Topic:Pathogenesis
Pathogenesis in horses refers to the biological mechanisms that lead to the development and progression of diseases within equine species. This process involves a complex interaction between the horse's immune system, genetic predispositions, environmental factors, and infectious agents such as bacteria, viruses, or parasites. Understanding pathogenesis is essential for identifying how diseases manifest and progress in horses, which can inform diagnostic and therapeutic strategies. Research in this area often focuses on specific diseases, examining factors such as pathogen entry, immune response, tissue damage, and recovery processes. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, contributing factors, and implications of pathogenesis in equine health.
Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype. Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremia associated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralizatio...
Distribution and numbers of mucous glands in the horse trachea. Horses commonly suffer from respiratory diseases associated with excess secretions in the airway lumen, some of which are presumably derived from airway mucous glands. However, these structures have been little investigated in the horse. Accordingly, we describe here the number, distribution and size of equine tracheal mucous glands, and compare the data with similar information for other mammalian species. Two types of gland acini were present. In the thick connective tissue, up to 400 microm beneath the epithelium, gland acini were grouped in thin sheets that, in cross-section, averaged 20 m...
Cytokine gene expression by peripheral blood leukocytes in horses experimentally infected with Anaplasma phagocytophila. Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected...
Sarcocystis neurona: parasitemia in a severe combined immunodeficient (SCID) horse fed sporocysts. Sarcocystis neurona was isolated from the blood of a 5-month-old Arabian foal with severe combined immunodeficiency. The foal had been inoculated approximately 3 weeks previously with 5 x 10(5) sporocysts that were isolated from the intestines of an opossum and identified by restriction enzyme analysis of PCR products as S. neurona. The isolate obtained from the blood of this foal was characterized by genetic, serologic, and morphologic methods and identified as S. neurona (WSU1). This represents the first time that S. neurona has been isolated from any tissue after experimental infection of a...
Equid herpesvirus 1 infection of endothelial cells requires activation of putative adhesion molecules: an in vitro model. Antisera to activated equine endothelial cells, which detected surface molecules of 116 kD, 97 kD, 42 kD and 38 kD, were made to investigate the role of endothelial adhesion molecules in equid herpes virus 1 infection. These putative adhesion molecules could be induced by 17-beta oestradiol, chorionic gonadotrophin, or IL-2, as well as by LPS and PWM. In an in vitro flow system, using equine veins or arteries, equid herpesvirus 1 in leucocytes was only transferred to infect endothelial cells if both leucocytes and endothelial cells expressed these surface molecules. Blocking of the membrane mo...
A study on the pathogenesis of equine sesamoiditis: the effects of experimental occlusion of the sesamoidean artery. In this study the potential role of circulatory disturbances in the pathogenesis of sesamoiditis was investigated by studying the clinical and histological effects of experimental occlusion of the sesamoidean artery, which is the main nutrient artery of the proximal sesamoid bone (PSB). For this purpose, five adult Dutch Warmblood horses were used in which the sesamoidean artery was occluded with polyvinyl alcohol foam particles. Bone labelling was carried out with oxytetracycline and calcein. All animal were checked clinically three times a week and radiographically at days 14, 21, 28 and 35....
Invasion, and short- and long-term survival of Babesia divergens (Phylum Apicomplexa) cultures in non-bovine sera and erythrocytes. In order to explore the feasibility of producing a Babesia divergens live vaccine free of bovine material contaminants the parasite's ability to grow in human, sheep and horse erythrocytes and serum and serum-free medium was investigated. B. divergens was successfully maintained in bovine erythrocytes overlaid with serum-free HL-1 medium. Supplementation of the culture medium with bovine or sheep serum improved parasite growth (monitored by measuring parasitaemia and uptake of tritiated hypoxanthine) whereas horse and human sera reduced parasite growth. As assessed by Giemsa's stained and FITC...
Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 1: Preparation and composition of HDS. Currently, heaves is investigated by exposing susceptible horses to dusty hay. Consequently, the response will be dependent on the organic dust content and composition of the hay. It was hypothesised that the use of a hay dust suspension (HDS) would reduce the variability of the challenge and therefore standardise experimental protocols. Furthermore, analysis of HDS would also permit further investigation of the organic dust components responsible for the response. Three hay dust suspensions (HDS-1, 2 and 3) were prepared for use in the diagnosis and investigation of heaves. HDS were produced ...
Modelling equine influenza 1: a stochastic model of within-yard epidemics. This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level impli...
Increased pulmonary activation of nuclear factor-kappaB (NF-kappaB) in foals inoculated with Rhodococcus equi is associated with increased expression of inflammatory cytokines. Previous studies revealed that foals inoculated with virulent Rhodococcus equi had significantly higher pulmonary levels of interleukin-1beta, interleukin-12 p40, interferon-gamma, and tumor necrosis factor-alpha mRNA compared to foals inoculated with an avirulent plasmid-cured derivative. The purpose of this study was to determine if the increases in cytokine expression were associated with increased pulmonary activation of nuclear factor-kappaB (NF-kappaB). Electrophoretic mobility shift assays were performed on pulmonary nuclear protein extracted from foals treated with phosphate-buffered s...
Growth characteristics of a highly virulent, a moderately virulent, and an avirulent strain of equine arteritis virus in primary equine endothelial cells are predictive of their virulence to horses. Equine viral arteritis (EVA) is an endotheliotropic viral disease of horses caused by equine arteritis virus (EAV). Although there is only one serotype of EAV, there is marked variation in the virulence of different strains of the virus. The replication and cytopathogenicity of three well-characterized strains of EAV of different virulence to horses were compared in rabbit kidney (RK-13) and primary equine pulmonary artery endothelial cells (ECs). Viral protein expression, plaque size, and cytopathogenicity of all three viruses were similar in RK-13 cells, whereas two virulent strains of EAV w...
Cytokine mRNA expression pattern in horses with large intestinal disease. The aim of this study was to investigate cytokine expression patterns in the large intestinal mucosa of horses, particularly in diseases associated with inflammation. Many cases of equine colitis remain without a definitive diagnosis and survival rates are poor. In humans, colitis is associated with increased expression of pro-inflammatory cytokines. To examine if similar responses occur in horses, we investigated il -2, il -4, il -5, il -10, tnfalpha, ifngamma and tgfbeta messenger rna expression in large intestinal mucosa. Samples were obtained from animals with large intestinal disease (n=1...
A novel model for equine recurrent airway obstruction. Equine recurrent airway obstruction (RAO; a term combining both chronic obstructive pulmonary disease (COPD) and summer pasture associated obstructive pulmonary disease (SPAOPD)) is one of the most common equine respiratory diseases with up to 50% of horses affected worldwide. The etiopathogenesis of RAO is unknown although pulmonary hypersensitivity to inhaled mold antigens may be involved. Recent work in our laboratory demonstrating elevated levels of IL-4 and IL-13 mRNA in the airways and peripheral blood of horses with RAO is consistent with an atopic component to RAO. Little is known rega...
Discriminant and multiple regression analysis of anemia and opportunistic infection in Fell pony foals. A condition resembling acquired immunodeficiency with anemia has been described in British Fell pony foals. The pathogenesis is unknown. The present study involved 322 foals of which 164 were of Fell breed and 12 were affected. Discriminant and multiple regression analyses were used to test the results of all clinical pathology parameters from these foals for statistical association with (1) breed origin and (2) presence of disease. Only hematocrit associated significantly with presence of disease. However, significant associations were found with Fell breed origin, including serum albumin con...
A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure and effect on macrophage cytokine production. Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and (1)H and (31)P and two-dimensional heteronuclear nuclear magnetic resonance studies. Key structural features of the lipoglycan are a linear alph...
