No curative treatment for lymphoma exists. However, supportive therapy may be indicated to reduce discomfort and prolong life long enough to remove valuable ova/embryos or calves or to harvest semen.
Until more information is available on the epidemiology of lymphoma, control and eradication hinge on success of efforts to eradicate BLV from a herd. Presently, no vaccines offer effective protection from BLV infection.358-361 Control and eradication of BLV require reduction of blood transmission through iatrogenic means and through physical contact among cattle.362 Transmission associated with physical contact between infected and susceptible cattle can be reduced by segregating infected and noninfected cattle.363-365 Separation of cattle by 10 feet is preferred, but a single fence may reduce sufficiently the degree of contact necessary for transmission. Transmission after physical contact may be through inhalation of BLV shed in nasal secretions.366-369 Experimental studies have found that under extreme conditions of blood contamination and mucosal irritation, BLV can be transmitted rectally.370-374 Under conditions typical of routine palpation during pregnancy examination, however, BLV appearance may not necessarily be transmitted to any measurable degree.372,374 If potential for rectal transmission is a concern, palpation sleeves may be rinsed or replaced between cows. Although insect transmission of BLV is theoretically possible,375 as demonstrated experimentally by interrupted feeding of tabanids from cattle with persistent lymphocytosis to uninfected cattle,376 studies of natural infection have not been able to link flies with new natural infections.377,378 Several studies have been unable to demonstrate transmission after use of a common needle.379-381 However, infection after use of a Tb needle dipped in blood of a BLV-infected animal could be prevented by wiping the needle with cotton before injection.382 Although data have not shown the use of common needles to be an important means of BLV transmission, it would be prudent to use individual sterile needles for treatment, testing, or vaccination.
Transmission of BLV has not been shown in cows inseminated artificially using commercially prepared frozen semen.383-387 However, infection resulting from the use of an infected bull in natural breeding may be possible.388-390 Semen of 27 bulls that were BLV PCR positive in peripheral blood had no evidence BLV on PCR.391 Embryo transfer recipients should be tested for BLV before transfer.392 Embryo transfer using noninfected recipients offers a means of producing phenotypically preferred cattle from BLV-infected cows and controlling in utero infection,377,383,393,394 because at harvesting, embryos are not infected.385 It is possible to produce transferable in vitro fertilized embryos that are free of BLV provirus from oocytes that are exposed to BLV during maturation, fertilization, or after fertilization, through a washing procedure.395
For most herds, control and eradication of the infection would require modification of facilities, alteration of management practices, and serologic surveillance at least annually. Planning a control program should include a cost/benefit analysis to evaluate potential return on the investment. Financial benefit of a BLV control program has been documented in herds in which the prevalence of BLV infection is 12.5% or higher.396 The selective culling of BLV-infected cattle based on positive lymphocyte BLV antigen expression in vitro was reported to be effective in preventing transmission of BLV infection.397
Lymphoma and lymphosarcoma are terms that have been used interchangeably to describe a group of neoplasias originating from the lymphoid system, including nodal lymphoma (lymph nodes) or extranodal lymphoma (thymus, spleen, and mucosal-, conjunctival-, or skin-associated lymphoid tissue [MALT, CALT, and SALT, respectively]). The mucosal-associated lymphoid tissue includes mucous membranes lining the digestive, respiratory, and urogenital systems. Metastasis can occur to other organs, including primary lymphoid tissues such as bone marrow. Based on its embryologic origin, lymphoma is classified as a mesenchymal neoplasm. Although the suffix -oma indicates a benign neoplasm and -sarcoma a malignant mesenchymal neoplasm, the Leukemia and Lymphoma Society determined that lymphoma is the appropriate term because all neoplasms of the lymphatic system in humans are malignant. In veterinary medicine, lymphomas are also malignant, so the term lymphoma has been adopted. It is important to emphasize that “lymphoid hyperplasia” is not synonymous with lymphoma. Clonality studies may determine if a specific clone of lymphocytes (B, T, natural killer, and plasma cells) are malignant versus hyperreactive.
Lymphoma is one of the most common malignant neoplasia in the horse. On postmortem examination, prevalence of lymphoma in the horse was estimated to be 2% to 5%.398,399 In contrast to other species, lymphoma development has not been associated with a viral etiology in the horse. However, virus-like particles in lymph nodes of neonatal foals with lymphoma have been described, although no causal relationship was proved.400,401 Lymphomas can occur at any age, from an aborted equine fetus to horses 30 years old.401-403 Typically, age of onset of all forms of lymphomas has been reported as 5 to 10 years; however, a recent study revealed that the mean age of intestinal lymphoma was 16 years.403,404 There is no apparent breed or gender predilection. The clinical signs vary depending on tumor location but most often include lymphadenopathy, lethargy, weight loss, edema, and pyrexia. Affected lymph nodes tend to be firm, cool, and nonpainful. In one retrospective study of 79 horses with lymphoma, 21 cases had ocular involvement.405 Paraneoplastic pruritus and alopecia were described in a horse with diffuse lymphoma.406 Neurologic alterations, lameness, osteolysis, and pathologic fractures have been described as the result of lymphoma.407-412
The hematologic features of lymphoma are varied. However, anemia is a relatively common finding. Anemia is thought to be caused by suppression of erythropoiesis, bone marrow infiltration, blood loss, or immune-mediated hemolytic anemia.81 There is only one report, in a 9-year-old warmblood mare, involving multicentric lymphoma and persistent paraneoplastic erythrocytosis.308 Frank leukemia is rare, but when present (reported counts as high as 256,500 cells/μL), neoplastic cells are generally found in the bone marrow.413 More often the lymphocyte count is within the reference range or low. Atypical lymphocytes may be noted in the blood smears of 20% to 50% of affected horses, especially late in the course of disease.414-417 A modest neutrophilic leukocytosis with an elevated fibrinogen is often seen. This inflammatory response can cause confusion when trying to differentiate neoplasia from internal abscessation.418 Serum biochemistry profiles may show internal organ involvement. Serum protein alterations are frequently observed and include hypoalbuminemia, hyperglobulinemia with polyclonal gammopathy (most cases), and decreased albumin/globulin ratio. However, deficiencies in IgG and IgA concentrations were reported in a horse.419 Neoplastic lymphocytes may arise from reactive B-cell clones producing antibodies responsible for gammopathies and immune-mediated processes (hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia).81 Although low serum IgM concentrations and hypercalcemia have been reported in a few cases, these are not consistent features of lymphoma in the horse.179,417,419-421
Lymphomas in horses have been classified based on anatomic distribution, morphology, and cell lineage.422-425 Based on its anatomic distribution, the classification of lymphoma in the horse is as follows: multicentric, generalized, alimentary or intestinal, splenic, mediastinal, thymic, and cutaneous forms. The spleen is the organ most frequently affected with lymphoma, and lymphoma is the most common neoplasia of the spleen.426
Morphologically, lymphocytes are classified as “small” if their nuclear diameters are 1.5 times or less the diameter of erythrocytes and “large” if their nuclei average twice or more the diameter of erythrocytes.423 Small-cell lymphoma consists of 60% or more small cells. Large-cell lymphoma consists of 60% or more large cells. A lymphoma designated as “mixed” is a tumor that contains both small and large neoplastic cells of the same immunophenotype.423
Immunohistochemical classification of lymphomas has been determined by using monoclonal antibodies, such as BLA36, CD79a (mb-1), and B29 for B-cell lymphomas and polyclonal antibodies to CD3 and CD5 for T-cell lymphomas. All three lymphomas—B cell, T cell, and mixed B and T cell—have been reported in the horse.423,424 The monoclonal antibody proliferating-cell nuclear antigen (PCNA) has been used to determine the proliferative status of the cells.423 Frequently, lymphomas are described as T-cell—rich B-cell lymphoma, or vice versa. T-cell—rich, large—B-cell lymphoma is a neoplastic proliferation of large B cells associated with a prominent component of nonneoplastic reactive T lymphocytes that constitutes a significant percentage of the cellular population.423 The presence of large numbers of nonneoplastic T cells within a B-cell lymphoma could result in an erroneous diagnosis of a T-cell tumor. Neoplastic cells are determined based on large cell size; large, vesicular, and irregularly shaped nuclei with coarse chromatin; atypical mitotic figures; and positive immunostaining to PCNA markers. Nonneoplastic cells are identified by their normal morphology and lack of immunoreactivity to proliferation markers. However, it may not be this simple to differentiate accurately between neoplasia and reactive inflammatory response; clonality assays are required to make this determination. Polyclonality is seen with lymphocytic hyperplasia and monoclonality with lymphoma. Accurate characterization and staging of lymphomas in humans have been critical to establish therapeutic management and prognosis. All forms of lymphomas are considered malignant in the horse.426
The multicentric form of lymphoma involves lymph nodes (veterinary oncology terminology: nodal = lymph node; multiple lymph nodes = multinodal = multicentric) regardless of location.426 Extranodal lymphoid tissue (lymphoid tissue other than lymph nodes) is not involved.426 However, multicentric lymphoma may metastasize to extranodal areas, in which case it will be classified as generalized (diffuse) lymphoma.426 In veterinary medicine the terms multicentric and generalized have been used interchangeably.
