The diagnostic challenge of leptospirosis

Leptospirosis is an infectious, zoonotic disease that is found throughout the United States. It is caused by a spirochete, which is present in moist environments after being shed in the urine of reservoir hosts such as raccoons and rats. Because it can affect dogs of any age, breed, and size, and the clinical signs can be vague, it is likely under-diagnosed in veterinary patients. “If you’re not testing for it, you won’t see it,” said Jessica Pritchard, VMD, MS, DACVIM, clinical assistant professor at the University of Wisconsin School of Veterinary Medicine.

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Due to its zoonotic potential, veterinarians should stay vigilant for the disease to protect our staff, clients, and other patients. Making the diagnosis can be challenging and understanding which patients to test and which tests to use is critical to accurately diagnosing the disease. During a session at the 2023 Fetch Coastal conference, Pritchard discussed current recommendations for the diagnosis, treatment, and prevention of leptospirosis.¹

Clinical presentation

“What a lot of us learned in vet school is leptospirosis is an icteric dog with renal failure,” said Pritchard. “But it can also be azotemia without liver involvement, liver involvement without azotemia, both, or, frustratingly, neither.” In a study of 51 dogs definitively diagnosed with leptospirosis, 75% had azotemia, 14% had liver involvement alone, and 1 dog had pulmonary involvement.² The most common clinical signs included anorexia, vomiting, lethargy, and polyuria and polydipsia (PU/PD).² Pulmonary involvement appears to be more common in Europe.

There are no pathognomonic clinical signs or laboratory changes. What is seen in the patient and on lab work will depend on which organs are affected by the leptospires. Dogs are exposed when the organism passes through their mucus membranes from the environment. Following infection, the leptospires travel through the blood stream to their organ of choice. Laboratory changes may include any combination of azotemia, elevated alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin.

“Because of all the different places lepto goes [in the body], diagnostics can be challenging,” Pritchard advised, stressing the importance of the timeline of infection:

• Day 0: Mucosal penetration of infectious organisms
• Day 4: Significant leptospiremia is present due to organism replication. IgM is measurable.
• Day 5-7: Vascular damage and thrombocytopenia can be observed.
• Dat 7: Clinical signs are noticeable.
• Day 10: Leptospiremia is clearing, and IgG levels increase.
• Day 15: Renal colonization has occurred (if it is going to) and urine shedding begins.

Diagnostic testing

Understanding the timeline of infection allows veterinarians to choose the tests that are most likely to give them a definitive diagnosis. Often, multiple tests are required. Tests either look for the organism directly or detect exposure through the presence of antibodies.

Direct detection of the organism is done through polymerase chain reaction (PCR) testing, which looks for Leptospirosis DNA. A positive PCR test demonstrates an active infection and is not influenced by prior disease or vaccination. However, a negative test does not rule out infection. Pritchard uses a fishing analogy to explain this to clients: just because you don’t catch a fish (or get a positive PCR) doesn’t mean there aren’t any fish (or Leptospires) at all, it means there aren’t any in the small area you checked.

PCR can be performed on urine, blood, or both. The best sample to submit will depend on where you think you are in the disease timeline and where you think the organisms are most likely to be. Samples should be collected prior to starting antibiotics, as even a short course of antibiotics can create a false negative.

Indirect tests look for antibodies in the submitted sample. The microscopic agglutination test (MAT) is used most commonly. One advantage to this test is that it may identify the serovar that is the cause of the infection. Because this test must be sent to a specific laboratory for testing, results will be delayed. Additionally, the test can be positive for 3 reasons: current infection, previous vaccination, or previous exposure.

Point of care antibody tests are available to provide more rapid results. The SNAP Lepto test from IDEXX looks for antibodies to the most abundant outer membrane protein in pathogenic strains (LipL32). While it provides rapid results, it can be affected by vaccination status. The Witness IgM test from Zoetis is also available as a point-of-care test. It appears to have high sensitivity and specificity, is less likely to be affected by vaccination, and tests for IgM, which can be detected by day 4 of infection, potentially providing an earlier diagnosis.

Pritchard’s recommendation is to draw samples for PCR and an acute MAT when leptospirosis is suspected then start antibiotic therapy. If the PCR test is positive, the diagnosis is clear. If the PCR test is negative, a convalescent MAT will be needed to demonstrate at least a 4-fold rise in antibody levels and confirm infection. Pritchard encourages veterinarians to confirm the diagnosis with paired titers because of the zoonotic potential. One recommendation is to charge for the paired titers up front to encourage clients to bring their pet back for the second sample.

Treatment, prognosis, and prevention

“Treatment for leptospirosis, unlike diagnosis, is actually pretty easy,” Pritchard said. In early stages of disease, potentiated penicillins are used to clear leptospiremia. Doxycycline at 5 mg/kg BID for 14 days is required to clear the tissues. Overall, an 80% survival rate for the disease is reported, though some patients need dialysis to survive, which is not an option for every client, due to location and/or cost. Those with pulmonary involvement often have a worse prognosis.

Pritchard shared that “the thing that is frustrating for me about leptospirosis and seeing it so commonly is that this is a vaccine preventable disease.” While leptospirosis is classified as a lifestyle vaccine in the American Animal Hospital Association’s vaccination guidelines,³ recent studies have shown that all dogs can be at risk, including small breed dogs.⁴ Though many clients worry about the safety of the Leptospirosis vaccine, adverse events are rare.⁵

Take-home points

Leptospirosis is found throughout the United States and is likely more common than once thought. Accurate diagnosis is essential for both treatment of the patient and protection of humans from zoonotic disease. Achieving an accurate diagnosis often requires multiple tests, and the best test choice will vary based on how long ago the patient was infected. Once samples are collected, treatment can be instituted. All dogs should be considered candidates for leptospirosis vaccine as the disease is widespread but highly preventable by vaccination.

References

1. Prtichard J. Leptospirosis updates: Current concerns and protecting our patients. Presented at Fetch dvm360 conference; Atlantic City, NJ. October 9-11, 2023.
2. Tangeman LE, Littman MP. Clinicopathologic and atypical features of naturally occurring leptospirosis in dogs: 51 cases (2000-2010). J Am Vet Med Assoc. 2013;243(9):1316-22.
3. Ellis J, Marziani E, Aziz C, et al. 2022 AAHA Canine vaccination guidelines. J Amer Anim Hosp Assoc. 2022;58:1-19. doi: 10.5326/JAAHA-MS-Canine-Vaccination-Guidelines
4. Lee HS, Guptill L, Johnson AJ, Moore GE. Signalment changes in canine leptospirosis between 1970 and 2009. J Vet Intern Med. 2014;28(2):294‐9.doi: 10.1111/jvim.12273
5. Moore GE, Morrison J, Saito EK, et al. Breed, smaller weight, and multiple injections are associated with increased adverse event reports within three days following canine vaccine administration. J Am Vet Med Assoc. 2023;14:1-7. doi: 10.2460/javma.23.03.0181