Vol. 24, No.

4 April 2002

277
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The Increasingly
Complicated Story
of Ehrlichia
KEY FACTS
University of Missouri-Columbia
Ehrlichial infection can result in
a wide range of manifestations
(from inapparent infection to
fatal illness).
Diagnosis can be problematic
because not all species of
Ehrlichia produce cross-reactive
antibody titers and positive titers
may reflect either inactive
infection or past exposure.
Dogs and other domestic species
have the potential to harbor ticks
that can transmit certain types of
ehrlichiosis to humans.

Diane E. Preziosi, DVM, DABVP*

Leah A. Cohn, DVM, PhD, DACVIM
ABSTRACT: Ehrlichiosis, once viewed as a rare disease in the United States, has become an
increasingly common diagnosis in many regions of the country. Although Ehrlichia canis was
the first species described and remains the best understood, many other species of Ehrlichia
are now known to infect dogs. The recognition of new types of ehrlichial infections has added
complexity to the diagnosis of ehrlichiosis. The importance of these pathogens has increased
with the recognition of human ehrlichiosis.

hrlichial infection was first recognized as a cause of canine disease in Algeria circa 1935.1 Veterinarians in the United States did not become familiar
with this disease until the Vietnam War era when military working dogs,
including many that had never left the country, developed what was then known
as tropical pancytopenia caused by Ehrlichia canis.2,3 Since then, other species of
Ehrlichia that cause disease in dogs have been identified. Classification of these
ehrlichial species has been reorganized, diagnostic testing options have increased,
and additional manifestations of ehrlichiosis have been recognized in a wider
geographic area. In the mid-1980s, an ehrlichial species was recognized as a
cause of disease in humans in the United States; since then, various other species
have been found to infect humans as well. Some ehrlichial species that infect
dogs can also infect humans (through tick bites), leading to concerns about the
role of dogs in harboring a disease that may be transmitted to humans. This article addresses these developments and their importance in the understanding,
diagnosis, and treatment of ehrlichiosis primarily in dogs.

CLASSIFICATION
Ehrlichia are gram-negative obligate intracellular bacteria that lack
lipopolysaccharide endotoxins and rely on arthropod vectors for transmission.
For many years, E. canis was the only ehrlichial species known to cause disease in
dogs, and it is by far the best described veterinary ehrlichial pathogen. Several
additional Ehrlichia species that infect dogs as either primary or incidental hosts
are now recognized. Previous classification schemes have made use of the cell
*Dr. Preziosi is currently affiliated with the University of Pennsylvania.

278 Small Animal/Exotics

Compendium April 2002

Table 1. Ehrlichial Agents Known to Infect Dogs

Type
Genogroup I
Ehrlichia canis
Ehrlichia chaffeensis
Ehrlichia ewingii
Genogroup II
Ehrlichia phagocytophila
Ehrlichia equi
Agent of human
granulocytic ehrlichiosis
Ehrlichia platys
Genogroup III
Ehrlichia risticii
Neorickettsia helminthoeca

Target Cells

Major Host

Known Vector(s)

Mononuclear cells
Mononuclear cells
Granulocytes

Dogs
Humans
Dogs

Rhipicephalus sanguineus
Amblyomma americanum, Dermacentor variabilis
R. sanguineus, A. americanum, D. variabilis

Granulocytes
Granulocytes
Granulocytes

Ruminants
Equidae
Humans

Ixodes ricinus
I. ricinus, Ixodes pacificus
Ixodes scapularis, I. ricinus, I. pacificus

Platelets

Dogs

R. sanguineus

Monocytes, enterocytes Equidae

Monocytes
Dogs

type infected by the ehrlichial organism. Although this

has proven useful, several species, such as Ehrlichia
ewingii, Ehrlichia chaffeensis, Ehrlichia risticii, and
Ehrlichia phagocytophila, may infect more than one cell
type. 4,5 Current classification schemes are based on
genetic analysis of the organisms 16S rRNA gene
sequence. This method produces three species
genogroups, with the members of any one genogroup
commonly producing cross-reactive antibody titers.58
Despite close genetic relatedness, the individual species
within a genogroup may infect different cells within
different hosts, use different vectors, and have different
geographic distributions (Table 1).

