Thomas J. Divers’s research while affiliated with Cornell University and other places

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Publications (375)


Figure 1-Borrelia burgdorferi PCR results from equine synovial samples (n = 163) submitted to the Cornell Animal Health Diagnostic Center over a 16-year period (2007 to 2023), including appendicular joint fluid and synovium, not otherwise specified (NOS) joint fluid and synovium, nuchal bursa fluid, and nuchal bursa tissue.
Figure 2-A-Lateral radiograph of the atlanto-occipital area of a horse with B burgdorferi PCR-positive nuchal bursitis showing mineralization in the region of the nuchal bursa (arrows). B-Ultrasonographic image of the cranial nuchal bursa at the level of the first cervical vertebra showing marked distension with anechoic fluid and synovial proliferation (arrows) in a horse with B burgdorferi PCR-positive nuchal bursitis.
Figure 3-Antibody response to various B burgdorferi protein antigens. A-Outer surface protein A (OspA) antibody value distribution (median fluorescence intensity [MFI]) for clinical cases of nuchal bursitis (n = 13) and control horses (15) compared by an unpaired t test (P < .001; t[26] = 4.750). Values above 2,000 MFI indicate OspA antibody levels within positive range on the Lyme multiplex assay. B-Antibodies detected by ELISA, measured in absorbance at 405 nm (A405), for 8 of the B burgdorferi nuchal bursitis cases. Fifteen different B burgdorferi proteins were evaluated; factor H-binding protein B (FhbB) is an unrelated protein to evaluate for nonspecific binding. The reference value, represented by a dotted line, is 3 times the measured blank value for the assay. For mean values greater than the reference value, the difference between the reference value as a hypothetical mean and the measured mean value is significant only for OspA (t[7] = 4.854; P = .0018).
Figure 4-Gross and histologic images of the nuchal bursa (incised) in a B burgdorferi PCR-positive nuchal bursitis case showing intraluminal fibrin (arrows) containing foci of inflammatory cells, mineralization (arrowheads), and thickening of the bursal capsule by inflamed granulation tissue (doubleheaded arrows).
Diagnostic results for equine nuchal bursitis cases with antemortem B burgdorferi molecular detection within the nuchal bursa.
Association of Borrelia burgdorferi with nuchal bursitis and elevated outer surface protein A–specific serum antibodies in horses of the northeastern United States
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September 2024

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23 Reads

Journal of the American Veterinary Medical Association

Erin K. Pearson

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Cassandra Guarino

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Toby Pinn-Woodcock

OBJECTIVE Evaluate the incidence of Borrelia burgdorferi in cases of equine nuchal bursitis (NB) and investigate the relationship between elevated serum outer surface protein A (OspA) antibodies and the molecular identification of B burgdorferi in bursal tissue or synovial fluid. Additionally, describe clinical cases and compare the histologic changes in NB with and without detection of B burgdorferi . METHODS This was a retrospective multicenter cohort study (2013 to 2022). Medical records from horses with a diagnosis of NB and B burgdorferi PCR testing on NB tissue or synovial fluid were reviewed. The study population included 11 horses with a postmortem diagnosis of NB, 19 horses from the northeastern US with an antemortem diagnosis of B burgdorferi PCR–positive NB, and 15 healthy controls without evidence of NB and unvaccinated for B burgdorferi . Where serum was available, Lyme multiplex assay results were compared with controls and ELISAs targeting individual B burgdorferi antigens were performed. Histologic findings in nuchal bursa tissue were compared between NB cases with and without B burgdorferi PCR detection. RESULTS Serum OspA antibody values in B burgdorferi –positive NB cases (n = 13) were significantly elevated ( P < .001) compared to controls (15), and OspA was the predominant antigen detected by ELISA (8). Histopathology did not vary between NB cases with (n = 9) and without (6) B burgdorferi PCR detection. CONCLUSIONS The presence of B burgdorferi in the nuchal bursa of horses is associated with increased serum OspA antibodies. CLINICAL RELEVANCE The role of B burgdorferi in equine NB may be underestimated, and targeted therapy requires investigation.

