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Nocardiosis is a chronic, noncontagious, pyogranulomatous, suppurative disease, refractory to conventional antimicrobial therapy. Nocardia sp are pleomorphic gram-positive, strictly aerobic, facultative intracellular bacteria. These organisms are partially acid-fast and in Gram smears appear as rods, cocci, coccobacilli, or form characteristic long or branching filaments and aerial hyphae.
Etiology, Epidemiology, and Pathogenesis
Recently, the genus Nocardia was reclassified based on biochemical properties, antimicrobial susceptibility, and molecular methods (16S RNA gene sequence). More than 70 species of Nocardia are currently identified. Of these, >25 have been recognized as causes of human infections, and >30 are responsible for animal diseases. The most important pathogenic species for humans and animals are N asteroides complex, N brasiliensis, N pseudobrasiliensis, N otitidiscaviarum, and N transvalensis. N asteroides complex includes types I–VI. Type III is called N nova and type V, N farcinica.
Although nocardiosis is considered to be uncommon in animals and humans, the disease has been reported worldwide. Nocardia are ubiquitous organisms and soil saprophytes. They are commonly found in soil, organic material, water, compost vegetation, and other environmental sources.
Nocardia spp are considered to be an environmental agent of mastitis in bovines and small ruminants. N asteroides, N nova, N otitidiscaviarum, and N farcinica are the most common species identified in mammary infections. Nocardial mastitis is usually observed in dairy herds submitted to inadequate milking management and/or poor hygienic conditions in pre- and post-milking. Mammary infections are predominantly caused by soil contamination of teat dips, udders, and milking equipment during washing procedures and intramammary infusions. Dairy herds affected by nocardial mastitis often have a history of use of inadequate concentrations of antiseptics in teat dips.
In companion animals, N asteroides, N brasilienis, N otitidiscaviarum, and N nova are the most frequent species. The transmission of disease in dogs and cats is related to inoculation of the organism through puncture wounds or foreign bodies and secondary to bites or scratches after cat fights. Sporadically, canine nocardiosis has been related to inhalation of the bacteria. The occurrence of the disease in dogs and cats is associated with immunosuppressive conditions, particularly in dogs infected by distemper virus and cats affected by leukemia or immunodeficiency virus. Canine nocardiosis affects females and males equally and involves mainly animals 1–2 yr old.
Pathogenicity of Nocardia in domestic animals is related to virulence of the strain, structure of bacterial cell wall, host susceptibility, route of transmission, co-infection with immunosuppressive diseases, and induction of pyogranulomatous lesions. Immune response against nocardial infections is primarily cell-mediated. These intracellular organisms are able to inhibit phagosomelysosome fusion in neutrophils and macrophages due to presence of mycolic acids in bacterial cell wall, and are resistant to acids, oxidative enzymes (catalase and superoxide), and other enzymatic mechanisms of phagocytic cells.
Clinical Findings
Bovine mastitis, cutaneous-subcutaneous abscesses, and pneumonia in companion animals are the most common clinical manifestations of nocardiosis.
Nocardial mastitis generally is characterized by a history of chronic evolution. Classically, clinical cases of mammary infection are observed in 1 or 2 animals in the herd during lactation or dry period. Clinical examination of the udder shows enlargement, edema, fibrosis, and occasionally draining tracts. Strip cup test reveals serous to purulent milk secretion with white to yellow particles (“sulfur granules”). Infected animals have high somatic cell counts. Occasionally, the organism can disseminate from the mammary gland to other organs, causing regional lymphadenitis and pyogranulomatous lesions.
In companion animals, pulmonary nocardiosis is characterized by mucopurulent oculonasal discharge, anorexia, hyperthermia, loss of weight, cough, dyspnea, and hemoptysis. Cutaneous-subcutaneous abscesses, mycetoma, and regional lymphadenitis are frequent in nocardiosis associated with skin lesions in dogs, particularly in animals co-infected with distemper virus. Other systemic or disseminated forms of the disease in dogs and cats are represented by the development of abscesses in kidneys, liver, spleen, and abdominal lymph nodes, as well as peritonitis, pleuritis, and pyothorax. GI infection can lead to gingivitis, ulceration of the oral cavity, and halitosis. The organism is rarely observed in the CNS, urinary tract, heart, bones, or joints. Clinical signs of feline nocardiosis are similar to those described in dogs. Cutaneous-subcutaneous abscesses and mycetoma are the most common clinical form of feline nocardiosis.
Bovine or equine oral infection secondary to ingestion of fibrous foods can lead to the development of pyogranulomatous lesions in the jaw. N otitidiscaviarum has been identified in horses affected by pleuritis and pneumonia. Nocardial abortion may occur in pigs and horses. Submandibular and mesenteric lymphadenitis has been observed in pigs. Bovine farcy caused by N farcinica is an uncommon cause of chronic lymphangitis, lymphadenitis and cutaneous nodules.
Nocardiosis in wild animals and fish is generally represented by the development of organ abscesses and pneumonia.
