phylogenetic analysis of concatenated mitochondrial and 18S sequences as well as cox1 amino acid sequence identified five distinct Piroplasmida groups, each of which possesses a unique mitochondrial genome structure. Specifically, our results confirm the existence of four previously identified clades (B. microti group, Babesia sensu stricto, Theileria equi, and a Babesia sensu latu group that includes B. conradae) while supporting the integration of Theileria and Cytauxzoon species into a single fifth taxon. Although known biological characteristics of Piroplasmida corroborate the proposed phylogeny, more investigation into parasite life cycles is warranted to further understand the evolution of the Piroplasmida. Our results provide an evolutionary framework for comparative biology of these important animal and human pathogens and help focus renewed efforts toward understanding the phylogenetic relationships within the group.}, number={11}, journal={PLOS ONE}, author={Schreeg, Megan E. and Marr, Henry S. and Tarigo, Jaime L. and Cohn, Leah A. and Bird, David M. and Scholl, Elizabeth H. and Levy, Michael G. and Wiegmann, Brian M. and Birkenheuer, Adam J.}, year={2016}, month={Nov} }
 @article{schreeg_marr_griffith_tarigo_bird_reichard_cohn_levy_birkenheuer_2016, title={PCR amplification of a multi-copy mitochondrial gene (cox3) improves detection of Cytauxzoon felis infection as compared to a ribosomal gene (18S)}, volume={225}, ISSN={["1873-2550"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84975504702&partnerID=MN8TOARS}, DOI={10.1016/j.vetpar.2016.06.013}, abstractNote={Cytauxzoon felis is a tick-transmitted protozoan parasite that infects felids. Clinical disease caused by acute C. felis infection rapidly progresses in domestic cats, leading to high morbidity and mortality. Accurately diagnosing cytauxzoonosis as soon as possible during acute infection would allow for earlier initiation of antiprotozoal therapy which could lead to higher survival rates. Molecular detection of parasite rRNA genes (18S) by PCR has previously been shown to be a sensitive method of diagnosing C. felis infections. Based on evidence from related apicomplexan species, we hypothesized that C. felis mitochondrial genes would exist at higher copy numbers than 18S and would be a more sensitive diagnostic target. In this study we have designed a PCR assay targeting the C. felis mitochondrial gene cytochrome c oxidase subunit III (cox3). Herein we demonstrate that (1) the cox3 PCR can detect as low as 1 copy of DNA target and can detect C. felis in samples with known mitochondrial sequence heterogeneity, (2) cox3 copy number is increased relative to 18S in blood and tissue samples from acutely infected cats, and (3) the cox3 PCR is more sensitive than 18S PCR for detection of C. felis during early infections.}, journal={VETERINARY PARASITOLOGY}, author={Schreeg, Megan E. and Marr, Henry S. and Griffith, Emily H. and Tarigo, Jaime L. and Bird, David M. and Reichard, Mason V. and Cohn, Leah A. and Levy, Michael G. and Birkenheuer, Adam J.}, year={2016}, month={Jul}, pages={123–130} }
 @article{schreeg_marr_tarigo_cohn_levy_birkenheuer_2015, title={Rapid High-Resolution Melt Analysis of Cytauxzoon felis Cytochrome b To Aid in the Prognosis of Cytauxzoonosis}, volume={53}, ISSN={["1098-660X"]}, DOI={10.1128/jcm.00635-15}, abstractNote={ABSTRACT}, number={8}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Schreeg, Megan E. and Marr, Henry S. and Tarigo, Jaime L. and Cohn, Leah A. and Levy, Michael G. and Birkenheuer, Adam J.}, year={2015}, month={Aug}, pages={2517–2524} }
 @article{schreeg_marr_tarigo_cohn_levy_birkenheuer_2013, title={Pharmacogenomics of Cytauxzoon felis Cytochrome b: Implications for Atovaquone and Azithromycin Therapy in Domestic Cats with Cytauxzoonosis}, volume={51}, ISSN={["0095-1137"]}, DOI={10.1128/jcm.01407-13}, abstractNote={ABSTRACT}, number={9}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Schreeg, Megan E. and Marr, Henry S. and Tarigo, Jaime and Cohn, Leah A. and Levy, Michael G. and Birkenheuer, Adam J.}, year={2013}, month={Sep}, pages={3066–3069} }
