Ehrlichia Infection in Dogs
What are Ehrlichia?
Ehrlichia, named for the Dr. Ehrlich who first described them, are a type of bacteria that infect and live within the white blood cells of their hosts. Different types of Ehrlichia live in different types of white blood cells. Hosts can be human, pet, or wild animals. Ehrlichia are spread from host to host by tick bites and their intracellular location makes them difficult to remove as most antibiotics do not penetrate to the inside of cells.
The Crazy Ehrlichia Name Game
Ehrlichia were originally grouped according to the type of white blood cell they attacked. The granulocytic line of white blood cells, used by the body in attacking more acute inflammatory invaders, has a lobulated nucleus and characteristic blood cell appearance. The monocytic line, used by the body for chronic forms of inflammation, has a more rounded nucleus. By finding Ehrlichia inside certain types of white blood cells, one could get a better idea for which type of Ehrlichia one was seeing. Or so we foolishly thought.
Ehrlichia equi - lives in what are called granulocytes (a type of white cell).
- Ehrlichia lewinii - lives in granulocytes as well.
- Ehrlichia canis - lives in what are called monocytes (a different type of white blood cell).
- Ehrlichia risticii (agent of Potomac Fever of horses) - also lives in monocytes.
- Ehrlichia platys - lives in platelets (blood clotting cells).
- With the advent of more specific molecular biology it was found that the rules above are not absolute. Today, RNA sequencing is used to identify the Ehrlichia at hand. In fact, some of the organisms previously believed to be Ehrlichia have been completely reclassified into other groups. We mention this as old terminology dies hard and many people still use the old names of organisms. Here is a current list of the organisms currently classified as Ehrlichia as of a massive renaming/reclassification that occurred in 2001:
- Ehrlichia canis (mostly a dog infection)
- Ehrlichia lewinii (mostly a dog infection)
- Ehrlichia chaffeensis (mostly a human infection)
- Ehrlichia ruminantium
- (Ehrlichia risticii is now reclassified as Neorickettsia risticii and Ehrlichia platys are now reclassified as Anaplasma platys. Ehrlichia equi, Ehrlichia phagocytophila, and Human Granulocytic Ehrlichial Agent have been deemed to all be the same species and have been reclassified as Anaplasma phagocytophila).
What is Tropical Pancytopenia?
Although it was known that dogs could be infected with Ehrlichia, the scope of the illness created became evident during the Viet Nam war as the military German Shepherd Dogs became ill with an infection that seemed to wipe out their blood cells. White blood cells as well as red blood cells were affected and the disease was named tropical canine pancytopenia. This condition was studied and found not to be limited to Southeast Asia but was in fact in the good old U.S.A. as well. In the 1980s it became clear that people could be infected by Ehrlichia, though not the same Ehrlichia as for dogs, and research intensified.
German Shepherd Dogs are said to get a particularly severe form of Ehrlichia infection.
What Ticks are Involved with Ehrlichia?
Different Ehrlichia species are spread by different types of ticks. (What ticks are located in a particular area limits what types of Ehrlichia infections are seen regionally.)
The Brown Dog Tick (Rhipicephalus sanguineus) usually spreads Ehrlichia canis, Ehrlichia lewinii, and other diseases.
The Lone Star Tick (Amblyomma americanum) is the main vector of Ehrlichia lewinii.
It is important to note, where there are ticks there are many tick-borne diseases: Lyme disease, Babesia infection, Anaplasma, Ehrlichia, and probably some agents we do not even know of yet. It is not surprising for a given patient living in a tick area to be infected with multiple blood parasites.
When Dogs get Sick
There are three phases of illness with Ehrlichiosis: acute, subclinical, and chronic.
- ACUTE PHASE: This is generally a mild phase and occurs 1 to 3 weeks after the host is bitten by the tick. The Ehrlichia organism is replicated in this time period and attaching to white blood cell membranes. During this time the platelet count will drop and an immune-mediated platelet destruction will occur. The dog will be listless, off food, and may have enlarged lymph nodes. There may be fever as well but rarely does this phase kill a dog. Most dogs clear the organism if they are treated in this stage but those that do not receive adequate treatment will go on to the next phase.
- SUBCLINICAL PHASE: In this phase, the dog appears normal. The organism has sequestered in the spleen and is essentially hiding out there. Dogs can stay in this phase for months or even years. The only hint that Ehrlichia is hiding is a somewhat reduced platelet count and/or elevated globulin level on a blood test. The blood protein level on a lab report is divided into albumin (an important carrier protein) and globulins (every other blood protein including antibodies.) Long-term stimulation of the immune system will elevate globulins.
- CHRONIC PHASE: In this phase the dog gets sick again. Up to 60% of dogs infected with Ehrlichia canis will have abnormal bleeding due to reduced platelets numbers. Deep inflammation in the eyes called uveitis may occur as a result of the long-term immune stimulation. Neurologic effects may also be seen. Glomerulonephritis, which results in serious urinary protein loss, can also occur. Increased globulin levels are almost always seen in this stage, and albumin is often low. Most dogs in the U.S. do not show the full pancytopenia (literally reduction in all blood cell lines).
Infections with Ehrlichia lewinii tend to produce arthritis in addition to the above scenario.
How the Diagnosis is Made
Diagnosis does not rest on a single test but instead on a collection of results. The first step is to find a constellation of typical findings:
- A dog with fever, enlarged lymph nodes, bleeding, or arthritis in multiple joints.
- Low platelet numbers, high globulin levels, and mild anemia on blood testing.
When Ehrlichiosis is suspected, a blood test for antibodies against Ehrlichia organisms can be ordered. A positive test indicates that the dog has been exposed to Ehrlichia and does not imply active current infection necessarily. A negative titer does not fully rule out Ehrlichia, either, as a very sick patient will be too sick to produce antibodies and an early case may not yet have started to produce antibodies.
The antibody level or titer can be done with an IFA (immunofluorescent antibody) or by ELISA (enzyme-linked immunosorbent assay). The IFA test is the traditional one and can be positive 7 to 28 days after the dog has become infected. The ELISA test is included in a new in-house test kit from IDEXX labs (the snap 4DX test) that also includes a Lyme disease test and a heartworm test. The 4DX test is geared specifically to detect antibodies against Ehrlichia canis. It is not entirely clear if antibodies against other types of Ehrlichia will be similar enough to be detected by either the IFA or ELISA tests reliably. It takes 6 to 9 months after infection for titers to begin to drop.
Recently PCR testing for the presence of Ehrlichia organisms has become available. The disadvantage of this test is that it gives either a positive or negative result rather than a quantitative number that can be tracked. Using a combination of PCR testing and antibody titers is currently recommended by the American College of Veterinary Internal Medicine. PCR testing remains positive for several weeks after infection has cleared as PCR testing does not distinguish between live and dead organisms. It takes time to clear dead organisms from the body.
If one is lucky one will actually see the organisms on a blood smear, and this, of course, clinches the diagnosis.
Despite being one of the oldest antibiotics in use, tetracycline is probably the most effective against Ehrlichia (and any other intracellular blood parasite for that matter). Doxycycline, a more modern derivative, has a more convenient dosing schedule and has become more popular. Expect at least a month of treatment to be needed. Response is initially rapid (improvement is notable in the first few days).
If immune-mediated secondary reactions to the Ehrlichia are a problem (such as immune-mediated arthritis, or immune-mediated platelet loss) corticosteroids such as prednisone can be used to palliate the situation while the antibiotics are starting to work.
After infection, it is possible to become re-infected; immunity is not lasting after a previous infection.
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