Goats in a pen, potential carriers of Corynebacterium pseudotuberculosis"

Key Characteristics of CL

Caseous lymphadenitis (CL) is a chronic disease that has created significant economic loss in farmed small ruminants for centuries. The term “caseous” comes from the cheese-like consistency of the pus. It is caused by Corynebacterium pseudotuberculosis, a bacterium that usually targets the lymph nodes and sometimes other tissues, including the lungs, liver, and spleen. It causes swelling, abscess formation in the affected area, and, in more severe cases, mortality. CL can be challenging to treat due to its complex characteristics, therefore ensuring proper diagnosis is critical. In this blog post, we discuss key characteristics of caseous lymphadenitis, Corynebacterium pseudotuberculosis, and the most effective ways to recognize it.

Symptoms

  • Swelling and abscessing can appear uniquely, either externally or internally. If external, CL typically presents as a lesion on the superficial lymph nodes around the neck, jaw, and shoulders. Internally, CL often occurs subcutaneously, or in the lungs, liver, and spleen. This can cause systematic infections, which can be fatal.
  • As the animal’s immune system fights the infection, it will become weaker, causing weight loss and decreased productivity.
  • Often the abscesses will rupture and discharge thick pus with a pungent odor.

Transmission

  • The pus holds Corynebacterium pseudotuberculosis, so once ruptured, it becomes extremely contagious. Animals can contract CL by direct contact with an affected animal or indirectly via contaminated bedding, fence posts, feeders, etc. Due to CL’s status as a notifiable disease, when diagnosed, it must be reported to the state laboratory. Therefore, accurate and fast diagnostic tests are required to control this disease.

Impact

  • CL can inflict severe economic losses on farmers due to a decrease in wool, milk, or meat production. Herd quality can also be affected because control of chronic cases can be difficult in larger herds.

Testing

Several forms of testing were used to identify Corynebacterium pseudotuberculosis. Some forms of testing commonly used include Polymerase Chain Reaction (PCR) testing, several types of Culture testing, and Next Generation Sequencing (NGS) testing.

Goats in a pen, potential carriers of Corynebacterium pseudotuberculosis

Challenges of Diagnosing and Treating Corynebacterium pseudotuberculosis

Corynebacterium pseudotuberculosis is a rod-shaped, facultative intracellular bacteria, meaning it replicates and lives inside the cell of the host organism. This makes it incredibly resilient and persistent in the environment, especially in soil, manure, contaminated equipment, or any atmosphere with low-oxygen conditions for up to 18 months. This environmental stability plays a leading role in the transmission of disease, particularly in farm settings where biosecurity is not always the number one concern.

The genus Corynebacterium is a gram-positive bacterium, which also includes Mycobacterium, Nocardia, and Rhodococcus (CMN group). Members of the CMN group share similar structural and biochemical features, such as slow growth rates and complex cell wall lipids. This group is highly diverse and falls under a broader category of actinomycetes: bacteria that exhibit a unique, filamentous growth pattern that closely resembles fungi. They grow best in anaerobic environments, with little to no oxygen. This can complicate identification and be easily mistaken for other similar-resembling pathogens, making it difficult to culture.

Why PCR and Culture Testing are Insufficient

PCR (Polymerase Chain Reaction) testing is a great resource for detecting certain bacteria, but it has its limitations compared to NGS (Next Generation Sequencing), especially in terms of depth and flexibility. PCR testing only detects what it is designed to detect; therefore, you must know the exact genetic sequence or pathogen you’re looking for. One of the main errors in PCR testing is how it manages mutations. If unexpected mutations occur in the primer-binding regions, the test cannot detect them and produces a false negative result.

Culture testing with intracellular bacteria can be challenging due to its complex needs. Intracellular bacteria need host cells’ nutrients, pH, and enzymes to survive and replicate components that a culture environment cannot replicate. In several cases, intracellular bacteria could take weeks to grow or may not grow at all under normal lab conditions. To have the opportunity to grow, they must have perfect conditions, including low oxygen, specific cell types, unique nutrients and cofactors, etc. With slow-growing bacteria, there is a big risk of overgrowth and contamination of other bacteria. Fast-growing contaminants can easily take over before the slow-growing pathogens have a chance to appear. This can create lots of false negatives and incorrect results.

