Canine tick-borne diseases: When to treat a positive patient-side test result

At a recent session on vector-borne diseases in dogs, CVC educator Adam Birkenheuer, DVM, PhD, DACVIM, leads with this joke:

What is the No. 1 presenting complaint of ehrlichiosis in a dog?

A wellness exam. 

First scenario: You just completed a wellness exam on an apparently healthy, 3-year-old Labrador retriever that's bouncing off the wall. Everything looks good until you check the result on your patient-side, rapid diagnostic test and see a positive result for Ehrlichia canis. What do you do next?

Second scenario: A dog presents with fever, thrombocytopenia, proteinuria and painful joints, but the test results are negative. What do you do next?

Don't feel bad if you're not sure. In the words of Dr. Birkenheuer, tick-borne disease is “kind of a pain” and nobody really feels like they know what they're doing.

In tick-borne disease, signs are caused by Type 2 and/or Type 3 immune-mediated hypersensitivities that affect multiple systems in the body, and the same pathogen in the same host can cause completely different signs. Furthermore, tick-borne diseases can be difficult to replicate in laboratory settings, making them difficult to completely understand. However, despite all that, Dr. Birkenheuer has some recommendations that may help you communicate to clients, choose appropriate diagnostics and make treatment recommendations for tick-borne disease.

The detection of antibodies indicates exposure to disease-causing organisms; the presence of antibodies does not always indicate disease.

Positive test results for tick-borne infections in apparently healthy animals can occur, but what do they mean? These in-house tests detect the presence of serum antibodies to tick-borne organisms (e.g. Borrelia burgdorferi, Anaplasma phagocytophilum/Anaplasma platys, Ehrlichia canis/Ehrlichia ewingii/Ehrlichia chaffeensis). The detection of antibodies indicates exposure to disease-causing organisms; the presence of antibodies does not always indicate disease.

So keep in mind that these tests should be used to screen for exposure and not to definitively diagnose an active infection or disease.

What do you do with a “healthy” dog that has a positive test result?

First, before testing, Dr. Birkenheuer recommends controlling the pet owner's expectations of what the test can detect. Instead of telling your client that you are testing for tick-borne disease, explain that you'll be testing to see whether her dog has been exposed to ticks and some of the infections they carry. Dr. Birkenheuer cautions against fearmongering-your clients are less likely to freak out if you tell them that their dogs have been exposed to ticks vs. that their dogs have Lyme disease.

“We need to run some further tests … You definitely should be using flea and tick prevention on your dog.”

In regards to positive test results in “healthy” dogs, Dr. Birkenheuer says the following to clients: “This tells me that your dog has been exposed to ticks-enough that infection may have been transmitted. We need to run further tests, including a complete blood count with a slide review, serum chemistry profile and urinalysis, to see whether your dog has evidence of disease. You should definitely be using flea and tick prevention on your dog.” Run the tests and get more information, so you can call the client later and accurately talk about the dog's health. This type of communication is a win-win for many reasons:

> You reduce anxiety for both you and your client.

> You get the owner's agreement for further testing.

> You don't lengthen the appointment.

> You increase compliance with flea and tick preventives.

Dr. Birkenheuer says it helps to mention the human health angle too. Most dogs go where their humans go, and a pet owner with a dog that has a positive test result for Borrelia burgdorferi has a risk of being exposed to disease-carrying ticks as well.

Dr. Birkenheuer recommends yearly testing with a CBC, serum chemistry profile and urinalysis for a dog that tests positive for exposure.

Dr. Birkenheuer recommends yearly testing for a dog that tests positive for exposure: a complete blood count (CBC), a serum chemistry profile, visual inspection of a blood smear and a urinalysis. Why yearly? While doxycycline alleviates signs of disease in dogs that have positive test results for Ehrlichia canis, a study showed that the organism was detected in dogs treated for 14 days with doxycycline and also in ticks that were fed on the treated dogs.1 This suggests that some treated dogs might remain reservoirs of tick-borne disease. Therefore, he thinks even dogs that are treated should be screened yearly for disease.

