Foal-related risk factors associated with development of Rhodococcus equi pneumonia on farms with endemic infection

OBJECTIVE: To identify foal-related risk factors associated with development of Rhodococcus equi pneumonia among foals on farms with endemic R. equi infection. DESIGN: Prospective case-control study. ANIMALS: 220 foals at 2 equine breeding farms in Texas during a 2-year period. PROCEDURE: Information collected for each dam included age, time housed on the farm prior to parturition, whether there were any peripartum illnesses, parity, and health of previous foals. Information collected for each foal included breed, sex, gestational age, month and year of birth, location of birth, type of flooring and bedding in stall, postpartum management and preventive health care, passive immunity status, supplementation of immunoglobulins, exposure to other farms or foals affected with R. equi pneumonia, stall and pasture exposure, commingling with other mare-foal pairs, age at weaning, and whether the foal developed R. equi pneumonia. RESULTS: 32 of the 220 (15%) foals developed R. equi pneumonia, of which 4 (13%) died. Foals at 1 of the 2 farms and foals born during the second year of the study were more likely to develop R. equi pneumonia. Foal-related factors that were examined were not significantly associated with risk of R. equi pneumonia in multivariate analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that there are farm- and year-related effects on the risk that foals will develop R. equi pneumonia. Other foal-related factors significantly associated with R. equi pneumonia were not identified.     

Chemoprophylactic effects of azithromycin against Rhodococcus equi-induced pneumonia among foals at equine breeding farms with endemic infections

OBJECTIVE: To determine the effect of azithromycin chemoprophylaxis on the cumulative incidence of pneumonia caused by Rhodococcus equi, age at onset of pneumonia, and minimum inhibitory concentration (MIC) of azithromycin for R equi isolates cultured from fecal and clinical samples. DESIGN: Controlled, randomized clinical trial. ANIMALS: 338 foals born and raised at 10 equine breeding farms; each farm had a history of endemic R equi infections. PROCEDURES: Group 1 foals were control foals, and group 2 foals were treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 48 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of azithromycin. Isolates of R equi were tested for susceptibility to azithromycin. RESULTS: The proportion of R equi-affected foals was significantly higher for control foals (20.8%) than for azithromycin-treated foals (5.3%). Adverse effects of azithromycin treatment were not detected, and there were no significant differences between groups for the MICs of azithromycin for R equi isolates cultured from fecal or clinical samples. CONCLUSIONS AND CLINICAL RELEVANCE: Azithromycin chemoprophylaxis effectively reduced the cumulative incidence of pneumonia attributable to R equi among foals at breeding farms with endemic R equi infections. There was no evidence of resistance to azithromycin. Nonetheless, caution must be used because it is possible that resistance could develop with widespread use of azithromycin as a preventative treatment. Further investigation is needed before azithromycin chemoprophylaxis can be recommended for control of R equi infections.     

Evaluation of equine breeding farm characteristics as risk factors for development of Rhodococcus equi pneumonia in foals

OBJECTIVE: To identify farm characteristics as risk factors for the development of Rhodococcus equi pneumonia in foals. DESIGN: Prospective matched case-control study. ANIMALS: 2,764 foals on 64 equine breeding farms with 9,991 horses. PROCEDURE: During 1997, participating veterinarians completed paired data collection forms, 1 for a farm with > or = 1 foal with R equi pneumonia and 1 for an unaffected control farm. Matched data were compared by use of conditional logistic regression analysis. RESULTS: Farm characteristics found in bivariate analyses to be associated with increased risk for pneumonia caused by R equi in foals included > 200 farm acres, > or = 60 acres used in the husbandry of horses, > 160 horses, > or = 10 mares housed permanently on the farm (resident mares), > 17 foals, > 0.25 foals/acre, and the presence of transient mares (mares brought temporarily to the farm for breeding or foaling) and their foals. Affected farms were significantly more likely to be > 200 acres in size and have > or = 10 resident dam-foal pairs, whereas control farms were significantly more likely to have > or = 75% of their dam-foal pairs housed permanently on the farm. CONCLUSIONS AND CLINICAL RELEVANCE: Breeding farms with large acreage, a large number of mares and foals, high foal density, and a population of transient mares and foals are at high risk for foals developing pneumonia caused by R equi.     

