Caseous lymphadenitis (CL) is a chronic, contagious disease caused by the bacterium Corynebacterium pseudotuberculosis. Although prevalence of CL varies by region and country, it is found worldwide and is of major concern for small ruminant producers in North America. The disease is characterized by abscess formation in or near major peripheral lymph nodes (external form) or within internal organs and lymph nodes (internal form). Although both the external and internal forms of CL occur in sheep and goats, the external form is more common in goats, and the internal form is more common in sheep.
Economic losses from CL include death, condemnation and trim of infected carcasses, hide and wool loss, loss of sales for breeding animals, and premature culling of affected animals from the herd or flock. Once established on a farm or region (endemic), it is primarily maintained by contamination of the environment with active draining lesions, animals with the internal form of the disease that contaminate the environment through nasal discharge or coughing, the ability of the bacteria to survive harsh environmental conditions, and lack of strict biosecurity necessary to reduce the number and prevent introduction of new cases. Although CL is typically considered a disease of sheep and goats, it also occurs more sporadically in horses, cattle, camelids, swine, wild ruminants, fowl, and people. Because of its zoonotic potential, care should be taken when handling infected animals or purulent exudate from active, draining lesions.
Etiology and Pathogenesis
C pseudotuberculosis is a gram-positive, facultative, intracellular coccobacillus. Two biotypes have been identified based on the ability of the bacteria to reduce nitrate: a nitrate-negative group that infects sheep and goats, and a nitrate-positive group that infects horses. Isolates from cattle are a heterogeneous group. All strains produce an exotoxin called phospholipase D that enhances dissemination of the bacteria by damaging endothelial cells and increasing vascular permeability. The bacterium has a second virulence factor, which is an external lipid coat that provides protection from hydrolytic enzymes in host phagocytes. Replication of bacteria occurs in the phagocytes, which then rupture and release bacteria. The ongoing process of bacterial replication, followed by attraction and subsequent death of inflammatory cells, forms the characteristic abscesses associated with CL.
To establish infection, C pseudotuberculosis must penetrate skin or mucous membranes. The most common site of entry is the skin after an injury that may result from shearing, tagging, tail docking, castration, or other environmental hazards resulting in skin trauma. Contact with purulent material draining from open, active lesions most commonly serves as the source of bacteria through these breaches in the skin. Although less common, entry across mucous membranes from inhalation or ingestion of the bacteria also serves as a means of infection.
Once the bacteria have entered the body, they move to the lymph nodes via the regional draining lymphatic system. Internally, the bacteria establish infection not only in the lymph nodes but also in the viscera. The incubation period varies from 1 to 3 months, culminating in development of encapsulated abscesses. C pseudotuberculosis is hardy in the environment and can survive on fomites such as bedding and wood for 2 months and in soil for 8 months. The presence of organic material, shade, and moisture favor and enhance survival.
The hallmark clinical finding in cases of external caseous lymphadenitis is the development of abscesses in the region of peripheral lymph nodes. Common sites of development include the submandibular, parotid, prescapular, and prefemoral nodes. Less commonly, abscessation of supramammary or inguinal lymph nodes occurs, in addition to an occasional ectopic location along the lymphatic chain. If left untreated, these lesions eventually mature into open draining abscesses. The purulent material from these lesions has no odor and varies in consistency from soft and pasty (more common in goats) to thick and caseous (more common in sheep). Once natural draining occurs, the skin lesion heals with scarring.
Recurrence is common, which can be months later. CL should be highly suspected in a sheep or goat with abscessation in these regions. Although other bacteria may cause abscessation in these locations (and in other animals), because of the ramifications of the presence of this disease within a herd or flock, these cases should be handled as CL until proved otherwise.
The internal form of CL most commonly presents as chronic weight loss and failure to thrive. The presence of other clinical signs depends on the organs of involvement, which may include any of the major organ systems. Lung abscessation is a common site of visceral involvement in internal CL; therefore, signs of chronic ill thrift with cough, purulent nasal discharge, fever, and tachypnea with increased lung sounds may be noted. The internal form is more common in sheep and has been termed the “thin ewe syndrome.”
The incidence of abscesses and development of clinical disease with either the external or internal form increases with age.
In sheep, abscesses often have the classically described laminated “onion-ring” appearance in cross section, with concentric fibrous layers separated by inspissated caseous exudate. In goats, the abscesses are less organized, and the exudate may be soft and paste-like.
