Rhodococcus equi infection in foals: control and prevention (Proceedings)

Pneumonia caused by Rhodococcus equi continues to be an important cause of disease and death in foals.1 Because case-fatality rates may be high and because treatment may be prolonged and expensive, controlling and preventing disease is more desirable than relying solely on treating affected cases. The purpose of this presentation is to review evidence regarding preventing R. equi foal pneumonia and using screening tests to control the disease.

Prevention: Three principal approaches to preventing R. equi pneumonia have been examined: 1) altering management practices; 2) chemoprophylaxis; and, 3) immunoprophylaxis. Management practices associated with R. equi foal pneumonia were reviewed in the presentation regarding epidemiology of the disease. To the author's knowledge, only foaling at pasture has been evaluated in a prospective, controlled manner.

Chemoprophylaxis – The use of antimicrobial agents to prevent R. equi pneumonia has been examined. Two studies have evaluated the use of azithromycin for chemoprophylaxis. In a randomized, controlled study conducted in the United States among 338 foals at 10 farms, a cumulative relative risk reduction of approximately 76% was observed when foals received azithromycin (10 mg/kg; PO; q 48 hr) for the first 14 days of life beginning on the first day of life. In a study conducted at a large breeding farm in Germany, the incidence of abscessing pneumonia was not significantly different between foals that received azithromycin (10 mg/kg; PO; q 24 hr for the first 28 days of life) for prevention of R. equi pneumonia (cumulative incidence = 60%) and foals that did not receive azithromycin for chemoprophylaxis (cumulative incidence = 69%) among 70 foals; however, the age at onset of abscessing pneumonia was apparently delayed in treated foals. Neither study was fully blinded, nor was a placebo used. The reason for the discrepancy between studies remains unknown, but does not appear to pertain to dosage or duration of azithromycin treatment. Possible explanations include differences in case definitions, selection bias, methods of randomization, incidence of disease/pressure(s) for disease development, and possibly drug formulation. Regardless, use of azithromycin is not considered an acceptable approach for chemoprophylaxis because widespread use of this drug would create greater pressure for emergence of macrolide-resistance among bacteria. Evidence exists that prognosis is worse for foals with R. equi pneumonia from which macrolide-resistant isolates have been recovered.

Gallium maltolate is a metal-based compound with antimicrobial properties that has been demonstrated to reduce replication of R. equi both in pure culture or within macrophages, to reduce tissue concentrations of R. equi in mice following experimental infection, to be bioavailable in foals, and to be safe in foals. Chemoprophylaxis with gallium maltolate (30 mg/kg; PO; q 24 hr for the first 14 days of life) failed to reduce the incidence of R. equi pneumonia in a placebo-controlled trial of 438 foals at 12 farms in the United States.

Immunoprophylaxis – Both active and passive immunomodulation have been investigated to prevent R. equi pneumonia. To date, despite considerable and innovative effort, a commercial vaccine is lacking. Although 2 studies have suggested some benefit in protecting foals from spontaneous disease by vaccinating mares, this strategy has reportedly failed in an experimental challenge study and a field study. Protection of foals against experimental challenge by enteral infection has twice been reported as successful; however, this strategy is not acceptable for field use.If the assumption that most foals become infected during the early perinatal period is correct, innate immune responses may play a dominant role in controlling infection. Active stimulation of innate immune responses using commercially available immunomodulators has been investigated by a number of groups; however, to date, no controlled clinical trials documenting efficacy of this approach in foals have been reported.

Transfusion of hyperimmune plasma has been demonstrated to reduce either the severity or cumulative incidence of experimentally-induced or spontaneous R. equi pneumonia. Although results of observational studies have not uniformly attained statistical significance, all but 1 study have demonstrated a relative reduction in risk.

In summary, there is conflicting evidence regarding the efficacy of chemoprophylaxis, and an acceptable preventive antimicrobial agent is lacking. There is no vaccine available commercially at this time. Transfusion of hyperimmune plasma is the only method that is both acceptable clinically and proven to reduce the incidence of disease; however, this method is not completely effective.

Screening:

Pneumonia caused by R. equi pneumonia is an insidious disease in which clinical signs usually are not apparent until pathological changes are well progressed. Consequently, screening to detect foals in the early stages of disease may improve therapeutic outcomes. A variety of screening techniques have been described, including visual inspection of foals, monitoring rectal temperatures, regularly observing foals for clinical signs of pneumonia or extrapulmonary disorders, monitoring hematological parameters, performing serological testing, and sequentially performing thoracic imaging using either radiography or ultrasonography. Serum concentrations of either antibodies against R. equi or serum amyloid A do not appear to be useful screening tests. Although blood fibrinogen concentration is not very useful for screening, white blood cell (WBC) concentrations appear to have reasonable sensitivity and specificity for detecting R. equi pneumonia.

Use of ultrasonography for screening has not been systematically evaluated. The procedure has proponents and opponents, based on the the various advantages and limitations associated with this approach. Thoracic sonography can be performed relatively rapidly and competence with the procedure can be rapidly developed. Results of sonography are immediately available, and may be more sensitive than radiography for detecting lesions in their early stages of development. Results are specific for the presence of pulmonary pathology (as contrasted with, for example, results of WBC concentrations). Because treatment of advanced disease can be difficult, early detection of disease can lead to reduced mortality. Disadvantages of the procedure include the costs borne by the farm for repetitive sonographic examinations, the increased labor needed to handle foals on a repetitive basis, and an increased number of foals treated for presumptive R. equi pneumonia. Anecdotal and observational data24 indicate that not all foals with evidence of pulmonary consolidation or abscessation will progress to develop clinical signs of pneumonia attributable to R. equi. Although the probability of disease given evidence of sonographic consolidation or abscessation remains unknown, it is generally accepted that this probability is less than 100%. As a result, the apparent incidence and thus the number of foals requiring treatment is increased by using sonographic screening. Greater numbers of treated foals results in higher costs to farms, increased risk of adverse events associated with treatment, and further pressure for development of resistance to macrolides by bacteria. Systematic comparison of WBC versus ultrasonographic screening is both lacking and needed. Although all screening methods have limitations, it is the author's opinion that diligent evaluation of foals for earlier detection of disease is an important tool for controlling disease at farms.

Conclusions: Transfusion of hyperimmune plasma and application of screening tests remain the most effective methods for controlling the incidence of R. equi foal pneumonia at breeding farms. There is tremendous need for development of a highly effective preventive strategy. Further evaluation and development of screening tests are greatly needed to address this important health problem of foals.

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