Nathan M. Slovis

Diagnosis, Treatment, Control, and Prevention of Infections Caused by Rhodococcus equi in Foals

Rhodococcus equi, a gram-positive facultative intracellular pathogen, is one of the most common causes of pneumonia in foals. Although R. equi can be cultured from the environment of virtually all horse farms, the clinical disease in foals is endemic at some farms, sporadic at others, and unrecognized at many. On farms where the disease is endemic, costs associated with morbidity and mortality attributable to R. equi may be very high. The purpose of this consensus statement is to provide recommendations regarding the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals.

Rhodococcus equi: Clinical Manifestations, Virulence, and Immunity

Pneumonia is a major cause of disease and death in foals. Rhodococcus equi, a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals. This article reviews the clinical manifestations of infection caused by R. equi in foals and summarizes current knowledge regarding mechanisms of virulence of, and immunity to, R. equi. A complementary consensus statement providing recommendations for the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals can be found in the same issue of the Journal.

Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi

OBJECTIVE To determine the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and to describe treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. DESIGN Cross-sectional study. SAMPLE POPULATION 38 isolates classified as resistant to macrolide antimicrobials or rifampin received from 9 veterinary diagnostic laboratories between January 1997 and December 2008. PROCEDURES For each isolate, the minimum inhibitory concentration of macrolide antimicrobials (ie, azithromycin, erythromycin, and clarithromycin) and rifampin was determined by use of a concentration-gradient test. Prevalence of R equi isolates from Florida and Texas resistant to macrolide antimicrobials or rifampin was determined. Outcome of antimicrobial treatment in foals infected with antimicrobial-resistant isolates of R equi was determined. RESULTS Only 24 of 38 (63.2%) isolates were resistant to >or= 1 antimicrobial. Two isolates were resistant only to rifampin, whereas 22 isolates were resistant to azithromycin, erythromycin, clarithromycin, and rifampin. The overall prevalence of antimicrobial-resistant isolates in submissions received from Florida and Texas was 3.7% (12/328). The survival proportion of foals infected with resistant R equi isolates (2/8 [25.0%]) was significantly less, compared with the survival proportion in foals that received the same antimicrobial treatment from which antimicrobial-susceptible isolates were cultured (55/79 [69.6%]). Odds of nonsurvival for foals infected with resistant R equi isolates were 6.9 (95% confidence interval, 1.3 to 37) times the odds for foals infected with susceptible isolates. CONCLUSIONS AND CLINICAL RELEVANCE Interpretation of the results emphasized the importance of microbiological culture and antimicrobial susceptibility testing in foals with pneumonia caused by R equi.

Periparturient hemorrhage in mares: 73 cases (1998–2005)

OBJECTIVE To determine signalment, physical examination and clinicopathologic abnormalities, outcome, and subsequent fertility of mares with periparturient hemorrhage (PPH) and identify factors associated with outcome (ie, survival vs death). DESIGN Retrospective case series. ANIMALS 73 mares. PROCEDURES Medical records were reviewed for information on age, breed, initial complaint, physical examination and clinicopathologic abnormalities, treatment, outcome, and subsequent fertility. RESULTS Median age was 14.0 years (range, 5 to 24 years), and median number of foals produced prior to the diagnosis of PPH was 8 (range, 1 to 16). Ten (14%) mares had prepartum hemorrhage and 63 (86%) had postpartum hemorrhage. Treatment was aimed at restoring cardiovascular volume, enhancing coagulation, controlling pain, and reducing the effects of endotoxemia. Sixty-one (84%) mares survived and 12 (16%) died or were euthanized. Common complications included fever, leukopenia, retained fetal membranes, increased digital pulses, thrombophlebitis, and cardiac arrhythmias. Of the 53 surviving mares for which subsequent breeding information was available, 26 (49%) produced 1 or more foals after recovering from PPH. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that PPH can develop in mares of any age and parity. Treatment was associated with a good prognosis for survival and a reasonable prognosis for future fertility.