Diagnosis
Routine diagnosis is based on clinical and epidemiologic findings and microbiologic examination. Samples of abscesses, skin, tracheobronchial lavage, milk, organs, or others tissues should be cultured on sheep blood agar or Sabouraud agar and incubated in aerobiosis for 3–7 days at 37°C and 25°C, respectively. Colonies are circular, convex, smooth or rough, firmly adherent to agar surface, with various pigments (cream, white, orange, or red-colored), and present aerial hyphae and characteristic powdery and dry surfaces like fungal organisms. Confirmation of diagnosis depends on biochemical characterization based on hydrolysis of different substrates (casein, xanthine, hypoxanthine, tyrosine) and carbohydrate assimilation (glucose, glycerol, galactose, glucosamine, inositol, adonitol, trehalose). More recently, diagnosis has been confirmed by molecular identification using 16S RNA gene sequence.
Microscopically, the organisms are gram-positive and characteristically filamentous, with a tendency to fragmentation. Modified Ziehl-Neelsen stain shows partial acid-fast organisms. Fine needle aspiration has been used in the diagnosis of skin nocardiosis in dogs and cats. Gram, Giemsa, and Panoptico stains show filamentous organisms from material aspired on biopsy. The leukogram generally shows leukocytosis with neutrophilia and monocytosis; an erythrogram reveals moderate anemia.
Radiographic images of lesions of dogs and cats affected by pulmonary nocardiosis reveal diffuse inflammation, nodules, abscesses, and lobar consolidation. Pathologic findings of nocardiosis are characterized by pyogranulomatous lesions, suppurative necrosis, and abscesses in various organs and tissues. Histologic findings show a suppurative, necrotic center containing the microorganisms surrounded by macrophages, lymphocytes, and plasma cells. Microcolonies of the organism, called “sulfur granules,” can be observed in histologic examinations.
Differential diagnoses in dogs and cats should include Actinomyces genera due to the similarities in microbiologic appearance and clinical signs. Differential diagnoses of face and jaw enlargement in bovines and equines caused by oral nocardiosis should include Actinomyces bovis (actinomycosis), Actinobacillus lignieresii (actinobacillosis), and Staphylococcus aureus (botryomycosis).
Treatment
Nocardiosis is usually refractory to conventional antimicrobial therapy because of the intracellular location of bacteria, the development of pyogranulomatous lesions, and resistance patterns. Trimethoprim-sulfonamides, amikacin, linezolid, and β-lactams (cefotaxime, imipenem, ceftriaxone) are considered drugs of choice in humans and animals. However, successful antimicrobial therapy occurs in only 30–50% of cases of bovine and goat mastitis, and pulmonary or extra-pulmonary (disseminated or systemic) infections in companion animals. Longterm therapy is required (1–6 mo in most animals; 6–12 mo in humans). Relapses can occur when using short-term protocols. Intramammary infusions of trimethoprim-sulfonamides, cephalosporins, or aminoglycosides have been used for 5–7 days in the treatment of bovine and goat clinical mastitis. In companion animals, surgical procedures (debridement, drainage, extirpation of foreign bodies, and washing of lesions with antiseptic solutions) are indicated in cutaneous-subcutaneous lesions and osteomyelitis.
Control and Prevention
There are no specific or effective measures to control nocardiosis due to wide distribution of the microorganism in the environment. In companion animals, immunosuppressive pathogens or debilitating conditions should be investigated as predisposing factors to the development of nocardiosis. Control and prevention of nocardial mastitis is based on measures indicated for environmental agents. Thus, early diagnosis of mastitis, adequate hygienic conditions and appropriately clean environment during milking, correct antiseptic concentrations in post- and pre-dipping solutions, and appropriate procedures of intramammary therapy remain the best measures to control and/or prevent nocardial mastitis. Due to the poor success rate in treating mammary infections, chemical drying of affected quarters or culling of infected animals are also recommended in the control of nocardial mastitis in dairy herds.
Zoonotic Risk
Human nocardiosis is considered an opportunistic disease. Reports of human nocardiosis have become more frequent all over the world. The disease is observed in both immunocompetent and immunocompromised people, and predominant manifestations are pulmonary, cutaneous-subcutaneous lesions, mycetoma, and neurologic signs. Clinical cases of human nocardiosis are frequently associated with immunosuppressive or debilitating illnesses such as AIDS, organ transplants, cirrhosis, diabetes, alcoholism, malignancy diseases (lymphosarcoma, lymphoma), or prolonged use of corticosteroids.
Most cases of transmission to humans occur probably by inhalation of the organism in dry, warm climate regions. Trauma with skin inoculation is another form of transmission. Several cases of human cutaneous-subcutaneous nocardiosis have been described secondary to bites or scratches from clinically ill dogs and cats. However, human nocardiosis is probably not transmitted directly person-to-person or nosocomially acquired. Experimental studies of temperature resistance using N asteroides and N brasiliensis isolated from bovine milk in time/temperature conditions employed in pasteurization indicate a potential risk of transmission by milk.
Precautions should be taken by immunocompromised people, with special attention to contact with soil or organic material from environments contaminated by domestic animals or direct contact with animals suspected of having nocardiosis.
Last full review/revision March 2012 by Márcio Garcio Ribeiro, DVM, PhD
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