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Epidemiology and Treatment of Rhodococcus equi Foal Pneumonia
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Take Home Message—Evidence indicates that increased density of mares and foals and airborne concentrations of virulent R. equi increase the likelihood of development of R. equi pneumonia in foals; however, controlled intervention trials are lacking. Alternatives to macrolides (in combination with rifampin) for treatment of R. equi pneumonia continue to be limited. The impact of screening and emergence of macrolide-resistance present a specter of limited effective treatment.
I. Introduction
Pneumonia caused by R. equi remains an important cause of disease and death in foals. This presentation will review current knowledge regarding epidemiology and treatment, with an emphasis on practical and novel information from research findings.
II. Epidemiology
Infectious diseases result from the interaction of factors pertaining to the infectious agent, the environment, and the host.1 Thus, it is convenient to consider epidemiology of R. equi pneumonia in this context.
Agent
Molecular epidemiological studies indicate that a wide array of virulent organisms may be found in the environment of foals (and even within individual foals with pneumonia);2-4 thus, it appears that any virulence-plasmid-bearing isolate can cause disease in foals. Recent evidence indicates that the plasmid is shared by conjugation, and that this process occurs among field strains with sufficient frequency to render it infeasible to attempt to eliminate virulent R. equi from the environment of foals.5,6
Evidence of macrolide-resistance in isolates of R. equi from foals is of concern.7,8 Effective alternatives to macrolides are limited for treatment of R. equi pneumonia in foals, and infection with these isolates appears to worsen prognosis.7 There is great need to further our understanding of the epidemiology and ecology of macrolide-resistant R. equi at horse farms.
Environment
The disease appears to occur predominately at well-managed breeding farms that use practices effective for controlling other infectious diseases of neonatal foals.9-11 Higher density of mares and foals at farms is associated with increased occurrence of R. equi pneumonia.9-12 The extent to which this is an alterable risk factor remains to be determined from both theoretical and practical standpoints. The cumulative incidence of diseases is positively associated with higher airborne concentrations of virulent R. equi, and concentrations of virulent R. equi tend to be higher in barns than in paddocks or pastures.13-15 Airborne concentrations of virulent R. equi are higher in foaling stalls among foals that subsequently develop R. equi pneumonia than among foals that remain free of disease.16,17 Strategies to reduce airborne R. equi in foaling stalls or having foals born and maintained in paddocks might reduce the incidence of R. equi pneumonia; however, controlled intervention trials for these possible control measures are lacking.
Host
Age is strongly associated with susceptibility to infection with R. equi; pneumonia is found almost exclusively among foals, and adult horses appear refractory. Evidence exists of reduced innate and adaptive immune responses in foals,18-21 but foals also are capable of mounting immune responses against bacterial pathogens.22-24 Thus, it remains unclear whether the immune system of foals is merely naïve or relatively deficient.
The finding that exposure to virulent R. equi is relatively widespread at breeding farms and that many foals remain clinically unaffected suggests that some foals are more susceptible to disease than others. It is possible that a genetic basis underlies this inter-individual variation in susceptibility to development of clinical signs. It is improbable that susceptibility to this complex disease is mono-genic. Several candidate genes have been identified that have modest associations either with disease development or burden of virulent R. equi in tracho-bronchial aspirate (TBA) fluid.25-29 One commonality of these various genes is that they relate to innate immunity, suggesting that innate immunity plays an important role in disease protection and that inter-individual variation in immune responses may explain the differences among foals in likelihood of disease development.
III. Treatment
Administration of a macrolide in combination with rifampin has been the standard of care for about 30 years. Because resistance mechanisms for macrolides tend to be class-specific, it is not surprising that resistance to macrolides appears to be increasing.7 This means that identifying alternatives is an important consideration. Gallium maltolate is a metal-based drug that has antimicrobial properties against R. equi, and achieves high intracellular concentrations.30-33 The minimum inhibitory concentrations of gallium maltolate are similar for macrolide-susceptible and macrolide-resistant isolates of R. equi.34 Although gallium maltolate was ineffective for chemoprophylaxis of R. equi pneumonia in foals,35 it may be effective as an adjunct or monotherapy for foals.
