Sepsis in horses is a systemic inflammatory response to infection, characterized by the presence of pathogenic microorganisms or their toxins in the blood or tissues. It can result from various bacterial, viral, or fungal infections and may lead to severe complications if not managed promptly. Clinical signs of sepsis in horses can include fever, increased heart and respiratory rates, altered mucous membrane color, and signs of organ dysfunction. Diagnosis often involves identifying the underlying infection source, alongside laboratory tests to detect inflammatory markers and organ function indicators. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, treatment, and prognosis of sepsis in equine patients.
Hough VA, Wycislo KL, Hofmeister EH, Piech TL, Maki LC, Shaver SL.Veterinary students' accuracy, confidence, and time required to diagnose bacterial sepsis in fluid cytology samples was evaluated using two different slide preparation methods: direct smears and cytocentrifuged concentrated preparations. We hypothesized veterinary students would diagnose fluids as septic on concentrated preparations more accurately and quickly than on direct smears. Thirty third- and fourth-year students who had previously participated in a clinical pathology course completed a survey regarding general cytology experience and reviewed 40 randomized Romanowsky-stained slides vi...
Divers TJ.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 intrar...
Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA.In humans, activated platelets contribute to sepsis complications and to multiple organ failure. In our prospective analytical study of cases of the equine systemic inflammatory response syndrome (SIRS), we adapted a standard human protocol for the measurement of activated platelets and platelet-leukocyte aggregates (PLAs) in equine platelet-leukocyte-rich plasma (PLRP) by flow cytometry, and we investigated the hypothesis that activated platelets and PLAs are increased in clinical cases of SIRS. We included 17 adult horses and ponies fulfilling at least 2 SIRS criteria, and 10 healthy equids ...
Ekstrand C, Nostell K, Gehring R, Bondesson U, Bröjer J.Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentrati...
Radcliffe RM, Liu SY, Cook VL, Hurcombe SDA, Divers TJ.Interpreting changes in peritoneal fluid helps clinicians manage colic and other diseases in horses. During abdominal problems in the horse, abdominal fluid characteristics such as color, turbidity, total nucleated and red blood cell counts, cytology, total protein, and l-lactate change in predictable ways, helping the clinician characterize the disease. Methods: Normal abdominal fluid in horses is odorless, clear to light yellow in color, and transparent. Peritoneal fluid becomes more turbid with increasing levels of protein, number of WBCs or RBCs, or with gross contamination following intes...
Ford MG, Nelson BB, Ford TS, Souza CRS, Easley JT, Hackett ES.Surgical repair is frequently effective at resolving uroperitoneum in foals, though complications occur. Despite their occurrence, management strategies used to address these complications, and their impact on survival are not clearly defined. To better describe the complications following surgical correction of uroperitoneum and to document treatment strategies and outcomes after intervention, a multi-center retrospective case series was performed. Medical record data of foals undergoing surgical treatment for uroperitoneum were retrieved from three surgical centers, and cases identified with...
Barr B, Nieman NM.Sepsis is a significant cause of morbidity and mortality in neonatal foals, especially during the first 7Â days of life. Diagnosing sepsis in neonatal foals can be challenging because initial clinical signs are often ambiguous and non-specific. Objective: To determine if the major acute phase protein serum amyloid A (SAA) as measured by a point-of-care SAA testing device can be used as an evidence-based biomarker of sepsis. Methods: Retrospective cohort. Methods: Clinical diagnosis of sepsis based on positive bacterial blood culture or a positive sepsis score was obtained and compared to SAA v...
Luethy D.Treatment of equine laminitis continues to be a challenge despite recent advancements in knowledge of the pathophysiology of laminitis. With more evidence supporting its use, distal limb hypothermia or cryotherapy has become a standard of care for both prevention of laminitis and treatment of the early stages of acute laminitis. Recent studies have demonstrated that cryotherapy reduces the severity of sepsis-related laminitis and hyperinsulinemic laminitis in experimental models and reduces the incidence of laminitis in clinical colitis cases. This article reviews the recent literature support...
