Diseases of Swine (8th edition)/Chapter 31
Swine erysipelas (SE) or its equivalent in other languages _Schweinerotlauf, vlekziekte, rouget du porc, mal rossino, entrace eresipelatoso, rozyca, and erisipela del cerdo_is a disease caused by the bacterium Erysipelothrix rhusiopathiae (Sneath et al. 1986) and manifested by acute or subacute septicemia and chronic proliferative lesions. The disease is worldwide in distribution and is of economic importance throughout Europe, Asia, and the Australian and American continents.
The identification of SE as a disease entity began in 1878 when Koch isolated from an experimental mouse an organism that he called "the bacillus of mouse septicemia. " In 1882-83 Pasteur and Thuillier briefly described the organism isolated from pigs with rouget. In 1886 Löffler published the first accurate description of the causative agent of Schweinerotlauf and described the infection in swine.
In the United States the recorded history of SE began when Smith (1885) isolated the causative organism from a pig. The disease was not considered important, however, until serious outbreaks were reported in South Dakota in 1928; by 1959 acute SE had been reported in 44 states. Since that time the prevalence of SE apparently has decreased overall (Wood 1984). However, the disease is still considered to be of economic importance, especially in the chronic form, and outbreaks of acute SE continue to occur sporadically in endemic areas.
E. rhusiopathiae occurs in most parts of the world, and SE occurs in most areas where domestic swine are produced. The organism also causes polyarthritis of sheep and lambs and serious death losses in turkeys. It has been isolated from body organs of many species of wild and domestic mammals and birds as well as reptiles, amphibians, and the surface slime of fish.
In humans E. rhusiopathiae causes erysipeloid, a local skin lesion that occurs chiefly as an occupational disease of persons engaged in handling and processing meat, poultry, and fish as well as of rendering-plant workers, veterinarians, game handlers, leather workers, laboratory workers, and the like. The organism occasionally is isolated from cases of endocarditis in humans and rarely causes acute septicemic disease.
ETIOLOGY
[edit]E. rhusiopathiae, the causative agent of SE, is a gram-positive bacillus with a marked tendency to form elongated filaments.
Physicochemical Characteristics
[edit]MORPHOLOGY AND STAINING. The morphology of E. rhusiopathiae is variable. In smears or cultures made directly from tissues in cases of acute infection, the organism appears as slender, straight or slightly curved rods, 0.2-0.4 by 0.8-2.5 µm, occurring singly or in short chains (Fig. 31.1). An occasional coccoid or clubbed form may be seen. Palisades and angular formations ("snapping division") are common. The organism is nonmotile, non-spore-forming, and non-acid-fast. It stains readily with ordinary dyes and is gram-positive but is easily decolorized. After several subcultures on an artificial medium, filamentous forms of the organism begin to appear. These forms may predominate in old cultures or in chronic lesions. Filamentous forms are somewhat thickened, are greatly elongated (4-60 µm), and may form a mass resembling mycelia, especially in a liquid medium (Fig. 31.1). The filamentous forms sometimes have a beaded appearance when Gram's stain is used.
GROWTH CHARACTERISTICS. Growth of E. rhusiopathiae at 37°C in a nutrient broth appears at 24 hours as a faint turbidity with no odor or pellicle. Shaking typically reveals a momentary appearance of rolling clouds. Slight sedimentation will be seen after 36-48 hours of incubation. Growth is much heavier in broth enriched with serum. In gelatin stabs incubated at 22ûC for 4-8 days, growth of the organism radiates out from the stab in all directions, resembling a test-tube brush.
Colonies of E. rhusiopathiae on agar media at 48 hours are tiny (less than 1 mm), are transparent, and vary from smooth to rough, depending on cellular morphology (Fig. 31.1). Colonies of most strains have entire edges, but some strains form colonies that are slightly larger and have somewhat undulate edges. Granulelike structures usually appear under a colony just below the surface of the agar. Dissociation from smooth to rough form may occur during the development of a colony, producing a sector (Fig. 31.1); the morphology of cells from these intermediate forms will include a variety of shapes from short, curved rods to short filaments.
Most strains of E. rhusiopathiae produce a narrow zone of partial hemolysis on blood agar, usually with a greenish color. Rough colonies do not induce hemolysis.
BIOCHEMICAL PROPERTIES. E. rhusiopathiae is relatively inactive in commonly used tests of biochemical activity (Cottral 1978). The organism produces acid but no gas from certain fermentable carbon compounds and produces hydrogen sulfide in triple-sugar iron agar (Vickers and Bierer 1958; White and Shuman 1961).
ANTIGENIC STRUCTURE. Most, if not all, strains of E. rhusiopathiae have one or more common heat-labile antigens, which are proteins or protein-saccharide-lipid complexes. The organism does not possess flagellar antigens, since no flagella are present.
Heat-stable antigens consisting of peptidoglycan fragments from the cell wall form the basis for identification of various serovars (formerly referred to as serotypes) within the species. The serovars are identified by precipitin reactions with specific hyperimmune rabbit sera, usually in a gel double-diffusion system. Most isolates of the organism (75–80%) from swine fall into two major serovars designated 1 and 2 (Wood and Harrington 1978; Takahashi et al. 1996). About 20% of isolates make up a group of less-common serovars. Under a numerical system introduced by Kucsera (1973), a total of 26 serovars have been described so far (Kucsera 1973; Wood et al. 1978; Nørrung 1979; Xu et al. 1984, 1986; Nørrung et al. 1987; Nørrung and Molin 1991). Strains that do not possess the specific antigen are referred to as serovar N.
Immunizing antigen is discussed in the section on prevention.
Biological Characteristics
[edit]GROWTH REQUIREMENTS. E. rhusiopathiae is facultatively anaerobic; some strains grow better in an atmosphere of reduced oxygen containing 5–10% carbon dioxide. The organism will grow at temperatures of 5–42˚C. Optimum growth occurs at 30–37˚C and at a pH range of 7.4–7.8. Growth is enhanced by serum, glucose, protein hydrolysates, or surfactants such as Tween-80. The organism is fastidious; that is, a complex medium is required, but specific nutrient requirements are not known.
RESISTANCE. E. rhusiopathiae is relatively resistant to adverse conditions for a non-spore-forming organism (see also the section on epidemiology). The organism is somewhat resistant to drying and can remain viable for several months in animal tissues under a variety of conditions. It can persist in frozen or chilled meat, decaying carcasses, dried blood, or fish meal. It is remarkably resistant to salting, pickling, and smoking and can survive several months in cured and smoked hams. The organism can survive in swine feces or fish slime for 1–6 months if temperatures remain below 12ûC. It is sensitive to penicillin and usually to the tetracyclines; it is quite resistant to polymyxin B, neomycin, and kanamycin and is relatively resistant to streptomycin and the sulfonamides (see the section on treatment). It is killed readily by common disinfectants, heat (15 minutes at 60ûC), and gamma irradiation.
