Equine proliferative enteropathy: a cause of weight loss, colic, diarrhoea and hypoproteinaemia in foals on three breeding farms in Canada

Proliferative enteropathy (PE) is a transmissible enteric disease caused by Lawsonia intracellularis. An outbreak of equine PE was diagnosed in foals from 3 breeding farms. Most foals had been weaned prior to the appearance of clinical signs, which included depression, rapid and marked weight loss, subcutaneous oedema, diarrhoea and colic. Poor body condition with a rough haircoat and a potbellied appearance were common findings in affected foals. Respiratory tract infection, dermatitis and intestinal parasitism were also found in some foals. Haematological and plasma biochemical abnormalities included hypoproteinaemia, transient leucocytosis, anaemia and increased serum creatinine kinase concentration. Postmortem diagnosis of PE was confirmed on 4 foals based on the presence of characteristic intracellular bacteria within the apical cytoplasm of proliferating crypt epithelial cells of the intestinal mucosa, using silver stains, and by results of PCR analysis and immunohistochemistry. Antemortem diagnosis of equine PE was based on the clinical signs, hypoproteinaemia and the exclusion of common enteric infections. Faecal PCR analysis was positive for the presence of L. intracellularis in 6 of 18 foals tested while the serum of all 7 foals with PE serologically evaluated had antibodies against L. intracellularis. Most foals were treated with erythromycin estolate alone or combined with rifampin for a minimum of 21 days. Additional symptomatic treatments were administered when indicated. All but one foal treated with erythromycin survived the infection. This study indicates that equine PE should be included in the differential diagnosis of outbreaks of rapid weight loss, diarrhoea, colic and hypoproteinaemia in weanling foals.     

Equine proliferative enteropathy caused by Lawsonia intracellularis

Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic work-up and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article reviews the aetiology, epidemiology, clinical signs, diagnosis, treatment and prevention of EPE.     

Equine proliferative enteropathy – a review of recent developments

Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed upon abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic approach and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article focuses on new developments in the field of EPE, including epidemiology, pathophysiology, clinical signs, diagnosis, treatment and prevention. The Summary is available in Chinese – see Supporting information.     

Lawsonia intracellularis proliferative enteropathy in a foal

A weanling foal was diagnosed with proliferative enteropathy caused by Lawsonia intracellularis based on history, clinical findings of depression, anorexia, weight loss, colic, diarrhea, and ventral edema, and a combination of serology and fecal PCR. An epidemiological investigation on the premises revealed that many of the other foals and adult horses were seropositive for L. intracellularis, despite being clinically normal, and identified a dog as a potential carrier and source of infection for the foal.The foal was successfully treated with a combination of azithromycin and rifampin.     

Oral Infection of Weanling Foals with an Equine Isolate of Lawsonia intracellularis,Agent of Equine Proliferative Enteropathy

Background: Equine proliferative enteropathy (EPE) is an emerging disease of weanling foals. Objectives: Describe clinical, hematologic, biochemical, serologic, molecular, and ultrasonographic findings in foals experimentally infected with Lawsonia intracellularis. Animals: Eight foals. Methods: Recently weaned foals were assigned to either the challenge (n = 3), the sentinel (n = 3), or the control (n = 2) group. Foals were experimentally challenged via intragastric inoculation of 3 × 10¹⁰L. intracellularis organisms grown in culture. Each experimentally infected foal was housed with a sentinel foal in order to assess feco‐oral transmission. All foals were monitored daily for the development of clinical abnormalities and were weighed once weekly for the duration of the study (90 days). Abdominal ultrasound examination was performed weekly. Feces were collected every other day for 60 days, then weekly for an additional 30 days for the quantitative molecular detection of L. intracellularis. Blood was collected weekly for hematologic, biochemical, and serologic analysis. Results: Only challenged foals developed transient clinical signs of EPE consisting of anorexia, lethargy, fever, loose feces, and peripheral edema. Two challenged foals developed transient hypoalbuminemia. Fecal shedding of L. intracellularis was first detected in the challenged foals between days 12 and 18 postinoculation and lasted for 7–21 days. Seroconversion was documented in all challenged foals and in 1 sentinel foal. The remaining sentinel and control foals remained unaffected. Conclusions and Clinical Importance: Clinical EPE of variable severity was induced in all foals infected with L. intracellularis. Furthermore, L. intracellularis can be transmitted via the feco‐oral route to susceptible herdmates.     

