Characterization of Clostridium difficile isolates from foals with diarrhea: 28 cases (1993-1997)

OBJECTIVE: To determine molecular characteristics of Clostridium difficile isolates from foals with diarrhea and identify clinical abnormalities in affected foals. DESIGN: Retrospective study. ANIMALS: 28 foals with C difficile-associated diarrhea. PROCEDURE: Toxigenicity, molecular fingerprinting, and antibiotic susceptibility patterns were determined. Information on signalment, clinical findings, results of clinicopathologic testing, whether antimicrobials had been administered prior to development of diarrhea, and outcome was obtained from the medical records. RESULTS: Twenty-three (82%) foals survived. Toxin A and B gene sequences were detected in isolates from 24 of 27 foals, whereas the toxin B gene alone was detected in the isolate from 1 foal. Results of an ELISA for toxin A were positive for fecal samples from only 8 of 20 (40%) foals. Ten of 23 (43%) isolates were resistant to metronidazole. Molecular fingerprinting revealed marked heterogeneity among isolates, except for the metronidazole-resistant isolates. Sixteen foals had tachypnea. Hematologic abnormalities were indicative of inflammation. Common serum biochemical abnormalities included metabolic acidosis, hyponatremia, hypocalcemia, azotemia, hypoproteinemia, hyperglycemia, and high enzyme activities. Passive transfer of maternal antibodies was adequate in all 12 foals evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a large percentage of C difficile isolates from foals with diarrhea will have the toxin A and B gene sequences. Because of the possibility that isolates will be resistant to metronidazole, susceptibility testing is warranted. Clostridium difficile isolates from foals may have a substantial amount of molecular heterogeneity. Clinical and hematologic findings in affected foals are similar to those for foals with diarrhea caused by other pathogens.     

Experimental Clostridium difficile enterocolitis in foals

Despite empirical clinical association of infection with Clostridium difficile with colitis in horses, a causal link has not been confirmed. The objective of this study was to develop a model of C. difficile-associated diarrhea in foals with normal transfer of passive immunity. Nine 1-day-old pony foals were inoculated intragastrically with spores or vegetative cells of C. difficile. Five foals were challenged with spores, with 2 receiving 10(5) colony-forming units (CFUs) and concurrently 3 receiving 10(7) CFUs once daily for 3 days. Clindamycin was administered orally to disrupt gastrointestinal flora. A further 4 foals were challenged by orogastric administration of 10(10) CFUs of vegetative cells once daily for 3 days or until diarrhea developed. This group did not receive clindamycin. Spore and vegetative cell preparations were negative for toxins of C. difficile and common enteropathogens. Clinical signs varied from mild abdominal discomfort and pasty feces to colic and watery diarrhea in 8 of 9 foals. Four of 5 foals challenged with spores developed mild diarrhea, whereas all foals challenged with vegetative cells developed moderate to severe diarrhea. C. difficile was isolated from feces of all foals between 24 and 72 hours after inoculation and toxins A or B or both were detected in the feces of all foals by an enzyme-linked immunosorbent assay. We concluded that spores and vegetative cells of C. difficile are capable of colonizing the gastrointestinal tract, producing toxins, and inducing clinical signs similar to those encountered in naturally occurring cases. This study fulfilled Koch's postulates for C. difficile-associated diarrhea in foals and provides a model for consistent reproduction of the disease for future studies.     

Epizootiological and virological studies of foal diarrhea associated with serotype 3 rotavirus

Epizootiological and virological studies were conducted on foal diarrhea occurring in 3 foal-raising locations in a light horse farm from March to July, 1987. At the first location, although 27 (75%) of 36 foals had developed diarrhea, the isolation rate of rotavirus (RV) was low (5/14 feces, 36%). Many of the foals had the disease as early as 23 days after birth. At the second and third locations, 21 (27%) of 78 foals and 41 (76%) of 54 foals were affected with diarrhea. Isolation rates of RV were 90% (20/22 feces) and 100% (26/26 feces), respectively. The diseased cases were observed throughout the short period from June to early July and on foals aged from 63 to 65 days. These findings suggested the importance of RV as a causal agent of foal diarrhea at the latter location, RV and/or other agents at the former location. All the 3 strains of RV represented from each location were identified as serotype 3 by plaque reduction neutralization test against the antiserums of serotypes 1 to 6 of RV. However, the 3 strains showed low cross-reactivity with antiserum of the serotype 3 of the equine RV.     