 @article{owens_downey_pressler_birkenheuer_chandler_scott-moncrieff_2012, title={Congenital Adrenal Hyperplasia Associated with Mutation in an 11 ss-Hydroxylase-Like Gene in a Cat}, volume={26}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.2012.00971.x}, abstractNote={A 3-year-old indeterminate sex domestic medium-hair cat was presented to the Purdue University Veterinary Teaching Hospital for further evaluation of chronic polyuria and polydipsia, foul-smelling urine, and increased serum androgen concentrations. The cat had been surrendered to a shelter 4 months previously for undetermined reasons. Diagnostic tests performed before referral included a serum biochemistry panel, CBC, urinalysis, urine culture, and ACTH stimulation testing (cortisol, aldosterone, and sex hormone assay). Abnormalities included minimally concentrated urine (specific gravity. 1.018), decreased baseline and stimulated serum cortisol and aldosterone concentrations, increased baseline progesterone, and increased baseline and stimulated 17-OH progesterone and androstenedione concentrations. The cat had a small body frame, thickened skin, gynecomastia, a fully formed penis with barbs, and an intact but empty scrotum. Initial indirect systolic blood pressure was 180 mm Hg, and remained persistently elevated during hospitalization. Clinicopathologic abnormalities included increased serum urea nitrogen concentration (41 mg/dL, reference range 15–35 mg/dL), hypernatremia (158 mmol/L, reference range 148–157 mmol/L), and hyperglobulinemia (5.2 g/dL, reference range 2.3–3.8 g/dL). Feline leukemia and feline immunodeficiency virus status were both negative, and a CBC did not reveal abnormalities. Urine specific gravity was 1.007, with no abnormalities on urine dipstick or sediment examinations. A repeated ACTH stimulation test including sex hormone assay confirmed the previously noted abnormalities (Table 1). Endogenous ACTH concentration was increased (>1,250 pg/mL, reference range 25–50 pg/mL).1 Abdominal radiographs did not reveal abnormalities and abdominal sonographic examination revealed anatomically normal adrenal glands and no identifiable internal genitalia. Baseline serum deoxycorticosterone (DOC), 11-desoxycortisol (11-DES), dehydroepiandrosterone (DHEA), pregnenolone, and corticosterone concentrations were measured by high-performance liquid chromatography with tandem mass spectrometry by specific assays validated to bioanalytical standards, and compared with 4 age-matched healthy cats (2 neutered males, 2 spayed females).1 Serum concentrations of DOC (1,177 ng/dL [healthy control cats, 4.6–18.0]), 11-DES (3,647 ng/dL [healthy control cats, 9–29]), DHEA (155 ng/dL [healthy control cats, 9–47]), and pregnenolone (552 ng/dL [healthy control cats, 115–311]) were markedly greater than results for any of the 4 healthy cats, whereas serum corticosterone concentration (9 ng/dL [healthy control cats, 164–550]) was lower. Exploratory laparotomy was performed with the aim to identify internal testes that would explain the cat's foul-smelling urine and physical examination abnormalities. The vas deferens and spermatic cords were bilaterally identified traversing through the inguinal rings and into the scrotum, consistent with prior castration; the identity of this tissue was confirmed histopathologically. The adrenal glands were free of gross lesions. The cat was confirmed as genetically male by DNA extraction of whole blood with identification of X and Y chromosome linked markers.2 The cat was complacent, easy to work with, and good natured during initial hospitalization. After evaluation the cat was adopted into a home with 2 other cats, and immediately demonstrated intercat and owner-directed aggression during play and handling. A diagnosis of intermale aggression was made, presumed secondary to excess androgen concentration or other hormonal imbalance. Behavior modification and fluoxetine (0.6 mg/kg PO q24h) failed to modify the undesired behavior. A presumptive diagnosis of 11β-hydroxylase deficiency resulting in congenital adrenal hyperplasia (CAH) was made based on results of the physical examination abnormalities and adrenal steroid testing, and prednisone therapy (0.2 mg/kg, PO, q24h) was prescribed. Two weeks after initiation of prednisone, the cat's mammary glands had decreased in size and systolic blood pressure had decreased to 150 mm Hg. Because of the partial but incomplete response, after 8 weeks the dose of prednisone was increased (0.5 mg/kg PO q24h). Complete regression of mammary tissue and gradual regression of the penile barbs were noted after 3 weeks at the increased prednisone dose: systolic blood pressure (165 mm Hg) and endogenous ACTH concentration (235 pg/mL), however, were still increased. The prednisone dose was increased further (0.8 mg/kg/d), which resulted in normalization of systolic blood pressure (120 mm Hg) and resolution of polyuria, polydipsia, and malodorous urine within 4 weeks. Secondary sex characteristics continued to resolve, with subjective reduction in skin thickening and regression of the penile barbs. However, despite resolution of clinical signs, repeat endocrine testing revealed persistently increased endogenous ACTH (617 pg/mL) and androstenedione (>10 ng/mL) concentrations. Therapy was changed to prednisolone (0.62 mg/kg PO q24h) because of increased bioavailability.2 The cat's systolic blood pressure (110 mm Hg) and endogenous ACTH (26 pg/mL) decreased to within reference range within 2 weeks of the change in therapy. Sex hormone assay revealed baseline concentrations of