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Diagnostic approach to polyuria/polydipsia (PU/PD). CFR, chronic renal failure; DI, diabetes insipidus; PPID, pituitary pars intermedia dysfunction; sCr, serum creatinine concentration; USG, urinary specific gravity.
ECEIM consensus statement on equine kidney disease

May 2024

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93 Reads

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3 Citations

The aim of this consensus statement is to summarize and appraise scientific evidence and combine this with the clinical experience of a panel of experts to optimize recommendations on how to recognize and manage kidney disease in horses.



Genomic hybrid capture assay to detect Borrelia burgdorferi : an application to diagnose neuroborreliosis in horses

July 2022

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25 Reads

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1 Citation

Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc

Antemortem diagnosis of neuroborreliosis in horses has been hindered by both the low sensitivity of PCR testing for Borrelia burgdorferi in CSF and the low specificity of serum:CSF ELISA ratios used to determine intrathecal antibody production against the bacterium. PCR testing of the CSF of an adult horse with acute neurologic disease for the B. burgdorferi flagellin gene was negative. However, we enriched B. burgdorferi DNA through nucleic acid hybrid capture, followed by next-generation sequencing, and identified B. burgdorferi in the CSF of the horse, confirming a diagnosis of neuroborreliosis.


The history of Theiler’s disease and the search for its aetiology

July 2022

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46 Reads

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5 Citations

The Veterinary Journal

Theiler’s disease (serum hepatitis) may occur in outbreaks or as single cases of acute hepatitis and is often associated with prior administration of equine-origin biologics approximately 4-10 weeks before the onset of clinical signs. Cases have also been described without any prior administration of blood products. The clinical disease has a low morbidity but high mortality and only adult horses are affected. The course of the disease is short, with horses either dying or completely recovering in a few days. Pathology in affected horses is predominantly centrilobular hepatocyte necrosis with mononuclear cell infiltration of the lesser affected periportal regions of the liver. Subclinical cases of the disease also occur. Based on the epidemiology and pathology of the disease, a viral cause, similar to hepatitis B in humans, has long been suspected. This paper reviews both historical and recent findings on Theiler’s disease. Reported epidemics of Theiler’s disease in the early 1900s are reviewed, along with their similarities to outbreaks of serum hepatitis in humans following yellow fever virus vaccinations in the 1930s and 1940s. Recent metagenomics-based studies to determine the aetiology of Theiler’s disease are discussed, along with both clinical and experimental findings supporting equine parvovirus-hepatitis (EqPV-H) as the likely cause of this 100-year-old disease.