The generalized form is considered an end-stage lymphoma characterized by involvement of both nodal and extranodal lymphoid tissue.426 This form is more common than the intestinal (extranodal) and mediastinal (nodal) forms alone. Horses often present with severe lethargy, emaciation, anorexia, generalized lymphadenopathy, and edema because of impaired lymphatic drainage.404,427 Anemia is common, and hypoproteinemia caused by hypoalbuminemia may be found. Although rare, leukemia is generally associated with this form of lymphoma.413 In addition to lymphoid tissue involvement, infiltration of tumoral cells has been reported in the spleen, liver, bladder, kidney, lung, heart, nasopharynx, eye, ovary, uterus, brain, and spinal cord.402,413,420 Multifocal eosinophilic granulomas have been identified in neoplastic lymph nodes, thought to be in response to paraneoplastic interleukin-5 (IL-5) and granulocyte-monocyte colony-stimulating factor (GM-CSF) produced by neoplastic cells.413
Alimentary tract lymphoma involves the GI tract, more frequently the small intestine.424,428 Lymphoma is the most common neoplasia of the intestinal tract in horses.403 This neoplasia has been reported most often in horses less than 5 years of age. However, a recent retrospective study on intestinal neoplasias revealed that the mean age of horses with lymphoma was 16 years (range, 2 to 30 years), with Arabian horses the most common breed associated with this type of lymphoma.403 Lymphoma arises from the lymphocytes of the lamina propria (extranodal lymphoid tissue) of the intestinal tract, resulting in diffuse or segmental thickening, focal masses, or scattered crater-like ulcers with raised margins of the intestinal wall.424,425,428 Lymphadenopathy is generally not present. Metastases to mesenteric lymph nodes, liver, and spleen have been reported.425 Transabdominal ultrasound may be very useful for the detection of intestinal thickening and cecal lymphadenopathy. These tumors could be of B-cell or T-cell origin. Although most of these tumors are considered to be of B-cell origin, clonality assays recently revealed that T-cell lymphomas are more common than B-cell lymphomas in the intestinal tract.403 This neoplasia is usually associated with malabsorption, protein-losing enteropathy (hypoalbuminemia), weight loss, edema, abdominal effusion, mild recurrent colic, and diarrhea.428-431 Affected horses frequently have an abnormal glucose or xylose absorption test, indicating small intestinal malabsorption. Taylor et al.403 reported that abdominal fluid cytologic analysis was useful for diagnosis of miscellaneous intestinal neoplasia in 38% of cases.
Lymphoma is the most common thoracic neoplasia in horses and may involve mediastinal lymph nodes, thymus, and lungs.432,433 Exclusive involvement of mediastinal lymph nodes is called mediastinal lymphoma, whereas exclusive involvement of thymus is called thymic lymphoma.426 Prevalence varies from 18% to 29% of all forms of lymphoma.110,430,434 Primary and secondary (metastatic) mediastinal lymphomas have been reported. Most often, however, the neoplasia results from metastasis.432 Primary mediastinal lymphoma is usually seen in adult horses (mean age of 10 years, range of 2 to 30 years), although it was reported in a 1-month-old foal with a 1-week history of respiratory distress.402 Metastasis from primary mediastinal lymphoma often occurs. In the early stages of the disease, minimal clinical signs may be observed. Common signs include nasal discharge, adventitious lung sounds, pleural effusion, thoracic ventral and limb edema, and regional lymphadenopathy at the thoracic inlet.430,432 Other signs include cough, pyrexia, pleurodynia, and in some cases, respiratory distress.432,435 Temperature, pulse, and respiratory rate are often elevated. Dysphagia may be observed in some cases with retropharyngeal lymphadenopathy.436 High nucleated cells counts of several thousand per microliter, with a large percentage of abnormal lymphocytes, are often evident on pleural fluid cytology; however, collection of multiple pleural fluid samples may be necessary to establish a definitive diagnosis.435 Some of the cytologic abnormalities include the presence of prolymphocytes, lymphoblasts, nuclear blebbing, indented and cleaved nuclei, amorphous nuclei, altered nuclei/cytoplasm ratio, and mitotic figures.435 Lymphomas could be of B-, T-, or mixed-cell origin, but T-cell lymphomas are more common.423,435
Cutaneous tumors are confined to the skin-associated lymphoid tissue. Single or multiple, subcutaneous, firm, nonpainful nodules ranging from less than 1 cm to greater than 20 cm in diameter can develop rapidly or slowly, regionally, or over most of the body surface.437,438 The nodules are usually covered with hair. In some cases the lesions tend to wax and wane spontaneously, or they are associated with hormonal influences, seasonality, and steroid therapy. There is one report of complete regression of cutaneous lymphoma after surgical removal of an ovarian tumor.439 Because of the waxing and waning response, there is controversy whether this may be lymphoid hyperplasia rather than lymphoma. Depending on anatomic location, lymphomas may cause mechanical lameness and limb edema as a result of vascular and lymphatic obstruction. In most cases, no hematologic abnormalities are present, and generalized lymphadenopathy and internal organ involvement are rare. This type of tumor is usually of B-cell origin. Mycosis fungoides is another form of cutaneous lymphoma in which there is diffuse infiltration of neoplastic T-cell lymphocytes in the epidermis, dermis, and subdermis. This type of lymphoma has been reported in a mare with a vulvar mass that infiltrated the skin of the perineum and ventral abdomen.440 Cutaneous lymphoma may involve mucocutaneous junctions and carries a poor prognosis if deeper tissues are involved.440
Also known as endotheliotrophic lymphoma and intravascular lymphangiomatosis, angiotrophic lymphoma has been described in humans, dogs, and cats.441-443 There is a single report in horses, in a 12-year-old pregnant thoroughbred mare with anorexia, tachycardia, and mild fever.444 The significant laboratory abnormalities were profound anemia (PCV of 12%), decreased RBC count, marked anisocytosis, mild lymphopenia, low IgM, and marked erythroid hyperplasia and erythrophagocytosis on bone marrow biopsy. Triglycerides, cholesterol, and total bilirubin were elevated on serum biochemistry. Coombs’ and Coggins’ tests were negative. Postmortem examination revealed generalized icterus, with moderately enlarged mediastinal and mesenteric lymph nodes. Histologic examination revealed thickened pulmonary alveolar septa and vessels crowded with atypical lymphoid cells with scattered mitoses. Similar atypical cells were evident in renal vessels. The neoplastic cells were determined to be of T-cell origin based on immunohistochemical staining. Angiotrophic lymphoma may represent an antemortem diagnostic challenge because of the lack of circulating neoplastic lymphocytes and identifiable masses.
Information about chemotherapy for lymphoma in horses is limited. One protocol used in two pregnant mares with lymphoproliferative disease consisted of a combination of cytarabine (200 to 300 mg/m2 SC or IM every 7 to 14 days), chlorambucil (20 mg/m2 PO every 14 days) or cyclophosphamide (200 mg/m2 IV every 14 to 21 days), and prednisolone (1.1 to 2.2 mg/kg PO every 48 hours).445 Vincristine (0.5 mg/m2 IV every 7 days) can be added if no clinical improvement is noticed in the first month of therapy. This protocol was continued for 2 to 3 months, followed by a maintenance protocol consisting of gradual decreases of prednisolone, and extending by 1 week the administration of other chemotherapeutic agents, for the next 2 to 3 months. This was followed by extending the administration interval by another week for 2 to 3 months, for a total of 6 to 9 months.445 Other protocols include drugs used alone or in combination, such as L-asparaginase (10,000 to 40,000 U/m2 IM every 14 to 21 days), doxorubicin (50 mg/m2 IV), vincristine (1.4 mg/m2 IV), and rituximab (375 mg/m2 IV). A horse with thoracic lymphoma was treated with cytarabine (170 mg/m2 IM) 2 weeks apart, alternating with cyclophosphamide (142 mg/m2 IV) 7 days after each dosage of cytarabine.435 In addition, the horse received prednisolone (86 mg/m2 PO every 48 hours) and was discharged 1 month after the initiation of chemotherapy, with instructions to continue prednisolone at the previous dosage for life. Eight months after discharge, the horse was in good health and resumed light exercise. Therapy may be attempted with dexamethasone (0.2 mg/kg IV or PO every 24 hours for 5 days), followed by prednisolone (1 to 2 mg/kg PO every 24 hours). Tapering dosages of corticosteroids is not recommended because this has no therapeutic benefit and may induce drug resistance to corticosteroids and chemotherapy.426
Complications associated with chemotherapeutic agents in horses include anorexia, lethargy, thrombosis, arrhythmias, laminitis, bone marrow damage, GI and genitourinary toxicoses, urticaria, and immunosuppression. Anemia, thrombocytopenia, leukopenia, and secondary infections may occur.446 Successful management of cutaneous lymphomas has been achieved using glucocorticoids such as dexamethasone, prednisolone, and betamethasone. As mentioned earlier, however, controversy surrounds the nature of cutaneous nodules as possible lymphoid hyperplasia and not true lymphomas. Other treatments include autologous tumor vaccine and radiation therapy.447,448 Although periods of remission have been reported with chemotherapy,435,445 the long-term prognosis has been poor for most horses.
Lymphoma is the most common neoplasia in New World camelids. Two forms of lymphoma, multicentric and generalized, have been reported in alpacas and llamas.449-456 There is no age or gender predisposition. The reported median age of affected alpacas was 0.8 year, with a range of 0.2 to 2 years.456 The median age of affected llamas was 5.5 years, with a range of 0.3 to 15 years.456 However, information from approximately 50 camelids with lymphoma (unreported and reported) revealed a mean age of 4 months and 4 years for alpacas and llamas, respectively.457 Lymphoma has been diagnosed in alpacas as early as a fetus and 2-week-old cria.457 The pathogenesis of lymphoma in camelids is unknown at present.