Evaluation of equine breeding farm management and preventative health practices as risk factors for development of Rhodococcus equi pneumonia in foals

OBJECTIVE: To determine whether foal management practices, environmental management, and preventative health practices are risk factors for development of Rhodococcus equi pneumonia in foals. DESIGN: Prospective matched case-control study. ANIMALS: 2,764 foals on 64 equine breeding farms with 9,991 horses. PROCEDURE: During 1997, participating veterinarians completed paired data collection forms for comparison; 1 for an affected farm (containing > or = 1 foal with pneumonia caused by R equi) and 1 for a control farm. Information collected pertained to stabling facilities, environmental management, foal husbandry, and preventative equine health practices. RESULTS: Matched farm data compared by use of conditional logistic regression indicated that personnel on affected farms were more likely to attend foal births, test foals for adequacy of passive immunity, administer plasma or other treatments to foals to supplement serum immunoglobulin concentrations, administer hyperimmune plasma prophylactically to foals, vaccinate mares and foals against Streptococcus equi infection, and use multiple anthelmintics in deworming programs. Affected farms were also more likely to have foals that developed other respiratory tract disorders and were approximately 4 times as likely to have dirt floors in stalls used for housing foals as were control farms. CONCLUSIONS AND CLINICAL RELEVANCE: Rhodococcus equi pneumonia does not appear to be associated with poor farm management or a lack of attention to preventative health practices. Housing foals in stalls with dirt floors may increase the risk for development of R equi pneumonia.     

Farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals

OBJECTIVE: To identify farm characteristics and management practices associated with development of Rhodococcus equi pneumonia in foals. DESIGN: Prospective case-control study. ANIMALS: 5230 foals on 138 breeding farms with 9136 horses. PROCEDURE: During 2003, participating veterinarians provided data from 1 or 2 farms with > or =1 foal with R equi pneumonia and unaffected farms. Data from affected and unaffected farms were compared by use of logistic regression analysis. RESULTS: A number of variables relating to farm size and desirable management practices were significantly associated with increased odds of farms being affected with R equi pneumonia. By use of multivariate logistic regression, affected farms were determined significantly more likely to have raised Thoroughbreds, housed > or =15 foals, used concrete floors in foaling stalls, and tested foals for passive transfer of immunity than unaffected farms. These results remained significant even after accounting for exposure of foals to other breeding farms during the first month of life. Conclusions and Clinical Relevance-Breeding farms with large acreage and a large number of mares and foals have greater odds of being affected by R equi pneumonia. Clinical relevance of associations with Thoroughbred breed and concrete flooring in foaling stalls remains uncertain. Desirable management factors commonly used on farms were not effective for controlling or preventing development of R equi pneumonia. This finding indicates a need to focus on host factors that influence disease development.     

The pathogenesis of Rhodococcus equi pneumonia in foals

The pathogenesis of Rhodococcus equi pneumonia in foals is reviewed. The main routes of infection are respiratory and alimentary. The latter is probably the chief route of exposure in all foals and probably leads to development of specific immunity. Susceptible foals, those whose maternal immunity wanes before generation of their own immune response, readily develop disease if exposed aerogenously to sufficient numbers of R. equi. Management and environmental circumstances have a major role to play in determining the magnitude of this challenge and, therefore, in the prevalence of the disease. Infection of a naive foal leads to severe, suppurative bronchopneumonia with suppurative lymphadenitis of regional nodes and, in approximately 50% of animals, to necrotizing enterocolitis. The foal is uniquely susceptible to R. equi pneumonia; comparable experimental infections do not produce progressive destructive pulmonary lesions in other animal species. In the naive foal lung, R. equi behaves as a facultative intracellular pathogen, avoiding destruction within the alveolar macrophage by inhibiting phagolysosome fusion and possibly by causing lysosomal degranulation. The role of putative virulence factors, such as equi factor, remains to be elucidated.     