Investigation of the Usefulness of Serum Amyloid A in Supporting the Diagnosis of Equine Proliferative Enteropathy

The objective of this study was to determine if serum amyloid A (SAA), a major acute-phase protein, could help support the diagnosis of equine proliferative enteropathy (EPE) caused by Lawsonia intracellularis infection in foals. Archived serum samples from 101 foals with enteric signs and hypoproteinemia were available for SAA testing. Based on immunodiagnostics for L. intracellularis, the foals were divided into EPE-suspect (67) and non–EPE-suspect cases (34). Serum amyloid A values ranged from 0 to 2,761 μg/mL (median 466 μg/mL) and from 0 to 2,555 μg/mL (median 192 μg/mL) for the EPE-suspect and the non–EPE-suspect cases, respectively. Although SAA can be measured patient-side and help determine the severity of the underlying inflammatory condition, SAA was unable to consistently support the diagnosis of EPE in hypoproteinemic foals with enteric signs.     

A follow up study on antibodies against Lawsonia intracellularis in mares and foals from two breeding farms in Germany

Equine proliferative enteropathy (EPE) caused by Lawsonia (L.) intracellularis is an emerging disease in foals, particularly in North America. Since a case report in Germany exists, the objective of this study was to examine the incidence of L. intracellularis-antibodies in healthy horses from two German breeding farms. In group 1, serum samples from 24 (year 1) and 16 (year 2) Haflinger mares and their foals were taken. In group 2, over a period of five months, serum samples of six warmblood mares and foals were collected monthly from birth until the foals became seronegative. Serum samples were tested using an ELISA system. Results are expressed as Percentage of Inhibiton (PI). All adult mares (100%) of both groups were seropositive at each point in time (PI-value > 30). In group 1,7/24 foals (29.2%) in year 1 and 4/16 foals (25%) in year 2 had antibodies.The seropositive foals from year 2 had the same dams as the seropositive foals from year 1. In group 2 five of six foals were seropositive after birth. Antibodies decreased from March to July in mares and foals. In July, all five foals tested negative for the first time between the ages of 82 and 141 days (median 115 days). PI-values of mares were significantly correlated with PI-values of their foals. Higher PI-values were seen in younger foals and early in spring. Loss of antibodies in foals at the age of three to five months could be a risk factor for infection and appearance of EPE.     

Evaluation of the humoral immune response and fecal shedding in weanling foals following oral and intra-rectal administration of an avirulent live vaccine of Lawsonia intracellularis

Equine proliferative enteropathy (EPE) caused by Lawsonia intracellularis has recently been recognized as an emerging disease in foals. Whilst the clinical entity, diagnostic evaluation and treatment of affected foals have been well established and described, preventive measures for EPE have remained largely unaddressed. The objectives of this study were to investigate the humoral immune response and onset and duration of fecal shedding in foals after oral and intra-rectal administration of a modified-live vaccine of L. intracellularis. Foals were vaccinated twice, 3 weeks apart, via oral drenching after pre-medication with a proton-pump inhibitor (omeprazole; group 1), intra-rectally (group 2) or orally without any pre-medication (group 3). The health status of the foals was monitored daily, with feces and serum collected at regular intervals for Polymerase Chain Reaction (PCR) and serology. All foals remained healthy and no adverse vaccine reactions were observed. Fecal shedding lasted from 1 to 12 days and was mainly detected in foals receiving the intra-rectal vaccine 11-15 days following the first vaccine administration. Serological responses were measured in the majority of the vaccinated foals. All foals vaccinated intra-rectally seroconverted after the first vaccine, compared to 50% and 0% of foals in groups 1 and 3, respectively. Pre-medication with omeprazole prior to oral vaccination in group 1 foals led to an earlier and stronger detectable humoral response compared to non pre-medicated foals.     