Other Species within the Genus
[edit]Another species within the genus Erysipelothrix has been proposed (Takahashi et al. 1987a). This species, designated E. tonsillarum, is distinguished from E. rhusiopathiae by DNA homology values. Phenotypic characteristics of the two species are indistinguishable by the usual diagnostic bacteriologic methods. E. tonsillarum has been isolated from a variety of sources, including the tonsils of healthy swine. Reported isolates of E. tonsillarum have little or no virulence for swine; therefore, the species is not considered significant in the etiology of SE.
Classification of Erysipelothrix has challenged taxonomists throughout the recorded history of this ubiquitous genus. It is likely that the use of current techniques in bacterial genetic analysis will continue to generate proposals of additional species among isolates from various animal hosts and other sources.
EPIDEMIOLOGY
[edit]Sources of Infection
[edit]The most important reservoir of E. rhusiopathiae is probably the domestic pig. It is estimated that 30-50% of apparently healthy or convalescent swine harbor the organism in their tonsils and other lymphoid tissues. These carriers can discharge the organism in their feces or oronasal secretions, creating an important source of infection. Swine affected with acute erysipelas shed E. rhusiopathiae profusely in feces, urine, saliva, and nasal secretions.
Although secondary to swine in importance as sources of infection, the large variety of wild mammals and birds known to harbor E. rhusiopathiae provides an extensive reservoir (Wood and Shuman 1981; Shuman 1971). Various species of domestic animals from which the organism has been isolated provide an additional potential reservoir on swine-producing farms; however, with the possible exception of turkeys and sheep, their importance is doubtful.
The belief that E. rhusiopathiae can lead a saprophytic existence in the soil, living on dead and decaying organic material, has persisted for many years. However, available research data have consistently indicated that the organism, like most other non-spore-forming pathogenic bacteria, finds an unfavorable environment in the soil and dies out in a relatively short time, most likely because of the action of protozoa. E. rhusiopathiae can be found in the soil of swine pens and in feces of apparently healthy swine inhabiting the pens. However, Wood (1973) found no evidence of growth or maintenance of the organism in test soils under various conditions of temperature, pH, moisture content, and organic matter content or in samples of swine-pen soils from which E. rhusiopathiae had been isolated previously. Rapid death curves were consistently demonstrated. This failure to establish a stable population of the organism in soil is similar to results reported by other investigators since 1955. Present information indicates that soil that is more or less continually inoculated by infected animals provides only a temporary medium for transmission of E. rhusiopathiae.
Factors of Susceptibility
[edit]AGE AND GENETICS. Swine less than 3 months or more than 3 years of age are generally least predisposed to SE. The relationship of age to susceptibility may be explained by naturally acquired passive immunity in the young and active immunity following subclinical infection in older animals. Suckling pigs of immune sows are immune to infection for several weeks after birth. The degree and duration of passive immunity are related to the immune status of the sow.
There is no experimental evidence that susceptibility to SE is related to genetics of the animal. Anecdotal accounts of apparent resistance (or susceptibility) of certain breeds or families of swine can most likely be explained by the presence of varying degrees of naturally acquired passive or active immunity.
NATURAL ACTIVE IMMUNITY. For many decades after SE research was begun in the 1880s, a major problem was the inability to consistently induce acute SE in swine by experimental infection with E. rhusiopathiae. The problem eventually was eliminated by use of specific- pathogen-free (SPF) pigs delivered aseptically by surgery, deprived of colostrum, and raised in isolation. This development revealed the importance of naturally acquired immunity as a factor in susceptibility to erysipelas.
Naturally acquired active immunity is induced by previous infection with E. rhusiopathiae. It is well known that immunity to acute SE follows clinical disease. Less well recognized is the immunity that can be induced by organisms of low virulence, which are capable of causing mild unnoticed subacute disease or subclinical infection.
PREDISPOSING FACTORS. SE can occur with other swine diseases, but the significance of preexisting infectious disease as a predisposing factor is uncertain. Parasitic infestations have been reported to increase the severity of clinical SE. In addition, Cysewski et al. (1978) showed that the susceptibility of swine to acute SE can be enhanced by subclinical toxicity from aflatoxin in the feed. This treatment also interfered with the induction of immunity to SE by vaccination.
Environmental and stress factors such as nutrition, ambient temperature, and fatigue, particularly sudden changes in these conditions, have long been linked to the appearance of SE. For example, acute disease has occurred following sudden changes in diet such as accidental access to tankage or to a field of corn, feeding new corn, or placing pigs on new pasture. Experimentally, sudden exposure to either excessive heat or cold or exposure to a sustained high temperature (30ûC) has been reported to enhance susceptibility. Under natural conditions, sudden changes in weather involving extreme temperature changes may have the same effect. Variations in prevalence of SE believed to be related to yearly cycles or to season of the year have been reported, but consistent patterns of prevalence corresponding to these factors have not emerged. Except for a possible relationship to temperature changes, the apparent variations remain unexplained.
When attempting to evaluate factors that may be related to the occurrence of SE on the farm, it should be kept in mind that a variety of stimuli in the animal's total environment can affect the level of susceptibility existing at any given time. Sudden outbreaks of acute SE may be the result of a combination of susceptibility of the animals and virulence of the causative organism, both of which are variable.
PATHOGENESIS
[edit]Investigations using germfree pigs have demonstrated that E. rhusiopathiae is the sole causative agent of SE and does not require the presence of any other infectious agent for its disease-producing ability.
Mode of Entry
[edit]E. rhusiopathiae can gain entry to the body by a variety of routes. Infection through ingestion of contaminated feed and water is considered a common mode. There is no information on specific areas within the digestive system where entry may occur, nor is it known whether the organism can invade normal mucosa. Early investigators postulated it gained entrance through lesions produced by intestinal parasites; however, their presence is unnecessary. The organism can readily gain access to the body through the palatine tonsils or other lymphoid tissue in the wall of the digestive tract, but entrance is probably not limited to these areas.
Natural infection no doubt can result from infected skin wounds, which may be concealed or too small to be readily noticeable. Experimental infection can be accomplished easily by inoculation of scarified skin (Shuman 1951); therefore, it is likely that infection in this manner from a contaminated environment is not uncommon.