The most common clinical signs are weight loss, palpable masses, lethargy, respiratory signs, and anorexia.449-453 Other signs are tachycardia, fever, weakness, and recumbency if the CNS is affected.451,456 The most common clinicopathologic abnormalities include anemia, left-shifted leukogram, hypoalbuminemia, and hyperglycemia. Cerebrospinal fluid (CSF) analysis may yield atypical, immature lymphocytes if the CNS is involved.456 Liver, kidney, heart, bone marrow, lymph nodes, stomach, and nervous system (extradural and subarachnoid spaces) have been reported to be involved.449-453456 Immunophenotyping analysis has been limited to three alpacas; two had T-cell and one had mixed B-cell and T-cell lymphoma.452,456 Treatment of lymphoma was attempted in a single case but was unsuccessful.451
Leukemia is a rare neoplasia of the hematopoietic system that originates from the bone marrow (primary leukemia).310 A leukemic phase (secondary leukemia) has been rarely reported in horses with lymphoma, in which blood and bone marrow were infiltrated with neoplastic cells.310,413,415,416 Based on cell of origin, the major forms of leukemia include myeloid and lymphoid leukemias, which can have an acute or chronic clinical course. According to the Leukemia and Lymphoma Society, acute leukemias are rapidly progressing disorders that affect mostly primitive or immature cells that lack normal function; whereas chronic leukemias progress slowly, allowing some growth and cell maturation, which may preserve limited normal function. Reported leukemias in the horse include myelomonocytic, monocytic, granulocytic, eosinophilic, and lymphocytic forms.76-79,413,415,458-472 Based on presence and numbers of cells in blood, other terms used are leukemic, subleukemic, and aleukemic leukemias. Leukemic leukemia is characterized by an increase in cell numbers in peripheral blood. Subleukemic leukemia is defined by an increase in abnormal blast cells in blood, with a total white blood cell (WBC) count within the reference range or low. Aleukemic leukemia is characterized by abnormal cells in the bone marrow, but not in peripheral blood.
There is no apparent breed or gender predisposition based on the few reported cases and horses seen at the University of California, Davis.76-79,413,415,458-472 The age at onset of clinical signs ranges from 2 to 25 years. The most common clinical signs are weight loss, lethargy, anorexia, pyrexia, and lymphadenopathy if associated with lymphoma. Other signs are weakness, ventral edema, exercise intolerance, colic, and recurrent or concurrent infections.
At the initial stages of the disease, the laboratory features may show mild hematologic abnormalities, including one or more of the following: anemia, neutropenia, lymphopenia, thrombocytopenia, hyperproteinemia, and hyperfibrinogenemia. As the disease progresses (days to months), marked leukocytosis (counts up to 270,000 WBCs/μL) and hyperproteinemia will be observed in leukemic leukemias.413 Thrombocytopenia is a common hematologic feature.413,468,469,472 Pancytopenia and high blast cell counts (up to 1.6 × 109 cells/μL) were reported in a lactating mare with myeloblastic leukemia.472 Pancytopenia caused by severe infiltration of leukemic cells in the bone marrow, ineffective hematopoiesis, and myelofibrosis have been reported.468 Horses with multicentric lymphoma, pancytopenia, severe leukocytosis (more than expected for severe inflammation), or presence of atypical or blast cells in peripheral blood should prompt the collection of a bone marrow aspirate or biopsy. Bone marrow aspirates may have normal to altered myeloid/erythroid ratio (reference range, 0.5 to 3.76), with a disproportionate number of atypical or poorly differentiated blast or mature cells of certain lineage. A decrease in or absence of megakaryocytes is often observed.
Hyperproteinemia is a consistent finding because of hyperglobulinemia. Serum electrophoresis typically shows a polyclonal increase of β2- and γ-globulin fractions, and in some cases α-globulin fraction as well. Marked increases in serum IgG and IgA concentrations have been detected in horses with lymphocytic leukemias.413 Deficiencies in IgA and IgM have been reported in a single horse with chronic lymphocytic leukemia.465
Necropsy findings may include mucosal ulceration, edema, thrombosis, and hemorrhages of various organs resulting from intravascular leukostasis (aggregates of leukemic cells in blood vessels), disseminated intravascular coagulopathy, and thrombocytopenia secondary to decreased production of megakaryocytes. Leukemic-induced cell lysis may occur as the result of mediators released by neoplastic cells. Peripheral and internal lymphadenopathy may also be observed. Other pathologic findings are those associated with concurrent disease.
The diagnosis is based on routine blood work, cytologic and histopathologic evaluation of bone marrow, immunocytochemical analysis, flow cytometry, and immunophenotyping.310 Previously, leukemic cells in peripheral blood and bone marrow were described based on their morphology; however, this may result in leukemia misclassification, especially in acute leukemias, in which mononuclear blast cells constitute the leukemic clone, which may lack specific identifying morphologic features. Numerous cytologic and cytochemical stains have been used to determine the type of leukemia, such as Wright, Giemsa, Sudan black B, peroxidase, periodic acid—Schiff, alkaline phosphatase, acid phosphatase, various esterases, and surface glycoproteins. However, leukemic cells may also lack specific cytochemical properties. Currently, the various types of leukemias are determined by the identification of specific cellular antigens using a panel of monoclonal antibodies and flow cytometry in peripheral blood and bone marrow; examples are B-cell/IgM-positive, B-cell/IgM-negative, CD3/CD4/CD5-positive T-cell, CD3-negative/CD4-positive T-cell, and CD13-positive myeloid leukemias.413,465,469 Table 37-2 lists the various monoclonal antibodies for specific equine leukocyte antigens.
Table 37-2 Monoclonal Antibodies for Specific Equine Leukocyte Antigens (ELAs)
| ELA Marker | Specificity |
|---|---|
| EqCD2 | T cells |
| EqCD3 | T cells |
| EqCD4 | T helper cells |
| EqCD5 | T cells |
| EqCD8 | T cytotoxic cells |
| EqCD11a/18 | Pan leukocyte |
| EqCD13 | Myeloid cells |
| EqCD44 | Pan leukocyte |
| CD79a | B cells |
| EqWC1 | Large T-cell and neutrophil subsets |
| EqWC2 | T cells and neutrophils |
| EqWC4 | Minor T-cell subset |
| MHCI | Nucleated cells |
| MHCII | B cells, macrophages, dendritic cells, and large T-cell subset |
| IgM | B cells |
Eq, Equine; CD, cluster of differentiation; WC, white cell; MHC, major histocompatibility complex.
Data from McClure JT, Young KM, Fiste M, et al: Immunophenotypic classification of leukemia in 3 horses, J Vet Intern Med 15:144, 2001.
The prognosis is poor, resulting in death within days to a few months after diagnosis. Treatment of leukemia has been attempted in horses with cytosine arabinoside, cytarabine, and prednisolone, but with little success.461,469,471
Myeloma is a neoplastic proliferation of plasma cells that primarily originate in the bone marrow but may have an extramedullary source.473 Both forms have been reported in the horse.474-476 Accumulations of neoplastic plasma cells outside the marrow is called extramedullary plasmacytoma.473 Plasmacytomas can form in several organs and tissues, including the skin. The most common extraosseous sites in horses are lymph nodes, kidneys, spleen, and liver.474,476,477 Multiple myeloma involves bone marrow at multiple locations and other tissues; and it is the most common form of myeloma in humans.478 In human medicine, causes of myeloma include chromosomal translocation, irradiation, and chronic antigenic stimulation.473
Myeloma is a rare neoplasia of the horse, with only 16 cases reported in the literature, at a median age of 14 years (range, 3 months to 25 years).474-477,479-489 Almost half these cases were quarter horses, but various breeds, including draft horses and ponies, were represented. There is no apparent gender predilection. The clinical signs vary with the degree of plasma cell infiltration, extent, and location. The most common clinical signs are weight loss, anorexia, fever, pale mucous membranes, lethargy, limb edema, and recurrent infections.474-477,488,489 Bone pain as the result of osteolytic disease is the most common early sign of myeloma in humans.478 Four horses from the literature were reported to have lytic lesions. The clinical signs in these horses included paresis, cervical pain, and lameness.476,480,482,485
The laboratory features are anemia, hyperproteinemia caused by hyperglobulinemia, hypoalbuminemia, and proteinuria. Anemia results from reduced erythropoiesis secondary to myelophthisis and infection, blood loss, and paraproteins’ osmotic effect. Pancytopenia is observed if myelophthisis develops. Hypercalcemia has been reported in a few cases.474,476,477 Exception to these features occurred in one gelding with systemic AL amyloidosis and multiple myeloma.489 This horse had hypoproteinemia, hypoglobulinemia, hypoalbuminemia, and hypocalcemia; thought to be the result of protein-losing enteropathy caused by the severe, diffuse gastrointestinal amyloidosis.489 Concurrent systemic amyloidosis and multiple myeloma are common in humans but extremely rare in domestic animals, with only one cat and one horse reported in the literature.489,490 Serum parathyroid hormone—related protein concentration was mildly elevated in one horse with multiple myeloma.477
In secretory myelomas the neoplastic plasma cells are responsible for overproduction of a monoclonal immunoglobulin called M protein, or paraprotein. M protein may be fragments (mainly light chains, also called Bence Jones protein) or a complete immunoglobulin. Subclasses of IgG are the predominant paraprotein associated with myeloma in horses.474,488 Recently, however, three horses were reported to have IgA paraprotein.476,477
Plasma cells are relatively sparse in normal bone marrow. The involvement of the marrow is usually focal rather than diffuse, requiring multiple marrow aspirates in some cases to confirm plasmacytosis. The diagnosis of multiple myeloma in humans is based on the presence of at least 10% of plasma cells in the affected tissue, monoclonal protein in serum or urine, and evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions). Renal insufficiency has not been reported in horses with myeloma.474,476 Bleeding and blood hyperviscosity syndrome are common complications of multiple myeloma in humans478; these complications have been reported in four horses.474,483 In addition, bone nuclear scan studies have been helpful in humans to detect single (monostotic) versus multiple (polyostotic) myeloma.