EPIDEMIOLOGY
Most ehrlichial species rely on arthropod vectors for
transmission, although the specific vectors are not well
described for every species of Ehrlichia. The geographic
distribution pattern of various ehrlichial species is
related to the distribution of the relevant vector(s). The
predominant vector for E. canis is the brown dog tick
(Rhipicephalus sanguineus), which is found worldwide.9,10
Accordingly, E. canis has been reported in dogs from
Africa, Europe, Asia, the Middle East, and the United
States. In contrast to E. canis, E. ewingii is known to use
at least three different vectors. In addition to R. sanguineus, both Dermacentor variabilis (American dog
tick) and Amblyomma americanum (lone star tick) are
capable of transmitting E. ewingii infection.10 The primary distribution of the lone star tick in the midwestern
and southeastern United States may account for the
increased incidence of E. ewingii infection in these
regions.5,6,10 Ehrlichia equi infection, which is transmitted by Ixodes ticks, is most often reported in the upper

Arthropods
Flukes

midwestern and northeastern United States.7,11,12

In addition to ticks, other known vectors of ehrlichial
infection include snails and flukes. E. risticii, the
causative agent of Potomac horse fever, is transmitted
through the ingestion of snails and can cause infection
in dogs as well as horses.13 Although not often thought
of as an ehrlichial species, Neorickettsia helminthoeca,
the causative agent of salmon poisoning disease,
belongs to the same genogroup as E. risticii. During a
complex life cycle, it is transmitted to dogs through the
ingestion of flukes harbored in certain types of fish.14
The vectors of some ehrlichial species that affect dogs
remain incompletely defined.
Concurrent infection with multiple arthropod-borne
pathogens is possible and may contribute to illnesses
described in some Ehrlichia-positive dogs. Dogs that
harbor one tick are likely to harbor several (of either the
same or different species). In addition, the same arthropod may serve as transmission vector for several genera
and species of infectious agents. For instance, R. sanguineus is capable of transmitting not only E. canis and
E. ewingii, but Babesia canis and Babesia gibsoni as
well.2,10,1517 Ixodes ticks, competent vectors for transmission of E. equi and the agent of human granulocytic
ehrlichiosis (HGE), can also transmit infection with
Borrelia burgdorferi and Babesia microti.1821 In addition
to many case reports in the literature describing such
concurrent infections, serologic surveys have documented these cases on a larger scale. In one such study,6
almost 50% of dogs diagnosed with Ehrlichia also harbored Bartonella vinsonii. Concurrent seropositivity has
also been documented for B. burgdorferi and E. canis.18
Such simultaneous infections may worsen the severity of
observed disease and impact the outcome of treatment.

Compendium April 2002

TRANSMISSION AND PATHOGENESIS

The transmission and pathogenesis of canine ehrlichiosis are best understood for E. canis infection. E.
canis organisms gain entry via salivary secretions during
the bite of an infected tick.4 Ticks acquire the organism
during their larval or nymph stage when they feed on
an infected canid. Infection is spread when the tick
feeds again on a new host. Because transovarial transmission does not occur, the tick vector cannot serve as a
reservoir of disease.4 Ticks can remain infected for long
periods, however, allowing for disease transmission in
early spring after the infected tick has overwintered.
The course of clinical infection with E. canis is traditionally divided into three stages, which vary in
length. These stages may be difficult to differentiate
in natural infections.4,22,23
Acute Phase
The acute phase occurs 1 to 3 weeks after the
infected tick bites a dog.9 During this phase, the organism invades leukocytes and divides to form morulae,
which are colonies bound by a vacuolar membrane.
Usually a specific ehrlichial species preferentially
invades either mononuclear or granulocytic leukocytes.
E. canis, E. chaffeensis, and E. risticii invade mononuclear cells, whereas E. ewingii, E. phagocytophila, and E.
equi invade granulocytic neutrophils or eosinophils
(Table 1). During acute infection, the most consistent
hematologic change is the development of thrombocytopenia.24 This multifactorial change results from vascular endothelial inflammation with resulting platelet
consumption, immunologically mediated destruction
of platelets, and splenic sequestration of platelets.9,24,25
Interestingly, thrombocytopenia seems to be a common
finding during infection with all species of Ehrlichia
described thus far. In addition to thrombocytopenia,
thrombocytopathia may accompany E. canis infection.26 Hyperglobulinemia during acute E. canis infection is usually the result of a polyclonal gammopathy,
but the gammopathy does not seem to be caused by
ehrlichial-specific antibody production.9,27 Few dogs
succumb to the acute disease; most either clear the
organism (likely via cell-mediated immunity) or enter
the subclinical stage of infection.4,9
Subclinical Phase
The subclinical phase of E. canis infection is characterized by persistence of the organism in the host in the
absence of clinical illness. It appears likely that organisms are retained at low numbers in splenic mononuclear cells during subclinical infection.28 The length of
the subclinical phase may range from weeks to years; in
fact, it is not known what percentage of subclinically