androstenedione (0.39 ng/mL), progesterone (<0.03 ng/mL), 17 OH progesterone (0.09 ng/mL), and testosterone (0.02 ng/mL) within or below reference ranges. Serum aldosterone concentration remained below reference range (<11 pg/mL). Eight weeks after therapy was changed to prednisolone, the cat was diagnosed with Klebsiella pyelonephritis based on acute lethargy and inappetance, abdominal pain, an inflammatory leukogram, azotemia, and a positive urine culture, and successfully treated with 6 weeks of amoxicillin/clavulanic acid3 (15.5 mg/kg/d PO divided q12h). After antibiotic treatment the prednisolone dose was decreased (0.5 mg/kg PO q24h). Nine months later the cat remained normotensive (systolic blood pressure 140 mm Hg), endogenous ACTH was within reference range (11.6 pg/mL), DOC was 102 ng/dL, and sex hormone concentrations were markedly reduced pre- and post-ACTH stimulation (Table 1). Mild inte-male aggression persisted; however, owner-directed aggression was almost nonexistent at this time and the cat is more relaxed in his home environment. Genetic mutations associated with 11β-hydroxylase deficiency in people have thus far all been identified within the coding regions of CYP11B1, the 11β-hydroxylase gene.3 Alignment4 of the 9 Homo sapiens CYP11B1 exons (GenBank accession no. NG_007954) to the 2X Felis catus whole genome shotgun (GenBank accession no. PRJNA10762) identified a CYP11B1-like gene within 3 nonoverlapping feline genome contigs (GenBank accession nos. ACBE01524914.1, ACBE01524915.1, ACBE01524916.1). To determine whether 11β-hydroxylase deficiency in the cat of this report was likewise because of mutation of the CYP11B1-like coding region, genomic sequence analysis of this cat's and clinically healthy control cats' CYP11B1-like gene was performed. The complete feline CYP11B1-like gene was amplified in 13 overlapping amplicons for the cat reported here and 1 healthy control cat with total DNA isolated5 from 200 μL whole blood (Table 2). After PCR, appropriately sized amplicons were isolated, purified as needed,6 and directly sequenced.7 Amplicons with unresolvable chromatograms were presumed to be secondary to intronic variation; sequencing was repeated7 after cloning into a plasmid vector,8 , 9 Chromatograms were manually inspected for heterogeneity, and contigs assembled by commercially available software.10 Intron-exon boundaries were annotated by alignment with human 11-β hydroxylase exons,10 with putative exons translated in tandem in silico. The initial CYP11B1-like gene sequence from the cat of this report suggested that 1 or more mutations were present in the region homologous to exon 7 of human CYP11B1 (Fig 1). The PCR amplification of the putative exon 7 region from the cat of this report and 5 healthy cats was performed using a proofreading polymerase (Table 2). Two exonic mutations within the putative CYP11B1 coding sequence were found exclusively in the cat of this report, including a silent (ie, not associated with a change in amino acid) guanosine-to-adenosine mutation in exon 1, and a guanosine-to-adenosine mutation in exon 7 that results in an arginine to glutamine amino acid substitution; this latter mutation results in 11β-hydroxylase deficiency-associated CAH in people.4 CAH syndrome is because of 1 or more adrenal enzyme deficiencies resulting in inadequate cortisol biosynthesis and altered production of androgens.5 CAH is the most common genetic endocrine disorder in humans.6 While mutations associated with dysfunction of any of the 5 adrenal enzymes required for cortisol biosynthesis could result in CAH, mutations of CYP21A (90–95% of cases) and CYP11B1 (5–8% of cases), the genes encoding 21-hydroxylase and 11β-hydroxylase, respectively, are most commonly implicated in people. Inheritance of all forms of CAH is autosomal recessive, with an overall worldwide prevalence of 1 in 15,000 live births.7 CAH is rare in domestic animals, reported thus far in 1 female cat and 1 Great Dane (sex not reported), suspected to be secondary to 11β-hydroxylase deficiency in the cat and 17-hydroxylase deficiency in the dog.8 , 11 11β-hydroxylase is a mitochondrial cytochrome P450 adrenal enzyme that converts 11-deoxycortisol to cortisol, and deoxycorticosterone to corticosterone.5 11β-hydroxylase deficiency results in insufficient cortisol production and secondary inadequate negative feedback to the hypothalamus and cranial pituitary gland, leading to overproduction of ACTH.5 Uninhibited ACTH production continuously stimulates the adrenal cortex to produce steroid precursors, which are inappropriately shunted toward production of sex hormones such as androstenedione. Clinical signs therefore result from increased circulating concentrations of androgens and mineralocorticoids. The hallmark of common forms of CAH in people is virilism of females.9 Human girls can be