Overall and time point‐specific least squares means and 95% CI for anti‐oxidants, pro‐oxidants and oxidative stress index: Total glutathione (A; μM, n = 14), coenzyme Q10 (CoQ10; B; μg/ml, n = 12), reactive oxygen and nitrogen species (RONS; C; RFU, n = 14), antioxidant potential (AOP; D; TE/μl, n = 14), oxidant status index (OSi; E, n = 14) and advanced oxidation protein products (AOPP; F; mg/g albumin, n = 14) in plasma samples from cases and controls taken immediately before (0 min), as well as 15 and 120 min after exercise. Cases and controls were identified based on a screening serum sample obtained by the veterinarian with high (≥50 IU/L, n = 7) and normal (≤36 IU/L, n = 7) GGT activity within 1 week prior to challenge. Controls were matched based on breed as well as exercise and training intensity within each stable for each case horse. P‐values for the fixed effect of case versus control (case), time point (time), as well as their interaction are shown. * Denotes differences between groups and a,b superscripts between time points at a level of p < 0.05 in Tukey's test controlled multiple comparisons. RFU, relative fluorescence units; TE, trolox equivalents.
Box and whisker plots of baseline (time 0) normalised concentrations of select oxylipids and isoprostanes that were significantly different between cases and controls. Analytes were selected based on differences set at greater than or equal to threefold change of normalised concentrations between paired samples shown on the Y‐axis. The lower and upper limits of the boxes represent the 25th and 75th percentile, respectively, the median is indicated by the middle line of the box, the mean of the group's values is shown by the yellow diamond and whiskers extend to 1.5 times the interquartile range. Cases and controls were identified based on a screening serum sample obtained by the veterinarian with high (≥50 IU/L, n = 7) and normal (≤36 IU/L, n = 7) GGT activity within 1 week prior to challenge. Controls were matched based on breed as well as exercise and training intensity within each stable for each case horse. 9,10‐EpOME, 9,10‐epoxyoctadecamonoenoic acid; 8,9‐EET, 8,9‐epoxyeicosatrienoic acid; 14,15‐DiHETE, 14,15‐dihydroxyeicosatetraenoic acid; 17,18‐DiHETE, 14,15‐dihydroxy‐eicosatetraenoic acid; 8,9‐DHET, 8,9‐dihydroxyeicosatrienoic acid; 14.15‐DHET, 14,15‐dihydroxyeicosatrienoic acid; 5‐iPF2α‐VI, 5‐isoprostane F2alpha.
Overall and time point‐specific least squares means and 95% CI of concentrations of serum cortisol (A; μg/dl), serum uric acid (B; mg/dl), plasma non‐esterified fatty acid (NEFA; C; mmol/L), serum insulin (D, μIU/ml), plasma triglyceride (E; mmol/L) and plasma cholesterol (F; mmol/L from cases and controls taken immediately before (0 min), as well as 15 and 120 min after exercise. Cases and controls were identified based on a screening serum sample obtained by the veterinarian with high (≥50 IU/L, n = 7) and normal (≤36 IU/L, n = 7) GGT activity within 1 week prior to challenge. Controls were matched based on breed as well as exercise and training intensity within each stable for each case horse. p‐values for the fixed effect of case versus control (case), time point (time), as well as their interaction are shown. * Denotes differences between groups and a,b superscripts between time points at a level of p < 0.05 in Tukey's test controlled multiple comparisons.
Case–control exercise challenge study on the pathogenesis of high serum gamma‐glutamyl transferase activity in racehorses

May 2022

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57 Reads

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2 Citations

Background High serum γ‐glutamyl‐transferase (GGT) activity syndrome in racehorses has been associated with maladaption to exercise. Investigation of affected horses before and immediately after standard exercise may provide critical insight into the syndrome's pathophysiology. Objectives To investigate blood biomarker changes in actively competing racehorses with high GGT activity associated with an exercise challenge. Study design Case–control study. Methods High GGT case (age: 2–3 years) and normal GGT control (age: 2–7 years) pairs (3 Thoroughbred, 4 Standardbred pairs) at least 3 months into their training/racing season were included. Horses with a recent history of high GGT activity (≥50 IU/L) without additional biochemical evidence of liver disease were identified by veterinarians. Horses were tested again in the week prior to a planned exercise challenge to confirm persistent increases in GGT activity. Controls from the same stable with similar training/racing intensity and serum GGT activity ≤36 IU/L were matched with each case. Blood samples were obtained immediately before, 15 and 120 min after exercise. Pre‐exercise serum samples were analysed for baseline select serum chemistries, selenium and vitamin E concentrations. Cortisol concentration and markers of oxidative status were measured in serum or plasma for all time points. Individual serum bile acid and coenzyme Q10 concentrations, plasma lipid mediator (fatty acids, oxylipids, isoprostanes) concentrations and targeted metabolomics analyses were performed using liquid chromatography‐mass spectrometry. Serum viral PCR for equine hepaci‐ and parvovirus was performed in each animal. Results Cases had higher baseline concentrations of total glutathione, taurocholic acid, cortisol and cholesterol concentrations and higher or lower concentrations of specific oxylipid and isoprostane mediators, but there were no case‐dependent changes after exercise. Main limitations Small sample size. Conclusions Results indicated that glutathione metabolism was altered in high GGT horses. Enhanced glutathione recycling and mild cholestasis are possible explanations for the observed differences.