Leise BS, Fugler LA.Sepsis or systemic inflammatory response syndrome (SIRS) -associated laminitis is a sequela to primary inflammatory conditions (eg, colitis, ischemic intestinal injury, pneumonia, metritis) and results from a dysregulated systemic inflammatory response that ultimately affects the digital lamellae. Local chemokine production, leukocyte migration, and proinflammatory mediator production occur within the lamellae that can lead to catastrophic lamellar failure. Controlling the primary disease, providing supportive care and anti-inflammatory therapy, applying digital cryotherapy, and providing mech...
de Souza TC, Suthers JM, Busschers E, Burford JH, Freeman SL.Synovial sepsis is a frequent cause of morbidity and mortality in horses. Despite advances in diagnostics and treatments, persistent infection or chronic lameness can occur. Objective: To perform a scoping review to identify and evaluate the current evidence on the factors implicated in the success of treatment for synovial sepsis. Methods: Joanna Briggs Institute scoping review. Methods: A protocol was registered, and a systematic literature search was performed on CAB abstracts, Medline, Scopus and Embase. Inclusion and exclusion criteria were developed and studies systematically reviewed ag...
Rings LM, Kamr AM, Kinsella HM, Hostnik LD, Swink JM, Burns TA, Christie K, David JB, Toribio RE.The enteroinsular axis (EIA) is an energy regulatory system that modulates insulin secretion through the release of enteroendocrine factors (incretins). Despite the importance of energy homeostasis in the equine neonate, information on the EIA in hospitalized foals is lacking. The goals of this study were to measure serum insulin and plasma incretin (glucose-dependent insulinotropic polypeptide [GIP], glucagon-like peptide-1 [GLP-1] and glucagon-like peptide-2 [GLP-2]) concentrations, to determine the insulin and incretin association, as well as their link to disease severity and outcome in ho...
Bernick A, Nieth J, Wehrend A.Urachal patency is an umbilical disease in newborn foals. Etiologically, either the closure of the urachus remains absent after birth (persistent urachus) or the urachus was already closed and reopens at a later time (patent urachus). The most common causes of patent urachus are congenital defects, tearing of the navel above the predilection site, trauma, increased intravesical or abdominal pressure and umbilical infections. Patent urachus occurs more frequently in premature or weak and immunocompromised foals. Colts are more often affected than fillies. Typical clinical signs are apparent imm...
Lu KG, Sprayberry KA.Selected conditions affecting broodmares are discussed, including arterial rupture, dystocia, foal support with ex utero intrapartum treatment, uterine prolapse, postpartum colic, the metritis/sepsis/systemic inflammatory response syndrome complex, and retained fetal membranes. Postpartum colic beyond third-stage labor contractions should prompt comprehensive evaluation for direct injuries to the reproductive tract or indirect injury of the intestinal tract. Mares with perforation or rupture of the uterus are typically recognized 1 to 3Â days after foaling, with depression, fever, and leukopen...
Krause DM, Pezzanite LM, Griffenhagen GM, Hendrickson DA.Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed. Objective: To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings. Methods: Retrospective cohort study. Methods: Records from the Colorado State University were evaluated (2014-2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising se...
Haralambus R, Florczyk A, Sigl E, Gültekin S, Vogl C, Brandt S, Schnierer M, Gamerith C, Jenner F.Synovial sepsis is a commonly occurring, potentially career-ending or even life-threatening orthopaedic emergency. Diagnosis of synovial sepsis is currently primarily based on synovial fluid analysis, which often leaves diagnostic ambiguity due to overlap of clinicopathological parameters between septic and aseptic inflammatory synovitis. Objective: To evaluate the reliability of lysozyme (LYS), myeloperoxidase (MPO) and elastase (ELT) as biomarkers for synovial sepsis in horses using a photometric assay to measure increased enzyme activity. Methods: Prospective, single-blinded, analytical, cl...