Association of soil concentrations of Rhodococcus equi and incidence of pneumonia attributable to Rhodococcus equi in foals on farms in central Kentucky

OBJECTIVE: To determine whether soil concentrations of total or virulent Rhodococcus equi differed among breeding farms with and without foals with pneumonia caused by R equi. SAMPLE POPULATION: 37 farms in central Kentucky. Procedures-During January, March, and July 2006, the total concentration of R equi and concentration of virulent R equi were determined by use of quantitative bacteriologic culture and a colony immunoblot technique, respectively, in soil specimens obtained from farms. Differences in concentrations and proportion of virulent isolates within and among time points were compared among farms. RESULTS: Soil concentrations of total or virulent R equi did not vary among farms at any time point. Virulent R equi were identified in soil samples from all farms. Greater density of mares and foals was significantly associated with farms having foals with pneumonia attributable to R equi. Among farms with affected foals, there was a significant association of increased incidence of pneumonia attributable to R equi with an increase in the proportion of virulent bacteria between samples collected in March and July. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that virulent R equi were commonly recovered from soil of horse breeding farms in central Kentucky, regardless of the status of foals with pneumonia attributable to R equi on each farm. The incidence of foals with pneumonia attributable to R equi can be expected to be higher at farms with a greater density of mares and foals.     

Dynamics of equi-factor antibodies in sera of foals kept on farms with differing histories of Rhodococcus equi pneumonia

The occurrence of equi-factor antibodies in sera of mares and their foals was studied on two horse breeding farms, one of which (Farm A) had a positive and the other (farm B) a negative history of R. equi infection of foals. The equi-factor neutralization (EFN) and the reverse Elek-Ouchterlony (REO) precipitation were used as assays. On Farm A, 25 mares positive in both tests (EFN+ REO+) and 25 mares negative in both tests (EFN- REO-) was chosen. On Farm B, a group of 25 EFN- REO+ mares and a group of 25 EFN- REO- mares were studied. The first serum samplings in mares were 1 week ante partum and the subsequent samplings in both mares and foals were in the first week after birth and at the end of every month of the foals' age up to 6 months, with further samplings at 8 and 12 months. A higher number of seropositive foals was found on Farm A, but the difference between Farms A and B was not significant. The smallest number, with the lowest titres, was among the foals of EFN- REO+ dams. The number of foals positive in the REO test was higher than in the EFN test. The onset of EFN positivity was found in foals on both farms in the first month of their age, always culminating in the third and fourth months in titres varying between 1:64 and 1:2048, after which time it fell until it disappeared altogether or reached values of 1:4. The results showed the widespread nature of subclinical infection with R. equi on horse farms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic contribution of thoracic ultrasonography in 17 foals with Rhodococcus equi pneumonia

The aim of this retrospective study was to determine the clinical usefulness of thoracic ultrasonography compared to thoracic radiography in evaluation of Rhodococcus equi pneumonia. Criteria for patient inclusion in this study were: (1) isolation of R. equi from transtracheal aspirate, (2) radiographic evaluation of the pulmonary parenchyma, and (3) sonographic evaluation of the pulmonary parenchyma. Seventeen foals met this criteria and their medical records were reviewed. Pyogranulomatous pneumonia was identified radiographically in 13 foals. Severe consolidative pneumonia with no detectable abscessation was identified radiographically in three others. Both consolidation and abscessation were identified radiographically in one. In this foal only consolidation was ultrasonographically identified. Ultrasonographically, pulmonary abscessation was identified in 12 foals and pulmonary consolidation with no detectable abscessation was identified in three others. Sonographic examination allowed detection of only pleural irregularities in one foal, which was subsequently found to have pyogranulomatous pneumonia radiographically. Results indicate that ultrasonography may be an accurate alternative imaging modality for detection of pulmonary pathology attributed to R. equi pneumonia in foals when thoracic radiography is not available.     

Humoral immune response of foals to experimental infection with Rhodococcus equi

Humoral immune response to Rhodococcus equi in experimentally infected foals was studied with the enzyme-linked immunosorbent assay (ELISA) method. Class-specific antibodies were measured by ELISA in the sera of foals after intratracheal or oral inoculation with R. equi ATCC 6939 or T 48 and in the lung washings of a foal after intratracheal inoculation or of normal horses. After intratracheal or oral inoculation with R. equi, serum antibodies were first detected in immunoglobulin G (IgG) followed by IgM and IgA classes, but significant levels of IgM and IgA developed only in the foal infected intratracheally with R. equi T 48. Only the foal infected intratracheally with T 48 developed pneumonia. Anti-R. equi IgG and IgA antibodies appeared in lung washings of the intratracheally infected foal. There were differences in the antibody response to R. equi among the intratracheally infected foals, the orally infected foal and the naturally infected foal. These results suggest that the humoral immune response to R. equi may be affected by the type of R. equi strain and the route and extent of R. equi exposure.     