Relevant Equine Renal Anatomy, Physiology, and Mechanisms of Acute Kidney Injury

March 2022

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37 Reads

Veterinary Clinics of North America Equine Practice

Regulation of renal blood flow is by both extrinsic and intrinsic systems. Intrinsic regulation occurs via the afferent and efferent arterioles and tubuloglomerular feedback mechanisms with activation of the juxtaglomerular apparatus. Mechanisms of acute kidney injury are frequently associated with changes in renal blood flow. Acute tubular necrosis and apoptosis are common in horses following ischemic or toxic insults and in sepsis-associated acute kidney injury. Sepsis-associated renal injury often has a complex mechanism of disease involving both functional and obstructive changes in intrarenal circulation. Acute interstitial nephritis may occur following Leptospira sp infection or can be secondary to tubular necrosis.


Acute Kidney Injury and Renal Failure in Horses

March 2022

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20 Reads

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13 Citations

Veterinary Clinics of North America Equine Practice

Nephrotoxic and hemodynamically mediated disorders are the most common causes of acute renal failure (ARF) in horses and foals. Leptospira spp. is the most common infectious cause of ARF. Initial treatments for ARF include elimination of nephrotoxic drugs, correction of predisposing disorders, and fluid therapy to promote diuresis. Horses and foals with polyuric ARF often have a good prognosis, while those with oliguric or anuric ARF have a guarded to poor prognosis. When fluid therapy is unsuccessful in improving urine production, various drugs treatments have been used in an attempt to increase urine production, but none are consistently effective in converting oliguria to polyuria.


Abdominocentesis using the 18‐Ga needle technique showing (A) the needle held at the center of the shaft on midline and (B) the needle inserted perpendicular to the skin and initially advanced 12–18 mm. Subsequent advancement of the needle in 2–3 mm increments is performed until fluid escapes, needle movement occurs, or until full needle penetration. Note the placement of the hand on the abdominal wall for stability during the procedure
Abdominocentesis using the 18‐Ga needle technique showing serosanguinous fluid flow through the hub opening. Independent rotary or linear movements of the needle during insertion likely indicate penetration of the peritoneal cavity and contact with adjacent intestine; the needle should be withdrawn 1–2 mm rather than advanced further to avoid enterocentesis
Abdominocentesis using the teat cannula technique showing the scalpel blade (A) held with a hand braced against the ventrum during insertion; (B) buried to the level where the neck joins the bayonet‐fitting slot to penetrate the skin and subcutaneous tissues; and (C) buried to where a release of tension indicates complete penetration of the external rectus sheath
Abdominocentesis using the teat cannula technique showing the cannula (A) inserted through a sterile gauze square and penetrating the skin, subcutaneous tissues, and external rectus sheath; (B) advanced perpendicular to the body wall through the internal rectus sheath (first “pop”); and (C) through the peritoneal membrane (“second pop”) into the abdominal cavity. Note the clear, pale‐yellow peritoneal fluid characteristic of a normal horse
Collection of peritoneal fluid and free‐catch of samples into three blood tubes for analysis using the (A) 18‐Ga needle techniques and (B) teat cannula. Note the use of the sterile gauze squares to minimize blood contamination of samples from the skin incision when using the teat cannula method
Abdominocentesis techniques in horses