Ehrlichiosis 279

infected dogs will ever develop clinical illness. In a single study of naturally infected dogs, 53% demonstrated
positive E. canis antibody titers 4 years after the presumed time of infection but remained clinically asymptomatic. Many of these dogs did, however, demonstrate
abnormalities suggestive of ehrlichial disease on complete blood cell counts (e.g., hyperglobulinemia,
thrombocytopenia).29 Although subclinical infection is
well documented for E. canis, it is less clear whether
other Ehrlichia species also induce persistent but subclinical infections. In at least one case,12 E. ewingii
morulae were observed in an asymptomatic dog.

Chronic Stage
The pathogenesis of the chronic stage of E. canis infection is poorly understood because adequate models are
not available. Not all infected animals progress to the
chronic stage, and the factors that influence progression
are still unknown. Persistent E. canis infection results in
persistent antibody formation (both nonspecific and
ehrlichial directed).9,30,31 Unfortunately, humoral immunity to E. canis provides no protection.4,32 In fact, many of
the manifestations of chronic ehrlichial disease may result
from an exuberant but nonprotective humoral immune
response.4,9 As in the acute stage, hemorrhagic tendencies
may be related to either thrombocytopenia or thrombocytopathia. In addition to the mechanisms mentioned
previously, hyperglobulinemia associated with chronic
infection is often more pronounced, and hyperviscosity
syndrome with resultant thrombocytopathy may result.26
Glomerulonephritis may result from the deposit of antigenantibody complexes with resultant inflammatory
damage.23 Bone marrow hypoplasia has been a classic
finding associated with chronic E. canis infection and
may result in pancytopenia.3,22,23 Nonregenerative anemia
commonly associated with chronic E. canis infection may
be caused by either anemia of inflammatory disease or by
pancytopenia due to bone marrow hypoplasia.22,23,33 Concurrent infectious diseases documented in dogs with E.
canis have been attributed to immunosuppressive effects
of chronic infection.23
CLINICAL FINDINGS
Ehrlichia canis
Clinical findings associated with E. canis infection
vary tremendously and are likely influenced by the
strain of organism, host immune status, and breed of
animal.4,34 German shepherds are classically thought to
be more susceptible to infection and to have a more fulminant course of infection than dogs of other
breeds.3436 By definition, no clinical signs are apparent
during the subclinical phase of infection, although
hematologic abnormalities may be identified.29 Often,