Evaluation of equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C for use in protecting foals against Rhodococcus equi-induced pneumonia

OBJECTIVE: To determine whether purified equine immunoglobulin specific for Rhodococcus equi virulence-associated proteins A and C (VapA and VapC) can confer passive protection against R. equi-induced pneumonia in foals. ANIMALS: Twenty-eight 3-week-old mixed-breed pony foals. PROCEDURE: 7 foals received IV injections of equine hyperimmune plasma (HIP) against whole-cell R. equi, and 7 received purified equine immunoglobulin specific for VapA and VapC 1 day prior to intrabronchial infection with R. equi strain 103+. Eleven foals were not treated prior to infection, and 3 control foals were neither treated nor infected. Heart rate, respiratory rate, and rectal temperature were recorded twice daily, and serum fibrinogen concentration and WBC count were determined every other day following infection. Foals were euthanatized 14 days following infection, and lung lesions and concentration of R. equi in lungs were assessed. RESULTS: The onset of clinical signs of pneumonia was significantly delayed in the HIP- and immunoglobulin-treated groups, compared with the untreated infected group. Moreover, pulmonary lesions were less severe in the treated groups, and significantly fewer R. equi organisms were cultured from the lungs of treated foals. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of protection against R. equi-induced pneumonia provided by purified immunoglobulin specific for VapA and VapC was similar to that provided by commercially available HIP. Results not only suggest that immunoglobulin is the primary component of HIP that confers protection against R. equi-induced pneumonia in foals but also indicate that antibodies against R. equi VapA and VapC are protective.     

Studies of the pathogenesis of Rhodococcus equi infection in foals

Pyogranulomatous pneumonia was induced in Thoroughbred foals by intranasal challenge with freeze-dried cultures of Rhodococcus equi (previously Corynebacterium equi). The incubation period was about 18 days and clinical signs were not seen for a further week. There were marked seasonal and individual foal differences in responses to infection. Elevations in serum caeruloplasmin oxidase activity and copper concentrations appeared to be sensitive indicators of infection. Serum zinc concentrations and serum alpha-mannosidase and alkaline phosphatase activities fell in the more severely infected foals. Use of trace elements and trace element-related parameters along with faecal culture for R. equi could prove useful for early diagnosis of field cases.     

Association of pneumonia in foals caused by Rhodococcus equi with farm soil geochemistry

OBJECTIVE: To quantify and compare geochemical factors in surface soils from horse-breeding farms with horses with pneumonia caused by Rhodococcus equi (affected farms) and horse-breeding farms with no history of pneumonia caused by R equi (unaffected farms). SAMPLE POPULATION: Soil from 24 R equi-affected farms and 21 unaffected farms. PROCEDURE: Equine veterinary practitioners throughout Texas submitted surface soil samples from areas most frequented by foals, on R equi-affected and unaffected horse-breeding farms in their practice. Soil samples were assayed for the following factors: pH, salinity, nitrate, phosphorus, potassium, calcium, magnesium, sodium, sulfur, zinc, iron, manganese, and copper. Median values for all factors were recorded, and differences between affected and unaffected farms were compared. RESULTS: Significant differences in soil factors were not detected between affected and unaffected farms; hence, there was no association between those factors and R equi disease status of the farms. CONCLUSIONS AND CLINICAL RELEVANCE: The surface soil factors monitored in this study were not significant risk factors for pneumonia caused by R equi. As such, it is not possible to determine whether foals on a given farm are at increased risk of developing disease caused by R equi on the basis of these factors. Data do not support altering surface soil for factors examined, such as alkalinization by applying lime, as viable control strategies for R equi.     