January 2022

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94 Reads

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2 Citations

Background Abdominocentesis is commonly used to evaluate the abdominal cavity of the horse. This technique provides valuable diagnostic information as well as the means to monitor patients with abdominal diseases being managed medically and to determine their need for surgical management. Complications are uncommon and include trauma to the gastrointestinal tract or spleen, septic peritonitis, or abdominal wall infection. Procedures This review describes the indications, utility, patient preparation, and instructions for performing abdominocentesis as well as possible complications reported in horses. Step‐by‐step instructions are provided for the two most commonly used abdominocentesis techniques in horses, which include the use of a needle (18 Ga, 3.8 cm [1.5 in]) and a teat cannula (9.5 cm [3.75 in]). Summary Peritoneal fluid collection and fluid analysis can be used to confirm diagnosis of intraabdominal pathology including inflammatory, infectious, neoplastic, obstructive, and bowel strangulation, leading to additional diagnostic and therapeutic plans. Key points Abdominocentesis is useful as a diagnostic procedure in horses suffering from colic, diarrhea, weight loss, or other conditions involving the abdominal cavity and is an integral component of diagnostic testing for colic at referral institutions or in the field. Abdominal fluid collection using an 18‐Ga, 3.8‐cm (1.5‐in) needle is recommended for adult horses because the needle is long enough to penetrate the peritoneal cavity. The teat cannula technique is recommended for use in adult horses, foals, and miniature horses to reduce the risk of enterocentesis, even though this procedure is more traumatic than using an 18‐Ga, 3.8‐cm needle. Ultrasonography of the abdomen is a valuable tool in the assessment of any horse with signs of colic, but it is not essential for performing an abdominocentesis successfully.


Collection and administration of blood products in horses: Transfusion indications, materials, methods, complications, donor selection, and blood testing

January 2022

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175 Reads

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7 Citations

Background Blood transfusion is a lifesaving treatment for horses with acute hemorrhage and other causes of anemia. Transfusions improve oxygen delivery to the tissues via increased blood volume and hemoglobin concentration. Certain aspects of equine blood transfusion are challenging, especially in the field situation, and practitioners may be unfamiliar or feel overwhelmed with the process. An understanding of the indications, materials, methods, and techniques as well as donor selection and possible complications will help practitioners successfully implement blood transfusion in clinical practice. Procedures Blood transfusion involves several steps including appropriate donor selection, cross‐matching, blood collection, and administration, as well as monitoring and handling of transfusion reactions. Guidance for each of these steps are detailed in this review. Summary Blood transfusion is an effective and often lifesaving treatment for managing diseases of blood loss, hemolysis, and decreased RBC production. Equine practitioners require a thorough understanding of the indications for blood transfusion, the immunological principles behind compatibility testing and transfusion reactions, and the technical skills to aseptically collect and administer blood products Key points Equine practitioners require a thorough understanding of the indications for blood transfusion, the immunological principles behind compatibility testing and transfusion reactions, and the technical skills to aseptically collect and administer blood products. Because there are over 400,000 possible equine RBC phenotypes, no universal donor exists, and some blood type incompatibilities are likely between any donor and recipient. Therefore, prior to any blood transfusion, donor and recipient blood should be cross‐matched Inadequate delivery of oxygen (Do2) to the tissues, resulting from low hemoglobin (Hb) concentration, is the most important indication for blood transfusion Neonatal isoerythrolysis most commonly occurs following an anamnestic response in late gestation; it rarely occurs following a primary exposure because the immune response is not strong enough to produce clinically significant alloantibody titers.


Citations (69)


... Another example is advice on the diagnosis of acute kidney injury in horses, which includes the detection of elevations in serum creatinine concentration from baseline values for the individual. 8 This review article briefly describes how biological variation studies are conducted and the parameters derived from them and provide examples of how information derived from biological variation studies can be used in the interpretation of equine laboratory results. ...

Reference:

Review of biological variation and its applications in interpretation of equine clinical pathology results
ECEIM consensus statement on equine kidney disease

... An additional consideration when administering biological products is horizontal transmission of disease. Theiler's disease has been linked to TAT administration and recent clinical and experimental studies support equine parvovirus-hepatitis virus as the likely aetiologic agent (Divers et al. 2018(Divers et al. , 2022. PCR testing of commercial equine serum pools supports a world-wide distribution of equine parvovirushepatitis virus, including positive isolation from two New Zealand herds (Meister et al. 2019), as well as positive detection in 6/188 (3.2%) serum samples from Australian horses (Fortier et al. 2021). ...