280 Small Animal/Exotics

either the acute stage of infection goes unnoticed or

signs are mild enough that owners do not seek veterinary care for their pets. When dogs are evaluated during
the acute stage of infection, signs are largely nonspecific
and include lethargy, fever, anorexia, weight loss,
splenomegaly, and generalized lymphadenopathy.4,37
Most diagnoses of E. canis infection occur during the
chronic stage of infection. As occurs with dogs presented during the acute stage, the owners of dogs with
chronic ehrlichiosis most commonly report nonspecific
signs, such as lethargy, anorexia, and weight loss.23,34
Signs attributable to bleeding tendencies, including
epistaxis, melena, petechial and/or ecchymotic hemorrhages, hyphema, retinal hemorrhage, and hematuria,
occur in 25% to 60% of cases.22,23,33,34 Additional physical examination findings include lymphadenopathy,
fever, pale mucous membranes, and splenomegaly.22,23,33,34
Anterior uveitis, retinal changes, or neurologic abnormalities are noted occasionally.23,38 Ataxia, paraparesis,
conscious proprioceptive deficits, head tilt, nystagmus,
and seizures have all been reported as neurologic manifestations of infection.23 The importance of lameness as
a clinical sign of E. canis infection is debatable.
Although lameness is often listed as a clinical sign of
infection in the older literature, many of the animals
displaying lameness were found to have granulocytic
morulae, suggesting that the infection may have been
caused by E. ewingii rather than E. canis.3941 Other clinical signs of chronic E. canis infection relate to complications, including glomerulonephritis with nephrotic
syndrome, or pancytopenia resulting in secondary infections and severe anemia.
Clinicopathologic abnormalities are also nonspecific.
Although normal platelet concentrations do not rule out
chronic ehrlichiosis, most cases display some degree of
thrombocytopenia. 22,23,33,34 Nonregenerative anemia
(often mild to moderate) is also identified in most
cases.22,23 White blood cell counts may fall below, within,
or above reference ranges in dogs with ehrlichiosis.22,23,33
Although hyperglobulinemia has not been reported consistently, it is observed in most cases.22,23,34 Albeit usually
due to polyclonal gammopathy, hyperglobulinemia may
present as a monoclonal gammopathy that can be easily
mistaken for multiple myeloma.27,42 Other serum biochemistry abnormalities noted with some regularity
include hypoalbuminemia, elevated alkaline phosphatase, and elevated alanine transaminase concentrations.22,23,33 Proteinuria may occur independently or concurrently with glomerulonephritis.22,23,33,43,44 Although
early descriptions of E. canis infection were of a tropical
pancytopenia, the pancytopenic manifestations now
appear to account for a small minority of cases in the
United States. Cytologic evaluation of bone marrow

Compendium April 2002

aspirates often displays increased numbers of plasma

cells, with either hypoplasia (suggesting chronic infection) or hyperplasia (suggesting acute or chronic infection) of the other marrow elements.3,22,23,37

Ehrlichia ewingii
E. ewingii is one of two ehrlichial agents known to
result in granulocytic infection in dogs, with the other
agent being E. equi.12 Unfortunately, identification of
granulocytic morulae does not differentiate E. equi infection from E. ewingii infection, which likely predominates in the southern and lower midwestern United
States. Because E. ewingii belongs to the same genogroup
as E. canis, E. canis titers should be positive during infection.12 Many descriptions of granulocytic ehrlichial infection are of dogs with acute-onset polyarthritis, and these
cases have more often than not been ascribed to E.
ewingii infection.5,3941,45 The lameness may involve more
than one leg or appear to shift from limb to limb. Joint
stiffness and occasional joint swelling due to effusion
may be noted, and dogs are often febrile. Splenomegaly
and hepatomegaly have been reported. Bleeding tendencies may be noted, and many infected dogs have mild to
moderate thrombocytopenia.12 Central nervous system
involvement, particularly meningitis, has been
reported.46 Dual infection with both E. canis and E.
ewingii has also been reported in association with profound ataxia and epistaxis.47 Polyarthritis resolves quickly
with appropriate therapy. Fatal granulocytic ehrlichial
infections seem to be extremely rare in dogs.
Ehrlichia equi
As with E. ewingii, the true incidence of E. equi infections in dogs is unknown, but E. equi may account for a
significant proportion of granulocytic ehrlichiosis in the
northeastern and upper midwestern United States and
California, where equine infections are endemic.7,11,12
Experimental infection with E. equi in dogs produced
only mild to inapparent clinical signs, but naturally
infected dogs have presented with nonspecific illness,
including fever, lethargy, and thrombocytopenia.11,48
There are no unique clinical findings attributed to infection with E. equi, but polyarthritis is described less frequently than for E. ewingii.11 Without an index of suspicion, veterinarians may not request the specific diagnostic
testing required to differentiate this ehrlichial infection
from others, and E. canis titers may be negative.11,12
Ehrlichia risticii
E. risticii, the causative agent of Potomac horse fever, can
infect dogs and cats as well as horses. This agent is transmitted not by a tick bite but rather by ingestion of snails,
perhaps explaining why canine infection is not commonly

