Date Published: February 7, 2018
Publisher: Public Library of Science
Author(s): Laura Huber, Steeve Giguère, Londa J. Berghaus, Amanda Hanafi, Sarah Vitosh-Sillman, Sarah L. Czerwinski, Roy Martin Roop.
Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent R. equi using inocula of 1×108 CFU (high inoculum; n = 16) or 1×107 CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. R. equi was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease.
Rhodococcus equi is a Gram-positive facultative intracellular pathogen that has the ability to survive and even replicate in macrophages. Infections caused by R. equi represent one of the most important causes of disease in foals. R. equi is also as a common cause of opportunistic infections in immunosuppressed people, particularly in individuals receiving chemotherapy or infected with the human immunodeficiency virus [1–3]. Pneumonia is the most common clinical manifestation of infections caused by R. equi in both species although numerous extrapulmonary disorders have been described [3, 4]. In a retrospective cohort of 150 foals with naturally acquired infections caused by R. equi, at least 1 of 39 extrapulmonary disorders were recognized in 74% of foals and detection of extrapulmonary disorders was associated with a worse prognosis .
There was a significant effect of inoculum (P < 0.001), day of post-infection (P < 0.001) and a significant interaction between inoculum and day of infection (P = 0.001) on rectal temperature. Beginning 9 days post-infection, foals infected with the high inoculum developed significantly higher rectal temperatures compared to their baseline values and to that of foals infected with the low inoculum (Fig 1). Heart rate and respiratory rate did not increase significantly relative to baseline and were not significantly different between the high and low inocula. Twenty of 28 foals (71%) developed polysynovitis of the fetlocks, stifles, carpi and tarsocrural joints. There was no apparent lameness in affected foals. The risk of development of polysynovitis was reduced by approximately 66.4% (hazard ratio = 0.336; 95% CI = 0.138 to 0.817; P = 0.016) in foals infected with the low inoculum relative to foals infected with the high inoculum (Fig 2). Fourteen of 25 foals (56%) subjected to an ophthalmic examination on day 14 post-infection had uveitis as defined by the presence of aqueous flare. Two of the 14 foals also had bilateral hypopyon. There was a strong and statistically significant (P < 0.001) association between polysynovitis and uveitis with all 14 foals with uveitis also having polysynovitis. Only 3 foals had polysynovitis without clinically detectable uveitis. Other clinical signs detected occasionally included intermittent cough (n = 4) and mild self-limiting diarrhea (n = 9). The present study documents the occurrence of polysynovitis and uveitis in a high proportion of foals experimentally infected with virulent R. equi. The culture of virulent R. equi from aqueous humor and synovial fluid indicates that these extrapulmonary disorders are septic and not immune-mediated processes. Multiple studies have described development of pneumonia in foals after experimental infection with 103 to 1010 CFU of virulent R. equi by instillation into the airways or by nebulization. However, uveitis had not been described in foals experimentally infected with R. equi and polysynovitis was only described in 4 foals after infection with 109 CFU . The reasons for the lack of detection or reporting of polysynovitis and uveitis in prior experimental infections are unknown but these complications would be easily missed without thorough ocular examination and palpation of the joints. In the present study, foals with polysynovitis did not have apparent lameness and foals with uveitis did not have obvious signs of ocular disease such as blepharospasm or ocular discharge. The clinical diagnosis of polysynovitis and uveitis is somewhat subjective and might vary depending on the experience or expertise of the clinician. Therefore we relied also on synovial fluid and aqueous humor protein concentration and histopathology by a blinded pathologist to more objectively detect and quantify inflammation at these sites. Source: http://doi.org/10.1371/journal.pone.0192655