Pathophysiology, diagnosis, treatment and prognosis of foals with Rhodococcus equi pneumonia (Proceedings)
The main routes of infection are via ingestion (gastrointestinal) and inhalation (respiratory). Ingestion is thought to be the most common route of exposure but inhalation is thought to be the major route of exposure that leads to respiratory disease. Experimental nebulization with R.equi leads to pyogranulomatous pneumonia similar to that seen in natural cases of R.equi pneumonia.
Antibodies against R.equi are transferred to the foal via colostrum, however these antibodies do not protect foals from infection. Maternally-derived antibodies wane at 1-2 months of age. It is thought that all foals may be exposed to R.equi at an early age and foals less than 1 week of age are more susceptible to infection.R.equi is a facultative intracellular organism that shares many characteristics with members of the genera, Mycobacterium. Virulence of R.equi is related to the presence of a large plasmid. After inhalation, R.equi are phagocytized by alveolar macrophages. Within the macrophages, R.equi inhibits phagosome-lysosome fusion to allow its survival within the macrophage. The organisms persist and multiply within the macrophage. Damaged macrophages release many organisms which then cause disease in surrounding tissues. Alveolar macrophages full of intracellular R.equi are usually contained within pyogranulomas of the pulmonary parenchyma. Alimentary infection occurs from ingestion of large numbers of R.equi from the environment or secondary to ingestion of R.equi expectorated from pulmonary infections.
The immunity to R.equi is highly complex and requires orchestrated activity of a variety of immune regulators and effectors . Antibodies are passed from the dam to the foal via colostrum. Immunity to R.equi in horses likely depends on both humoral and cell-mediated immune responses. R.equi-specific antibodies enhance phagosome-lysosome fusion, thereby enhancing the ability of alveolar macrophages to kill R.equi. Antibodies to the VapA proteins do not provide complete protection from R.equi but have been shown to enhance the pulmonary clearance of R.equi following heavy intrabronchial challenge in foals (Hooper-McGrevy 2001). Clearance of R.equi in adult horses is associated with a significant increase in bronchoalveolar lavage fluid CD4+ and CD8+ lymphocytes, lymphoproliferative responses to R.equi antigens, development of R.equi-specific cytotoxic T lymphocytes, and IFN-γ induction (Hines 2001 and 2003; Lopez 1002; Patton 2004). It is speculated that foals are immunocompromised in some way or that infection with virulent R.equi alters the immune responses in foals. Deficiency of IFN-γ may be at the reason for foal's susceptibility to R.equi infections.
Pulmonary lesions consist of suppurative bronchopneumonia with miliary to multifocal pyogranulomas. The typical findings include multiple firm, nodules separated by congested and partly atelectic lung. Nodules vary in size and some foci coalesce to form large lesions. Lesions are bilateral in most foals, although exceptions do occur. Suppurative tracheobronchial lymphadenopathy often is present. Pyogranulomas are sometimes encapsulated. Bronchial lymph nodes are typically enlarged, swollen and edematous and caseonecrotic foci may be present.
Histologically, the lesions are predominately pyogranulomatous. Early lesions are characterized by cellular influx into alveolar spaces, with macrophages, multinucleate giant cells and neutrophils. Neutrophils and macrophages contain intracellular gram-positive coccobacilli. As the disease progresses, necrosis involves alveolar sepate and spread to affect larger areas of the lungs, producing the caseous necrotic foci seen macroscopically.
Concurrent multifocal ulcerative colitis and typhlitis, and mesenteric lymphadenopathy occurs in about 50% of cases. Occassionally, a large abdominal abscess will form most often in a mesenteric lymph node. Peritonitis and adhesions frequently are present. Abscesses and pyogranulomatous lesions can occur anywhere in the body.