Wong DM, Young L, Dembek KA.Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals. Objective: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals. Methods: Fifteen healthy and 27 ill (septic and sick-nonseptic [SNS]) foals were evaluat...
Colmer SF, Luethy D, Abraham M, Stefanovski D, Hurcombe SD.Plasma cell-free DNA (cfDNA) levels have been associated with disease and survival status in septic humans and dogs. To date, studies investigating cfDNA levels in association with critical illness in foals are lacking. We hypothesized that cfDNA would be detectable in the plasma of foals, that septic and sick-nonseptic foals would have significantly higher cfDNA levels compared to healthy foals, and that increased cfDNA levels would be associated with non-survival. Animals used include 80 foals of 10 days of age or less admitted to a tertiary referral center between January and July, 2020 wer...
Noll CV, Kilcoyne I, Nieto JE, Thio T, Byrne BA.To determine the ability of 0.2% polyhexamethylene biguanide (PHMB)-impregnated gauze to inhibit the growth of bacteria isolated from equine infected sites. Methods: In vitro study. Methods: Nine bacterial isolates were obtained from cultures submitted from equine patients presenting with penetrating injuries of the hoof (n = 4), septic osteitis (n = 1), synovial sepsis (n = 1), wounds (n = 2), and incisional infection following laparotomy (n = 1). Two standardized strains were also included. A standard inoculum of each isolate was placed on 12 Muller-Hinton agar plates. Squares (2.5 cm ×â€...
Mosichuk AP, Smith JS, Tatarniuk DM, Troy JR, Kreuder AJ.Septic synovitis is a critical orthopedic condition in horses. Early intervention is key, with antibiotic therapy typically initiated prior to culture and susceptibility reports becoming available. The pharmacokinetics of several antibiotics have been studied in horses for use in intravenous regional limb perfusion (IVRLP) for septic synovitis, including the carbapenem antibiotic, meropenem. For a variety of factors, some veterinary clinicians may select IVRLP meropenem as therapy for these cases. Meropenem is a vital antibiotic in human medicine, making veterinary use divisive. However, verif...
Scilimati N, Pepe M, Pressanto MC, Angeli G, Beccati F.A 4-month-old Thoroughbred filly was referred for evaluation of severe left forelimb lameness of 24 hours duration. Radiographic projections of the shoulder revealed mild irregularity and sclerosis of the proximal humeral apophysis. Ultrasonographic examination showed a moderate increase in the amount of anechogenic synovial fluid within the intertubercular bursa and scapulohumeral joint, and irregularity of the ossifying bone surface of the intermediate tubercle of the humerus. Computed tomographic (CT) examination revealed a circular hypoattenuating area at the level of the proximal apophysi...
Catunda APN, Alves GES, Paes Leme FO, Carvalho AM, Leise BS, Johnson PJ, Faleiros RR.Inflammation and apoptosis in the hoof lamellar interface both contribute to the early stages of sepsis-associated laminitis, but it is not clear whether apoptosis is occurring before the onset of inflammation or is being provoked by inflammation. Apoptosis and inflammation were therefore measured in lamellar tissues obtained at different time points throughout the early stages of experimentally induced laminitis. Apoptotic cells and leukocyte were enumerated in archived paraffin embedded lamellar tissue samples from previous experiments in which acute laminitis was induced using Black Walnut ...
Borba LA, Nogueira CEW, Bruhn FRP, da Silva GC, Feijó LS, Canisso IF, Curcio BDR.Neonatal sepsis is a leading cause of neonatal death during the first-week postfoaling. Despite recent advancements in the diagnosis and treatment of sepsis in the newborn foal, the non-specific clinical signs and subtle nature of this disease may result in delayed diagnosis until severe progression of the disease; thus, early detection of sepsis remains critical for a favourable outcome. This study aimed to identify early blood markers as predictive of sepsis on foals. Thirty-five foals were allocated into three groups: healthy control foals (n=7) and foals born from mares with placentitis: s...