Compendium April 2002

described. When dogs are infected, lethargy, vomiting,

bleeding disorders, and arthralgia have been reported.13
Because E. risticii belongs to a different genogroup than E.
canis, antibody cross-reactivity may be lacking. Unless
genogroup-specific titers are requested, dogs with E. risticii
infection may display negative ehrlichial titers.13

Ehrlichia chaffeensis
Although E. chaffeensis is primarily notable as a
human pathogen, dogs are also susceptible to infection
with this organism. Experimentally infected dogs seem
to have mild or inapparent disease.49 However, a report
of three dogs infected naturally with E. chaffeensis documented more serious signs, including vomiting, epistaxis, lymphadenopathy, and anterior uveitis.6 Because
E. chaffeensis shares genogrouping with E. canis, routine
titers should prove positive in infected dogs.6
Ehrlichia platys
E. platys is unique among the Ehrlichia species because
of its predisposition for platelets rather than leukocytes.
E. platys does not share serologic cross-reactivity with E.
canis, but co-infections have been documented.8,15,50,51
Although infection with E. platys results in cyclic thrombocytopenia in dogs, it is seldom the cause of clinical

Ehrlichiosis 281

bleeding unless trauma or surgery is performed during

the thrombocytopenic cycle.52,53 The disease manifestations associated with E. platys may be more severe in
strains found outside the United States.5456 Veterinarians
should consider specific testing for E. platys infection in
dogs with recurring evidence of thrombocytopenia for
which another cause (including the more common
ehrlichial infections) cannot be documented.

Feline Ehrlichiosis
The topic of feline ehrlichiosis deserves separate mention from canine ehrlichiosis.57 Cats have been experimentally infected with both E. risticii and E. equi, producing either subclinical infection or mild illness.48,58 To
date, experimental infection with E. canis or E. ewingii
has not been attempted. Naturally occurring feline ehrlichiosis has been documented in only 31 cats worldwide.
These cats presented with various clinical signs, including fever, anorexia, arthropathy, gastrointestinal signs,
and general malaise.57,5962 Until a clearer picture of the
importance and clinical presentation of feline ehrlichiosis
is developed, ehrlichiosis should remain a consideration
in cats with various unexplained clinical illnesses. Diagnosis relies on ruling out other causes for the described
clinical illness in combination with either identification

282 Small Animal/Exotics

Figure 1A round, basophilic morula of E. ewingii is seen in

the cytoplasm of the neutrophil. (Courtesy of Steve Stockham, DVM, MS, Kansas State University.)

of morulae within the peripheral blood cells or serologic

evidence of exposure to an ehrlichial agent as well as resolution of clinical signs after appropriate antibiotic therapy.57 Both granulocytic and monocytic infections have
been described, with the expected variations in serologic
reactivity to different ehrlichial agents.57,60,62

DIAGNOSIS
Ehrlichiosis is usually diagnosed based on clinical
signs, consistent laboratory abnormalities, and
Ehrlichia-specific testing. Although observation of
intracellular morulae is diagnostic, the search for morulae is most often unrewarding.35 The use of concentration techniques, such as buffy coat examination with a
Romanovsky-type stain, maximizes the chance of identifying morulae.3 Morulae may be observed in white
blood cells from peripheral blood or other fluids,
including cerebrospinal and joint fluids.39,40,46,47 In general, morulae are more readily apparent during the
acute phase of monocytic E. canis infection or during
infection with the granulocytic species E. ewingii and
E. equi (Figure 1).5,11,23,35
The most commonly employed diagnostic test for
suspected ehrlichial infection is indirect fluorescent
antibody (IFA) serology. This form of testing does not
detect the actual ehrlichial organism but rather
ehrlichial-reactive antibody in the serum. Veterinarians
employing IFA testing must understand that a positive
titer in a dog from an endemic area does not confirm
that the disease under investigation is caused by
ehrlichial infection. Rather, a positive titer confirms
exposure to the organism but may be observed after
exposure and clearance of the organism, during the
subclinical stage, or after successful treatment, as well as
during active infection. Likewise, a negative titer does
not rule out infection. Moribund animals may cease to