Characterization of the interferon gamma response to Lawsonia intracellularis using an equine proliferative enteropathy challenge (EPE) model

Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanlings, in particular, appear to be most at risk for infection, though the reasons for their particular susceptibility is unknown. Using an infectious challenge model for EPE, we demonstrate that EPE, like porcine proliferative enteropathy, can exhibit three clinical forms: classical, subclinical and acute. Out of six pony weanlings, one developed signs of classic EPE, one developed acute EPE, and two developed subclinical EPE. Attempts to induce pharmacological stress through the use of dexamethasone failed to have any effect on outcome. Peripheral blood cells collected from those weanlings that developed clinical EPE exhibited decreased expression of interferon-gamma (IFN-γ) following in vitro stimulation with L. intracellularis. By contrast, those weanlings that did not develop clinical disease generated a robust IFN-γ response. These results indicate IFN-γ likely plays a significant role in protection from disease caused by L. intracellularis in the equid.     

Outbreak of Lawsonia intracellularis on a Standardbred breeding farm in North Carolina

Lawsonia intracellularis is a cause of protein‐losing enteropathy in weanling foals commonly causing signs including diarrhoea, oedema and unthrifty appearance. It has previously been reported as sporadic cases throughout the USA, Canada and Europe. Only recently have outbreaks on a single farm location been reported. The cases reported here are an example of multiple foals on a single farm testing serologically positive for L. intracellularis. These foals ranged in severity from asymptomatic to severely hypoproteinaemic and septic; however, none of the foals ever displayed diarrhoea, which is the most common presenting sign of this disease process.     

Persistent Frenulum of the Epiglottis in Four Foals

OBJECTIVE: To report the clinical signs and management of 4 foals with persistent frenulum of the epiglottis. STUDY DESIGN: Case report. ANIMALS: Four newborn foals. METHODS: Foals were admitted with a complaint of oronasal reflux after nursing. Variable systemic signs of aspiration pneumonia were evident. Nasal endoscopy confirmed persistent dorsal displacement of the soft palate. Persistent frenulum of the epiglottis, confirmed by oral endoscopic examination, was transected. RESULTS: After surgery, all foals had the epiglottis positioned normally, dorsal to the soft palate. Clinical signs of oronasal reflux resolved by the second nursing attempt in 3 foals, whereas this was difficult to assess in one foal that was nursed intermittently because of the mares behavior. This foal died 2 days later. The other 3 foals have had normal epiglottic function for 2-4 years. CONCLUSIONS: Persistent frenulum of the epiglottis should be considered in foals with oronasal reflux from birth. With appropriate medical and surgical management the prognosis for resolution should be good.     

An unusual case of generalized soft-tissue mineralization in a suckling foal

An atypical case of severe soft-tissue mineralization in a 3-week-old foal from a herd of Andalusian horses is described. The herd clinical history and the laboratory findings were compatible with a diagnosis of secondary hyperparathyroidism due to a mineral imbalance in the diet (low calcium and high phosphorus intake). Mares showed a marked increase in serum parathyroid hormone (PTH) approximately 10 times normal levels. Serum PTH was marginally elevated in foals. Clinical signs (unthriftiness, painful joints, lameness in one or more limbs, and stiff gait) were more pronounced in foals than in mares. Two foals died and necropsy of one of them revealed extensive soft-tissue mineralization of arterial walls and pulmonary parenchyma. Clinical signs in mares and foals resolved by 4 weeks after diet adjustment.     

Squamous gastric ulceration complicated by gastric stenosis in a foal

A 2-month-old Warmblood colt presented with recurrent colic and regurgitation. Gastroscopy, performed on several occasions, and barium-contrast radiography revealed severe squamous gastric ulceration and stenosis at the level of the margo plicatus. Treatment with omeprazole reduced the extent and severity of the gastric ulcers but did not affect the stenosis. The foal was euthanised because of a poor prognosis, and post-mortem examination confirmed the clinical diagnosis. Severe squamous gastric ulceration, granulation tissue formation and cicatrisation of deep gastric lesions were considered to have caused the stenosis. Gastroduodenal outflow obstruction is a recognised disorder in foals, but stenosis at the level of the margo plicatus has not been reported in foals or adult horses. To the authors' knowledge, this is the first case of severe squamous gastric ulceration, complicated by stenosis at the level of the margo plicatus, in a foal. Although rare, gastric stenosis should be considered in foals suffering recurrent colic and regurgitation.     