Frydendal C, Nielsen KB, Berg LC, van Galen G, Adler DMT, Andreassen SM, Jacobsen S.To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. Methods: Experimental studies and retrospective clinical study. Methods: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivac...
McNeal CD, Ryan CA, Berghaus LJ, Credille BC, Lo CP, Fajt VR.Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidim...
Barton AK, Richter IG, Ahrens T, Merle R, Alalwani A, Lilge S, Purschke K, Barnewitz D, Gehlen H.The purpose of the study was to compare the results of sepsis scoring (clinical examination and clinical pathology) to the concentrations of matrix-metalloproteinases (MMPs) -2, -8, and -9; tissue-inhibitor of metalloproteinases (TIMPs) -1 and -2; and inflammatory chemokines interleukin (IL) 1β and tumor-necrosis-factor-alpha (TNF-α) in plasma and peritoneal fluid of equine colic patients. A modified sepsis scoring including general condition, heart and respiratory rate, rectal temperature, mucous membranes, white blood cell count (WBC), and ionized calcium was applied in 47 horses presented...
Ehrmann C, Engel J, Moritz A, Roscher K.In addition to maintaining hemostasis, platelets have an important role in modulating innate and adaptive immune responses. A low platelet count has been found to be a negative prognostic factor for survival in humans and horses with critical illnesses, such as sepsis or systemic inflammatory response syndrome (SIRS). Decreased platelet aggregation, caused by in vivo activation, has been found in human patients with severe sepsis. In our prospective controlled study, we assessed platelet biology in blood samples from 20 equine SIRS cases and 120 healthy control horses. Platelet variables such ...
Swink JM, Rings LM, Snyder HA, McAuley RC, Burns TA, Dembek KA, Gilsenan WF, Browne N, Toribio RE.Information on steroids derived from the adrenal glands, gonads, or fetoplacental unit is minimal in newborn foals. Objective: To measure androgen concentrations in serum and determine their association with disease severity and outcome in hospitalized foals. Methods: Hospitalized (n = 145) and healthy (n = 80) foals. Methods: Prospective, multicenter, cross-sectional study. Foals of ≤3 days of age from 3 hospitals and horse farms were classified as healthy and hospitalized (septic, sick nonseptic, neonatal maladjustment syndrome [NMS]) based on physical exam, medical history, and laborato...
Scavone D, Sgorbini M, Borges AS, Oliveira-Filho JP, Vitale V, Paltrinieri S.Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, pre...
Alonso JM, Martins ES, Peccinini RG, Rosa GS, Guerra ST, Ribeiro MG, Santos B, GarcÃa HDM, Watanabe MJ, Takahira RK, Rodrigues CA, Alves ALG....Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25Â mg/kg bwt) in additi...
Furr M, McKenzie H.Bloodstream infections (BSI) are common in sick foals and increase foal morbidity and mortality when they occur. Recognition of risk factors for BSI could be an important means to limit their occurrence, but studies on this topic are limited. Objective: Historical as well as maternal and foal physical examination findings will predict risk of BSI in neonatal foals. Methods: Foals <14 days of age admitted to a referral equine hospital for care. Methods: Retrospective case-control study with univariate and multivariable logistic regression analysis. Results: Four hundred twenty-nine (143 cases...
Lohmann KL, Vandenplas M, Barton MH, Moore JN.Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaero...
Leise B.Equine laminitis is a devastating disease in which failure of the adhesion between the digital dermal and epidermal laminae at the basement membrane results in crippling lameness and structural damage to the foot of the horse. Laminitis occurring secondary to sepsis is known to result from a significant inflammatory response that includes leukocyte emigration into the lamellar tissue. These leukocytes, in particular the neutrophil, have been extensively evaluated in experimental models of sepsis-related laminitis in the horse. This review will discuss the relevant findings elucidated from thes...