Veterinarian examining lymph node swelling in small ruminant for signs of CL

Next Generation Sequencing (NGS) offers a more inclusive result by not only testing the eight primary bacteria involved in the infection but also the known and unknown pathogens or mutations as well, which ensures the most error-free results. NGS can sequence the DNA of bacterial cells in a sample, allowing identification of a wide range of pathogens. In addition to identifying bacteria and fungi, our test also provides valuable information about the antibiotic resistance of the bacteria identified. This allows for more tailored, effective treatment strategies and contributes to proper antimicrobial stewardship.

Here at MiDOG Animal Diagnostics, we offer Next Generation Sequencing (NGS) testing, which allows us to see a wide range of pathogens and analyze their antimicrobial resistance (AMR) profiles. This equips veterinarians with the tools needed to make quicker, more reasoned treatment decisions. By using NGS, we promote better animal health and responsible use of antimicrobials.

Herd of sheep on farm where CL transmission can occur

Final Thoughts

Caseous lymphadenitis is a disease caused by Corynebacterium pseudotuberculosis that causes abscesses in the lymph nodes and other tissues. Caseous lymphadenitis is easily transmissible and can have a big economic impact on production. Because Corynebacterium pseudotuberculosis is an actinomycete and produces antibodies that can linger for several months, culture testing and PCR testing are notorious for producing numerous false negatives. Fortunately, NGS testing can address these limitations and produce better results to identify the key bacterial markers involved in CL and antibiotic resistance to overall more precise diagnosis and effective treatments.

 

Written by: Kaitlyn Kavanagh


Categories: Antibiotic Resistance, Bacterial Infections, Next-Gen DNA Sequencing Technology

animal diagnostics

Validated by Veterinarians

“Clients expect their veterinarians to stay up to date on all matters that affect the health and well-being of their non-human family members. The current technique that we have used to determine the presence and antibiotic sensitivity of organisms causing disease in our pets is over a century old.

With the emergence of dangerous antibacterial resistance, it is critical that veterinarians are able to offer laser-focused diagnostics and treatment. MiDOG enables us to offer care that exceeds the typical standard of care.”

Bernadine Cruz, DVM, Laguna Hills Animal Hospital Laguna Woods, CA

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Michael Morgan, DVMQuail Animal Hospital, Tustin, CA

“The MiDOG All-in-One Test is amazing, I would use it instead of culture and sensitivity.  Such rapid and detailed results, I will reach for MiDOG before culture next time!

Thank you very much MiDOG, for sharing the opportunity to try your technology.”

Martha Smith-Blackmore, DVM, President of Forensic Veterinary Investigations, LLC – Boston, MA

The MiDOG All-in-One Microbial Test is our new gold standard of pathogen identification. The results are so accurate and valuable – especially with assessing both bacterial and fungal infections with the same sample.

Thank you MiDOG!”

Kathy Wentworth, DVM, Diplomate ABVP Canine and Feline Practice – PetPoint Medical Center, Irvine, CA

“The MiDOG staff was extremely helpful and supportive.”

Cathy Curtis, DVM – London, UK

“I have had great results using the MiDOG Test. Compared to traditional culture tests, I am better able to target the treatment for dogs because the MiDOG Test is so sensitive that it identifies all pathogens, including bacteria and fungi, as well as antibiotic sensitivity.

The cost and turnaround time are about the same as a culture test, but I get much more data. The test has great performance, and I believe the NGS technology will be a game changer for veterinarians treating dogs with lesions or other infections.”

Michael Kavanagh, DVM, Practice owner – Saddleback Animal Hospital, Tustin, CA

“It’s helpful to have an NGS spectrum because it gives you a broader insight of what’s happening and what might be going on.”