Median survival after diagnosis in humans is approximately 3 years.478 Because of poor prognosis or deterioration, most reported horses were euthanized within a few days to months after diagnosis. However, two horses survived for 1 and 2 years, respectively.484,487 A quarter horse with multiple myeloma was euthanized at age 29 years, 3.5 years after diagnosis, because of deterioration.476 This horse had weight loss, intermittent limb and ventral edema, recurrent infections, and colic. Serial blood work revealed mild anemia, hyperproteinemia, hyperglobulinemia, hypoalbuminemia, hypercalcemia, and hyperproteinuria.
Lymphangioma is a rare tumor in horses that originates from lymphatic vessels. Morphologically, lymphangiomas are classified into three types: simplex or capillary, cavernous, and cystic.491 This neoplasia has been described involving cutaneous tissue of the mammary gland, thigh and inguinal regions, pleural cavity, and intestines.492-494 Lymphangioma has only been observed in young horses. The clinical signs vary depending on tumor location. Because of the extent of these tumors, surgical removal has not been possible, resulting in euthanasia.
Anthrax is a soil-borne bacterial disease primarily affecting herbivores. It most often presents as an acute septicemia with high mortality. Other animal species, including humans, can be infected. Anthrax occurs worldwide and is noteworthy because of its impact on agriculture and its potential to cause zoonotic infections. The anthrax bacillus has recently garnered increased attention because it is one of the microbes most likely to be used as a bioterrorism agent.
Bacillus anthracis is the etiologic agent of anthrax. In the vegetative form, it is a large, rectangular-shaped, gram-positive rod. Vegetative cells are predominantly found in tissues of infected animals; however, B. anthracis exchanges genetic information with other Bacillus species in the environment, indicating vegetative cells exist, to some extent, outside animal hosts.495 Under nutritionally limiting conditions, vegetative cells are induced to form spores. Sporulation is an oxygen-dependent process and does not occur under anaerobic conditions. The spore form of B. anthracis is highly stable and resists many chemical and heat treatments, as well as adverse environmental conditions.496 Spores can survive and remain infectious in the environment for decades.
Exposure of animals occurs primarily from grazing contaminated pastures and ingesting spores.497 Fodder grown in contaminated soil and contaminated animal by-products are other sources for infection. In swine, consumption of contaminated animal by-products in feed is the usual source of infection.
Ingested anthrax spores cross mucosal barriers, are phagocytosed by macrophages, and are transported to regional lymph nodes. As spores convert to their vegetative phase, they are able to avoid the antimicrobial action of the phagocyte and escape into the extracellular environment. The production of plasmid-encoded virulence factors, particularly a poly-D-glutamic acid capsule and a three-component toxin, are key to survival in the host.497 Production of a capsule is important in evasion of the host’s phagocytic defenses. The three components of the toxin are protective antigen (PA), lethal factor (LF), and edema factor (EF). PA attaches to host cells through surface receptors, polymerizes to form a prepore, and binds one or both of the other two toxin components, LF and EF. This entire complex enters the cell by endocytosis. In the endosome the polymerized prepore becomes a functional pore and allows LF and EF to enter the host cytoplasm.498 The enzymatic effects of EF and LF disrupt host cell functions, including innate and adaptive immune responses.499 EF increases cyclic adenosine monophosphate (cAMP), leading to tissue edema and suppression of phagocytic capability. LF causes cell death through interruption of signal transduction pathways and increases numerous proinflammatory cytokines. The result is rapid proliferation of B. anthracis in the host and an overwhelming septicemia. Death is caused by toxic shock with hypotension and multiorgan failure.
As mentioned, anthrax occurs worldwide, and frequency of outbreaks depends on geographic location. Some parts of the world (sub-Saharan Africa, central and southern Asia), with high concentrations of spores in the soil are referred to as “anthrax zones.” In the United States, certain states or geographic regions, such as Texas and the plains regions, have more occurrences of anthrax than other areas. Some areas with greater incidence of disease follow old cattle trails, which may have been the primary source for contaminating those environments.500,501
Environments favorable for anthrax spores include soils with elevated pH and concentrations of selected cations (Ca++, Mn++) and soils rich in organic material.497 Droughts followed by heavy rainfall or flooding often precede outbreaks, as do earth-disturbing activities such as excavations. Topography that favors collection of runoff and establishment of temporary water storage areas (seasonal ponds) may promote the concentration of spores.500,501 Outbreaks usually occur during warmer months of the year.
Bites from bloodsucking insects can spread anthrax organisms from infected septicemic animals through mechanical transmission.502 Scavenging animals can also disseminate organisms.501 Carcasses of affected wildlife are an additional source for contaminating environments because they are unlikely to be disposed of properly.
Susceptibility to B. anthracis infection depends on the individual animal species. Ruminants (cattle, sheep, and goats) are most susceptible. Because of the often peracute nature of anthrax in ruminants, clinical signs before death may not be observed. If seen, nonspecific clinical signs include fever, depression, respiratory distress, congestion of mucous membranes, and convulsions.503 In more protracted cases, bloody diarrhea, hematuria, and localized tissue swelling may be observed.
Horses develop an acute intestinal form of anthrax. Associated clinical signs include colic, diarrhea, fever, and depression followed by a fatal septicemia. A more localized form, possibly initiated by insect transmission, typically involves the neck region with massive edema. A dependent edema may result involving the thorax, abdomen, prepuce, or mammary gland.
SWINE are less susceptible to anthrax infection. Oropharyngeal involvement with swelling of the head and neck is the most common presentation.497 If severe enough, edematous tissue may obstruct breathing and swallowing. Cervical lymph nodes are prominently involved. An intestinal form may present as dysentery. Pregnant animals may abort.
Animals that die of anthrax sometimes produce bloody exudates from body orifices and show incomplete rigor mortis. Blood is poorly clotted. Carcasses undergo rapid decomposition. If a carcass is opened, the spleen is frequently enlarged and has a “blackberry jam” consistency. Lymph nodes may be edematous and hemorrhagic. Hemorrhages may be present on the surface of other organs. Signs of enteritis may be apparent. The more localized edematous form shows regional swelling. In the oropharyngeal form the cervical lymph nodes are edematous and hemorrhagic.503 Histologically, large numbers of bacilli are observed in most tissues of septic animals. Spleen and lymph node architecture is obscured by the massive hemorrhages.
Initially, anthrax may be confused with clostridial infections, lightning strikes, plant poisoning (e.g., oleander), other intoxications, or mineral deficiencies. Carcasses of animals with suspected anthrax should not be opened, in an effort to prevent sporulation of vegetative cells and further contamination of the environment. Laboratory diagnosis is necessary for definitive diagnosis of index cases. Diagnosis is made by examining direct blood or tissue smears and performing bacteriologic cultures. Samples that minimize the potential for environmental contamination but still provide good-quality cultures include unclotted blood collected from superficial veins and ocular fluid collected in a sterile syringe using a large-gauge needle. An intact eye can also be removed and submitted to the laboratory for diagnostic evaluation. In the more localized form of anthrax, samples from regional lymph nodes may be required. Because anthrax carcasses undergo rapid putrefaction, and vegetative B. anthracis cells are destroyed during the putrefactive process, the time between death and sample collection can substantially affect the recovery rate of B. anthracis. As a good safety practice, whenever a case of anthrax is suspected, this should be relayed to laboratory personnel performing the diagnostic testing.
Examination of direct smears by Gram stain is performed to demonstrate the typical, large, gram-positive, squareended rods found singly or in chains of two to four cells. A polychrome methylene blue (M’Faydean) capsule stain is performed to demonstrate the presence of the B. anthracis capsule surrounding organisms observed in direct smears. Frequently it is necessary to distinguish anthrax bacilli from postmortem invading clostridial species, which have more rounded ends and are acapsular when examined with the M’Faydean stain. B. anthracis also stains well with common laboratory stains, including Wright and Giemsa stains, and displays morphology similar to that observed on Gram staining.
Isolation of B. anthracis is readily made on standard sheep blood agar. Colonies are apparent after as soon as 6 hours of incubation. Typical B. anthracis colonies after 24 hours of incubation are large, gray-white, with a bee’s-eye texture. Colonies are usually nonhemolytic. Gram stains of young colonies show very long chains (≥10 cells) of large, square-ended, gram-positive rods often described as having the appearance of a row of “railway boxcars.”
Identification of B. anthracis isolates is confirmed by demonstrating lack of motility, lysis by a specific bacteriophage (gamma phage), and protoplast formation in the presence of penicillin (string of pearls test).504 Capsules are demonstrated in culture by growing isolates on bicarbonate agar under an increased CO2 atmosphere. Spores develop in cultures after approximately 48 hours of incubation. They are centrally located in the cell and do not cause the cell to bulge.
A number of molecular-based and rapid screening tests for detecting B. anthracis directly from samples or for identifying individual isolates are available. Most of these are primarily used in bioterrorism surveillance programs. PCR-based assays using primers specific for the capsule and PA genes are useful for differentiating field strains from the vaccine strain. Because of the sporadic nature of the natural disease, molecular-based identification may not be available in all veterinary diagnostic laboratories.
Any suspected anthrax case should be reported to appropriate local or state veterinary regulatory officials as soon as possible. Because of the peracute nature of many anthrax infections, successful treatment requires early intervention; however, treatment is often unrewarding. Penicillin and tetracycline remain the drugs of choice for treating animals. Treatment should be continued for a minimum of 5 days. Rare B. anthracis strains resistant to these antibiotics have been reported.
Carcass management is critical in controlling anthrax outbreaks. Carcasses should not be opened or moved from the area where they are discovered. Carcasses are destroyed either by burning or deep burial. Burning of carcasses is preferred to burial because it is more effective at destroying spores. Any contaminated bedding or soil should be handled similarly.