Acute SE
[edit]Acute systemic SE begins with bacteremia, which quickly results in clinical signs of generalized infection (septicemia). A nonsystemic infection consisting only of a local skin lesion may occur upon cutaneous exposure to a strain of low virulence or when the pig is partly immune. In such cases the organism is eliminated without inducing septicemia and the lesion disappears. In the more typical systemic infection caused by virulent organisms, bacteremia usually develops within 24 hours after exposure. The organism usually can no longer be cultured from blood or most body organs after a few days but may persist, often for months, in the joints and in lymphoid tissue such as tonsils, Peyer's patches, and spleen.
According to Schulz et al. (1975b, 1977), pathogenesis of the early septicemic phase consists of changes involving capillaries and venules of most body organs, including synovial tissues. As early as 36 hours after subcutaneous exposure of swine to virulent E. rhusiopathiae, they observed swelling of endothelium, with adherence of monocytes to vascular walls and evidence of widespread hyaline thrombosis. This process was referred to as a shocklike generalized coagulopathy leading within 4 days to fibrinous thrombosis, diapedesis, invasion of vascular endothelium by bacteria, and deposition of fibrin in perivascular tissues. They stated that this process leads eventually to connective-tissue activation in predisposed sites such as joints, heart valves, and blood vessels.
In severe acute SE, hemolysis is commonly observed. Ischemic necrosis of perivascular tissues may occur, caused by interference with microcirculation. Drommer et al. (1970) observed a high incidence of encephalomalacia in acute experimental SE and theorized that certain strains of the organism are endotheliotropic and damage the endothelial cell barrier in the central nervous system (CNS).
Mild, delayed hypersensitivity responses to E. rhusiopathiae can be elicited and transferred by lymphoid cells. It is doubtful, however, that delayed hypersensitivity has a significant part in the pathogenesis of acute SE.
Chronic SE
[edit]Information on the pathogenesis of chronic SE is derived primarily from studies on development of the arthritic lesion, which has stimulated interest because of its apparent similarity to the lesion of rheumatoid arthritis of humans.
According to observations by Schulz et al. (1975a, 1977), the joint lesion in chronic SE begins with acute synovitis that may occur as early as 4-10 days after exposure to E. rhusiopathiae. Within 3 months, fibrinous exudation, proliferation, and pannus formation occur, developing further into severe fibrosis and destruction of articular cartilage in 5-8 months. During this time, the organism can be found sequestered within chondrocytes in addition to its presence in synovial tissue and fluid (Franz et al. 1995). The earliest changes in the synovial tissue are described as consisting of coagulopathy and fibrinous exudate into perivascular tissues. Fibrin deposited during the vascular phase, not bacterial colonization, is believed to act as mediator of the subsequent connective-tissue proliferation.
Affected joints appear to become culture-negative after 3-6 months, yet the arthritic lesions usually undergo a progressive development that can continue at least 2 years. The development of such lesions in the apparent absence of the infectious agent has stimulated investigation of the role of immunopathologic processes in chronic arthritis. Hypersensitivity may be a significant factor in the chronic proliferative and destructive changes but probably not in initiation of the lesion.
There is evidence that the bacteria do not entirely disappear from chronically affected joints, and the longterm progressive lesion may occur in response to the continued presence of either whole bacterial cells or their antigens. Schulz et al. (1977) reported that living E. rhusiopathiae was occasionally isolated from such joints for up to 2 years. Furthermore, they stated that E. rhusiopathiae antigen could be detected by immunofluorescence and whole or fragmented bacteria could be seen with the electron microscope in culturally negative joints. Denecke and Trautwein (1986) reported detection of E. rhusiopathiae in arthritic joints microbiologically and immunohistologically for up to 3 years. Specific antibodies to the organism have been detected in synovial fluid of chronically arthritic joints and apparently are produced locally by plasma cells in the synovial tissue, which can assume a lymphoid function. It is not known whether the chronicity of the joint lesion is maintained entirely by specific immune reactions against E. rhusiopathiae antigen or whether superimposed autoimmune reactions are involved.
A preponderance of evidence exists to indicate that erysipelatous arthritis is initiated by active infection of the joint. Mild synovitis and arthritis have been induced in rabbits and rats by massive intravenous or intraarticular injections with nonliving whole cells or fractions of the organism (White et al. 1975; Hermanns et al. 1982), but the lesions were not as severe as those typically caused by infection. White et al. (1975) suggested that the mild response induced by such antigens may predispose the joint to infection during a subsequent transient septicemia.
Studies on the pathogenesis of endocarditis indicate that the valvular lesions begin with vascular inflammation and myocardial infarcts, possibly resulting from bacterial emboli. These processes, together with exudation of fibrin, lead to destruction of valvular endocardium.
Mechanism of Pathogenicity
[edit]The mechanism by which E. rhusiopathiae incites disease processes is not clearly understood. The organism is not known to produce toxins. Considerable evidence has accumulated indicating that neuraminidase, an enzyme produced by a number of species of pathogenic bacteria, is a factor in pathogenicity of E. rhusiopathiae. This enzyme specifically cleaves alpha-glycosidic linkages in neuraminic acid (sialic acid), a reactive mucopolysaccharide on surfaces of body cells. The enzyme is produced by E. rhusiopathiae during logarithmic growth, and the amount of activity is reported to be less in avirulent strains or strains of low virulence than in fully virulent strains (Müller 1981). Specific antibody activity against E. rhusiopathiae neuraminidase has been demonstrated in sera of swine with chronic SE, in commercial equine antierysipelas serum, and in serum of rabbits hyperimmunized with a preparation of neuraminidase from the organism. This latter preparation also induced a low level of protection in mice to E. rhusiopathiae infection. Neuraminidase is not a toxin; it must be produced in large amounts to be pathogenically active. It can act on substrates in cell membranes throughout the body, and no doubt its activity reaches high levels in an acute septicemia. Therefore, its activity could be a major factor mediating the widespread vascular damage, thrombosis, and hemolysis described (see the section on pathogenesis of acute SE). The ability to adhere to cell surfaces may also play a role in the pathogenicity of E. rhusiopathiae, and there is evidence that the process involves neuraminidase. Takahashi et al. (1987b) reported that virulent strains of the organism adhered better to porcine kidney cells in vitro than did avirulent strains. Nakato et al. (1987) reported that neuraminidase was essential for adherence of E. rhusiopathiae bacteria to vascular endothelial cells.
Although neuraminidase activity may be largely responsible for the pathogenicity of E. rhusiopathiae, it does not explain virulence, which is the ability of an infectious agent to overcome the host's defenses and initiate the pathologic process. There is evidence that the virulence of E. rhusiopathiae, which is known to be variable, is related to the organism's ability to resist the action of phagocytes (see also Mechanism of Immunity in the section on prevention), and resistance to phagocytosis is correlated with the presence of a protective capsulelike structure on the surface of virulent bacteria but not on avirulent mutants (Shimoji et al. 1994).
