[Show abstract][Hide abstract] ABSTRACT: Background:
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 hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals.
Methods and results:
One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3 <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D3 and 1,25(OH) 2D3 concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)2D3 concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D3 <9.51 ng/mL and 1,25(OH) 2D3 <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively).
Low 25(OH)D3 and 1,25(OH)2D3 concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine perinatal diseases. Hypocalcemia and hyperphosphatemia together with decreased 1,25(OH)2D3 but increased PTH concentrations in septic foals indicates that PTH resistance may be associated with the development of these abnormalities.
PLoS ONE 06/2015; 10(6):e0127684. DOI:10.1371/journal.pone.0127684 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
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.Hypothesesp[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival.AnimalsEighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1 week of age.Methods
Multicenter, prospective observational clinical study. Venous blood was collected at admission from septic and sick nonseptic foals and from clinically healthy foals at 24 h of age. A diagnosis of sepsis was made based on positive blood culture or a sepsis score >11, and p[CRP] and p[Hp] were measured by using ELISA tests. Data were analyzed by using the Mann-Whitney U-test and forward stepwise multivariable linear regression. P < .05 was considered significant.ResultsPlasma [CRP] was positively associated with age, serum globulin, adrenomedullin, and bilirubin concentrations, aspartate aminotransferase activity, glutamyl-transferase activity, band neutrophil count, and rectal temperature, and was increased in foals with toxic neutrophils, enterocolitis, colic, rib fractures and septic arthritis. Surprisingly, p[Hp] was lower in septic foals than in sick nonseptic foals. Neither p[CRP] or p[Hp] was predictive of survival in critically ill foals.Conclusions and Clinical ImportancePlasma [CRP] increases with inflammation in neonatal foals but is not indicative of sepsis. Single time point, admission sampling of p[CRP] and p[Hp] do not appear to be useful biomarkers for sepsis in foals.
Journal of Veterinary Internal Medicine 03/2015; 29(2). DOI:10.1111/jvim.12568 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reasons for performing the studySerum IgG assessment in neonatal foals is considered standard of care in equine hospitals to determine immunity and overall health. However, cut-off values of IgG to predict complete or partial failure of transfer of passive immunity (FTPI) were developed 30 years ago, are largely empirical, with little prospective or statistical data to support their use or association with outcome.Objectives
To critically evaluate the traditional cut-off values of IgG in the assessment of FTPI (IgG <8 g/l), to determine the association between various degrees of FTPI and likelihood of non-survival, and to examine whether FTPI can be predicted by serum total protein (TP), albumin, and globulin in hospitalised foals.Study DesignMulticentre, cross-sectional study.Methods
We evaluated clinicopathologic variables in 597 foals ≤7 days old from 3 equine hospitals including serum IgG, fibrinogen, TP and albumin. Foals were divided into 3 groups by diagnosis: healthy, sick non-septic and septic. The aforementioned variables in addition to globulin concentrations were evaluated in a subset of 118 foals. Univariate, multivariate and multinomial logistic regression were used to compute odds ratios for non-survival in these foals.ResultsOur findings support use of the traditional cut-off value of >8 g/l as adequate transfer of passive immunity (ATPI). Odds of non-survival increased in proportion to lower IgG concentrations. Higher TP concentrations were associated with lower likelihood of FTPI, however, higher albumin concentrations were associated with a greater likelihood of FTPI. A regression equation was created to predict IgG in foals using serum proteins.Conclusion
Serum IgG values of <8 g/l in hospitalised foals were proportionally associated with mortality. We recommend immediate assessment of IgG concentrations in hospitalised foals and those with FTPI should receive prompt immunotherapy.
[Show abstract][Hide abstract] ABSTRACT: Lawsonia intracellularis is the etiologic agent for equine proliferative enteropathy (EPE), which typically affects weanling and yearling horses. In North America, EPE cases often occur between August and January, although cases outside of this time frame have been reported. Clinical signs of EPE are usually nonspecific and include lethargy, pyrexia, anorexia, peripheral edema, weight loss, colic, and diarrhea. Diagnosis is based on the presence of hypoproteinemia and hypoalbuminemia along with clinical signs and positive commercial serologic and/or molecular testing. Treatment requires the use of antimicrobials with good intracellular penetration and supportive care to prevent or decrease secondary complications.