In the face of an outbreak, regulatory officials will likely quarantine affected premises. All potentially exposed animals should be closely observed for clinical signs that suggest they might be infected. All clinically normal animals should be vaccinated using a commercially available, live, acapsular vaccine strain (Sterne strain).* Prophylactic antibiotic treatment of unaffected herdmates is sometimes practiced; however, the combined use of antibiotics and vaccination in individual animals is not recommended. Because the vaccine is a live attenuated strain, concurrent use with antibiotics may lessen effectiveness of the vaccine. Combined vaccination and prophylactic antimicrobial treatment should be undertaken only after consultation with local veterinary public health or regulatory officials. Vaccination of neighboring herds should be initiated to prevent new infections resulting from either exposure to similar predisposing environmental conditions or through spread from initial outbreak sources. Controlling insects and both avian and mammalian scavengers will aid in preventing dissemination to neighboring premises.501
Vaccination is the major prophylactic measure undertaken to protect animals in endemic areas. Vaccination should be performed annually 4 weeks prior to turning animals onto pastures where outbreaks have occurred. A single dose of vaccine is given subcutaneously in the neck. In heavily contaminated areas, a second dose may be given 2 to 3 weeks later to afford better protection. The vaccine manufacturer’s recommendations or local regulatory official’s instructions should be followed regarding postvaccination market-withholding time for meat and discard time for milk. A minimum 42-day, postvaccination withholding period before slaughter is recommended. Localized swelling may occur at the site of vaccination. Goats and llamas may exhibit serious adverse reactions to the vaccine.
Ensuring that pastures are of good quality so that animals will not graze close to the soil will minimize exposure to spores. Avoiding rough feed that might traumatize mucosal surfaces will also decrease incidence rates. If possible, grazing animals on highly contaminated pastures should be avoided altogether and alternate uses encouraged for the land.
Anthrax is a zoonotic disease. Humans develop three forms of anthrax: cutaneous, inhalational, and gastrointestinal.497 Occurrence of the different forms depends on the route of exposure. Naturally acquired anthrax cases in humans in the United States are rare. When they occur, the cutaneous form is most common. Veterinarians are included among at-risk individuals because of the potential for contact with organisms while handling infected carcasses. If anthrax is suspected, proper personal protective equipment, including physical barriers (e.g., gloves) and respiratory protection, should be used when collecting diagnostic samples and during carcass disposal. Naturally acquired inhalational anthrax in humans is rare because of the relatively high median lethal dose (LD50, 8000 to 10,000 spores) required for infection and because spores carry static charges. These charges result in spores binding to larger particles, making aerosolization of spores more difficult.500
Concern about biologic weapons and terrorism has focused the public health community’s attention on B. anthracis because it is an agent well suited for such use. Dissemination of a powdered form of anthrax spores through the mail in a bioterror attack on the eastern coast of the United States in 2001 demonstrated the effectiveness of B. anthracis as a biologic weapon. In that incident, both cutaneous and inhalational anthrax cases in people occurred.505B. anthracis is now classified as a “select agent,” meaning that possession of virulent strains is federally restricted. Any isolation of B. anthracis, even from naturally occurring cases, must be reported to appropriate federal regulatory agencies (USDA) and any B. anthracis isolates securely stored or destroyed.506
Lyme disease, also known as borreliosis, is one of the most important arthropod-borne bacterial infections in the United States. The disease is caused by the spirochete Borrelia burgdorferi and affects humans, horses, dogs, and cats.507-510 Lyme borreliosis was first identified as a causative agent of an epidemic of juvenile inflammatory arthritis in children and adults in Old Lyme, Lyme, and East Haddam, Connecticut.511,512 Therefore, medical references usually cite “Lyme disease” when referring to infection with B. burgdorferi.
B. burgdorferi is widely distributed in the Northern Hemisphere. Prevalence of infection or exposure in horses has been reported to be high in the northeastern United States (50%), Midwest, Texas, and California.513 Lyme borreliosis has been reported extensively in Europe, England, Russia, China, Japan, Southeast Asia, and South Africa.514B. burgdorferi is transmitted from ticks to humans and animals by ticks belonging to the Ixodes ricinus complex.515 These ticks each feed three times, during the larval, nymphal, and adult stages.511 The larvae and nymphs feed on wild animals, and adults are found most often on deer.515 On the East Coast, Ixodes scapularis ticks are the principal vector, whereas on the West Coast, Ixodes pacificus, the western black-legged tick, is the main vector identified.516I. scapularis is seen from the Atlantic coast to Oklahoma and Texas.517 A much higher percentage of I. scapularis ticks (12% to 99%) will carry the spirochete compared with I. pacificus, in which the maximum number of infected ticks is 4% to 5%.516,517I. scapularis larval ticks acquire the spirochete principally from Peromyscus leucopus, the white-footed mouse, and the nymphal stages are the major transmitters of disease to animals and humans.518 With I. pacificus the California kangaroo rat, Dipodomys californicus, and the dusky-footed wood rat, Neotoma fuscipes, are the likely enzootic reservoirs of B. burgdorferi.519
Borrelia burgdorferi is found in many arthropods, but the major route of transmission to animals and humans is believed to be limited to the Ixodes species ticks. Experimental studies have demonstrated that ticks may harbor and transmit several pathogens, including the human granulocytic ehrlicheal agent and B. burgdorferi, at the same time.520 Exposure to ticks infected with B. burgdorferi produced seroconversion without detectable histopathologic changes except for skin lesions in experimental horses.521B. burgdorferi is maintained in a 2-year enzootic cycle that involves Ixodes species ticks and mammals. Ticks are usually attached for at least 24 hours for B. burgdorferi transmission.521 Birds are frequently infected with B. burgdorferi and may be responsible for the spread of the disease to new areas.515
Surveillance for Lyme disease was initiated by the U.S. Centers for Disease Control and Prevention (CDC) in 1982, and in January 1991 it became nationally reportable. Cases have been reported from 46 states, and the annual number of Lyme disease cases has increased 18-fold, from 497 to 8803. It is now the most common tick-transmitted disease in the United States.
Borrelia burgdorferi organisms have been recovered from the urine of feral white-footed mice, Peromyscus leucopus.522 Contact transmission has been reported among white-footed mice,522 further complicating the understanding of transmission. Because of lack of any proof to the contrary, it is generally believed at this time that any potential increased risk to humans from infected animals is attributable to animals bringing ticks into areas of human habitation rather than any animal transmission.523
Immunochemical analysis of North American strains of B. burgdorferi reveal two abundant surface proteins, termed outer surface protein A (OspA, 30 to 32 kD) and outer surface protein B (OspB, 34 to 36 kD).524 The 41-kD antigen is located on the flagellum and is similar to the flagellar antigens of other spirochetes.525 All isolates to date have four to nine pieces of extrachromosomal plasmid DNA. Plasmid may code for proteins that are important in pathogenicity because the loss of infectivity of isolates that have been heavily passaged in the laboratory correlates with the loss of particular plasmid in culture.526 Recent work suggests that B. burgdorferi can vary its antigenicity similar to the relapsing fever—causing Borrelia (e.g., B. hermsii), although by a different mechanism and by using subtle alterations in the genome.527
Clinical signs are not specific but may include low-grade fever, stiffness, lameness in more than one limb, muscle tenderness, hyperesthesia, swollen joints, and behavioral changes.528,529 The most common signs are lameness and hyperesthesia. These signs have been reported more often in performance horses. Borrelia may be found concurrently with Anaplasma phagocytophila in Ixodes ticks, resulting in dual infection in the horse.520
Horses from endemic areas have serologic evidence of exposure.530-533 Attempts have been made to correlate individual cases of arthritis, uveitis, or brain infection with this organism.532,534,535 Experimental infection has produced seroconversion and shedding of the organism in the urine and seroconversion in contact controls.536 In the United Kingdom, most seropositive horses do not show clinical signs of disease.537
Although there are some reports in the literature of seropositive animals with arthritis, the evaluation performed on the patients makes it difficult to determine if B. burgdorferi was the cause of the signs.538 It appears at this time that many ruminants are seropositive to B. burgdorferi but do not have clinical signs. Whether these tests lack specificity in the ruminant or represent a host-adapted strain of the Borrelia organism is unknown.539 A recent report correlates exposure of I. scapularis ticks in dairy cattle with titers to B. burgdorferi.540 An attempt to develop a more specific test in cattle using the 41-kD flagellin antigen has recently been reported.541
A number of diagnostic methods are available, including IFA, ELISA, indirect CF, and Western blot.535,538 Culture of the organism requires special media (BSK) and is difficult but may be possible from blood, urine, or CSF. Diagnosis of recent or active Borrelia infection has been based on high ELISA titers (>300 units kinetics-ELISA [KELA]), positive Western blot, or PCR.542 In an experimental infection study, I. scapularis ticks infected with B. burgdorferi were placed in healthy ponies for 7 days. These ponies developed detectable antibody at 5 to 6 weeks.542 KELA units were elevated at 3 to 4 months postexposure and remained elevated for several months until euthanasia. Western blot became positive at 10 to 12 weeks postexposure.542 Throughout the study the organism was isolated from the skin where infected ticks were attached. Histopathologic examination revealed lymphohistiocytic nodules in the dermis, lymph node enlargement, and perivascular and perineural lymphocytic infiltrates in the skin, fascia, and perisynovial membranes. PCR was useful for the detection of organisms in the skin, lymph nodes, skeletal muscle, fascia, and synovial membranes. Less often, the organisms were detected in heart, pericardium, kidney, bladder, and meninges.542 More recently, detection of serum antibodies to B. burgdorferi in horses was improved (84% detection) by using an ELISA based on whole-cell and recombinant antigens.543
Antibiotic susceptibility of B. burgdorferi has been reported but may lack appropriate standardization.544 B. burgdorferi is sensitive to tetracycline and moderately sensitive to penicillin. Amoxicillin, ceftriaxone, and imipenem are highly active against B. burgdorferi. Aminoglycosides, ciprofloxacin, and rifampin lack activity.545 Doxycycline twice daily in humans has been frequently used. Probenecid and ampicillin or amoxicillin also have been used.544 When CNS involvement is present, ceftriaxone or IV penicillin G has been used. The appropriate duration of therapy is unknown but is related to the stage of infection.