Serial use of serologic assays and fecal PCR assays to aid in identification of subclinical Lawsonia intracellularis infection for targeted treatment of Thoroughbred foals and weanlings

OBJECTIVE To assess the serial use of serum immunoperoxidase monolayer assays (IPMAs) and fecal PCR assays, combined with other diagnostic methods, to identify subclinical Lawsonia intracellularis infections for targeted treatment of Thoroughbred foals and weanlings at farms in which the pathogen was endemic or nonendemic. DESIGN Evaluation study. ANIMALS 100 foals and weanlings (53 and 47 at farms in which L intracellularis was endemic and nonendemic, respectively). PROCEDURES Serum was collected every 4 weeks and tested via IPMA, for antibodies against L intracellularis. Fecal samples were collected every 2 weeks and tested by use of an L intracellularis-specific PCR assay. When results for IPMAs or PCR assays were positive or clinical signs compatible with equine proliferative enteropathy (EPE) were detected, clinicopathologic testing was performed to determine treatment. RESULTS No foals had positive results for the L intracellularis-specific IPMA until after weaning; 32 of 53 (60.4%) weanlings at the farm in which L intracellularis was endemic and 8 of 47 (170%) at the farm in which L intracellularis was nonendemic had positive IPMA results, whereas the number of weanlings that tested positive via fecal PCR assays at those farms was 6 and 0, respectively. Nineteen of 32 weanlings with positive IPMA results at the farm in which L intracellularis was endemic were treated for EPE; 5 of these had clinical signs of EPE. No weanlings at the nonendemic farm had clinical signs of or were treated for EPE. CONCLUSIONS AND CLINICAL RELEVANCE IPMA appeared to be a useful means of identifying weanlings exposed to L intracellularis.

Evaluation of the field efficacy of an avirulent live Lawsonia intracellularis vaccine in foals.

Equine proliferative enteropathy caused by Lawsonia intracellularis is an emerging disease with as yet unaddressed preventative measures. The hypothesis of this study was that vaccination will prevent clinical and sub-clinical disease. Weanling Thoroughbreds (n=202) from Central Kentucky were randomly assigned into two groups (vaccinated and non-vaccinated). Vaccinated foals received 30 mL of an avirulent, live L. intracellularis vaccine intra-rectally twice, 30 days apart. Foals were monitored for clinical disease, total solids and average weight gain until yearling age. There was an overall decreased disease incidence on the farms involved in the study that did not differ significantly between the groups. This decreased disease prevalence in the study population may be associated with the ongoing vaccine trial on these farms, as disease prevalence in Central Kentucky did not change in 2009 compared to 2008.

Comparison of Feces versus Rectal Swabs for the Molecular Detection of Lawsonia Intracellularis in Foals with Equine Proliferative Enteropathy

The purpose of the current study was to compare the molecular detection rate of Lawsonia intracellularis between feces and rectal swabs collected from 42 foals with suspected equine proliferative enteropathy (EPE). Fecal samples and rectal swabs were processed for DNA purification by using an automated extraction system. The purified DNA was then analyzed by real-time polymerase chain reaction (PCR) for the presence of the aspartate ammonia lyase (aspA) gene of L. intracellularis. Absolute quantitation was calculated by using a standard curve for L. intracellularis and expressed as copy numbers of the aspA gene of L. intracellularis per microliter of purified DNA. The combined PCR detection rate for L. intracellularis was 90%, with 38 foals testing PCR positive in feces (33 samples), rectal swabs (32), or both (27). Six foals tested PCR positive only in feces, whereas 5 tested positive only in rectal swabs. Feces yielded a significantly higher aspA gene copy number of L. intracellularis than rectal swabs. Feces and rectal swabs tested PCR negative from 4 foals. In conclusion, the results showed that feces yielded similar numbers of PCR-positive results, with a higher L. intracellularis aspA gene load than rectal swabs. By analyzing dual samples, the PCR detection rate for L. intracellularis increased from 76% and 79% for rectal swabs and feces, respectively, to 90%. Rectal swabs should be considered as an alternative sample type for EPE-suspected patients with decreased or no fecal output.

Lawsonia intracellularis and Equine Proliferative Enteropathy

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.

Vitamin D Metabolites and Their Association with Calcium, Phosphorus, and PTH Concentrations, Severity of Illness, and Mortality in Hospitalized Equine Neonates

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). Conclusions 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.