Veterinary Clinics of North America Equine Practice 10/2014; 30(3). DOI:10.1016/j.cveq.2014.08.001 · 0.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Bacterial sepsis remains a leading cause of morbidity and mortality in neonatal foals, but accurate diagnostic and prognostic markers are lacking. Adrenomedullin (AM) is a polypeptide with diverse biologic effects on the cardiovascular system that increases in septic humans and laboratory animals.HypothesesPlasma AM concentration (p[AM]) is increased in septic neonatal foals compared to sick nonseptic and healthy control foals, and p[AM] is predictive of survival in septic neonatal foals.AnimalsNinety critically ill (42 septic, 48 sick nonseptic) and 61 healthy foals <1 week of age.MethodsA prospective observational clinical study was performed. Venous blood was collected from critically ill foals at admission and from healthy foals at 24 hours of age. Critically ill foals were categorized as septic or sick nonseptic based on blood culture results and sepsis score. Plasma [AM] was measured by using a commercially available ELISA for horses. Data were analyzed by using the Mann-Whitney U-test and P < .05 was considered significant.ResultsPlasma [AM] was not significantly different between septic and sick nonseptic foals (P = .71), but critically ill foals had significantly increased p[AM] compared to healthy controls (P < .0001). In critically ill foals, p[AM] was not predictive of survival (P = .051). A p[AM] cutoff concentration of 0.041 ng/mL provided a test sensitivity of 91% and specificity of 54% to predict illness.Conclusions and Clinical RelevancePlasma [AM] shows promise as a marker of health in neonatal foals, but p[AM] increases nonspecifically during perinatal illnesses and is not necessarily associated with sepsis.
Journal of Veterinary Internal Medicine 04/2014; 28(4). DOI:10.1111/jvim.12358 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The epidemiology of equine neorickettsiosis (EN) has been extensively studied but limited clinical and clinicopathological data are available concerning naturally infected horses.
Factors predictive of survival will be identified in horses diagnosed with EN.
Convenience sample of 44 horses with EN admitted to 2 referral institutions.
A retrospective study was performed. A diagnosis of EN was based on the presence of positive blood or fecal PCR.
The most common clinical signs included diarrhea (66%), fever (50%), anorexia (45%), depression (39%), colic (39%), and lameness (18%). The median duration of hospitalization was 6 days and 73% of horses survived to discharge. Laminitis was present in 36% of horses, 88% of which were affected in all 4 feet. Serum creatinine and urea nitrogen concentrations, as well as RBC count, blood hemoglobin concentration, hematocrit, band neutrophils, serum AST activity, serum CK activity, and anion gap, were significantly (P < .05) higher in nonsurvivors. Serum chloride and sodium, concentrations as well as duration of hospitalization were significantly lower in nonsurvivors. The results of forward stepwise logistic regression indicated that blood hemoglobin concentration on admission and antimicrobial treatment with oxytetracycline were independent factors associated with survival.
Severity of colitis as reflected by electrolyte loss, hemoconcentration, and prerenal azotemia were predictors of survival in horses diagnosed with EN. Treatment with oxytetracycline was associated with increased survival.
Journal of Veterinary Internal Medicine 10/2013; 27(6). DOI:10.1111/jvim.12209 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: REASONS FOR PERFORMING STUDY: Diarrhoea caused by infectious agents is common in foals but there is no comprehensive molecular workup of the relative prevalence of common agents and the appearance of coinfections. OBJECTIVES: To determine the prevalence of 9 infectious agents in GI diseased and healthy foals with ages ranging from one to 20 weeks of age, and to what degree co-infections are associated with clinical signs of GI disease. STUDY DESIGN: Retrospective controlled observational study. METHODS: The population consisted of 88 Thoroughbred foals ages 2 days to 17 weeks born on 32 different stud farms in Kentucky. Healthy (n = 37) and GI diseased (n = 51) foals were identified based on clinical presentation. Fecal samples were analysed for 9 infectious agents by real-time PCR: equine rotavirus, equine coronavirus, Clostridium difficile toxin A & B, Neorickettsia risticii, Clostridium perfringens alpha toxin, Lawsonia intracellularis, Rhodococcus equi, Cryptosporidium spp., and Salmonella spp. Salmonella was also cultured from overnight selenite enrichment broth. RESULTS: The prevalence of infectious pathogens under study was between 0% (Lawsonia intracellularis) and 34.6% (equine rotavirus). The overall prevalence for any infectious agent was 63.2% in the GI diseased group and 43.2% in the healthy group. Coinfections were significantly more frequent in the sick group (15 monoinfections versus 22 coinfections) than in the healthy group (12 versus 4, respectively, p = 0.0002). Six of the 8 infectious agents were associated with the GI diseased group, the other 2 were not (equine coronavirus and R. equi). CONCLUSIONS: The use of panels rather than individual tests in combination with quantitative toxin gene analysis enables the detection of co-infections that are significantly associated with risk of disease. Several infectious diseases previously not tested for or considered unimportant were found at high prevalence and require further investigation.