Three different antimicrobials—ceftiofur sodium (2.2 mg/kg/day IM), doxycycline (10 mg/kg/day PO), and tetracycline (5 mg/kg/day IV)—were used for a 28-day period in experimentally infected ponies.546 High KELA titers and B. burgdorferi isolation from skin biopsies confirmed infection. Antimicrobial therapy was initiated 3 months postexposure. Tetracycline was the most effective antimicrobial; it decreased KELA antibody titers (<110 units) during and months after treatment, and bacterial isolation became negative in tissues. However, tissues were still positive for the spirochete on PCR.546 The efficacy of decreasing titers of tetracycline in the clinical setting has not been highly successful.547 Proposed treatment for Borrelia infection includes tetracycline (6.6 mg/kg IV every 12 hours), doxycycline (10 mg/kg PO every 12 hours), or ceftiofur (2.2 mg/kg IM every 12 hours) for 3 to 4 weeks.542
A recombinant outer surface protein A (rOspA) subunit vaccine was shown to be effective in preventing infection in challenged horses with infected ticks.520,548 Specific recommendations for its use in the clinical setting are lacking.
Tularemia is an infectious disease of humans, wild animals, livestock, and pets caused by Francisella (Pasteurella) tularensis. The organism is a facultative, intracellular, non-spore-forming, gram-negative coccobacillus that survives frozen or in mud and water for long periods (>1 year),549 but it only survives for hours in carcasses. The natural hosts are rabbits and rodents, and transmission to livestock occurs chiefly through ticks, fleas, deerflies, and other insects.550 Sheep are the most frequently affected livestock species. Massive epidemics with a high mortality in range sheep have been reported.550 Humans are stricken with a plaguelike illness when bitten by infected ticks, fleas, or insects and from handling infected rabbits or other infected animal carcasses.551 Sheep shearers may become infected by bites of parasites from the sheep. Disease in horses has also been documented.552 Oral infection from contaminated water occurs, so fresh water should be provided.550
The disease causes an acute septicemia, with localization and granulomatous lesions in the organs (particularly the liver and spleen). Signs are very nonspecific, as expected with bacteremia, and include fever, anorexia, lethargy, and in some cases cough, rapid respiration, or diarrhea. Stiffness and edema of the limbs may be seen. The course of disease is usually 2 to 14 days.
Agglutination titers in recovered affected sheep range from 40 to 5000. Agglutination titers persist for very short periods (21 days) in horses,550 probably because they measure mainly IgM. Diagnosis is based on culture of the organism from blood or organs. Diagnosis can also be made by IFA testing or PCR.553
Necropsy usually reveals ticks on the carcass. Often, reddened or necrotic areas appear in and under the skin at the site of infected bites. Regional lymph nodes may be swollen and congested. Congestion and edema of the lungs are common. Differentials include other bacteremias such as Mannheimia (Pasteurella) haemolytica in sheep, Histophilus somni (Haemophilus somnus), in cattle, Mycoplasma mycoides subspecies mycoides in goats, and anthrax in all livestock. Treatment early in the course of infection is effective. Aminoglycosides, tetracyclines, or cephalosporins all are probably beneficial initially, until results of antimicrobial susceptibility testing are available. Insecticide removal of ticks from affected animals and herdmates is important. No vaccine is currently available, so insect and tick control in endemic areas remains the major prevention. Because oral infection from contaminated water has also been documented, fresh water should be provided.
Corynebacterium pseudotuberculosis infections occur worldwide and cause external and internal caseous lymphadenitis in sheep and goats; cutaneous excoriated granulomas and mastitic, visceral, or mixed infection in cattle; and ulcerative lymphangitis and external and internal abscesses in horses.554-557 Subacute to chronic lymphadenitis and pneumonia have been reported in humans handling infected sheep.558,559 Several zebras in the United States developed severe or multiple internal abscesses and died weeks after being exposed to horses in California.560 There have been reports of the disease in camels, alpacas, and buffalo.561-563
C. pseudotuberculosis infection is caused by a 2-μm, gram—positive, intracellular, nonmotile, pleomorphic rod-shaped, facultative anaerobe.554,564C. pseudotuberculosis grows well at 37° C on blood agar in 24 to 48 hours, and it forms small, pinpoint-diameter, whitish, opaque colonies that are surrounded by a weak zone of hemolysis. Because of the high content of lipids in the bacterial cell wall, particularly corynomycolic acid, the colonies spatter in a flame can be pushed across the agar surface.554 The high content of lipids may facilitate survival of the organism in macrophages.565 Two species-specific biotypes of C. pseudotuberculosis have been identified based on differences in nitrate reduction559 and DNA fingerprinting techniques.566-568 Strains isolated from small ruminants are nitrate negative, strains from horses are nitrate positive (except for two horses that were nitrate negative), and both strains have been isolated from cattle.555,559,567,569 From DNA studies the terms “biovar equi” for nitrate-positive and “biovar ovis” for the nitrate-negative strains were proposed.566 Recent studies revealed that there is more heterogeneity of the isolates of C. pseudotuberculosis from small ruminants and from horses567,568,570 and concluded that nitrate reduction may not absolutely distinguish between the isolates as does ribotyping.567 On the basis of ribotyping, sheep and goats have specific isolates throughout the world, and horses and cattle have two distinct groups of isolates depending on geographic location, with one from the United States and the other from South Africa and Kenya.567 Natural cross-species transmission does not seem to occur.554
Corynebacterium pseudotuberculosis produces various exotoxins, including phospholipase D (PLD), sphingomyelinase, inhibitory factor of staphylococcal beta hemolysin, hemolysis factor, dermanecrotoxins, and mouse lethality toxins.571 PLD and sphingomyelinase are important in the pathogenesis of the disease because they hydrolyze lysophosphatidylcholine and sphingomyelin, respectively, thus degrading the endothelial cell wall and increasing vascular permeability.572 The synergistic activity of sphingomyelinase with the exotoxin of Rhodococcus equi in lysing RBCs in agar forms the basis for the synergistic hemolysis inhibition (SHI) test.573
Most recently, molecular characterization of C. pseudotuberculosis isolates from four different states (California, Colorado, Kentucky, and Utah) was determined by random-amplified polymorphic DNA (RAPD) PCR.574 The identity of C. pseudotuberculosis in these isolates was confirmed by the presence of the gene encoding the PLD toxin by PCR. Ten distinct genotypes (I to X) were identified. Types IV to VIII and X were isolated only from horses, whereas types III and IX were isolated from horses and cattle. This study also found differences in genotypes among states as follows: California (III, IV, V, VI, IX, X), Colorado (III, VI, VII, IX, X), Kentucky (III, IV, V, VI, VIII), and Utah (III). In horses, types III, VI, and X were isolated from internal abscesses from California and Kentucky, and types III to VI and VIII to X were isolated from external abscesses from one or more states.574
C. pseudotuberculosis causes caseous lymphadenitis (CLA) in sheep and goats worldwide. CLA is a major cause of poor production, premature culling, and mortality. The two forms of CLA are external and internal abscesses.575 The infection in small ruminants is primarily characterized by suppuration and necrosis of the large, superficial lymph nodes. External abscesses are found more often involving the mandibular, parotid, prefemoral, or prescapular lymph nodes. The exudate present in those abscesses is thick or inspissated and may appear white in sheep and greenish in goats.554 A breed association with the type of CLA cutaneous lesions was observed in an outbreak in a commercial ram stud in Scotland.576 The disease is commonly known as “cheesy gland” in Australia. Differential diagnosis should include abscesses caused by other organisms, trauma, seroma, hematoma, foreign body, injection reaction, and less frequently, tumors. Because C. pseudotuberculosis infection represents a major herd health problem, culturing of the abscess to determine the causative agent is important. Mastitis occasionally develops.556
Internal abscesses can be found in the lungs, kidneys, and mediastinal, bronchial, mesenteric, and lumbar lymph nodes.575 Chronic weight loss is the most common presenting complaint. Other clinical signs are related to the organ or tissues affected. Other diagnostic procedures may be necessary for the differentiation of internal abscesses as the cause of weight loss. Signs of spinal cord compression by vertebral abscesses have been seen in lambs born in unsanitary conditions.554 Knowledge of the local prevalence can help in the diagnosis of the infection when uncommon anatomic locations are affected. The prevalence in large breeding operations in endemic areas is estimated at 5% to 10%.