Serovar and Clinical Form
[edit]In the United States, reports of field cases frequently have described serovar 1 (usually subserovar 1a) as the predominant isolate from acute septicemic disease and serovar 2 as the most common isolate from subacute and chronic cases of SE. However, experimentally, all clinical forms of SE can be induced readily in susceptible swine by strains of serovar 1 or 2. The less-common serovars (3 through 26; N) tend to have low virulence for swine, and their clinical significance is doubtful.
CLINICAL SIGNS
[edit]The clinical signs of SE can be divided into three general classifications: acute, subacute, and chronic. In addition, subclinical infection can occur in which no visible signs of acute disease are evident but which can lead to chronic SE.
Acute SE
[edit]Acute SE is characterized by sudden onset, sometimes with sudden death of one or more animals. Other animals in the herd may be noticeably sick, and some of these may subsequently die. Those visibly sick will have temperatures of 104–108˚F (40–42˚C) and over, and those with the higher temperatures may show signs of chilling. Some pigs may appear normal and yet have temperatures of around 106˚F (41˚C). In surviving pigs, temperatures usually return to normal within 5–7 days.
Affected animals withdraw from the herd and will be found lying down. When approached, they resent being disturbed but usually will get up and move away. This usually is accompanied by squealing; when walking, they show a stiff, stilted gait. Upon stopping, they may be seen to shift their weight in an apparent effort to ease the pain in their legs. If left alone, they will soon lie down carefully. Pigs showing severe depression are nevertheless usually aware of activities around them. They may show some resentment at being disturbed but will make little or no effort to rise. Upon being forced to get up, they may stand for only a few moments before lying down again. While standing, the feet are carried well under them and the head is hung dejectedly, giving the back line a marked arched appearance. Others will not be able to stand even when assisted.
Most affected animals will show partial or complete inappetence. Bowel movements are usually retarded and the feces firm and dry in pigs of market age and older, although as the disease progresses, a diarrhea may appear in younger animals. Abortion may occur in sows that contract acute or subacute SE during pregnancy.
Cutaneous lesions (urticarial, or “diamond-skin” lesions) appear as early as the second and usually by the third day after exposure to E. rhusiopathiae (Fig. 31.2). On the light-skinned pig they can be seen as small, light pink to dark purple areas that usually become raised, are firm to the touch, and in most instances are easily palpated. In animals with dark-pigmented skin, one must rely mainly on palpation, although the weltlike lesions may be detected by observing raised areas in the hair coat. The lesions may be few in number and easily overlooked or so numerous it would be difficult to count them all. An animal also may die before recognizable urticarial lesions are evident. Individual lesions, by extension of the borders, assume a characteristic square or rhomboid shape. In acute nonfatal erysipelas, these lesions may spread considerably but will gradually disappear within 4–7 days after their first appearance, with no subsequent effect other than a superficial desquamation to mark the site. The intensity of skin lesions has a direct relationship to the outcome of the disease. Light pink to light purplish-red lesions are characteristic of acute nonfatal SE, whereas angry dark purplish-red lesions usually precede death of the animal. In acute fatal disease, extensive dark purplish discoloration often occurs over the belly, ears, tail, posterior aspect of the thighs, and jowls. Infrequently, severely affected pigs do not die, and skin necrosis may follow the severe cutaneous lesions. The areas of necrotic skin are dark, dry, and firm and eventually become separated from the healing underlying tissue. Affected areas, particularly the ears and tail, will eventually slough. Healing may require many weeks as a result of secondary infection.
Subacute SE
[edit]Subacute SE includes signs that are less severe in their manifestations than the acute form. The animals do not appear as sick; temperatures may not be as high or may not persist as long; appetite may be unaffected; a few skin lesions may appear that may be easily overlooked; and, if visibly sick, the animals will not remain so for as long as those acutely ill. Some cases of subacute SE are so mild as to remain unnoticed.
Chronic SE
[edit]Chronic SE may follow acute or subacute disease or subclinical infection and is characterized most commonly by signs of arthritis. Signs of cardiac insufficiency may be seen occasionally and will be most noticeable following exertion, sometimes causing sudden death. Chronic arthritis results in joints that show various degrees of stiffness and enlargement, sometimes as early as 3 weeks after infection. Interference with locomotion ranges from a slight limp to complete refusal to put weight on the limb, depending upon the extent of damage. Arthritis is the most important clinical manifestation of SE from an economic standpoint. The condition not only affects growth rate but is responsible for significant losses of prime cuts at the packing plant.
LESIONS
[edit]Rhomboid urticarial lesions ("diamond-skin" lesions) are characteristic of acute SE, and when generalized (Fig. 31.2), they are a reliable indicator of septicemia. This observation is important in meat inspection as well as in field diagnosis (see also the section on clinical diagnosis).
Acute SE
[edit]Most lesions of acute SE are similar to those of septicemia caused by a variety of organisms.
MACROSCOPIC LESIONS. In swine dead from acute SE, evidence of diffuse cutaneous hemostasis is often prominent, particularly in the skin of the snout, ears, jowls, throat, abdomen, and thighs. The lungs may be congested and edematous. Petechial and ecchymotic hemorrhages may be seen on the epicardium and in the musculature of the atria, particularly the left atrium. Catarrhal to hemorrhagic gastritis is common, and hemorrhage of the serosa of the stomach may be present. The liver usually is congested. The appearance of the spleen is of particular note, for it may be congested and markedly enlarged, particularly in animals affected for several days. Petechial hemorrhages may be present in the cortex of the kidneys. The appearance of the lymph nodes will depend upon the degree of involvement in the area they drain. There is some degree of enlargement with moderate to marked congestion; subcapsular hemorrhage of peripheral nodes may be seen after several days of illness. The mucosa of the urinary bladder usually appears normal but may present areas of congestion.
MICROSCOPIC LESIONS. A histologic examination of skin lesions reveals damage to the capillaries and venules, with perivascular infiltration by lymphoid cells and fibroblasts. The pathologic changes occur in the papillae and upper layers of the derma. Blood vessels of the papillae are congested and may contain microthrombi and bacteria. The papillae may also present focal necrotic areas as a result of circulatory stasis. Vascular lesions can be seen in the heart, kidney, lung, liver, nervous system, skeletal muscle, and synovial membranes. Cellular response to infection by E. rhusiopathiae consists predominantly of mononuclear leukocytes and macrophages. Neutrophils may appear but do not predominate. Purulent lesions are not characteristic of E. rhusiopathiae infection.