The seroprevalence of Lawsonia intracellularis in horses in The Netherlands

Equine proliferative enteropathy caused by Lawsonia intracellularis is an emerging disease of weanling foals and affects their growth and development. The prevalence of Lawsonia intracellularis in The Netherlands is not known. The aim of the study was to investigate the seroprevalence of Lawsonia intracellularis in horses in The Netherlands. Blood samples were taken from healthy foals before and after weaning and from healthy yearlings and mature horses on farms throughout The Netherlands. These samples were analysed for the presence of Lawsonia intracellularis-specific antibodies with a blocking ELISA. White blood cell count, packed cell volume, and total protein concentration were also measured in all foals. Information regarding housing, pasture access, and contact with pig manure on the premises was obtained for all animals. The prevalence of Lawsonia intracellularis antibodies in foals increased significantly from 15% before weaning to 23% after weaning (p = 0.019); it was 89% in yearlings and 99% in horses older than 2 years. There was no significant difference in seroprevalence between the pasture-kept and stable-confined adult horses (97% and 100%, respectively), and there was no significant influence of contact with pig manure. None of the sampled animals showed clinical disease. In conclusion, the results suggest that Lawsonia intracellularis is widespread in The Netherlands and that seropositivity is not necessarily associated with clinical problems. The high seroprevalence in adult horses suggests long-term persistence of antibodies against Lawsonia intracellularis or constant exposure to the bacterium.     

Enzyme-linked immunosorbent assay for diagnosis of Corynebacterium (Rhodococcus) equi infection in foals

An enzyme-linked immunosorbent assay (ELISA) was used to diagnose Corynebacterium (Rhodococcus) equi infection in foals. In tests done with different antigen-extraction procedures (sodium dodecyl sulfate, sodium deoxycholate, polyoxy-ethylene [9] p-tert-octylphenol, polyoxy-ethylene [9-10] p-tert-octylphenol, sonification, homogenization, and heat treatment at 121 C), Tween 20 was a satisfactory reactive antigen. Using hyperimmune rabbit sera or infected foal sera, we investigated the specificity and the sensitivity of the ELISA with the Tween 20 antigen of the different serotypes or of the isolates. Corynebacterium equi strain ATCC 6939 antigen had the best activity for detecting antibodies to C equi in foals. Sera from 218 healthy horses, 11 healthy foals, 17 healthy newborn foals, a foal with suspected C equi infection, and 5 infected foals were evaluated for antibodies to C equi, using ELISA. The optical density values of 206 healthy horses, 17 healthy newborn foals, and 9 healthy foals were less than 0.1. Infected foal sera, except from foal 3, and serum from a foal with suspected C equi infection had higher optical density values. Using ELISA, specific antibodies against C equi were detected in a naturally infected 6-week-old foal after the foal had a rapid increase in the number of bacteria in the feces and after the initial development of clinical signs of illness at 5 weeks of age. Therefore, ELISA was useful for the early diagnosis of C equi infection in foals.     

Enzootic viral abortion on a stud farm in east Switzerland

An outbreak of abortion due to the equine herpesvirus-1 (EHV-1) in the eastern part of Switzerland is reviewed. Seven of eleven pregnant mares aborted within twenty-three days in January 1989. Four weeks later another foal died a few minutes after parturition. Three mares delivered live foals in February, March and April without any complications. The examination of the eight dead foals revealed an EHV-1 Infection. The clinical signs and the pathology are discussed. Severe complications during the early post-parturient time are in contrast to the uncomplicated outcome mentioned by other authors. Procedures for prevention and control are listed.     