Diarrhea associated with enterotoxigenic Bacteroides fragilis in foals

Enterotoxigenic Bacteroides fragilis (ETBF) was isolated from the feces of 10 of 40 Thoroughbred foals with naturally acquired diarrhea. Of the 10 foals positive for ETBF, 6 were less than or equal to 7 days old. Fecal specimens from 4 of the 10 foals also were positive for rotavirus, and one fecal specimen was positive for Salmonella enteritidis. Clinical or hematologic differences were not evident between foals infected with ETBF only and those infected with ETBF and another recognized enteric pathogen. Only 1 of 10 foals infected with ETBF died. Of 25 adult rabbits with ligated ceca, 23 developed mucoid, often hemorrhagic, diarrhea after inoculation of 5 X 10(9) viable ETBF cells into the ileum. Nine of 13 (69%) rabbits inoculated with 1 of 3 isolates of ETBF died, but none of 12 inoculated with 1 of 6 other isolates of ETBF died. Enteric disease did not develop in 15 rabbits inoculated with nonenterotoxigenic B fragilis.     

Electrolyte Disturbances in Foals with Severe Rhabdomyolysis

Marked electrolyte abnormalities characterized by profound hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia were noted in 4 neonatal foals with acute rhabdomyolysis and pigmenturia. In 2 foals, rhabdomyolysis developed 4–6 days after admission for dysmaturity, and in 2 foals, rhabdomyolysis was evident on presentation. Rhabdomyolysis was a consequence of selenium deficiency with or without vitamin E deficiency, possibly combined with increased oxidant stress due to sepsis or hypoxia and reperfusion injury after parturition. Foals gained from 7 to 15% of their initial body weight within 48 hours of developing rhabdomyolysis. Three of the foals developed cardiac arrhythmias characterized by spiked T waves and decreased-amplitude P waves. Postmortem examination of 2 foals revealed extensive myodegeneration and renal tubular nephrosis; renal cortical necrosis with myocardial necrosis was noted in 1 foal. Destruction of the major intracellular compartment (intracellular fluid [ICF]) through extensive myonecrosis combined, in some cases, with myoglobinuric renal insufficiency produced major fluid shifts and life-threatening electrolyte derangements. With the major ICF compartment disrupted, hyperkalemia was most effectively treated using mineralocorticoids, loop diuretics, and ion exchange resins to enhance elimination. In addition, IV calcium, glucose, insulin, and sodium bicarbonate were administered, which helped redistribute potassium to the ICE Severe rhabdomyolysis should be included in the differential diagnoses of hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia in neonatal foals.     