Compendium April 2002

produce antibody, resulting in a diminished or negative

titer, and acutely infected dogs require 7 to 21 days for
seroconversion, potentially resulting in negative titers
in infected dogs.63 Depending on the particular IFA test
used, serology can be more or less specific for a species
of Ehrlichia. Antibody generated to one species of
Ehrlichia may cross-react with other species. Species
that fall within the same genogroup are likely to possess
serologic cross-reactivity. Likewise, titers to one
genogroup may be negative during infection with
members of a different genogroup (i.e., E. canis titers
may be negative during infection with E. equi). Currently, titers are commercially available for members of
each genogroup, including E. canis, E. equi, E. risticii,
and E. platys.a
Polymerase chain reaction (PCR) detects actual DNA
from the ehrlichial organism. Primers are chosen to
amplify a portion of the bacterial DNA, allowing detection of that genetic material. The use of generic
ehrlichial primers allows detection of any of several
species of Ehrlichia using one test. Alternatively, by
using primers directed at a specific, highly variable portion of the bacterial gene, PCR can identify the specific
species of Ehrlichia in an affected animal. Such primers
are currently available for E. canis, E. ewingii, E. equi,
E. chaffeensis, E. risticii, and E. platys.6 Many commercial laboratories use generic primers and then may or
may not speciate positive samples.b,c Although PCR can
be a sensitive test, the choice of sample will influence
results. Most commercial laboratories that perform
PCR request whole blood samples, but organisms
might at times be sequestered in low numbers in such
tissues as the spleen or bone marrow.64 PCR may be
used occasionally in conjunction with IFA to differentiate between exposure to Ehrlichia and true infection
(such as after completion of treatment and in the presence of continued clinical signs and persistent ehrlichial
titers).65 The laboratorys quality control is crucial for
reliable PCR results.
A commercial in-house screening kit that tests for B.
burgdorferi antibodyd has been marketed. Screening
ELISA tests of this kind are designed to produce a positive response in animals with an antibody titer corresponding to an IFA titer of greater than 1:500.
Reported sensitivity and specificity of these test kits are
98.9% and greater than 99%, respectively. As with any
test, predictive value is more important than either sensitivity or specificity, but it depends on both as well as
a

ProtaTek International, Inc., Chandler, AZ.

Antech Diagnostics, Irvine, CA.
c
Tick-borne disease testing facility, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
d
Snap 3Dx Test, IDEXX Laboratories, Inc., Westbrook, ME.
b

Compendium April 2002

on the prevalence of the disease in question. Thus a

positive screening test in an endemic area is more likely
to be a true positive than is the same result in an area
with a lesser disease prevalence. As is true of the IFA
test, a positive titer must be interpreted with caution
because it may represent current or resolved infection
or merely exposure.

TREATMENT
Tetracycline-related antibiotics have been the treatment of choice for ehrlichial infections for years. 3
Excellent absorption and an infrequent dosing interval
make doxycycline the preferred drug.32,66 Although a 7to 14-day course of doxycycline at 10 mg/kg/day has
been previously recommended,4,6,32 this length of treatment may be inadequate.66,67 In fact, in a study of subclinically infected dogs treated with doxycycline for 6
weeks, ehrlichial organisms could still be identified by
PCR in one of four dogs.67 Although the appropriate
length of treatment has not been clearly determined,
treatment for dogs with chronic infection may be quite
long in duration and titers may remain elevated for
months to years, regardless of the treatment length.
Even long courses of treatment (average, 210 days) did
not produce negative titers in a significant proportion