Laboratory abnormalities to screen for include anemia, thrombocytopenia, hyperglobulinemia and proteinuria. Sometimes the changes are subtle. Dr. Birkenheuer recommends treating any dog with a platelet count lower than 200,000. If the platelets counts don't increase adequately in serial CBCs, then look for another cause of thrombocytopenia. He also recommends re-evaluating the dog once more and performing a fundic examination to look for retinal lesions. Any abnormalities? Treat with tetracyclines-Dr. Birkenheuer recommends doxycycline or minocycline (10 mg/kg/day for 28 days).

What do you do if the owner won't approve further testing or if further tests don't show abnormalities?

At present, there are no clear evidence-based recommendations, Dr. Birkenheuer says, so the decision needs to be made by you and the client-you give the information and the client helps make the decision. It helps if your practice partners develop similar styles and education plans for owners to minimize confusion. What would Dr. Birkenheuer do if his own dog had a positive test result? He thinks he would treat with tetracyclines. Whether or not you treat, recommend yearly CBCs for the rest of the dog's life.

What if you do treat, and the test results remain positive?

Dr. Birkenheuer thinks a persistent positive test result after treatment means nada. Zip. Zilch. In some animals, you treat them and they test negative. In other animals, you treat and they maintain a persistent antibody response and test positive. It is impossible to tell if a persistent positive test result means persistent infection or reinfection or is simply a persistent immune response that is expected in some dogs. For these reasons, persistent positive test results are not diagnostically valuable. What you should be looking for is evidence of exposure to different organisms, as Dr. Birkenheuer says this is evidence of inadequate flea and tick prevention.

What if you have a sick dog and suspect tick-borne disease?

Dr. Birkenheuer recommends broader testing with sample submission to an outside laboratory for serology and polymerase chain reaction (PCR) testing in parallel.

Many of the infections can look a lot alike! Co-infections of tick-borne diseases are also common, Dr. Birkenheuer reminds us-up to half of all patients with positive test results for tick-borne diseases may have evidence of co-infection or co-exposure.2 Therefore, it is important that your tick-borne disease testing includes some of the less common infections. And if you diagnose immune-mediated hemolytic anemia (IMHA), Dr. Birkenheuer says to test forBabesia and Bartonella species. (Ehrlichiosis only rarely seems to cause IMHA, and Lyme disease and Rocky Mountain spotted fever are not associated with IMHA.)

None of the tests out there are perfect. You can have false negative results. If the dog is acutely ill (less than two weeks), the dog hasn't had a chance to mount an immune response, and antibody test results may be negative. Paired titers are recommended, and a fourfold increase is diagnostic. If the dog has been sick for a long time, only one titer is needed.

A negative result on a PCR cannot rule out infection.

While a PCR test is fast and cheap-and although a positive result means infection-a negative result cannot rule out infection. In PCR testing, only 1 to 10 µl of blood is tested. Dr. Birkenheuer uses the analogy of fish in the ocean. If you scoop a bucket of water out of the ocean and there's a fish in it, then you've proven there are fish in the ocean. If you don't get fish, that doesn't disprove the presence of fish in the ocean. The same goes for blood-borne organisms.

Don't forget empirical treatment! Even if all the test results are negative, failure to respond to treatment makes Dr. Birkenhauer more comfortable moving on to the next differentials. Of course, not all tick-borne diseases respond to doxycycline, so treatment alone is not a replacement for testing.

References

1. Schaefer JJ, Needham GR, Bremer WG, et al. Tick acquisition of Ehrlichia canis from dogs treated with doxycycline hyclate. Antimicrob Agents Chemother 2007;51(9):3394-3396. Available here.

2. Maggi RG, Birkenheuer AJ, Hegarty BC, et al. Comparison of serological and molecular panels for diagnosis of vector-borne diseases in dogs. Parasit Vectors 2014;7:127. Available here.

Sarah Wooten, DVM, divides her professional time between private practice at Sheep Draw Veterinary Hospital in Greeley, Colorado, and writing articles and filming video content for various media outlets.