Glycogen branching enzyme deficiency in quarter horse foals

Seven related Quarter Horse foals that died by 7 weeks of age were examined for glycogen branching enzyme (GBE) deficiency. Clinical signs varied from stillbirth, transient flexural limb deformities, seizures, and respiratory or cardiac failure to persistent recumbency. Leukopenia (5 of 5 foals) as well as high serum creatine kinase (CK; 5 of 5), aspartate transaminase (AST; 4 of 4), and gamma glutamyl transferase (GGT; 5 of 5) activities were present in most foals, and intermittent hypoglycemia was present in 2 foals. Gross postmortem lesions were minor, except for pulmonary edema in 2 foals. Muscle, heart, or liver samples from the foals contained abnormal periodic acid Schiff's (PAS)-positive globular or crystalline intracellular inclusions in amounts proportional to the foal's age at death. Accumulation of an unbranched polysaccharide in tissues was suggested by a shift in the iodine absorption spectra of polysaccharide isolated from the liver and muscle of affected foals. Skeletal muscle total polysaccharide concentrations were reduced by 30%, but liver and cardiac muscle glycogen concentrations were normal. Several glycolytic enzyme activities were normal, whereas GBE activity was virtually absent in cardiac and skeletal muscle, as well as in liver and peripheral blood cells of affected foals. GBE activities in peripheral blood cells of dams of affected foals and several of their half-siblings or full siblings were approximately 50% of controls. GBE protein in liver determined by Western blot was markedly reduced to absent in affected foals, and in a half-sibling of an affected foal, it was approximately one-half the amount of normal controls. Pedigree analysis also supported an autosomal recessive mode of inheritance. The affected foals have at least 2,600 half-siblings. Consequently, GBE deficiency may be a common cause of neonatal mortality in Quarter Horses that is obscured by the variety of clinical signs that resemble other equine neonatal diseases.     

Bacteremia in equine neonatal diarrhea: a retrospective study (1990-2007)

Background: Bacteremia in sick foals is associated with survival, but the association of bacteremia and diarrhea is not reported.
Hypothesis: Neonatal foals with diarrhea will commonly be bacteremic.
Animals: One hundred and thirty-three neonatal foals.
Methods: Records of all foals <30 days of age presenting with diarrhea between January 1990 and September 2007 were reviewed.
Results: Sixty-six of 133 foals (50%) were bacteremic at admission, with 75 isolates from the 66 samples. The blood culture from a further 18 foals (13.5%) grew coryneform bacteria. Nine foals (6.8%) had 2 or more organisms grown on blood culture. One foal had 5 different organisms, interpreted as contamination. Forty-eight foals (36%) had no growth on admission blood cultures. No cultures isolated fungal organisms. Excluding coryneform bacteria, 43 isolates (57%) were Gram-negative organisms and 32 isolates (43%) were Gram-positive organisms. The most common isolate was Enterococcus spp. (22 isolates, 29%), followed by Pantoea agglomerans (13 isolates, 17%). IgG concentration at admission was not associated with blood culture status. Blood culture status was not associated with survival to hospital discharge.
Conclusions and Clinical Importance: Bacteremia is common in neonatal foals with diarrhea. Decisions regarding antimicrobial selection should be made with these differences in mind.     

The Effects of Ivermectin Given Postpartum on the Incidence and Severity of Foal Heat Diarrhea

Foal heat diarrhea (FHD) is a major factor in the management of foals between 2 and 3 wk of age. The objective of this on-farm study was to determine the efficacy of postpartum anthelmintic treatment of mares for reducing the incidence and/or the severity of FHD in foals caused by parasitic infestation. Twenty-four Quarter Horse mares and their foals were alternately assigned to a treated or non-treated group according to expected foaling date. Treatment consisted of oral administration of Zimectrin® (Farnam Companies, Inc., Phoenix, AZ) to the dam within 12 h post-foaling. From d l through 25, foals were weighed, and vital signs and severity or absence of diarrhea were recorded. Incidence scores of 0 to 3 were assigned to each foal based on severity of diarrhea: 0 = no affliction and 3 = severe, watery diarrhea. There was no difference in incidence scores because of treatment; however, there was a trend for foals from treated mares to experience more severe diarrhea with a shorter duration. There was no difference in BW gain related to treatment or nontreatment of mares. Postpartum administration of Zimectrin to mares did not significantly decrease the incidence or severity of diarrhea in foals. Additionally, it did not affect growth rate of foals. The trend for foals from treated mares to have a shorter duration of FHD may be beneficial to farm managers who spend time and money treating and cleaning foals.     