Affected lymph nodes usually show acute hyperplastic lymphadenitis, with hyperemia and hemorrhage. In some nodes there may be evidence of thrombosis and necrosis of small blood vessels and capillaries. Hemorrhagic nephritis with inflammatory changes in glomeruli may be seen occasionally. In addition, necrosis of renal tubules with hyaline and granular casts has been reported. Focal accumulations of mononuclear cells may be seen in subcapsular sinuses of the adrenal cortex. Lesions of skeletal muscle may occur, associated with vascular lesions. These consist of a segmented hyaline and granular necrosis of muscle fibers, which may be followed by fibrosis, calcification, and regeneration. Lesions of the CNS have been described, consisting of angiopathies with disturbances in permeability, degeneration of neurons, swelling of endothelial cells, and malacic foci in the cerebrum, brain stem, and spinal cord.
CLINICAL PATHOLOGY. Leukocytosis may occur in field cases of SE that last for several days or possibly from mixed bacterial infection, but in uncomplicated acute SE a leukopenia accompanied by a relative lymphocytosis is characteristic during the first 3-5 days. There may be a relative increase in the number of eosinophils. Hemoglobin and hematocrit values decrease during acute disease, followed later by the appearance of nucleated erythrocytes. The sedimentation rate increases. Changes in plasma components during acute SE include a decrease in glucose and increases in glutamic oxaloacetic transaminase activity, blood creatinine, and blood urea nitrogen.
Chronic SE
[edit]The predominant lesion of chronic SE in swine is a proliferative, nonsuppurative arthritis, occurring most commonly in hock, stifle, elbow, and carpal joints. Spondylitis is occasionally seen. Vegetative proliferation on the heart valves is less common.
MACROSCOPIC LESIONS. Animals affected with chronic arthritis have an enlargement of one or more joints, most readily visible in hock and carpal joints. The joint capsule is thickened with fibrous connective tissue. The joint cavity contains an excessive amount of serosanguinous synovial fluid, which may be slightly cloudy, indicating a small amount of purulent material. The presence of frank pus, however, is not characteristic of the lesion. The synovial membrane presents varying degrees of hyperemia and proliferation (Fig. 31.3), which gives the tissue a swollen, somewhat granular appearance, and often takes irregular forms, producing fringes (“tags”) that project into the joint cavity. These fringes may be caught between the articulating surfaces and produce severe pain. The proliferating tissue also may extend across the surface of articular cartilage, forming a pannus that leads to destruction of the articular surface and eventually to fibrosis and ankylosis of the joint. Lymph nodes associated with arthritic joints are usually enlarged and edematous.
Vegetative endocarditis consists of proliferative granular growths on the heart valves and may be accompanied by lesions resulting from cardiac insufficiency. Other internal organs may show chronic inflammatory changes such as infarcts of kidneys and spleen. Enlargement of the adrenal gland has been reported.
MICROSCOPIC LESIONS. Lesions of the synovial tissue may vary in severity, from slight perivascular accumulation of mononuclear cells to an extensive proliferative process. The typical synovial lesion in chronic SE is characterized by pronounced hyperplasia of the synovial intima and subintimal connective tissue, with vascularization and accumulation of lymphoid cells and macrophages, forming a villous pad of inflammatory tissue. Deposition and organization of fibrin may be seen. As the lesion progresses, proliferation of fibrous connective tissue becomes more prominent, and long fronds of hyperplastic synovium may be seen. The surface lining may become necrotic, with deposition of a fibrinous to fibrinopurulent exudate. Some tendency to follicle formation may be evident in the heavy accumulations of lymphoid cells. There may be erosion of the articular cartilages along with periostitis and osteitis. In old lesions ankylosis of the involved joint by fibrous adhesion may be accompanied by calcification.
Vegetative growths on the heart valves are composed of granulation tissue and superimposed masses of fibrin. Connective-tissue proliferation occurs with additional fibrin formation, which can be the source of emboli.
DIAGNOSIS
[edit]Clinical and bacteriologic examinations are the most reliable means of diagnosis of acute SE.
Clinical Diagnosis
[edit]Acute SE often cannot readily be differentiated clinically from other septicemic diseases, such as Actinobacillus suis septicemia (Miniats et al. 1989). Nevertheless, certain clinical features of an outbreak in a herd are more characteristic of SE than of other diseases if viewed in combination. For example, the following are presumptive of SE: a history of a few sudden deaths with no prior evidence of illness; several others sick with high temperatures and apparent stiffness in legs; reluctance of sick pigs to move but unexpected vitality when aroused; and clear, alert eyes. Other characteristic signs include a fair appetite in some visibly sick animals; normal to dry feces; death or recovery of sick animals within a few days; and, when present, the characteristic rhomboid skin lesions. Marked improvement within 24 hours after treatment with penicillin supports the diagnosis. At necropsy the presence of an enlarged spleen is suggestive.
Bacteriologic Diagnosis
[edit]Isolation of E. rhusiopathiae from the acutely affected animal provides a definite laboratory diagnosis of SE. Hemoculture is a useful diagnostic aid in living animals, but specimens should be taken from several affected animals in the herd, as the presence of the organism in the blood of an individual may be inconstant. At necropsy of a pig that has died in the acute phase, the organism is easily cultured from a variety of body organs (heart, lungs, liver, spleen, kidneys, joints). If the illness has persisted for several days, however, the organism often can no longer be cultured from internal organs but may still be found in the joints. Under these conditions it is important to take several specimens of fluid and synovial tissue from as many synovial sacs of a joint as possible, because the organisms may be present in small numbers and limited to certain areas.
Culture of E. rhusiopathiae from tissue specimens is relatively simple and requires only basic laboratory equipment and culture media such as tryptose or meat infusion media with or without blood or serum added. Care should be taken to avoid accidental skin infection, as the organism is pathogenic for humans. Selective culture methods for isolation of the organism from contaminated specimens are described elsewhere (Cottral 1978).
The use of immunofluorescence for rapid identification of E. rhusiopathiae has been reported; however, the method may not be sufficiently specific and sensitive for routine diagnostic purposes (Harrington et al. 1974).
Serologic Diagnosis
[edit]A variety of serologic tests have been used in attempts to diagnose SE. These include plate, tube, and microtitration agglutination; passive hemagglutination; hemagglutination inhibition; complement fixation; enzyme-linked immunosorbent assay (ELISA); and indirect immunofluorescence. An agglutination test involving the use of growing culture as antigen was developed by Wellmann (1955). In this test, called the Wachstumsprobe or growthagglutination test, a culture of E. rhusiopathiae growing in liquid medium in the presence of sterile test serum agglutinates if sufficient specific antibody is present.