misclassified as males at birth because of ambiguous genitalia as excess androgen concentrations in utero can result in an enlarged penis-like clitoris, a common urogenital sinus replacing a divided urethra and vagina, and partial fusion of the labia majora, which may be mistaken for a scrotum.9 Despite the presence of external male genitalia in the cat of this report, medical records before initial evaluation were unavailable, and it was unclear if he had been neutered or if the cat was a genotypic female with ambiguous genitalia; without this information definitive sexual classification as a male required histopathology and genotyping. Additional phenotypic changes observed in people with 11β-hydroxylase deficiency include precocious puberty, gynecomastia, and benign testicular nodules in males,5 hirsutism in females,9 and premature physeal closure, stunted growth, acne, and infertility in both sexes.5 Although these findings may be difficult to identify in domestic animals, the cat reported here did have gynecomastia, a greasy haircoat, and a small body frame. Whether or not precocious puberty, testicular nodules, or infertility would have been encountered is unknown because of the cat's age at presentation and prior castration. 21-hydroxylase deficiency, the most common cause of CAH in people, results in defective DOC production, absence of aldosterone, massive salt-wasting, and life-threatening systemic hypotension, whereas 11β-hydroxylase deficiency-associated CAH results in excess DOC, salt retention, volume expansion, and hypertension. Despite the weak mineralocorticoid effects (one-thirtieth the potency of aldosterone) of DOC, 10–100-fold increases in production of this hormone in 11β-hydroxylase deficient CAH patients often results in hypertension-associated adverse effects.10 Treatment with corticosteroids reduces the production of DOC and may resolve hypertension. The 1 previously reported 11β-hydroxylase deficiency cat was too aggressive for accurate blood pressure measuring; therefore this is the first report in which hypertension, and successful therapy, is documented in a cat with CAH.8 Consistent with reports of CAH in people, the systolic blood pressure of the cat in this report normalized synchronously with reduction of endogenous ACTH and serum androgen concentrations.5 Treatment of choice for human patients with 11β-hydroxylase deficiency is supplementation with corticosteroids, usually hydrocortisone because of its similarity to cortisol.11, 12 Differences in 24-hour cortisol demand, and at different life stages, frequently complicates therapy in people: for example, infants and adolescents routinely require higher doses of glucocorticoids than do adults.13 A more aggressive alternative to medical therapy, particularly when adverse effects secondary to increased exogenous glucocorticoid administration become intolerable, is bilateral adrenalectomy and treatment for hypoadrenocorticism.14 Serum concentrations of renin, 17-OH progesterone, androstenedione, testosterone (in females), and DOC can be used in people as markers of adequate hormonal control.5, 15 We used multiple criteria to evaluate adequate adrenal suppression for the cat of this report, including endogenous ACTH concentration, serum androgen concentrations, systemic blood pressure, physical examination findings, and serum DOC concentration. Psychological disorders are strongly associated with CAH in people, including higher aggression scores in females presumptively secondary to increased in utero androgen concentrations,16 increased anxiety and depression, and overall impaired general quality of life.6 The behavioral abnormalities noted in the cat of this report might be consistent with these findings, as standard behavior modification both with and without psychopharmacologic therapy was not effective until after the cat's hormonal status was equivalent to that of a castrated male cat, and therefore more consistent with intermale aggression rather than territorial aggression. 11β-hydroxylase is capable of catalyzing the terminal biosynthesis reactions of both aldosterone and cortisol.17 CYP11B1 encodes 11β-hydroxylase, which is responsible for cortisol biosynthesis in the zona fasciculata and zona reticularis, whereas CYP11B2 encodes aldosterone synthase, the enzyme necessary for aldosterone biosynthesis in the zona glomerulosa.18 These 2 unique genes have been identified in people and several rodent species,17-21 whereas other animals, including frogs,22 pigs,8 and cows22 have a single isozyme that catalyzes both reactions. It is unclear whether or not cats have 2 distinct enzymes or a single isozyme. In people, serum aldosterone concentration is decreased with 11β-hydroxylase deficiency because increased DOC concentration provides adequate and even excessive amounts of mineralocorticoid activity, and