Surgical Treatment of Gastroduodenal Obstructions in Foals

Thirteen foals that ranged in age from 4 days to 4 months were presented for treatment of gastroduodenal obstruction. The site of obstruction was determined from examination of standing right lateral contrast radiographs of the caudal part of the thorax and abdomen. Depending on the site, the obstruction was bypassed by esophagogastrostomy, gastroduodenostomy, partial gastrectomy with gastroduodenostomy, duodenojejunostomy, or gastrojejunostomy followed by jejunojejunostomy. Six of the 13 foals (46%) survived. All foals with pyloric stenosis survived. Seven of eight foals with duodenal stenosis died. Deaths were due to complications unrelated to the primary gastroduodenal obstruction.     

Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996)

OBJECTIVE: To determine whether foals with pneumonia that were treated with erythromycin, alone or in combination with rifampin or gentamicin, had a higher risk of developing adverse effects, compared with foals treated with trimethoprim-sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and PGP (control foals). DESIGN: Retrospective study. ANIMALS: 143 foals < 240 days old. PROCEDURE: Information on age, sex, breed, primary drug treatment, total days of treatment with the primary drug, and whether the foal developed diarrhea, hyperthermia, or respiratory distress was obtained from the medical records. Relative risk (RR) and attributable risk (AR) were calculated to compare risk of adverse reactions between foals treated with erythromycin and control foals. RESULTS: Only 3 (4.3%) control foals developed diarrhea; none developed hyperthermia or respiratory distress. Foals treated with erythromycin had an 8-fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of erythromycin to treat foals with pneumonia was associated with an increased risk of diarrhea, hyperthermia, and respiratory distress, compared with use of TMS or PGP.     

Epidemiologic survey of diarrhea in foals

Epidemiologic and etiologic data about diarrhea in foals were collected under a planned prospective recording and monitoring study. The survey and monitoring procedures included a survey to obtain an overview of current horse management practices on participating farms, a daily health record survey to obtain information on mares and their foals, and collection of feces from 19 of 144 diarrheic foals and 10 age-matched nondiarrheic foals for electron microscopy, ELISA for rotavirus, and bacteriologic culture. Coronavirus was detected in the feces of diarrheic as well as clinically normal foals. Rotavirus was detected in the feces of diarrheic foals only. With regard to agents found in the feces, there was no significant (P less than 0.05) difference between diarrheic and nondiarrheic foals. Half of the 297 foals on which data were available developed diarrhea. Most foals that developed diarrhea lacked other clinical manifestations of disease. Basic cleanliness at foaling was associated with a lower percentage of foals developing diarrhea. Prophylactic use of antibiotics and vitamins in newborn foals was associated with a higher percentage of foals developing diarrhea. A higher percentage of foals born to visiting mares developed diarrhea, compared with foals born to resident mares.     

Foal-Heat Diarrhea Is Not Caused by the Presence of Yeasts in Gastrointestinal Tract of Foals

The aim of this study was to evaluate whether a normal yeast flora is present in the intestine of healthy foals and whether establishing yeast flora or yeast overgrowth might be associated with foal-heat diarrhea. Among the sampled foals, 49% showed foal-heat diarrhea and 28.3% were positive for yeasts. Candida famata was isolated 9 times; Geotrichum sp., 6; Saccharomyces cerevisiae, 5; Cryptococcus laurentii, 4; Rhodotorula sp., 3; Zygosaccharomyces sp., 2; and Candida colliculosa, Candida globosa, and Candida pelliculosa 1 time, respectively. The colony-forming unit ranged from 1 to 10 in all positive cultures. Fifteen of 92 (16.3%) foals with heat diarrhea and 11 of 92 (11.9%) asymptomatic animals yielded positive samples for yeasts. None of the animals shed the same yeast more than 2 times consecutively, and yeasts were found in pure or mixed culture. Equine gastrointestinal tract did not appear to be colonized by yeasts during the first 15 days of life, and yeasts are not involved in foal-heat diarrhea.     