Peek SF, Semrad S, McGuirk SM, Riseberg A, Slack JA, Marques F, Coombs D, Lien L, Keuler N, Darien BJ.This prospective study compared survival rates of critically ill and septic foals receiving 1 of 2 different types of commercial equine plasma and analyzed admission variables as possible predictors of survival. Standardized clinical, hematologic, biochemical, and hemostatic admission data were collected and foals received either conventional commercially available hyperimmune equine plasma or equine plasma specifically rich in antiendotoxin antibodies in a double-blinded, coded fashion. Sepsis was defined as true bacteremia or sepsis score >11. Overall survival rate to discharge was 72% (4...
Fessler JF, Bottoms GD, Coppoc GL, Gimarc S, Latshaw HS, Noble JK.Endotoxin (LPS) was quantitated in experimental subjects and in horses with naturally occurring gastrointestinal strangulation obstruction and/or septicaemic diseases to establish the fate of LPS and the clinical usefulness of the Limulus amoebocyte lysate (LAL) assay. The assay was validated for sensitivity (10 pg/ml), recovery (90 to 106 per cent), intra-assay precision (CV = 5.5 per cent) inter-assay precision (CV = 11 per cent), and stability of diluted, heat treated, frozen samples (at least 90 days). Plasma concentrations of LPS after sublethal (3 micrograms/kg) jugular or portal vein bo...
Theelen MJ, Wilson WD, Edman JM, Magdesian KG, Kass PH.Monitoring the development of antimicrobial resistance is important for the rational selection of appropriate antimicrobial drugs to initiate treatment of foals with sepsis. Objective: To identify temporal trends in antimicrobial susceptibility patterns of bacteria isolated from foals with sepsis. Methods: Retrospective review of medical records. Methods: Foals aged <30 days with a diagnosis of sepsis, confirmed by culture of bacteria, were included. Susceptibility data, expressed as minimum inhibitory concentrations (MICs) (MIC50 , MIC90 , MIC range) and percent of isolates that were suscepti...
Holcombe SJ, Jacobs CC, Cook VL, Gandy JC, Hauptman JG, Sordillo LM.Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin toler...
Stack JD, Cousty M, Steele E, Handel I, Lechartier A, Vinardell T, David F.Synovial fluid analysis is utilized to diagnose septic synovitis. However, not all cases are clearly and rapidly discernible with the diagnostic tools available in the laboratory. Serum amyloid A (SAA), an acute phase protein, has been shown to be elevated in synovial fluid from inflamed synovial structures. The goal of this study is to describe the correlation between two diagnostic tests measuring equine SAA levels in septic and non-septic synovial structures and to understand the correlation between an elevated SAA result and synovial sepsis. Prospective estimation of sensitivity (Se) and s...
Black SJ, Lunn DP, Yin C, Hwang M, Lenz SD, Belknap JK.The mechanisms that initiate the pathophysiologic changes in the digital laminae in equine laminitis are poorly understood. Due to the fact that (1) the horse at risk of laminitis has many similarities clinically to the human sepsis patient and (2) our recent finding of marked laminar proinflammatory cytokine expression at the developmental time point of the black walnut extract (BWE) model of laminitis, we tested the possibility that, similar to organ damage in human sepsis, leukocyte emigration is an early event in laminitis. Using immunoperoxidase methods with an anti-equine CD13 monoclonal...
Hammond RA, Hannon R, Frean SP, Armstrong SJ, Flower RJ, Bryant CE.To determine the amount of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes induced in vitro in equine alveolar macrophages in response to lipopolysaccharide (LPS). Sample Population-Alveolar macrophages obtained from 12 horses. Methods: Alveolar macrophages were collected by bronchoalveolar lavage from 12 horses and incubated for 6 hours with LPS (0.001 to 10 microg/ml) or vehicle. Total RNA was extracted and purified. After first-strand cDNA synthesis, mRNA induction was measured, using a polymerase chain reaction (PCR) technique for COX-2, iNOS, and glyceraldehyde...