Evaluation of leukotriene biosynthetic capacity in lung tissues from horses with recurrent airway obstruction. To evaluate leukotriene (LT) biosynthetic capacity in lung tissue from healthy horses and horses with recurrent airway obstruction (RAO). Methods: Lung parenchyma and airway specimens from 8 RAO-affected and 5 healthy horses. Methods: Horses were stabled for > or = 72 hours. Blood was drawn before euthanasia, after which lung specimens were collected. Tissue strips from small airways and parenchyma were incubated in organ baths with the precursor LTA4 or stimulated with calcium ionophore A23187 or the tripeptide N-formyl-Met-Leu-Phe (fMLP), with or without exogenous arachidonic acid, in the...
Characterization of Aqx and its operon: the hemolytic RTX determinant of Actinobacillus equuli. Actinobacillus equuli, a member of the family Pasteurellaceae is the etiologic agent of a frequently lethal septicemia in neonatal foals as well as other more chronic diseases like arthritis, pleuritis, pneumonia or peritonitis. It may also be isolated from the oral cavity of healthy horses. Hemolytic isolates of A. equuli are known but so far no virulence determinants have been described for this bacterial species. By screening hemolytic A. equuli strains with specific gene probes, a hemolysin, designated Aqx (A. equuli RTX (repeats in the structural toxin)) was identified. This hemolysin was...
Localisation and activity of cathepsins K and B in equine osteoclasts. Cathepsin K and cathepsin B were immunolocalised in equine osteoclasts (OC s) present in ex vivo cartilage/subchondral bone samples. Samples were obtained post mortem from the lateral trochlear ridge (LTR) of six horses and ponies aged between 303 days gestation to 8 months. Strong expression of cathepsin K was detected in OC s, particularly those located at the osteochondral junction, apparently involved in the resorption of calcified cartilage. Cathepsin K expression was also detected in hypertrophic chondrocytes and in the endothelial cells of some blood vessels penetrating the hypertrophic...
Isoxsuprine hydrochloride in the horse: a review. Isoxsuprine hydrochloride has been suggested for use in horses for treatment of navicular syndrome and laminitis. The drug has been shown to be a beta-adrenoreceptor antagonist with beta-adrenoreceptor agonistic properties, with both characteristics contributing to vasodilation and uterine relaxation. In addition, the drug is capable of decreasing blood viscosity and platelet aggregation. Studies have shown i.v. isoxsuprine to have a plasma half-life of <3 h with a large apparent volume of distribution. Cardiovascular effects resolve rapidly following i.v. administration, but are absent wit...
Reduced levels of nitric oxide metabolites in cerebrospinal fluid are associated with equine protozoal myeloencephalitis. Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NO(x)(-)) in the cerebrospinal fluid (CSF) is correlated with...
Experimental infection of horses with West Nile virus. A total of 12 horses of different breeds and ages were infected with West Nile virus (WNV) via the bites of infected Aedes albopictus mosquitoes. Half the horses were infected with a viral isolate from the brain of a horse (BC787), and half were infected with an isolate from crow brain (NY99-6625); both were NY99 isolates. Postinfection, uninfected female Ae. albopictus fed on eight of the infected horses. In the first trial, Nt antibody titers reached >1:320, 1:20, 1:160, and 1:80 for horses 1 to 4, respectively. In the second trial, the seven horses with subclinical infections developed Nt a...
EHV-1 gene63 is not essential for in vivo replication in horses and mice, nor does it affect reactivation in the horse: short communication. The aim of this study was to investigate the role of immediate early gene (gene63) in the pathogenesis of equine herpesvirus 1 (EHV-1) acute and latent infections in equine and murine models. EHV-1 gene63 mutant virus (g63mut) along with EHV-1 (Ab4) was used for intracerebral and intranasal infection of 3 and 17-day-old mice. Both viruses were recovered at the same frequency from tissues after infection. Two Welsh ponies were infected via the intranasal route with each of the viruses. Acute infection was monitored by virus isolation from nasal swabs and peripheral blood leukocytes. Six weeks p...