While long-term use of macrolides for treating R. equi undoubtedly has contributed to the emergence of macrolide resistance, evidence exists that the program of treating foals with pulmonary lesions identified sonographically during screening of non-clinically affected foals also has contributed.8 Again, the limited number of effective and acceptable alternatives to macrolides makes this problem therapeutically challenging. We are investigating whether use of gallium maltolate is an acceptable alternative to macrolides plus rifampin for treating foals that have ultrasonographic evidence of pulmonary lesions and mild clinical signs of disease.
References
- Lilienfeld AM, Lilienfeld DE. Foundations of epidemiology. New York: Oxford Unversity Press, 1980;46-48.
- Cohen ND, Smith KE, Ficht TA, et al. Epidemiologic study of Rhodococcus equi isolates from horses and horse farms using pulsed-field gel electrophoresis. Am J Vet Res 2003;64:153-161
- Bolton TA, Kuskie K, Halbert N, et al. Detection of strain variation in isolates of Rhodococcus equi from an affected foal using repetitive sequence-based polymerase chain reaction (rep-PCR). J Vet Diagn Invest 2010;22:611-615.
- Morton AC, Baseggio N, Peters MA, et al. Diversity of isolates of Rhodococcus equi from Australian Thoroughbred horse farms. Antonie van Leeuwenhoek 1998;74:21-25.
- Tripathi VN, Harding WC, Willingham-Lane JM, et al. Conjugal transfer of a virulence plasmid in the opportunistic intracellular actinomycete Rhodococcus equi. J Bacteriol 2012;194:6790-6801.
- Stoughton WB, Poole T, Kuskie KR, et al. Transfer of the virulence-associated protein A-bearing plasmid between field strains of virulent and avirulent Rhodococcus equi. J Vet Intern Med 2013;27:1555-1562.
- Giguère S, Lee E, Williams E, et al. 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. J Am Vet Med Assoc 2010;237:74-81.
- Burton AJ, Giguère S, Sturgill TL, et al. Emergence of widespread macrolide and rifampin resistance in Rhodococcus equi isolates from a horse breeding farm. Emerging Infect Dis 2013;19(2):282-285.
- Chaffin MK, Cohen ND, Martens RJ. Evaluation of equine breeding farm characteristics as risk factors for development of Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2003; 222:467-475.
- Chaffin MK, Cohen ND, Martens RJ. Evaluation of equine breeding farm management and preventive health practices as risk factors for development of Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2003;222:476-485.
- Cohen ND, O’Conor MS, Chaffin MK, et al. Farm characteristics and management practices associated with Rhodococcus equi pneumonia in foals. J Am Vet Med Assoc 2005;226:404-413.
- Cohen ND, Carter CN, Scott HM, et al. Association of soil concentrations of Rhodococcus equi and incidence of pneumonia attributable to Rhodococcus equi in foals on farms in central Kentucky. Am J Vet Res 2008;69:385-395.
- Muscatello G, Gerbaud S, Kennedy C, et al. Comparison of concentrations of Rhodocococcus equi and virulent R. equi in air of stables and paddocks on horse breeding farms in a temperate climate. Equine Vet J 2006;38:263-265.
- Muscatello G, Anderson GA, Gilkerson JR, et al. Associations between the ecology of virulent Rhodococcus equi and the epidemiology of R. equi pneumonia on Australian Thoroughbred farms. Appl Environ Microbiol 72:6152-6160.
- Cohen ND, Kuskie KR, Smith JL, et al. Association of airborne concentrations of virulent Rhodococcus equi with location (foaling stall versus paddock) and month (January through June) at 30 horse breeding farms in central Kentucky. Am J Vet Res 2012;73:1603-1609.
- Kuskie K, Smith JL, Sinha S, et al. Associations between the exposure to airborne virulent Rhodococcus equi and the incidence of R. equi pneumonia among individual foals. J Equine Vet Sci 2011;31:463-469.
- Cohen ND, Chaffin MK, Kuskie KR, et al. Association of perinatal exposure to airborne Rhodococcus equi with risk of pneumonia caused by R. equi in foals. Am J Vet Res 2013;74(1):102-109. [...]
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