The infection in cattle occurs as a herd problem with a sporadic incidence. The most common clinical form affecting cattle is cutaneous excoriated granuloma; other forms include mastitis and visceral and mixed infections.556 In the most common form the lesions do not occur as abscesses; instead, they appear as ulcerative, exuding granulomatous lesions as large as 20 cm in diameter with necrotic areas that are easily removed surgically, leaving granulation tissue underneath.554,557 The location of the lesions is usually in the lateral exposed areas of the body: face, neck, thorax, and flanks. The exudate varies from bloody to thick and greenish in color. The lesions heal spontaneously in 2 to 4 weeks and do not appear to cause significant illness or decrease milk production in cattle, as reported in California.554 However, monthly milk production was decreased by 6% in Israeli cattle.557 Prevalence of the infection has been reported as high as 10% in California dairies.554 Morbidity was reported as high as 35% in Israeli herds.557 Management problems, such as broken posts or exposed wires, traumatize the skin of cattle, allowing penetration of the organism. Young cattle appeared to be less susceptible to the disease than older cattle in Israel.557 The differential diagnoses include trauma, foreign body, and other masses (e.g., tumors). Cutaneous lesions and mastitis were seen in 6% and cutaneous lesions with concurrent visceral involvement in 1.6% of the Israeli cases.557 The rest of the cows (92%) only had the cutaneous form.557 The most affected organ in the visceral form was the lung.557 The infection has been reported in bison from Egypt, resulting in severe emaciation and edema in the ventral areas and flanks.561
Caseous lymphadenitis has been reported in alpacas in South America.577 A recent study documented five young alpacas (22 days to 14 months old) in North America with CLA or subcutaneous abscesses that developed during late summer and early fall.563 The alpacas did not appear clinically ill but developed swellings that progressed to abscesses. The abscesses (1 to 3 per alpaca) were located in the submandibular and cervical areas and in one case adjacent to the eye. Abscess excision appeared to be the most effective treatment in those cases. Differential diagnoses include abscesses caused by Streptococcus species, Corynebacterium species, and A. pyogenes.578 Severe lymphadenitis was reported in camels in Asia.562 A study on experimental infection of adult alpacas resulted in abscesses at the inoculation site and renal lymph nodes.579
Three forms have been described in horses: ulcerative lymphangitis, external abscesses, and internal abscesses. In a study of C. pseudotuberculosis infection in horses from California, ulcerative lymphangitis was diagnosed in 1%, external abscesses in 91%, and internal abscesses in 8% of the cases.580 There appears to be no breed or gender predilection for development of the infection. Ulcerative lymphangitis appears as a severe cellulitis, in which the lymphatics are affected in one or more limbs, with multiple draining ulcerative lesions. Horses often develop a non-weight-bearing lameness, fever, lethargy, and anorexia. This form of the disease has a worldwide distribution and often becomes chronic, resulting in limb edema, lameness, weakness, and weight loss.554 The differential diagnosis should include blunt trauma, fracture, foreign body, puncture wounds, nonseptic cellulitis, staphylococcal cellulitis, and other septic cellulitis.
The median age for horses with external abscesses is 5 years (range, 3 months to 28 years).580 Young horses appear to be predisposed to infection because 52% of the cases in a large retrospective study were 5 years or younger.580 Only a low number of cases involved foals under 6 months of age, suggesting that foals born to mares in endemic areas may be protected for several months by colostral antibodies.580 The external abscesses located primarily in the pectoral and ventral abdominal regions are common in geographically restricted areas of the western United States (Texas, New Mexico, Nevada, California) and Brazil.554,555,580,581 However, the infection has been diagnosed in other states, such as Arizona, Colorado, Kentucky, Utah, and Wyoming.574,582 This form of infection is commonly known as “pigeon fever” because of the large size of the pectoral abscesses with the appearance of a pigeon’s breast. “Dryland distemper” is another name given in relation to its geographic distribution primarily in the arid areas. Other common anatomic locations are the prepuce, mammary gland, axilla, inguinal region, limbs, and head. Abscesses involving the head include the ears, eyelids, forehead, and maxillary and mandibular regions.580 Severe facial suppurative cellulitis and panniculitis with skin sloughing has also been reported.583 Other, less common areas are the thorax, neck, parotid gland, guttural pouches, larynx, flanks, umbilicus, tail, and rectum. Septic joints and osteomyelitis have been reported.580
A large area of edema develops in the area of abscess formation. As the abscess matures, the area becomes hard and painful, and some become very large, particularly in the pectoral area. The abscesses typically have a thick capsule, measuring up to 10 cm, and can cause severe lameness if located in the axillary or inguinal region.555,580 Maturation can be slow and drainage difficult to establish if the abscess lies deep to muscle. Once drainage is established by spontaneous rupture or lancing, the majority of the cases resolve within 10 to 14 days without complications. The abscesses may contain 5 to 400 mL of thick, tan, purulent exudate.555 The majority of the horses present with a single abscess rather than multiple abscesses.580 About 25% of animals develop fever up to 40° C (104° F). Other signs are nonhealing wounds, lameness, ventral dermatitis, and less often, depression, anorexia, mastitis, and other signs, depending on the abscess location.580
The vast majority of horses (91.4%) had complete recovery, with no recurrence of infection in subsequent years, implying a long-lasting immunity. However, 8.6% of the infections persisted for more than 1 year or had recurrence as external or internal abscesses.580 In sheep and goats, humoral and cellular immune responses develop after infection, and macrophages acquire the ability to kill the organism.558 The case fatality for horses with external abscesses is very low (0.8%).580 The differential diagnosis for external abscess, particularly pectoral, should include trauma, seroma, hematoma, foreign body, and abscess caused by a different organism.
In a large retrospective study of C. pseudotuberculosis infection in the horse, 8% of 538 horses developed internal abscesses.580 In two different studies, almost half to 63% of horses that had internal abscesses also had concurrent or a history of external abscesses.580,584 In a study of 30 horses with internal abscesses, a female predilection (70%) was apparent.584 The mean age is 8 years (range, 10 months to 23 years).580,584 The most common clinical signs are anorexia, lethargy, fever (up to 41.1° C), tachycardia, and weight loss. Other signs are colic, pale mucous membranes, ventral/limb edema, ventral dermatitis, ataxia, hematuria, nasal discharge, and abortion.580 The most frequently affected anatomic location is the liver, followed by mesentery, mediastinum, lungs, kidneys, diaphragm, spleen, pericardium, blood, and uterus.575,584,585 A postmortem examination on an aborted fetus from a mare with pneumonia revealed C. pseudotuberculosis abscesses in the liver, lungs, spleen, diaphragm, kidney, and bladder.584 Bacteremia may also occur. Both single-organ and multiple-organ involvement have been documented.584 The case fatality for horses with internal abscesses ranges from 30% to 40%.580,584 The differential diagnosis should include other types of abscesses, such as those caused by Streptococcus, Actinomyces, Staphylococcus, Rhodococcus equi in foals, Coccidioides immitis, and anaerobes, as well as neoplasia and other causes of weight loss. The clinical signs and differential diagnosis will depend on the location of the abscess.
Human infection may result from the consumption of unpasteurized infected milk or milk products, continued close contact with infected animals, handling contaminated equipment, and exposure of wounds with exudates.558,586 Human infection has been reported from strains of small ruminants.558 Transmission from horses to humans has not been reported, but precautions when handling infected horses should be taken. Infection in humans occurs as a subacute to chronic lymphadenitis and pneumonia.558
Almost half the horses with external and/or internal abscesses had anemia of chronic disease in one study.580 Leukocytosis with neutrophilia and elevated fibrinogen are common features of developing bacterial infections, particularly in the case of internal abscesses.580 Leukocytosis with neutrophilia was seen in 36% and 76% of the horses with external and internal abscesses, respectively.580 Hyperproteinemia caused by increased globulins was observed in 38% and 59% of the horses with external and internal abscesses, respectively.580 Similarly, infected cattle and small ruminants had increases in WBC counts.557,576
Peritoneal fluid from 93% of the horses with abdominal abscesses was abnormal.580 The remaining horses with abdominal abscesses and normal peritoneal fluid had abscesses located retroperitoneally in the kidneys without involvement of other abdominal structures. C. pseudotuberculosis was isolated in 32% of the samples of peritoneal fluid.580 Failure to isolate the organism from peritoneal fluid does not rule out the disease. The organisms could be located retroperitoneally, or sequestered within a thick capsule, or suppressed by local factors or nucleated cells.587
The ELISA test for the detection of cell wall antigens is reportedly not very accurate in horses.554,571 ELISA appears to be more useful for detection of infection in sheep.588-591
Another useful diagnostic aid is the synergistic hemolysis inhibition (SHI) test, which measures IgG response to the exotoxin in the patient’s serum by detecting the highest dilution that will prevent hemolysis of R. equi exotoxin—sensitized bovine RBCs when mixed with C. pseudotuberculosis exotoxin of a known concentration.573,592 The IgG response to the exotoxin depends on the chronicity and severity of the infection and antibody availability.554 It has been reported that a serum antibody titer of 1:128 indicates exposure, whereas 1:512 or higher indicates the presence of infection.554 Studies in goats have demonstrated that most animals have serum antibody titers that correlate with bacterial culture results.593 The SHI test can be used in sheep and goats to monitor prevalence and exposure of incoming animals and to detect subclinical infections.554,592 Only 40% of horses with external abscesses, in which the infection was confirmed by culture, had serum antibody titers of 256 or higher. However, a low SHI titer does not rule out the disease. Possible reasons for lack of titers include (1) acute onset of infection and rapid maturation of the abscess before developing an immunoglobulin response, (2) presence of a thick capsule isolating the organisms and preventing a serologic response, and (3) consumption of antibody during active infection.554,580 Many horses that are seronegative at drainage of an external abscess seroconvert at a later time. In contrast, almost all horses with confirmed C. pseudotuberculosis internal abscesses have SHI titers of 512 or higher.575,584 The high titers in horses with internal abscesses probably reflect the chronicity of the disease and the resulting prolonged immune stimulation. Prolonged seropositivity has been observed in horses and goats.580,592,594 The SHI test appears to be a reliable ancillary aid for the diagnosis of internal abscesses in horses.580,584 Presence of a SHI titer greater than 512 can occasionally be found in horses with external abscesses and exposed herdmates.