No serologic test has proved useful for routine diagnosis of acute infection or for differentiation between immune and susceptible pigs. Serologic diagnosis may have some value in detection of chronic infection, primarily on a herd basis. Microtitration agglutination, growth agglutination, and ELISA are probably the most reliable for this purpose but may be difficult to interpret. It can be concluded that serologic testing has limited practical application in clinical diagnosis of SE in the field. The chief value of serologic procedures resides in research.
TREATMENT
[edit]The treatment of SE with hyperimmune serum, usually obtained from horses, was introduced in 1899, several years after it had been developed for use in conjunction with live-culture vaccination. Until the introduction of antibiotics nearly 50 years later, the administration of antiserum was the only worthwhile available form of treatment. Although now considered obsolete by some veterinarians, antiserum can still be useful. For maximum effectiveness the serum must be given early in the course of the disease. The recommended therapeutic dose, given subcutaneously, varies from 5 to 10 mL for pigs weighing less than 50 pounds (23 kg) to 20-40 mL for pigs weighing more than 100 pounds (45 kg).
It is generally accepted that the treatment of choice for acute erysipelas is administration of penicillin. E. rhusiopathiae is highly sensitive to this antibiotic, and treatment early in an acute outbreak usually results in dramatic response within 24-36 hours. Specific treatment regimens generally involve giving penicillin alone or in combination with other antibiotics or antiserum (occasionally both) to provide a longer action. For example, long-acting penicillin (available under various proprietary names), consisting of a combination of 150,000 units procaine penicillin G and 150,000 units benzathine penicillin G/cm3, may be given intramuscularly at a single dose of 5000-10,000 units/pound (454 g) to visibly sick pigs (the entire herd may be treated with tetracycline in the drinking water: 500 mg/gallon, 132 mg/L) until 5 days after no sick pigs are observed. The entire herd may also be given antiserum if the outbreak is very severe. As an alternative, long-acting penicillin may be given in severe outbreaks, and procaine penicillin G in less severe cases. The use of antiserum for treatment of suckling pigs is a fairly common practice. Initiation of a vaccination program in previously unvaccinated herds where outbreaks occur is strongly recommended.
Although penicillin has been consistently found to be the most effective antibiotic for treatment of acute SE, satisfactory results have been reported also with tetracyclines (including chlortetracycline and oxytetracycline), lincomycin, and tylosin. The organism is sensitive in vitro to erythromycin, but this antibiotic has been reported to be relatively ineffective in vivo. Streptomycin, dihydrostreptomycin, chloramphenicol, bacitracin, polymyxin B, neomycin, and sulfonamides are not effective against SE. There have been no published reports of development of resistance by E. rhusiopathiae to penicillin in the field since use of the antibiotic for treatment of SE was first reported in 1949. However, some isolates of the organism from swine have been found to be resistant to tetracyclines.
There is no practical treatment for chronic SE. Experimentally, the administration of antiinflammatory agents has provided some alleviation of the effects of chronic arthritis, and they may be used in treatment of especially valuable individual animals.
PREVENTION
[edit]Prevention of SE is best accomplished by sound practices of herd health management, including a program of immunization.
General Management Practices
[edit]Swine should be raised according to sound husbandry practice relative to nutrition, housing, and condition of lots and pastures, and they should be observed regularly for deviations from their usual attitude. Replacements should be obtained from clean sources. The recent introduction of a new boar is a relatively common historical finding preceding acute outbreaks of SE in a herd. New ly purchased animals should be isolated for at least 30 days.
It is advisable to eliminate chronically affected swine from the herd, as they can remain carriers of the organism indefinitely.
Good sanitation is important in general herd management and is essential following the cessation of an outbreak. Walls and floors should be cleaned and disinfected. Phenolic, alkali, hypochlorite, or quaternary ammonium disinfectants are effective against the organism but must be applied to clean surfaces.
Immunization
[edit]A variety of biological products have been produced for the purpose of conferring immunity to SE in swine. The simultaneous or serum-culture method of immunization was introduced in 1893 and consists of concomitant injections of virulent culture and antiserum. This method was first used in the United States in 1938, and its use continued for about 20 years until safer products became available. The method is no longer used. Active immunization against SE is now carried out by the use of either attenuated (so-called avirulent) vaccines or nonliving products (bacterins).
ATTENUATED VACCINES. Vaccines made from E. rhusiopathiae of reduced virulence were first licensed in the United States in 1955. Attenuation of virulence has been accomplished by passage through rabbits or chicken embryos, by air-drying, or by growth in media containing acridine dyes. Although these vaccines are commonly referred to as avirulent, they are in fact strains of extremely low virulence for swine, often retaining some virulence for mice. They stimulate immunity in swine by limited multiplication in the body; therefore, the response to vaccination is subject to such variables as status of passive or active immunity already existing in the animal. In addition, there is some evidence that antiserum given concomitantly may interfere with development of immunity in response to attenuated vaccines. Manufacturers generally do not recommend use of serum with their attenuated products except when immediate protection is necessary, as in the case of suckling pigs being given both vaccine and serum during a herd outbreak. In this case, repeated vaccination at weaning is recommended.
Attenuated vaccines should not be given to swine being treated with antibiotics to which E. rhusiopathiae is sensitive. Antibiotic treatment should be discontinued at least 8-10 days before vaccination.
Attenuated vaccines are usually given by injection or administered orally in drinking water. Some manufacturers provide a product that can be given either way. In some parts of Europe and the former Soviet Union, vaccination by aerosol has been practiced. Elaborate equipment for generating and distributing the aerosol is necessary.
Use of living vaccines leaves open the possibility, however remote, of vaccinated animals becoming carriers and disseminators of the organism, which conceivably could undergo increased virulence through serial passage. There is no experimental evidence, however, that attenuated SE vaccines can regain their virulence and pose a hazard to susceptible swine.
BACTERINS. Use of a bacterin consisting of a formalin- killed whole culture adsorbed on aluminum hydroxide gel was first reported in 1947. This type of product has been used in the United States since 1953. It is typically made from selected strains of serovar 2 that produce a soluble immunogenic product when grown in a complex liquid medium containing serum. This substance, most of which is released into the medium, has been described as a glyco-lipoprotein (White and Verwey 1970). It is considered by most investigators to be a necessary ingredient for stimulation of immunity by the bacterin. The most active component of the immunogenic substance has been identified as a protein fraction with a molecular weight of 64-66 kDa (Timoney and Groschup 1993; Sato et al. 1995; Goodman 1996; Zarkasie et al. 1996). The combination of the soluble immunogenic product and whole killed bacteria, concentrated and adsorbed on aluminum hydroxide gel or other suitable adjuvant, constitutes the basic features of an E. rhusiopathiae bacterin.