Prevalence of Cryptosporidium sp in equids in Louisiana

In 1985, 22 pony foals reared in a helminth-free environment were tested daily for oocysts of Cryptosporidium sp by use of fecal flotation. Oocysts were found in all foals. Oocysts were first observed in feces collected from foals 9 to 28 days after birth. The mean period of oocyst shedding was 10 days and ranged from 2 to 18 days in individual foals. Diarrhea was observed in 14 of 22 (64%) foals and began before the period of oocyst shedding. Fecal samples also were examined for other infective agents. Salmonella poona was isolated from 1 foal that did not have diarrhea, and coronavirus particles were observed in the feces of 2 foals with diarrhea. Cryptosporidium sp oocysts also were observed in feces of 2 of 17 Thoroughbred foals, 3 of 14 Quarter Horse foals, and 3 of 26 pony foals reared on pastures with their dams. Samples from pasture-reared foals were collected at irregular intervals. Of the 11 Cryptosporidium-positive fecal samples collected from pastured foals, 2 were from foals with diarrhea. A similar survey was conducted during the 1986 foaling season, using the same procedures. Examination of 300 samples from 58 Quarter Horse, Arabian, and pony foals did not detect oocysts. Daily examination of feces from 10 pony foals reared under helminth-free conditions for 30 days also failed to detect Cryptosporidium oocysts.     

Ulcerative dermatitis, thrombocytopenia, and neutropenia in neonatal foals

This report describes transient ulcerative dermatitis, severe thrombocytopenia, and mild neutropenia in 6 foals from 4 mares from geographically diverse regions of the United States. The foals presented at <4 days of age with oral and lingual ulcers, and crusting and erythema around the eyes, muzzle, and perineal, inguinal, axillary, trunk, and neck regions. There was a severe thrombocytopenia (0-30,000 platelets/microL), leukopenia (1900-3200 white blood cells/microL), and mild neutropenia (500-1800 neutrophils/microL). Four of the 6 foals had petechiae and ecchymotic hemorrhages and 3 had bleeding tendencies. Results of examination of a bone marrow biopsy from 1 foal were normal and results of a platelet surface immunoglobulin test in another were negative. Histopathology of the skin in all foals showed subepidermal clefting with subjacent vascular dilation, dermal hemorrhage, and superficial papillary necrosis. The foals were treated supportively with broad-spectrum antibiotics (5/6), corticosteroids (3/6), gastric ulcer prophylaxis (6/6), whole-blood transfusion (4/6), and platelet-rich plasma (1/6). The skin lesions and thrombocytopenia (>50,000 platelets/microL) improved in 2 weeks (4/6). Two foals had a decline in their platelet counts when the steroids were decreased and needed protracted treatment. All foals survived and were healthy as yearlings. Two mares that had 2 affected foals each, upon subsequent pregnancies to different stallions, had healthy foals when an alternate source of colostrum was given. The findings in the cases in this report suggest a possible relationship between colostral antibodies or some other factor in the colostrum and the thrombocytopenia and skin lesions, although further investigation is warranted to confirm or refute this hypothesis.     

Hypocalcemia in a four-week-old foal

Intake of Rumex, a plant genus of the Polygonaceae family, probably led through the assimilation of oxalic acid, to hypocalcaemia in a four-week old foal. This foal was presented with muscle rigidity and a stiff gait. Both the total and ionized calcium concentrations were low, 1.38 mmol/l and 0.54 mmol/l respectively. The foal was treated with a total of 150 ml of a 20% calcium solution IV. The foals neuromuscular signs resolved within a few hours after receiving calcium solution.     

Rotavirus infection in foals

Fecal samples from 86 foals with diarrhea were examined by electron microscopy during a 2.5 year period. Of these, 26 (30%) were positive for rotavirus. All of the cases were found in epizootic areas. The disease was produced in an experimental foal by inoculation via stomach tube of a bacteria-free fecal filtrate containing rotavirus. Examination of postmortem tissues from the duodenum and jejunum of 2 naturally infected foals and an experimentally infected foal revealed replicating virus in the intestinal epithelial cells. A limited survey of complement-fixing antibody to rotavirus in horses from Kentucky, Virginia, and France indicated that all horses had antibody to the virus. The sole exception was 1 foal from which blood samples were collected prior to suckling. These results were presumptive evidence that rotavirus is a major cause of diarrhea in foals, and the presence of antibody in horses from diverse areas is evidence for the ubiquitousness of this infection.     

