Rhodococcus equine infection in foals: epidemiology (Proceedings)

The epidemiology of R. equi remains ill-defined and continues to evolve. Two epidemiologic questions of clinical importance regarding Rhodococcus equi foal pneumonia are "Why are some foals affected while others in the same environment remain unaffected?", and "Why does the disease occur recurrently at some farms but not at others?". To answer these questions, studies performed at the level of the foal and farm, respectively, are needed. The evidence from foal-level and farm-level studies will be reviewed in this presentation.

FOAL-LEVEL STUDIES:

Rhodococcus equi is widespread in the environment of mares and foals. This is reflected by high seroprevalence, and the fact that R. equi can be isolated from feces, soil, air, and feed at horse breeding farms. Consequently, most (if not all) foals are exposed to virulent organisms, yet only some foals develop disease. These findings imply that some foals are more susceptible to infection than others, are exposed to higher concentrations of virulent organisms, or both. One study has examined fecal concentrations of virulent R. equi of dams in relation to subsequent disease in their foals. Although the fecal concentrations of individual mares did not explain the occurrence of disease in their particular foals, the finding that all mares at a breeding farm were shedding virulent R. equi in their feces during the periparturient period indicates that mares are a source of virulent R. equi for the environment into which foals are born. A subsequent study has demonstrated that the high prevalence of fecal shedding of virulent R. equi can be generalized to other breeding farms in central Kentucky. To date, only 1 study has specifically attempted to address the association between signalment, history, and management factors for foals and R. equi pneumonia. That study identified significant differences in disease incidence between farms and between years, but no foal-level factors were significantly associated with the disease.

Anecdotally, some mares are described as being more likely to have affected foals. These anecdotes along with aforementioned evidence that some foals are predisposed to developing disease suggest the possibility of genetic contributions to susceptibility to R. equi pneumonia. Polymorphisms in microsatellites, and the transferrin, IL1-receptor, and NRAMP1 genes have been associated with susceptibility to R. equi pneumonia, but the strength of these associations have not been compellingly strong. Mice lacking the galectin-3 gene are more resistant to R. equi infection than mice with that gene. Thus, genetic factors influence host susceptibility to R. equi, but the trait is likely complex and polygenic in nature, and is undoubtedly modulated by environmental factors such as the density of mares and foals at farms.

Both innate and adaptive immune responses of the host play a critical role in the pathogenesis of R. equi pneumonia. The concentrations of neutrophils (cells that play a key role in innate immune responses) and the ratio of CD4+:CD8+ lymphocytes (reflective of adaptive immunity) were significantly lower at 2 weeks of age among foals that subsequently developed R. equi pneumonia than among age-matched controls from the same environment that failed to develop the disease.

In summary, few studies have examined foal-level risk factors, and these studies have not yielded strong evidence for any particular causal factor(s).

FARM-LEVEL STUDIES:

A number of recent studies have documented that the presence or concentration of R. equi in soil fails to explain the incidence of R. equi at breeding farms. There is great diversity in the genotypes (DNA "fingerprints") of isolates within and among farms. To date, evidence that soil geochemistry influences the risk of R. equi pneumonia has not been reported.2 The proportion of virulent isolates of R. equi in soil at breeding farms in central Kentucky was increased later in the breeding/foaling season. Airborne concentrations of R. equi have been correlated with the incidence of R. equi pneumonia in Australia. Factors that were associated with increased airborne concentration of R. equi included: site (holding pens/lanes relative to paddocks); warmer ambient temperature; less soil moisture; reduced grass height; and, later date during the breeding/foaling season. One needs to be careful in differentiating significant statistical associations with causal associations in environmental/ecological studies of R. equi. Causes must precede effects, and sorting out whether factors associated with disease preceded infection or disease development can be very difficult because of the insidious nature of R. equi pneumonia.

Some evidence exists that foaling in pasture may reduce the risk of R. equi pneumonia.5 The density of mares and foals appears to be positively correlated with incidence of the disease.2,3,5 The disease appears to be associated with well managed farms that use management practices generally deemed to be desirable for preventing infectious diseases of foals.2 This association is not likely causal, but does indicate that practices effective for preventing other infectious diseases of neonates are of limited benefit against R. equi.

SUMMARY: Relatively few studies have addressed the fundamental epidemiological issues that are of greatest clinical importance regarding R. equi pneumonia in foals. Much work remains to be done to elucidate these factors. Our laboratory continues to seek support support and resources – including veterinarians and farms willing to collaborate on projects - to address these aims.

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