[Show abstract][Hide abstract] ABSTRACT: Reasons for performing studyResistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals. Objectives
To investigate components of the somatotropic axis (ghrelin, growth hormone and insulin-like growth factor-1 [IGF-1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase and IGF-1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals. Study designProspective multicentre cross-sectional study. Methods
Blood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged <7 days. Foals with positive blood cultures or sepsis scores 12 were considered septic, foals with sepsis scores of 5-11 were classified as SNS. Data were analysed by nonparametric methods and multivariate logistic regression. ResultsSeptic foals had higher ghrelin, growth hormone and triglyceride and lower IGF-1 and glucose concentrations than healthy foals (P<0.01). Sick nonseptic foals had higher growth hormone and triglycerides and lower IGF-1 concentrations than healthy foals (P<0.05). Growth hormone:IGF-1 ratio was higher in septic and SNS foals than healthy foals (P<0.05). Hormone concentrations were not different between septic nonsurvivors (n = 14) and survivors (n = 30), but the growth hormone:IGF-1 ratio was lower in nonsurvivors (P = 0.043). Conclusions
Somatotropic axis resistance, characterised by a high growth hormone:IGF-1 ratio, was frequent in sick foals, associated with the energy status (hypoglycaemia, hypertriglyceridaemia) and with mortality in septic foals. Potential relevanceA functional somatotropic axis appears to be important for foal survival during sepsis. Somatotropic resistance is likely to contribute to severity of disease, a catabolic state and likelihood of recovery.
[Show abstract][Hide abstract] ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals.
To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals.
A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals.
Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals.
ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals.
RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals.
Journal of Veterinary Internal Medicine 02/2013; 27(2). DOI:10.1111/jvim.12043 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macrolide and rifampin resistance developed on a horse breeding farm after widespread use was instituted for treatment of subclinical pulmonary lesions in foals. Resistance occurred in 6 (24%) of 25 pretreatment and 8 (62%) of 13 (62%) posttreatment isolates from affected foals. Drug-resistant isolates formed 2 distinct genotypic clusters.
[Show abstract][Hide abstract] ABSTRACT: Objective-To determine whether the concentration of airborne virulent Rhodococcus equi varied by location (stall vs paddock) and month on horse farms. Sample-Air samples from stalls and paddocks used to house mares and foals on 30 horse breeding farms in central Kentucky. Procedures-Air samples from 1 stall and 1 paddock were obtained monthly from each farm from January through June 2009. Concentrations of airborne virulent R equi were determined via a modified colony immunoblot assay. Random-effects logistic regression was used to determine the association of the presence of airborne virulent R equi with location from which air samples were obtained and month during which samples were collected. Results-Of 180 air samples, virulent R equi was identified in 49 (27%) and 13 (7%) obtained from stalls and paddocks, respectively. The OR of detecting virulent R equi in air samples from stalls versus paddocks was 5.2 (95% confidence interval, 2.1 to 13.1). Of 60 air samples, virulent R equi was identified in 25 (42%), 18 (30%), and 6 (10%) obtained from stalls during January and February, March and April, and May and June, respectively. The OR of detecting virulent R equi from stall air samples collected during May and June versus January and February was 0.22 (95% confidence interval, 0.08 to 0.63). Conclusions and Clinical Relevance-Foals were more likely to be exposed to airborne virulent R equi when housed in stalls versus paddocks and earlier (January and February) versus later (May and June) during the foaling season.
American Journal of Veterinary Research 10/2012; 73(10):1603-9. DOI:10.2460/ajvr.73.10.1603 · 1.34 Impact Factor