Physical examination of lesions associated with lymph nodes
Bacterial culture of suspected lesions
The presence of an external abscess on a small ruminant is highly suggestive of caseous lymphadenitis, especially in locations of peripheral lymph nodes. However, definitive diagnosis is only by bacteriologic culture of purulent material from an intact abscess. Although other pyogenic organisms such as Trueperella pyogenes (formerly Arcanobacterium pyogenes), Staphylococcus aureus, Pasteurella multocida, and anaerobes such as Fusobacterium necrophorum can cause abscessation, affected animals should be kept isolated pending culture results.
Animals with visceral abscesses pose a greater diagnostic challenge. Radiography and ultrasonography can be useful to detect internal lesions. Culture of a transtracheal aspirate obtained from an animal with pneumonia can help determine whether CL is the cause. Excluding other causes of chronic weight loss and ill thrift in the face of proper nutrition and good appetite such as Johne’s disease, parasitism, and poor dentition further raise suspicion.
In the absence of accessible abscesses for bacterial culture, definitive diagnosis of active cases of caseous lymphadenitis is challenging. Although many diagnostic tools are available, results of these tests must be interpreted with caution and with consideration of herd or flock history, the presence or absence of active infection within the herd or flock, and vaccination status. A synergistic hemolysin inhibition (SHI) test that detects antibodies to the phospholipase D exotoxin is available at many diagnostic laboratories. Positive titers indicate past resolved infections, recent exposure, recent vaccination, or active lesions or their development. Titers of 1:256 or higher have been correlated in past studies with the presence of active, developing abscesses; however, in a more recent study, a high titer was poorly correlated with presence or development of abscesses over an 18-month period.
When the status of an animal with a positive titer is in doubt, the titer should be repeated in 2–4 weeks. If the titer is rising and clinical signs of abscesses are noted, then CL can be assumed to be the cause. False-negative results can occur if testing is done in the first 2 weeks after exposure before the animal has seroconverted. Also, animals with chronic, walled-off abscesses can have a false-negative result. Colostrum titers usually disappear by 3–6 months of age, so serologic testing of lambs or kids <6 months old should be interpreted with caution.
Treatment and Control
Antimicrobial treatment (intralesional and/or systemic)
Strict biosecurity measures
Elimination of diseased animals from the herd/flock
Disinfection of shearing equipment and other instruments used for production procedures (castration, ear tagging, etc) between animals
Removal of hazards in the environment that could potentially injure the skin
Prepurchase examination for lesions, serologic screening and a period of quarantine before introduction of new animals
Once a diagnosis of caseous lymphadenitis has been established, owner education stressing the persistent, recurrent nature of the disease is necessary. The most practical approach for commercial animals infected with CL is to cull them from the herd or flock. However, animals with draining abscesses should not be sent through sale barns until draining has ceased and the wound has healed. Treatment of individual animals should be undertaken with the understanding that CL is not considered a “curable” disease. Animals with genetic or emotional value are treated mainly for aesthetic reasons and to limit their infectivity to the rest of the herd or flock. Treatment options have included lancing and draining, surgical excision, formalin injection of lesions, systemic antibiotics, and intralesional antibiotics.
If external abscesses are lanced and drained, the cavity should be lavaged with dilute iodine solution and the animal isolated in an area that can be disinfected until the lesion stops draining and heals. Drained purulent material should be carefully collected and disposed of. Dilute bleach and chlorhexidine solutions are effective disinfectants of hard surfaces and fomites, but the presence of organic material on these surfaces inactivates them and drastically reduces or prohibits effectiveness. Intact accessible abscesses can be surgically removed; however, this option is more expensive, and undetected abscesses are often present and continue to develop. Recurrence rates with either lancing or surgical removal are high.
The practice of injecting abscesses with formalin should be strongly discouraged, because the FDA has zero tolerance for extra-label use of a potent carcinogen in food-producing animals. The efficacy of systemic antimicrobial therapy and, more recently, intralesional antimicrobial therapy has been investigated. It must be noted here that the use of any antimicrobial for treatment of CL is extra-label; therefore, strict adherence to published guidelines on withdrawal times and an established veterinarian-client-patient relationship are mandatory. Longterm administration of procaine penicillin G and rifampin has been successful in some cases. Penicillin alone, although effective in vitro, is unlikely to penetrate the capsule of developed abscesses, as are many, if not most, of the water-soluble or moderately lipid-soluble antimicrobials.