Presentation,stabilisation and contrast-enhanced computed tomographic (CT) diagnosis of a left gastrocaval portosystemic shunt in a pony foal

A 2-week-old pony foal was presented for recurrence of neurological dysfunction, obtunded-comatose mentation and collapse. Signalment, history, haematological and clinical chemical measurements and response to treatment prompted a presumptive diagnosis of hepatic encephalopathy secondary to a portosystemic shunt. This case differs from previous reported cases of  congenital portosystemic shunts in horses due to the early onset of clinical signs, which usually occur at 2–6 months of age. In addition, in comparison with previously reported cases, this foal stabilised rapidly with minimal intervention. Contrast-enhanced computed tomography (CT) confirmed a left gastrocaval extrahepatic portosystemic shunt. Surgical intervention was not attempted due to financial constraints, so the foal was subjected to euthanasia, and on post-mortem examination, the anomalous vascular connection could clearly be identified.     

Pathogenicity of Rhodococcus equi expressing a virulence-associated 20 kDa protein (VapB) in foals

Rhodococcus equi strains of intermediate virulence (IMV) for mice possess a 20kDa protein designated Virulence Associated Protein B (VapB) and a virulence plasmid of 79-100kb, and can be recovered from the submaxillary lymph nodes of pigs. The pathogenicity of such R. equi strains for foals is unknown. In this study, two foals, 42 and 43 days of age, were infected intratracheally with 10(6) and 10(9) cells of R. equi IMV strain A5, respectively. The foal infected with 10(9) cells of strain A5 became clinically ill, with the onset of illness (pyrexia and depression) occurring 21 days after inoculation. R. equi was isolated from the feces and tracheal washings of the foal from 14 to 28 days after inoculation. The foal infected with 10(6) cells of A5 showed no clinical signs, and no R. equi was isolated from any of the samples of feces or tracheal washings during the 28 days of observation. Two foals of 45 and 50 days of age were infected with 10(5) or 10(6) of virulent R. equi ATCC 33701 having 15-17kDa surface proteins designated VapA. Both exhibited severe clinical signs (pyrexia, depression and anorexia) at 12 and 13 days after inoculation. Histopathological examination revealed that strain A5 caused focal granulomatous pneumonia in the foals. R. equi IMV strain A5 was isolated from lung lesions of both foals and from the contents of the intestinal tracts of the foal infected with 10(9) bacteria. These results suggest that IMV R. equi having VapB is less virulent than virulent R. equi having VapA in foals. This finding supports our previous results on the pathogenicities of R. equi strains having these virulence-associated antigens assessed by mouse pathogenicity tests.     

Lawsonia intracellularis infection in horses: 2005-2007

Background: Lawsonia intracellularis is an emerging equine pathogen that is a cause of equine proliferative enteropathy (EPE).
Objective: To describe the signalment, month of presentation, common clinical signs, clinicopathologic values, diagnostic tests used, antimicrobial use, and survival status in horses affected with EPE; to evaluate how affected horses sold at public auction as yearlings; and to determine results of fecal polymerase chain reaction (PCR) and serum immunoperoxidase monolayer assay (IPMA) results in age matched, clinically normal herdmates.
Animals: The study group was 57 horses treated for disease associated with L. intracellularis infection between August 2005 and January 2007.
Methods: Retrospective study examined horses exhibiting evidence of infection with L. intracellularis and testing positive for fecal PCR or serum IPMA.
Results: Horses ranged in age from 2 to 8 months with a median age of 6 months, and all were examined between August and January. Ventral edema was present in 81% of horses and hypoalbuminemia occurred in all horses. Only 50% of horses tested positive on both PCR and IPMA. Ninety-three percent of horses survived, and survival was unrelated to antimicrobial administered. Affected horses sold as yearlings an average of 68% less than other yearlings by the same sire. Age matched, clinically normal herdmates also tested positive for L. intracellularis on fecal PCR (6%) and IPMA (33%).
Conclusion: L. intracellularis infection should be considered in young horses with ventral edema and hypoalbuminemia that are examined between August and January. Both fecal PCR and serum IPMA are needed to help determine disease status. Treated animals usually survive, although they do not sell for as high a price at public auction as other yearlings by the same sire. Age matched, clinically normal herdmates also test positive for L. intracellularis on fecal PCR and serum IPMA.