Lysate bacterin, first reported in 1953, has been used in the United States since 1955. It is similar to whole-culture bacterin except that the bacterial cells have been lysed.
Bacterins are given by subcutaneous or intramuscular injection; a second (booster) injection in 3-5 weeks is generally recommended. Breeding animals should be given an additional booster injection annually.
PASSIVE IMMUNITY. Temporary passive immunity can be induced by administration of commercially available antiserum. Pigs given antiserum subcutaneously receive immediate passive protection, which persists for about 2 weeks. The preventive dose is half the therapeutic dose (see the section on treatment). Antiserum may be useful during a herd outbreak for temporary protection of suckling pigs until they are old enough to be vaccinated.
MECHANISM OF IMMUNITY. The mechanism of immunity to E. rhusiopathiae infection is not clearly defined, but there is little doubt that opsonization is a major factor. Studies have shown that virulent E. rhusiopathiae bacteria opsonized with immune serum were readily eliminated by polymorphonuclear leukocytes (Sawada et al. 1988) and by macrophages (Shimoji et al. 1996). Nonopsonized virulent organisms were resistant to phagocytosis.
EFFICACY OF BIOLOGICS. No presently available immunizing product adequately fills the need for effective long-term protection against SE. Some veterinarians consider living vaccines to be superior to bacterins, but Shuman (1959) found no significant difference in their efficacies under experimental conditions. According to most reports, vaccination generally can be expected to induce immunity lasting 3-5 months. A second (booster) injection may increase this duration to 6 months and is recommended, especially for bacterins. Development of immunity in vaccinated swine may be adversely affected by such environmental factors as overheating or poor nutrition.
A serious deficiency of SE vaccination is its inability to prevent the chronic form. Most investigators agree that vaccination has little effect on the incidence of arthritis caused by E. rhusiopathiae, although this observation is difficult to evaluate in the field, since SE vaccination is not universally practiced in the United States. It is possible that vaccination reduces the overall prevalence of arthritis by reducing the prevalence of acute erysipelas. On the other hand, some believe vaccination actually causes an increase in arthritic lesions by initiating a state of hypersensitivity to subsequent contact with the organism. An alternative explanation for the failure of vaccination to prevent arthritis may exist, however. The organism may be carried to synovial tissues by loaded macrophages soon after exposure, thereby escaping the opsonic effects of humoral immunity (Drommer et al. 1970). Sequestration of the bacteria in chondrocytes (Franz et al. 1995) might provide similar protection from immune mechanisms.
It is possible that certain uncommon serovars of E. rhusiopathiae may be refractory to the immunity induced in mice and swine by standard SE vaccines. However, such serovars are usually isolated from healthy carrier pigs or nonporcine sources, and none have been directly associated with cases of acute SE in the field.
Although vaccination against SE is not entirely effective in preventing the disease, it provides a worthwhile means of control when used with other good management practices. A regular vaccination program for both breeding and market animals is recommended. Because of the ubiquity of E. rhusiopathiae, together with its poorly understood ability to exist in nature, the possibility of eradication of the organism seems remote.
REFERENCES
[edit]Cottral, G. E. 1978. Manual of Standardized Methods for Veterinary Microbiology. Ithaca, N.Y.: Cornell Univ Press, pp. 429-436, 671, 672, 679, 687. Cysewski, S. J.; Wood, R. L.; Pier, A. C.; and Baetz, A. L. 1978. Effects of aflatoxin on the development of acquired immunity to swine erysipelas. Am J Vet Res 39:445-448.
Denecke, R., and Trautwein, G. 1986. Lokale Antigenpersistenz und Chronizität der experimentellen Rotlauf-Polyarthritis. Berl Münch Tierärztl Wochenschr 99:200-208.
Drommer, W.; Schultz, L. C.; and Pohlenz, J. 1970. Experimenteller Rotlauf beim Schwein: Permeabilitatsstorungen und Malazien im zentralen Nervensystem. Pathol Vet 7:455-473.
Franz, B.; Davies, M. E.; and Horner, A. 1995. Localization of viable bacterial antigens in arthritic joints of Erysipelothrix rhusiopathiae-infected pigs. FEMS Immunol Med Microbiol 12:137-142.
Goodman, S. A. 1996. USDA: Progress toward in vitro tests and other trends. Dev Biol Stand 86:41-47.
Harrington, R., Jr.; Wood, R. L.; and Hulse, D. C. 1974. Comparison of a fluorescent antibody technique and cultural method for the detection of Erysipelothrix rhusiopathiae in primary broth cultures. Am J Vet Res 35:461-462.
Hermanns, W.; Jessen, H.; Schulz, L. C.; Kerlen, G.; and Böhm, K. H. 1982. Über die Induktion einer chronischen Polyarthritis mit Bestandteilen von Rotlaufbakterien (Erysipelothrix rhusiopathiae). II. Mitteilung: Versuche zur Arthritis-Induktion bei Ratten. Zentralbl Veterin ärmed (B) 29:85-98.
Kucsera, G. 1973. Proposal for standardization of the designations used for serotypes of Erysipelothrix rhusiopathiae (Migula) Buchanan. Int J Syst Bacteriol 23:184-188.
Miniats, O. P.; Spinato, M. T.; and Sanford, S. E. 1989. Actinobacillus suis septicemia in mature swine: Two outbreaks resembling erysipelas. Can Vet J 30:943-947.
Müller, H. E. 1981. Neuraminidase and other enzymes of Erysipelothrix rhusiopathiae as possible pathogenic factors. In Arthritis: Models and Mechanisms. Ed. H. Deicher. Berlin: Springer-Verlag, p. 58. Nakato, H.; Shinomiya, K.; and Mikawa, H. 1987. Adhesion of Erysipelothrix rhusiopathiae to cultured rat aortic endothelial cells: Role of bacterial neuraminidase in the induction of arteritis. Path Res Pract 182:255-260.
Nørrung, V. 1979. Two new serotypes of Erysipelothrix rhusiopathiae. Nord Vet Med 31:462-465.
Nørrung, V., and Molin, G. 1991. A new serotype of Erysipelothrix rhusiopathiae isolated from pig slurry. Acta Vet Hung 39:137-138.
Nørrung, V.; Munch, B.; and Larsen, H. E. 1987. Occurrence, isolation and serotyping of Erysipelothrix rhusiopathiae in cattle and pig slurry. Acta Vet Scand 28:9-14.
Sato, H.; Hirose, K.; and Saito, H. 1995. Protective activity and antigenic analysis of fractions of culture filtrates of Erysipelothrix rhusiopathiae. Vet Microbiol 43:173-182.
