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.