Richard Harvey BVSc DVD DipECVD PhD FRSB FRCVS – European Specialist in Veterinary Dermatology – Head of Dermatology, Willows Veterinary Centre & Referral Service – Solihull, England UK

“I have been using MiDOG for over 4 years now, and exclusively as my test of choice for all cultures for 3 years.  It is so great to submit a culture and feel confident that there will be a result when it comes back, especially for urine cultures.  The reports were intimidating at first because they contain so much information.  After the first few, I am now quickly able to glance over it and pick out the highlights.  I can then come back later and pore over all the details.  I have been extremely pleased with my patients’ results using the test as well.  I don’t envision ever going back to traditional culture and susceptibilities again.”

Brian M. Urmson, DVM, Columbiana Veterinary Associates

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Dr. Melissa Giese, Chicago Exotics Animal Hospital

“MiDOG’s diagnostic approach offers the unique ability to identify pathogens that evade traditional culture and sensitivity testing. I have found that adding a molecular based testing approach in the form of Next Generation Sequencing (NGS) from MiDOG to my routine diagnostic cultures can be extremely helpful in the identification and diagnosis of uncommon pathogens in veterinary medicine.”

Dr. Wayne Rosenkrantz, Animal Dermatology Clinic – Tustin

“She [Dr. Krumbeck] really did a great job of making complicated concepts accessible and demonstrating the value of your services. I’m really looking forward to working with MiDOG on my research project!”

Dr. Yaicha Peters, Animal Dermatology Clinic – San Diego

“As a proud collaborator with MiDOG, I deeply appreciate their dedication to fostering partnerships between industry and veterinary experts. Their commitment to enhancing diagnostic quality for veterinarians is commendable. In my experience, their support has been invaluable, earning them a ‘Double A+, Triple Star’ rating. Their assistance has been faultless, contributing significantly to the success of my projects and studies. I eagerly anticipate our continued collaboration.”

Dr. Richard Harvey, BVSc DVD DipECVD PhD FRSB FRCVS; European Specialist in Veterinary Dermatology

“We’re seeing that, if we prescribe too many antibiotics or they’re taken too frequently, animals are developing inappropriate or pathogenic strains of bacteria. We’re also seeing that our antibiotics are just not working against them anymore… It’s a good example of why we need better diagnostic testing, like MiDOG, so that we’re selecting the correct antibiotic every time our patients have an infection.”

Dr. Alissa Rexo, DVM, CVA, DACVD, Mid-Atlantic Veterinary Dermatology

“The NGS technique as offered by MiDOG is wonderful because pathogens like Melissococcus plutonius, for example, are difficult to grow and keep alive in the laboratory. A standard laboratory cannot truly examine or even properly diagnose this pathogen in bee hives at this time. But with NGS, we can reliably diagnose it.”

Dr. Joerg Mayer, Entomologist and Microbiologist at the University of Georgia

“For me, as a clinician and as a researcher, I see the immense value in the product [the All-in-One Test]. I have had great success using MiDOG clinically, including identifying Mycoplasma in a 24 year old pigeon, a Nannizziopsis spp in a ball python from a large pet distributor, Mycoplasma and Fusobacterium necrophorum co-infection in a peacock, and to identify an abnormal gut GI in a technician’s dog that tested negative for everything else (but we were able to establish what was abnormal, and work toward fixing it).”

Dr. Jeremy Rayl – Veterinarian, Block House Creek Animal Hospital, Cedar Park, Texas

“With MiDOG results, I not only receive a list of organisms detected in the sample, but also cell counts, which allow me to target the most abundant pathogens or the most pathogenic. The identification of antimicrobial resistance genes is also helpful in selecting an appropriate antibiotic. Another benefit is that sample handling is less prone to the risk of overgrowth and is stable at room temperature. Easy and informative. A great tool in our diagnostic toolbox!!”

Lauren Palmer DVM, MPH, Marine mammal Care Center Los Angeles

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Patricia Latas, DVM, Wild Parrot Coalition

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Dr. Tara Klimovitz, Stay Pet Veterinary Hospital