Other serodiagnostic tests used in sheep and goats are tube agglutination, complement fixation, and gel immuno-diffusion.571,595
A presumptive diagnosis can be made based on the history, local prevalence, time of the year, clinical signs, and characteristics of the exudate.554 For the diagnosis of internal abscesses, the previous features must be considered, in addition to the presence of an inflammatory leukogram with elevated fibrinogen, serum chemistry abnormalities, abnormal peritoneal fluid or transtracheal wash, positive blood culture, SHI titer of 512 or higher, and ultrasonographic or radiographic evidence of masses.580,584 The definitive diagnosis is established through the isolation of the organism from abscesses or draining wounds. The organism is readily isolated and grows well in blood agar in 24 to 48 hours, even when contaminant bacteria are present.580
C. pseudotuberculosis is a soil-borne organism that survives for months to years, even in direct sunlight at environmental temperatures.558,596,597 The incidence of infection in horses varies considerably from year to year. External and internal abscesses in horses can present at any time of the year but are seen more often during the fall and early-winter months, with the highest incidence in September, October, and November.580 However, internal infections are more frequently seen in November through January, 1 to 2 months after the peak number of cases with external abscesses.584 The largest numbers of equine cases have been observed during the dry months of the year, after heavy rainfall, which may result in optimal breeding conditions for insects.555,580,581 The seasonal incidence in horses has been associated with the presence of biting insects such as Haematobia irritans (horn fly), which causes ventral midline dermatitis from its feeding pattern. Insect vectors involved in the transmission of disease in horses, such as H. irritans, Stomoxys calcitrans, and Musca domestica, were identified by detecting the PLD exotoxin gene of C. pseudotuberculosis in an endemic area.598 The results of one study suggest that the disease could be transmitted through horse-to-horse contact, vectors, or contaminated soil.599 Temporal and spatial analysis indicated an incubation period of 3 to 4 weeks in horses. There is no breed or gender predilection580; however, a retrospective study indicated a predilection for internal abscesses in females.584 A case-control study in an endemic area revealed that young adult horses less than 5 years of age had increased risk of infection.600 Horses housed outside or with access to an outside paddock, or in contact with other horses on pasture, appeared to be at higher risk than stabled horses.600
The disease in cattle from Israel occurred during the spring and summer dry season, from March to October, when the housefly population is high.557 C. pseudotuberculosis was isolated from houseflies collected over an Israeli cow lesion.601 The infection in cattle may spread by direct contact or indirectly by houseflies or fomites.557 The disease in sheep and goats is not seasonal, and transmission is through contact of exudate from a draining abscess from animal to animal or through contaminated equipment.555 Lambs born in contaminated surroundings can be infected through the umbilicus, mouth, or inhalation.554 Sheep that acquire the organism orally or from shearing wounds tend to have parotid, submandibular, prefemoral, or thoracic abscesses.554 Goats can be infected when wounds are exposed to contaminated milking equipment. The incubation period is long and variable. In experimental infections in small ruminants, the incubation period was 2 weeks to several months.
The pathogenesis of the disease in horses is not clear, but it has been speculated that the organism enters the equine host through skin or mucous membrane abrasions or wounds, as confirmed in sheep.602,603 Experimentally induced infections in small ruminants revealed that once C. pseudotuberculosis gains access through wounds or abrasions, the organisms spread to the subcutaneous or submucosal lymphatics, where they are phagocytosed by macrophages that migrate to the invasion site to engulf the organism.604 The organism survives intracellularly because of its high content of lipids (e.g., corynomycolic acid), which resist the action of lysosomal enzymes.564,604 C. pseudotuberculosis replicates in the phagolysosome; if large numbers of organisms are engulfed, phagocytic cells die. Experimental inoculation of the organism in sheep revealed a massive infiltration with polymorphonuclear neutrophil leukocytes (PMNs),605 which are believed to carry the bacteria to regional lymph nodes.554 A PLD toxin of approximately 31.5 kD, produced by all C. pseudotuberculosis isolates, increases the vascular permeability, causing spread of the organism regionally and systemically.558,593,606 Development of abscesses at secondary locations in horses can occur in up to 25% of the cases.580 PLD toxin can cause necrosis and thrombosis of the lymphatics and may enhance survival and multiplication of the organism through complement depletion and inhibitory effects on phagocytic cells.558 The corynomycolic acid and PLD toxin contribute to the inflammation, edema, and pain during abscess development.607 The profound reaction of these compounds is probably responsible for the thick abscess capsule that develops as phagocytes accumulate in the abscess core. The abscess eventually matures and drains, but if removal of infected material is incomplete, recurrence may be expected, particularly in small ruminants.554 The development of internal abscesses in horses is unclear but has been postulated to result from hematogenous or lymphatic spread of bacteria from more superficial sites.554,580,584
Important considerations when treating external abscesses are (1) to allow for the abscess to mature; (2) to establish drainage, then collect and dispose of the infective exudate; and (3) to lavage the wound with an antiseptic solution. In a retrospective study in horses, most external abscesses were incised to establish drainage, and some animals received antimicrobials after drainage in an effort to decrease cellulitis. Many horses received no treatment, and the abscesses broke and drained on its own. Other horses were treated only with antimicrobials. The outcome was successful for 99% of the horses with external abscesses.580 Horses with abscesses in the axillary region or deep within muscles have considerable pain, necessitating incision and drainage. Ultrasound is useful for the detection of the location of deep abscesses.584
In one report the median resolution time for horses with external abscesses that did not receive antimicrobial therapy before abscess drainage was 18 days, versus 30 days for the horses that received antimicrobials.580 These data suggest that systemic antimicrobial therapy before abscess drainage in horses with external abscesses may prolong the course of the disease.580 However, when abscesses recur, drainage and concurrent antimicrobials may improve the chance of resolution. Conversely, long-term (minimum 4 to 6 weeks) antimicrobial therapy is necessary for the treatment of internal abscesses and ulcerative lymphangitis. The median resolution time for horses with internal abscesses treated with antimicrobials was 36 to 42 days, with a maximum duration of 97 days.580,584 The case fatality for horses with internal abscesses treated with antimicrobials was 30% to 40%, but 100% if not treated.580,584 In vitro, C. pseudotuberculosis is susceptible to almost all common antimicrobials, including penicillin, trimethoprim-sulfonamide, tetracycline, cephalosporin, chloramphenicol, erythromycin, and rifampin.608,609 Most isolates are resistant to nitrofurans, cycloheximide, and nalidixic acid.609 Bacitracin has marked activity against the bacterium.610 In selecting an antimicrobial, the clinician must consider (1) the intracellular location of the organism, (2) presence of a thick abscess capsule and presence of pus, (3) lengthy course of treatment that may be required, (4) risk of complications (e.g., diarrhea), and (5) cost. Antimicrobial-associated diarrhea was seen in 6% of horses receiving antimicrobials (rifampin, trimethoprim-sulfas, penicillin) for C. pseudotuberculosis infection in a retrospective study.580 Additional therapies include marsupialization of internal abscesses if location allows. NSAIDs such as phenylbutazone or flunixin meglumine may be used to control the pain and fever while waiting for external abscesses maturation.
The prognosis for external abscesses is good. Most resolve in 3 weeks from the day of drainage.554 The prognosis for horses with internal abscesses and ulcerative lymphangitis is guarded. The prognosis improves if infection is detected early and appropriate therapy administered.
In a bovine study the skin lesions on individual cows healed on average in 23 days after local or parenteral treatment; 17% of severely affected cattle were culled.557 Simple drainage in small ruminants does not usually result in resolution of the disease and creates potential sources of infection. Dilute iodine solutions can be used for abscess lavage. Complete excision of the abscess under general anesthesia may be necessary to keep the abscess from draining and to prevent the spread of infection to other animals.554 The treatment of choice in small ruminants is surgical removal of the affected lymph nodes.
Even though C. pseudotuberculosis infection is one of the most frequently diagnosed infectious diseases in California, little is known about its prevention and control. General recommendations to prevent the spread of the infection are isolation of infected animals, fly control, good sanitation, careful shearing practices, disinfection of contaminated fomites, and careful disposal of bedding. In small ruminant farms the morbidity can reach 100%, with depopulation being the most economic option. Because of the ability of the organism to survive in soil and fomites, the potential for environmental contamination is very high.596,600
Immunization trials using whole cells, cell walls, toxoids, and bacterin-toxoid combinations have been performed in the prevention of CLA in small ruminants.611-615 These vaccines have been shown to provide a high degree of protection, decreasing the number of infected sheep and the number of abscesses per sheep. Corynebacterium pseudotuberculosis toxoids are commercially available for sheep and goats.* The use of autogenous bacterin-toxoid in horses resulted in fewer abscesses and less postchallenge pain in experimentally inoculated horses, but did not reduce the incidence of infection in one farm because of a low prevalence of disease.616 Use of an experimental bacterin-toxoid demonstrated increased SHI titers after two injections; however, the protection remains to be established.617
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* Author(s) of discussions in this section indicated by initials (as listed) after disorder.
* Arvac, Fort Dodge Animal Health, Livestock Division, Overland Park, Kan.
* VMRD Inc., Pullman, Wash.
* AnaVac, PHL Associates, Davis, Calif.
* Experimental Anaplasmosis Vaccine, University Products LLC, Baton Rouge, La.
* Berenil (Intervet Inc., St. Millsboro, Del) and Ganaseg (Squibb and Sons de Mexico, Mexico City).
† Lomidine, May and Baker Ltd., Dagenham, England.
‡ Imizol, Pitman-Moore, Middlesex, England.
§ Diampron, May and Baker Ltd., Dagenham, England.
* Butalex, Coopers Animal Health Limited, Hertfordshire, United Kingdom.
* Merck Sharp & Dohme, Rahway, NJ.
* HerdChek Bovine Leukemia Virus Antibody Test Kits (IDEXX Laboratories, Westbrook, Maine); Bovine Leukemia Virus Antibody Test Kit, ELISA (VMRD, Pullman, Wash); SVANOVIR BLV gp51-Ab ELISA (Svanova Biotech AB, Uppsala, Sweden).
* Anthrax spore vaccine, Colorado Serum Co., Denver, Colo.
* Caseous D-T (Colorado Serum Co., Denver, Colo.); Glanvac (Australia).