Hawkins JF, Bowman KF, Roberts MC, Cowen P.Peritonitis was diagnosed in 67 horses between 1985 and 1990: 14 horses developed septic peritonitis after intestinal rupture, 25 horses developed peritonitis after abdominal surgery, and 28 horses had peritonitis not associated with intestinal rupture or abdominal surgery. Forty of 67 horses (59.7%) did not survive. Nonsurvivors had higher heart rates (P = 0.01), RBC count (P = 0.039), serum creatinine concentration (P = 0.036), PCV (P = 0.007), and anion gap (P = 0.005); lower venous blood pH (P = 0.002); and a greater number of bacterial species cultured from peritoneal fluid samples (P = 0...
Barton MH, Morris DD, Norton N, Prasse KW.Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities ...
Werners AH, Bryant CE.Pattern recognition receptors (PRRs) on host cells detect pathogens to activate innate immunity which, in turn, initiates inflammatory and adaptive immune responses. Successful activation of PRRs is, therefore, critical to controlling infections and driving pathogen-specific adaptive immunity, but overactivity of PRRs causes systemic inflammation, which is detrimental to the host. Here we review the PRR literature as it relates to horses and speculate on the role PRRs may play in sepsis and endotoxaemia.
Kamr AM, Dembek KA, Reed SM, Slovis NM, Zaghawa AA, Rosol TJ, Toribio RE.Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hor...
Zabrecky KA, Slovis NM, Constable PD, Taylor SD.Accurate diagnostic markers for sepsis in neonatal foals are needed. Plasma C-reactive protein concentration (p[CRP]) and haptoglobin concentration (p[Hp]) are well-established biomarkers of infection in humans, but studies are lacking in foals. Objective: p[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival. Methods: Eighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1Â week of age. Methods: Multicenter, prospective observational clinical study. Venous blood was collected at a...
Paltrinieri S, Giordano A, Villani M, Manfrin M, Panzani S, Veronesi MC.A field study was undertaken to investigate plasma protein electrophoresis (PPE) and serum amyloid A (SAA) concentrations at 1, 3 and 7 days of age in foals born by oxytocin-induced (group A, n =17) or spontaneous (group B, n =12) parturition. The putative diagnostic role of PPE and SAA in four septicaemic foals was also examined. At birth, beta-gamma-globulins were higher in group B, and then increased in both groups, probably due to colostrum intake. At day 3, no significant differences between the groups were detectable. In both groups, SAA values increased from day 0 to day 3, then decreas...
Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA.Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TL...
Hart KA, Barton MH, Ferguson DC, Berghaus R, Slovis NM, Heusner GL, Hurley DJ.Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. Objective: In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. Methods: Fifty-one septic foals; 11 healthy foals; 6 healthy horses. Methods: In this prospective clinical study, foals meeting criteria for sepsis at admiss...
Wormstrand B, Østevik L, Ekman S, Olstad K.Failure of the cartilage canal blood supply leads to ischemic chondronecrosis which causes osteochondrosis, and osteochondral lesions. Osteochondrosis is a disease with a heritable component and usually occurs under aseptic conditions. Because bacteria can bind to growth cartilage and disrupt the blood supply in pigs and chickens, we considered whether this might play a role in development of equine osteochondrosis. The aim of this study was to examine whether bacteria are present in canals in the growth cartilage of foals with septic arthritis/osteomyelitis, and whether this is associated wit...
Vinther AM, Skovgaard K, Heegaard PM, Andersen PH.In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic inflammation ...