Recent studies have shown that administration of one dose of tulathromycin at 2.5 mg/kg, either SC directly into the abscess cavity, or two doses at 2.5 mg/kg, administered at the same time, one SC and one intralesionally, can resolve the lesions without lancing the abscess. Further, effective concentrations of tulathromycin can be achieved within walled-off abscesses caused by C pseudotuberculosis after a single dose at 2.5 mg/kg, SC. The highly lipid-soluble property of tulathromycin may be particularly helpful in cases of internal CL, when abscesses are not accessible for other forms of treatment. Despite the efficacy of intralesional and parenteral administration of tulathromycin in many cases, recurrence remains a problem. Therefore, use of these drugs cannot be considered curative but rather an acceptable alternative to manage cases of CL when culling from the herd or flock is not an acceptable option for the owner.
Because of the nature of the causative organism, common means of exposure, chronicity of the disease, and difficulty in completely eliminating the organism from individual animals, control of CL focuses on strict biosecurity measures. The overriding goals of any control program are to eliminate the disease from the herd or flock and to reduce the number of new cases either from the spread of disease or introduction to the farm.
Ideally, animals identified as infected should immediately be culled. If immediate removal is not possible, infected animals should be isolated from the rest of the herd or flock. Diligence in this practice will eventually result in decreased prevalence as animals that develop active cases are identified and removed and given there are no new animals incubating the disease introduced to the premises.
When elimination through culling is not a viable option for the owner, control of CL is challenging at best. Dividing the herds or flocks into “clean” and “infected” groups and eliminating older and less genetically valuable animals over time is one control strategy.
Lambs and kids from infected dams can be raised on pasteurized colostrum and milk away from infected animals. However, the internal form of CL and animals incubating the disease can maintain infection within the “asymptomatic clean” group and limit the success of this approach.
Commercial CL vaccines are currently licensed for use in sheep and goats. These vaccines should only be used in the species they are labeled for, because adverse reactions have been reported in goats given vaccine labeled for sheep. Rigidly adhering to vaccination schedules according to the manufacturer's labeling can help reduce the prevalence and incidence of CL within herds or flocks. However, it is important to emphasize that efficacy of these vaccines is not 100%, and vaccination will not clear infected animals. Vaccination of young replacement stock should be considered, and older infected animals should be gradually culled as economics allow. Once the disease is at a low prevalence rate, vaccination should be stopped and all seropositive unvaccinated animals culled. In "clean" herds or flocks that have no history of CL, vaccination is not recommended.
The risks of disease transmission among animals should be recognized when shearing or dipping, and management practices should be adjusted accordingly. Animals with noted lesions should be shorn last, and clipper blades disinfected between animals. Shearers should recognize the hazards associated with contact with purulent material and the possibility of acting as mechanical vectors, either on clothing or via equipment, for spread of the bacteria to new animals. Further, dipping tank solutions should be kept as fresh as possible, because C pseudotuberculosis can survive within them and serve as a source of infection of freshly shorn sheep that have skin abrasions.
Owners should remove hazardous items (barbed wire, exposed nails, rough feeders) from the environment to decrease injury and potential CL transmission from the presence of bacteria on these fomites.
One of the most common ways CL can be introduced into a previously “clean” herd or flock, or reintroduced to one in which CL has been reduced or eliminated, is through the addition of replacement stock. Often, animals from other farms that are asymptomatic on arrival are incubating the disease and then manifest infection weeks to months later. Purchasing animals from sources with unknown histories is hazardous to maintaining a "clean" herd or flock. Newly arrived animals should be examined thoroughly for signs of CL, such as abscesses or scars near peripheral lymph nodes. They should remain isolated from the rest of the herd or flock until their serologic status is determined, and only animals that are seronegative with no evidence of present or past CL lesions should be allowed to enter the herd or flock.
Caseous lymphadenitis is a chronic disease that is challenging, if not impossible, to eliminate within an individual animal. Sustained antimicrobial therapy may lead to apparent resolution of lesions, but recurrence is common. The internal form of CL is characterized clinically as chronic weight loss, is difficult to definitively diagnose antemortem, and serves as a means to unknowingly maintain potentially infective animals within the herd/flock.
Despite reported success with various antimicrobial regimens coupled with strict biosecurity measures, eliminating affected animals from the herd or flock remains the best way to eliminate caseous lymphadenitis. Vaccination protocols can aid in reducing the numbers of new cases within a herd or flock, but adhering rigidly to the manufacturer's label directions is paramount to efficacy.
In situations where elimination of affected animals is not desirable, dividing "clean" and "infected" animals into separate herds/flocks, prompt antimicrobial treatment, isolation of animals with active lesions, and culling of aged infected animals may eventually lead to decreased prevalence of CL.
Owners/managers of clean herds/flocks should carefully evaluate potential additions of animals by close examination for potential CL lesions, serologic testing, and mandating periods of quarantine before introduction to the herd/flock.