Ehrlichiosis 283

of naturally infected dogs.30 Although most studies have

been directed at E. canis infections, doxycycline has
proven effective for E. equi and E. ewingii infections
but less effective for E. chaffeensis.6,12,32
Imidocarb dipropionate, only recently available in
the United States, has also been used successfully to
treat canine ehrlichiosis. Although a study in 1980
found that imidocarb produced more effective clearance of E. canis than did a 2-week course of tetracycline, recent studies using doxycycline have documented no difference in the clinical response of dogs
treated with either drug alone or with both drugs
simultaneously. 68,69 Imidocarb is administered at 5
mg/kg IM, with a second injection 2 weeks after the
first. 4,69 Pretreatment with atropine may lessen the
occurrence of unpleasant anticholinergic side effects,
including salivation, serous nasal discharge, diarrhea,
and dyspnea.
Other antibacterial agents have also been evaluated
for the treatment of ehrlichial infections. Chloramphenicol may be used in puppies to avoid the discoloration of erupting teeth associated with tetracycline.4
Quinolones cannot be recommended currently as a
treatment for ehrlichiosis. Although enrofloxacin has
been used successfully to treat experimental Rickettsia

284 Small Animal/Exotics

rickettsii infection in dogs, it does not seem an effective

treatment for E. canis. Most dogs with experimental E.
canis infections that were administered dosages of 10
mg/kg PO q12h for 21 days remained thrombocytopenic and blood culture positive. 32 Similarly,
ciprofloxacin was unsuccessful in eliminating infection
with E. chaffeensis in humans.70
In addition to antibiotics, other supportive therapies
may be required during ehrlichial infection. Glucocorticosteroids can attenuate the immune-mediated
destruction of platelets associated with infection, and
thus a short course (2 to 7 days) of prednisone may be
indicated if thrombocytopenia is severe or pending
diagnostic testing to differentiate ehrlichiosis from
immune-mediated thrombocytopenia.4,23 Steroids may
also be indicated for the treatment of polyarthritis, vasculitis, or meningitis associated with certain types of
ehrlichial infections.4,46,47 Other supportive treatments
might include the administration of parenteral crystalloid or colloidal fluids or blood transfusion, as indicated.3,4 Complications of chronic E. canis infection
(e.g., glomerulonephritis, pancytopenia) may likewise
require specific supportive therapy.

EVALUATING TREATMENT
Evaluation of treatment remains problematic. Resolution of clinical signs and normalization of platelet
counts are usually noted within days of initiating
proper treatment for acute cases and often for mild
chronic cases as well. 4,23,69 Even after rapid clinical
improvement, studies have found that platelet counts
may again decrease after completion of doxycycline
therapy, titers remain elevated, organisms can still be
cultured, and PCR results remain positive.64,69 Serum
antibody titers can remain elevated for months to years
after appropriate treatment in dogs that remain clinically and hematologically normal.30,31,64,69 These persistently positive titers, which tend to correlate with the
highest initial titers, may indicate continued infection
or re-infection or may be indicative of a past infection
only.23,30 PCR may offer the best option for documenting clearance of the organisms after therapy, but even
PCR evaluation can be problematic. PCR detects bacterial DNA but cannot distinguish between living and
nonliving organisms. However, it is unlikely that killed
ehrlichial organisms would persist in the body for
more than several weeks, rendering a positive PCR
result strongly suggestive of active infection. The
greater problem is related to false-negative results when
sampling tissues that contain low levels of organisms
(e.g., blood, bone marrow).64,65 Practically speaking,
treated dogs for which the clinical and laboratory evidence of disease is resolved need not be further evalu-

Compendium April 2002

ated for the presence of organisms. In animals treated

appropriately for infection but in which evidence of
disease remains, a positive PCR would warrant continuation or alteration of therapy, while a negative PCR
should prompt consideration that the observed disease
may not be due to ehrlichiosis.