Infectious Agents Detected in the Feces of Diarrheic Foals: A Retrospective Study of 233 Cases (2003–2008)

Background: Diarrhea is common in foals but there are no studies investigating the relative prevalence of common infectious agents in a population of hospitalized diarrheic foals.
Objectives: To determine the frequency of detection of infectious agents in a population of hospitalized foals with diarrhea and to determine if detection of specific pathogens is associated with age, outcome, or clinicopathologic data.
Animals: Two hundred and thirty-three foals ≤ 10 months of age with diarrhea examined at a referral institution.
Methods: Retrospective case series. Each foal was examined for Salmonella spp., viruses, Clostridium difficile toxins, Clostridium perfringens culture, C. perfringens enterotoxin, Cryptosporidium spp., and metazoan parasites in feces collected at admission or at the onset of diarrhea.
Results: At least 1 infectious agent was detected in 122 foals (55%). Rotavirus was most frequently detected (20%) followed by C. perfringens (18%), Salmonella spp. (12%), and C. difficile (5%). Foals < 1 month of age were significantly more likely to be positive for C. perfringens (odds ratio [OR] = 15, 95% confidence interval [CI] = 3.5–66) or to have negative fecal diagnostic results (OR = 3.0, 95% CI = 1.7–5.2) than older foals. Foals > 1 month of age were significantly more likely to have Salmonella spp. (OR = 2.6, 95% CI = 1.2–6.0), rotavirus (OR = 13.3, 95% CI = 5.3–33), and parasites (OR = 23, 95% CI = 3.1–185) detected compared with younger foals. Overall 191 of the 223 foals (87%) survived. The type of infectious agent identified in the feces or bacteremia was not significantly associated with survival.
Conclusions and Clinical Importance: In the population studied, foals with diarrhea had a good prognosis regardless of which infectious agent was identified in the feces.     

An artificial rearing method to produce optimum growth in orphaned foals

Eleven foals were fed a dilute (1 to 10) milk replacer diet (15% fat, 23% milk protein; dry matter) from 1 to 8 weeks of age. Two suckled foals served as controls. Maximum consumption of formula was limited to 25% of body weight per day divided into 5 feedings per day during week one, 4 per day during week 2 and 3 feedings per day from weeks 3 through 8. Supplemental grain was offered to all foals beginning at week 2. Body weight was measured twice weekly and increased linearly over time. Height at withers, croup, elbow and hock were measured once a week and increased at a rate best described by a second order polynomial equation. Increases in body length were linear. There were no statistical differences between suckled and formula-fed foals for any growth parameter. Scours (foal diarrhea) occurred during weeks 1 or 2 in both the control and experimental groups. Diarrhea was mild and of short duration. This regimen resulted in growth and weight gains that were comparable to those of normally suckled foals.     

Long-term effects of desmotomy of the accessory ligament of the deep digital flexor muscle in standardbreds: 23 cases (1979-1989).

Desmotomy of the accessory ligament of the deep digital flexor muscle (inferior check desmotomy) permitted Standardbred foals affected with flexural deformities to reach their full athletic potential. Long-term effects of inferior check desmotomy were examined in 23 Standardbreds over a 10-year period. Six of 11 foals that were treated surgically either raced 6 times and obtained a race record or were training sound (if yearlings). All 12 horses with flexural deformity that did not receive an inferior check desmotomy had an unfavorable outcome (no race record). Foals that had surgery performed at a younger age apparently had a better chance of racing or training sound because no foals treated surgically after 8 months of age had a favorable outcome and only 1 foal that was older than 5 months at the time of surgery had a favorable outcome. In 5 foals that had surgery with an unsuccessful outcome, 3 were greater than or equal to 1 year old at the time of surgery and were lame when training was started on the limb(s) with the desmotomy.