Effects of equine recombinant interleukin-1alpha and interleukin-1beta on proteoglycan metabolism and prostaglandin E2 synthesis in equine articular cartilage explants. To evaluate the effects of equine recombinant interleukin-1alpha (rEqIL-1alpha) and recombinant interleukin-1beta (rEqIL-1beta) on proteoglycan metabolism and prostaglandin E2 (PGE2) synthesis by equine articular chondrocytes in explant culture. Methods: Near full-thickness articular cartilage explants (approx 50 mg) harvested from stifle joints of a 3-year-old and a 5-year-old horse. Methods: Expression constructs containing cDNA sequences encoding EqIL-1alpha and EqIL-1beta were generated, prokaryotically expressed, and the recombinant protein purified. Near full-thickness articular cartilag...
The molecular basis of Streptococcus equi infection and disease. Streptococcus equi is the aetiological agent of strangles, one of the most prevalent diseases of the horse. The animal suffering and economic burden associated with this disease necessitate effective treatment. Current antibiotic therapy is often ineffective and thus recent attention has focused on vaccine development. A systematic understanding of S. equi virulence, leading to the identification of targets to which protective immunity can be directed, is a prerequisite of the development of such a vaccine. Here, the virulence factors of S. equi are reviewed.
Equine abortion associated with the Borrelia parkeri-B. turicatae tick-borne relapsing fever spirochete group. Direct amplification and sequencing of the 16S rRNA gene and a variable region of the flagellin gene from fetal liver-associated spirochetes belonging to the Borrelia parkeri-B. turicatae tick-borne relapsing fever spirochete group with a late-term abortion in a mare are described.
Equine herpesvirus type 1 (EHV-1) myeloencephalopathy: a case report. An outbreak of neurological disease occurred in a well-managed riding school. Ataxia and paresis were observed in several horses, five of which became recumbent and were euthanized. Post-mortem analysis revealed scattered haemorrhages along the spinal cord, that were reflected by multiple haemorrhagic foci on formalin-fixed sections, with the thoracic and lumbar segments being the most affected. Pathohistologically, perivascular mononuclear cuffing and axonal swelling, especially in the white matter, were evident. Parallel to the course of disease, alterations in myelin sheets and activation o...
Plasma concentrations of endothelin-like immunoreactivity in healthy horses and horses with naturally acquired gastrointestinal tract disorders. To compare plasma endothelin (ET)- like immunoreactivity between healthy horses and those with naturally acquired gastrointestinal tract disorders. Methods: 29 healthy horses and 142 horses with gastrointestinal tract disorders. Methods: Blood samples were collected from healthy horses and from horses with gastrointestinal tract disorders prior to treatment. Magnitude and duration of abnormal clinical signs were recorded, and clinical variables were assessed via thorough physical examinations. Plasma concentrations of ET-like immunoreactivity were measured by use of a radioimmunoassay for huma...
Cultivation and characterisation of primary and subcultured equine keratinocytes. We describe the establishment and characterisation of equine keratinocyte cultures with maintenance of a high proliferative capacity up to the second passage. Improved attachment and growth were obtained by seeding primary cells on equine feeder layers. Subcultured keratinocytes showed optimal growth when seeded on collagen type I. The proliferation rate of cells on this substrate exceeded that seen for cells seeded on equine feeder layers. By immunohistochemistry, epithelial origin and state of differentiation of the equine keratinocytes were determined. They expressed keratin and desmoplakin...
Influence of equine herpesvirus type 2 infection on monocyte chemoattractant protein 1 gene transcription in equine blood mononuclear cells. Representational difference analysis (RDA) was used to compare gene expression in equine mononuclear cells either infected with equine herpesvirus-2 (EHV-2) or adsorbed with inactivated EHV-2. Seven clones identified in non-infected cells after three rounds of selective subtraction and enrichment for differentially expressed genes contained sequences homologous to equine monocyte chemoattractant protein 1 (MCP-1). This suggested that EHV-2 may down-regulate MCP-1 transcription in infected cells. These findings correlate well with similar findings described for human cytomegalovirus and support...