Raisis AL, Hodgson JL, Hodgson DR.Equine neonatal septicaemia was confirmed in 24 foals hospitalised at the Rural Veterinary Centre between 1989 and 1992 with suspected septicaemia. Septicaemia was confirmed by culture of bacteria from blood of live foals and tissues obtained at necropsy of foals that died or were euthanased. Pathogenic bacteria isolated were predominantly Enterobacteriaceae (including Escherichia coli and Salmonella serovars) and Actinobacillus equuli. Clinical manifestations of septicaemia included signs of depression, dehydration, abnormalities in body temperature and manifestations of localised infection i...
Scalco R, de Oliveira GN, da Rosa Curcio B, Wooten M, Magdesian KG, Hidai ST, Pandit P, Aleman M.Rapid and accurate markers to aid diagnosis of sepsis are needed in neonatal foals. The CBC variable red blood cell distribution width (RDW) to platelet ratio (RPR) is associated with inflammatory response and linked to poor outcomes of sepsis in human patients. Objective: Explore the correlation of RPR with sepsis in neonatal foals and evaluate RPR predictive and prognostic value. Methods: Three hundred seventeen hospitalized neonatal foals ≤7 days of age that had a CBC and physical exam performed at admission between 2012 and 2021. Methods: Retrospective case-control study. Clinical reco...
Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A.Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species. Objective: To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures. Methods: Six healthy adult female donkeys. Methods: Endotoxemia was in...
Radcliffe RM, Liu SY, Cook VL, Hurcombe SDA, Divers TJ.Interpreting changes in peritoneal fluid helps clinicians manage colic and other diseases in horses. During abdominal problems in the horse, abdominal fluid characteristics such as color, turbidity, total nucleated and red blood cell counts, cytology, total protein, and l-lactate change in predictable ways, helping the clinician characterize the disease. Methods: Normal abdominal fluid in horses is odorless, clear to light yellow in color, and transparent. Peritoneal fluid becomes more turbid with increasing levels of protein, number of WBCs or RBCs, or with gross contamination following intes...
Himler M, Hurcombe SD, Griffin A, Barsnick RJ, Rathgeber RA, MacGillivray KC, Toribio RE.Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. Objective: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. Objective: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic f...
Godman JD, Burns TA, Kelly CS, Watts MR, Leise BS, Schroeder EL, van Eps AW, Belknap JK.Sepsis-related laminitis (SRL) is a common complication in the septic/endotoxemic critically-ill equine patient, in which lamellar injury and failure commonly lead to crippling distal displacement of the distal phalanx. Similar to organ injury in human sepsis, lamellar injury in SRL has been associated with inflammatory events, including the influx of leukocytes into the lamellar tissue and markedly increased expression of a wide array of inflammatory mediators at the onset of Obel grade 1 (OG1) laminitis. The only treatment reported both clinically and experimentally to protect the lamellae i...
Cotovio M, Monreal L, Armengou L, Prada J, Almeida JM, Segura D.Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals < 1-day old. Objective: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. Met...
Martin EM, Messenger KM, Sheats MK, Jones SL.Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These recepto...
McTaggart C, Yovich JV, Penhale J, Raidal SL.Flow cytometric assays were used to compare phagocytic and oxidative burst activity of neutrophils from healthy foals less than 7 days of age with the activity of cells from healthy adult horses. The phagocytosis of Staphylococcus aureus by foal neutrophils was less than that observed for adult neutrophils when autologous serum was used as the source of opsonins in the assay. The use of adult serum did not significantly improve the ability of foal neutrophils to attach bacteria. The oxidative burst activity of foal neutrophils was equivalent to that of adult cells. However, when serum or plasm...
Gold JR, Perkins GA, Erb HN, Ainsworth DM.Septicemia initiates the production of pro-inflammatory (interleukin [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], IL-6), and anti-inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8, IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMC). Objective: Septic foals fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit distinctive cytokine profiles. Methods: Twenty-one septic and 20 healthy neonatal foals. Methods: Using real-time polymerase chain reaction, gene...