aldosterone production (which is stimulated by hyperkalemia and the renin-angiotensin system) is down-regulated.5, 23, 24 When ACTH production decreases after corticosteroid supplementation, DOC production declines as well, eliminating the low-renin hypertension and returning the sodium-potassium balance to normal: serum aldosterone concentrations should consequently return to normal, precluding the need for mineralocorticoid supplementation.5 It is assumed that reduction in DOC concentrations in species with a single isozyme would result in a state of mineralocorticoid deficiency, with life-threatening hyperkalemia and hyponatremia. Hyponatremia or hyperkalemia were never recorded in the cat of this report despite persistent hypoaldosteronism, likely because DOC was maintained at high enough concentrations. Although there is not sufficient clinicopathologic evidence to support 2 functional isoenzymes in this cat, it is still possible that 2 distinct isoenzymes are present but DOC concentration did not decrease low enough to allow stimulation of aldosterone biosynthesis. Congenital adrenal hyperplasia is the most common genetic endocrine disorder in humans, yet this is just the 2nd report of the disease in a cat. Although a genetic disorder, clinical signs might not be clinically apparent until later in life and could vary considerably from neonatal hypovolemic shock to male precocious puberty and mild hypertension. While many patients with this disorder might not survive the neonatal period, many others may go unnoticed with subtle clinical signs. CAH should be a differential diagnosis for cats with unexplained hypertension, polyuria, polydipsia, presence of secondary sex characteristics postneutering, and behavioral abnormalities, including intercat aggression. The information presented in this manuscript was presented in part at the Society of Comparative Endocrinology in Fort Collins, CO in May 2011. We acknowledge Dr Alison Muehrcke, for her referral of this case to the Purdue University Veterinary Teaching Hospital. Work described here was not supported by any grant or funding agency. Conflict of Interest: Dr Pressler is an Associate Editor for the Journal of Veterinary Internal Medicine.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Owens, S. L. and Downey, M. E. and Pressler, B. M. and Birkenheuer, A. J. and Chandler, D. W. and Scott-Moncrieff, J. C.}, year={2012}, pages={1221–1226} }
 @article{lewis_cohn_downey_whitney_birkenheuer_2012, title={Evaluation of Cytauxzoon felis infection status in captive-born wild felids housed in an area endemic for the pathogen}, volume={241}, ISSN={["0003-1488"]}, DOI={10.2460/javma.241.8.1088}, abstractNote={Abstract}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Lewis, Kristin M. and Cohn, Leah A. and Downey, Megan E. and Whitney, Marlyn S. and Birkenheuer, Adam J.}, year={2012}, month={Oct}, pages={1088–1092} }
 @article{di cicco_downey_beeler_marr_cyrog_kidd_diniz_cohn_birkenheuer_2012, title={Re-emergence of Babesia conradae and effective treatment of infected dogs with atovaquone and azithromycin}, volume={187}, ISSN={["0304-4017"]}, DOI={10.1016/j.vetpar.2012.01.006}, abstractNote={Babesia conradae (B. conradae) causes hemolytic anemia in dogs. This organism has not been reported clinically since it was originally described in southern California in 1991. To date, no anti-protozoal therapies have been associated with clearance of B. conradae. This report describes the use of atovaquone and azithromycin for the treatment of dogs naturally infected with B. conradae and report the re-emergence of B. conradae in southern California. Twelve dogs naturally infected with B. conradae were identified by practicing veterinarians and public health officials in southern California. Treatments consisted of a 10 day course of atovaquone (13.3mg/kg PO q 8h) and azithromycin (10-12.5mg/kg PO q 24h). Four dogs were treated in a randomized blinded placebo-controlled fashion, four additional cases were treated in a non-random, non-blinded fashion and one dog received no treatment. All dogs were tested for B. conradae DNA by polymerase chain reaction (PCR) initially and then once or 3 times post treatment (60-210 days). B. conradae infected dogs that received treatment did not have any detectable Babesia DNA by PCR after treatment. In contrast, dogs receiving placebo had detectable Babesia DNA by PCR throughout the study period. Combination therapy with atovaquone and azithromycin appears to be effective for acute and chronic babesiosis caused by B. conradae.}, number={1-2}, journal={VETERINARY PARASITOLOGY}, author={Di Cicco, Michael F. and Downey, Megan E. and Beeler, Emily and Marr, Henry and Cyrog, Peter and Kidd, Linda and Diniz, Pedro Paulo V. P. and Cohn, Leah A. and Birkenheuer, Adam J.}, year={2012}, month={Jun}, pages={23–27} }