The history of Theiler’s disease and the search for its aetiology
  • Citing Article
  • July 2022

The Veterinary Journal

... Estas bacterias gramnegativas helicoidales no sobreviven fuera de un huésped y se mantienen en un ciclo de vida de 2 años que involucra garrapatas del género Ixodes y mamíferos (Divers et al., 2022). ...

Genomic hybrid capture assay to detect Borrelia burgdorferi : an application to diagnose neuroborreliosis in horses
  • Citing Article
  • July 2022

Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc

... However, recent studies indicated that infection with these viruses did not associate with high GGT syndrome in TBs. 5,6 In TBs from the east coast of the United States (NY, FL and KY), serum GGT activity above the reference interval (0-50 IU/L) 5 was detected in 18% of horses tested, with similar prevalence estimates across 4 training farms. 5 Although significantly higher in control horses, selenium concentrations were within the reference interval for all horses sampled. ...

Case–control exercise challenge study on the pathogenesis of high serum gamma‐glutamyl transferase activity in racehorses

... This rise fits or approaches the definition of acute kidney injury in horses (an increase of 0.3 mg/dL within a 48-hour interval). 37,38 Only the horse treated for an acute colic episode had a Crea concentration above of the reference interval. Baseline values before treatment could be critical to early detection of kidney injury. ...

Acute Kidney Injury and Renal Failure in Horses
  • Citing Article
  • March 2022

Veterinary Clinics of North America Equine Practice

... Common clinicopathologic values analyzed in equine PF include white blood cell count and differential, total protein concentration, lactate concentration, glucose concentration, and a cytological evaluation for cellular morphology and the presence of microorganisms [3]. Gross fluid characteristics, including color and turbidity, are also routinely included in the fluid analysis. ...

Interpreting abdominal fluid in colic horses: Understanding and applying peritoneal fluid evidence

... Since the patient was a young gelding that had no prior exposure to blood products accord-ing to the owner, the risk of a blood transfusion reaction was thought to be low. An incidence of 16% for blood transfusion reactions, with only a fraction of the blood transfusion reactions being related to red blood cell alloantigen incompatibility has been described (Radcliffe et al., 2022). Routine crossmatching evaluates the hemagglutination. ...

Collection and administration of blood products in horses: Transfusion indications, materials, methods, complications, donor selection, and blood testing

... In this study, ALT and ALP levels were significantly increased in the serum of the FB 1 -exposed group than in the control group. However, the levels of DBIL and TBA, two key factors crucial in hepatic metabolic function (Delvescovo et al., 2021), were also changed significantly in the serum of the FB 1exposed group. DBIL was significantly increased at the three time points, while TBA was significantly increased at only 14 days. ...

Bile Acids, Direct Bilirubin and Gamma-glutamyltransferase as Prognostic Indicators for Horses with Liver Disease in the Eastern United States: 82 Cases (1997-2019)
  • Citing Article
  • August 2021

Journal of Equine Veterinary Science

... In the last decade, a recently discovered virus, the equine hepacivirus (hereon EqHV; family: Flaviviridae; genus: hepacivirus), initially described as non-primate hepacivirus in 2012 [3], then classified as hepacivirus A in 2016 [4], and recently renamed hepacivirus equi [2], gained greater attention due to its high genetic homology with the human hepatitis C virus (HCV) [3] and due to its global diffusion. As the virus is present worldwide, several studies focused on its transmission routes, which remain elusive and subject of scientific debate: to date, only parenteral transmission [5][6][7][8] and sporadic cases ...

Pathogenesis, miR‐122 gene‐regulation, and protective immune responses after acute equine hepacivirus infection

Hepatology