Sawada, T.; Tamura, Y.; and Takahashi, T. 1988. Mechanism of protection induced in mice against Erysipelothrix rhusiopathiae infection by treatment with porcine antiserum to the culture filtrate of an attenuated strain. Vet Microbiol 17:65-74.
Schulz, L. C.; Drommer, W.; Seidler, D.; Ehard, H.; Leimbeck, R.; and Weiss, R. 1975a. Experimenteller Rotlauf bei verschiedenen Spezies als Modell einer systemischen Bindegewebskrankheit. II. Chronische Phase mit besonderer Berucksichtigung der Polyarthritis. Beitr Pathol 154:27-51.
Schulz, L. C.; Drommer, W.; Seidler, D.; Ehard, H.; Von Mickwitz, G.; Hertrampf, B.; and Böhm, K. H. 1975b. Experimenteller Rotlauf bei verschiedenen Spezies als Modell einer systemischen Bindegewebskrankheit. I. Systemische vaskulare Prozesse bei der Organmanifestation. Beitr Pathol 154:1-26.
Schulz, L. C.; Drommer, W.; Ehard, H.; Hertrampf, B.; Leibold, W.; Messow, C.; Mumme, J.; Trautwein, G.; Überschär, S.; Weiss, R.; and Winklemann, J. 1977. Pathogenetische Bedeutung von Erysipelothrix rhusiopathiae in der akuten und chronischen Verlaufsform der Rotlaufarthritis. Dtsch Tierärzt Wochenschr 84:107-111.
Shimoji, Y.; Yokomizo, Y.; Sekizaki, T.; Mori, Y.; and Kubo, M. 1994. Presence of a capsule in Erysipelothrix rhusiopathiae and its relationship to virulence for mice. Infect Immun 62:2806-2810.
Shimoji, Y.; Yokomizo, Y.; and Mori, Y. 1996. Intracellular survival and replication of Erysipelothrix rhusiopathiae within murine macrophages: Failure of induction of the oxidative burst of macrophages. Infect Immun 64:1789-1793.
Shuman, R. D. 1951. Swine erysipelas induced by skin scarification. Proc Am Vet Med Assoc, p. 153.
___. 1959. Comparative experimental evaluation of swine erysipelas bacterins and vaccines in weanling pigs, with particular reference to the status of their dams. Am J Vet Res 20:1002-1009.
___. 1971. Erysipelothrix. In Infectious and Parasitic Diseases of Wild Birds. Ed. J. W. Davis, R. C. Anderson, L. H. Karstad, and D. O. Trainer. Ames: Iowa State Univ Press, p. 141. Smith, T. 1885. Second Annual Report of the Bureau of Animal Industry. Washington, D.C.: U.S. Department of Agriculture, p. 187. Sneath, P. H. A.; Mair, N. S.; Sharpe, M. E.; and Holt, J. G. 1986. Bergey's Manual of Systematic Bacteriology. Vol. 2. Baltimore: Williams & Wilkins, pp. 1245-1249. Takahashi, T.; Fujisawa, T.; Benno, Y.; Tamura, Y.; Sawada, T.; Suzuki, S.; Muramatsu, M.; and Mitsuoka, T. 1987a. Erysipelothrix tonsillarum sp. nov. isolated from tonsils of apparently healthy pigs. Int J Syst Bact 37:166-168.
Takahashi, T.; Hirayama, N.; Sawada, T.; Tamura, Y.; and Muramatsu, M. 1987b. Correlation between adherence of Erysipelothrix rhusiopathiae strains of serovar 1a to tissue culture cells originated from porcine kidney and their pathogenicity in mice and swine. Vet Microbiol 13:57-64.
Takahashi, T.; Nagamine, N.; Kijima, M.; Suzuki, S.; Takagi, M.; Tamura, Y.; Nakamura, M.; Muramatsu, M.; and Sawada, T. 1996. Serovars of Erysipelothrix strains isolated from pigs affected with erysipelas in Japan. J Vet Med Sci 58:587-589.
Timoney, J. F., and Groschup, M. M. 1993. Properties of a protective protein antigen of Erysipelothrix rhusiopathiae. Vet Microbiol 37:381-387.
Vickers, C. L., and Bierer, B. W. 1958. Triple sugar iron agar as an aid in the diagnosis of erysipelas. J Am Vet Med Assoc 133:543-544.
Wellmann, G. 1955. Die subklinische Rotlaufinfektion und ihre Bedeutung für die Epidemiologie des Schweinerotlaufs. Zentralbl Bakteriol (Orig A) 162:265-274.
White, R. R., and Verwey, W. F. 1970. Solubilization and characterization of a protective antigen of Erysipelothrix rhusiopathiae. Infect Immun 1:387-393.
White, T. G., and Shuman, R. D. 1961. Fermentation reactions of Erysipelothrix rhusiopathiae. J Bacteriol 82:595-599.
White, T. G.; Puls, J. L.; and Hargrave, P. 1975. Production of synovitis in rabbits by fractions of a cell-free extract of Erysipelothrix rhusiopathiae. Clin Immunol Immunopathol 3:531-540.
Wood, R. L. 1973. Survival of Erysipelothrix rhusiopathiae in soil under various environmental conditions. Cornell Vet 63:390-410.
___. 1984. Swine erysipelas: A review of prevalence and research. J Am Vet Med Assoc 184:944-949.
Wood, R. L., and Harrington, R., Jr. 1978. Serotypes of Erysipelothrix rhusiopathiae isolated from swine and from soil and manure of swine pens in the United States. Am J Vet Res 39:1833-1840.
Wood, R. L., and Shuman, R. D. 1981. Erysipelothrix infection. In Infectious Diseases of Wild Mammals, 2d ed. Ed. J. W. Davis, L. H. Karstad, and D. O. Trainer, 297-305. Ames: Iowa State Univ Press. Wood, R. L.; Haubrich, D. R.; and Harrington, R., Jr. 1978. Isolation of previously unreported serotypes of Erysipelothrix rhusiopathiae from swine. Am J Vet Res 39:1958-1961.
Xu, K.; Hu, X.; Gao, C.; and Lu, Q. 1984. A new serotype of Erysipelothrix rhusiopathiae. Anim Infect Dis 4:11-14.
Xu, K.; Gao, C.; and Hu, X. 1986. Study on a new serotype of Erysipelothrix rhusiopathiae isolated from marine fishes. Anim Infect Dis 3:6-7, 48. Zarkasie, K.; Sawada, T.; Yoshida, T.; Takahashi, I.; and Takahashi, T. 1996. Growth ability and immunological properties of Erysipelothrix rhusiopathiae serotype 2. J Vet Med Sci 58:87-90.