Survival of foals with experimentally induced Rhodococcus equi infection given either hyperimmune plasma containing R. equi antibody or normal equine plasma

The purpose of this study was to determine if colostrum-deprived foals with experimentally induced Rhodococcus equi pneumonia have a decreased severity of the disease and decreased mortality rate when given hyperimmune (HI) R. equi antibody plasma (R. equi titer at least 100 % and virulence-associated protein A [VapA] at least 10000) prophylactically versus when given normal equine plasma (R. equi titer less than 20 % and VapA less than 160). Sixteen colostrum-deprived foals (R. equi titer less than 5 %) each received normal equine plasma in the first 24 hours of life (R. equi titer less than 20 %). At 14 days of age, six foals were given normal equine plasma and 10 foals were given HI plasma. All foals were subsequently infected intrabronchially with a pathogenic strain of R. equi (2.5 x 10 sup 8; organisms) at 21 days of age. Repeated physical examinations, weight measurements, complete blood cell counts, fibrinogen measurements, and thoracic radiographs (ventrodorsal and lateral) were performed to help determine the severity of the disease. Foals given HI plasma had significantly higher R. equi ELISA titers (42.4 %) than those given normal plasma (20.9 %) on the day of experimental infection. Mortality rates and severity of disease were statistically similar (P >.05) for the groups. Although none of the foals was treated with antibiotics, several with severe R. equi pneumonia recovered. Either HI or normal equine plasma administered to foals in the first few weeks of life caused no adverse effects and may be protective against R. equi, although the exact constituent responsible for protection is undetermined and requires further investigation.     

Rhodococcus equi infection in foals: the science of 'rattles'

Infection with Rhodococcus (Corynebacterium) equi is a well-recognised condition in foals that represents a consistent and serious risk worldwide. The condition manifests itself primarily as one of pulmonary abscessation and bronchitis, hence the terminology of 'rattles' derived from its most obvious clinical sign, frequently terminal when first identified. This review addresses the clinical manifestation, bacteriology and pathogenesis of the condition together with recent developments providing knowledge of the organism in terms of virulence, epidemiology, transmission and immune responses. Enhanced understanding of R. equi virulence mechanisms and biology derived from the recently available genome sequence may facilitate the rational development of a vaccine and the improvement of farm management practices used to control R. equi on stud farms in the future. Reliance on vaccines alone, in the absence of management strategies to control the on-farm challenge is likely to be disappointing.     

Evaluation of 5 serologic assays to detect Rhodococcus equi pneumonia in foals

OBJECTIVE: To determine the sensitivity and specificity of 5 serologic assays used to diagnose Rhodococcus equi pneumonia in foals and to determine whether any of the assays could be used to identify affected foals prior to the onset of clinical signs or to differentiate between affected and unaffected foals when clinical signs first become apparent. DESIGN: Nested case-control study. ANIMALS: 26 foals. PROCEDURE: Serum samples were obtained from all foals at 2, 4, and 6 or 7 weeks of age. Additional samples were obtained from affected foals at the time of diagnosis of R equi pneumonia and from age-matched unaffected foals. Samples were tested with 3 ELISA, an agar gel immunodiffusion assay, and a synergistic hemolysis inhibition assay. RESULTS: Sensitivity and specificity data indicated that none of the assays could be used to reliably differentiate affected from unaffected foals at any testing period. Proportions of foals that had an increase in test values between paired samples collected at 4 and 6 or 7 weeks of age were not significantly different between affected and unaffected foals. For all assays, result values increased significantly over time; however, the rate of increase was not significantly different between affected and unaffected foals. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serologic assays, whether performed on single or paired samples, cannot be used to reliably establish, confirm, or exclude a diagnosis of R equi pneumonia in foals.     

Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus equi infection on foals from endemically affected farms

The effect on foals of prophylactic administration of hyperimmune plasma to prevent R. equi infection was investigated on three farms at which R. equi infection was endemic. Sixteen foals between 10 and 39 days of age were intravenously given 1-21 of hyperimmune plasma. ELISA antibody titres against R. equi were significantly increased and maintained at high levels for over 30 days in most of the recipient foals. The prevalence of R. equi infection was 6.3% (1/16) in the foals that received the immune plasma, and 26.3% (5/19) in the control foals not given the immune plasma on the three farms. For 2 years before and after this field trial on the three farms, 18 of 64 foals (28.1%) showed clinical signs of respiratory tract infection and four of them died of R. equi pneumonia. Heavy contamination of horses and their environment with virulent R. equi was detected by colony blotting, and plasmid profiles also suggested that foals on the three farms were constantly exposed to virulent R. equi. The results of this field trial support previous observations by some researchers that the administration of hyperimmune plasma to foals in the early days of life promotes prevention of R. equi infection on endemic farms; however, the mechanism of hyperimmune plasma protection remains unclear.