PREVENTION AND CONTROL

Unfortunately, exposure to E. canis does not confer
protective immunity. Effective tick control is the most
important preventive measure for infection or re-infection. Several highly efficacious products are available
for direct application to dogs, including Frontline Top
Spot (Merial Ltd, Iselin, NJ), Preventic collars (Virbac, Inc., Fort Worth, TX), and Kiltix Topical Tick
Control for Dogs (Bayer Animal Health, Shawnee Mission, KS). In addition, many premise sprays are available to decrease tick populations in the dogs local environment. The prophylactic use of tetracycline
antibiotics during tick season has also been advocated
for prevention of infection, but this option is not free
from either the cost or risk associated with antibiotic
use.4 To prevent disease associated with chronic E. canis
infection, it has been suggested that dogs in endemic
areas be serologically monitored and positive animals
treated regardless of the presence of clinical signs.4 We
suggest that a positive screening test (e.g., ELISA) be
used as evidence that further evaluation is needed. At a
minimum, such evaluation should include a thorough
physical examination, quantitative platelet count, and
measurement of serum globulin. Positive screening tests
might also prompt confirmatory tests, including either
IFA or PCR, prior to initiation of antibiotic therapy.
ZOONOTIC POTENTIAL
Since the first description of human monocytic ehrlichiosis (HME) in the United States in 1986,71 the disease has garnered both scientific and public attention.
The agent of HME, which shares a penchant for
monocytic cell infection and produces antibodies crossreactive to E. canis, was named E. chaffeensis.72 E. chaffeensis infection in dogs has been identified in both
experimental and natural settings, with the organism
persisting for months.6,49 These long-lasting infections
raise the concern that dogs may serve as a reservoir of
infection for human disease. 72 Adding to those concerns, it seems that doxycycline may not easily clear the
organism from naturally infected dogs.6 In addition to
HME, HGE has been recognized as well. The causative
agent of HGE, which differs from that of HME, has
proven to be nearly identical to E. phagocytophila and
E. equi. Although these agents are most commonly
associated with infection in small ruminants and/or

Compendium April 2002

horses, respectively, both organisms have been isolated

from dogs, again raising the possibility that dogs may
serve as a reservoir for human infection.8,11,73,74 Additionally, the common agents of canine ehrilichiosis, E.
canis, and E. ewingii can occasionally cause clinical disease in humans.75 The symptoms of HME and HGE
are quite similar and include fever, headache, and myalgia. Left untreated, either infection may prove fatal to
humans.8,71,72,76

CONCLUSION
Ehrlichiosis is a bacterial infection transmitted largely
through the bite of infected ticks. Dogs with ehrlichiosis
can no longer be assumed to have an E. canis infection
alone. Veterinarians should be aware of the similarities
and differences between E. canis and other arthropodborne infections. Dogs with suggestive clinical signs and
laboratory abnormalities may be started on doxycycline
pending specific diagnostic testing. Veterinarians practicing in endemic areas are confronted with the often
difficult task of sorting out ehrlichial infection from
mere exposure. Once a diagnosis is established, treatment should continue for at least 3 weeks. Tick prevention for animals in endemic areas should be maintained
throughout tick season, not only to prevent disease but

Ehrlichiosis 285

also to lessen the potential for dogs to become carriers of

disease for their human companions.

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ARTICLE #1 CE TEST
The article you have read qualifies for 1.5 contact hours of Continuing
Education Credit from the Auburn University College of Veterinary
Medicine. Choose the best answer to each of the following questions; then
mark your answers on the postage-paid envelope inserted in Copendium.

CE

1. Ehrlichial organisms are best classified by the

a. type of tick involved in transmission.
b. type of host cell infected.
c. genetic analysis of the 16S rRNA segment.
d. species of host animal infected.
2. Which is the primary transmission vector for E. canis?
a. D. variabilis
c. A. americanum
b. R. sanguineus
d. Ixodes scapularis
3. Which statement regarding transmission of ehrlichiosis by ticks is true?
a. Ticks can infect dogs only in the fall.
b. Ticks serve as the reservoir for ehrlichial organisms.
c. The ehrlichial organism is passed transovarially prior to infection of dogs.
d. Ticks transmit the infection through salivary secretions released during a bite.
4. What are the most common presenting complaints in ehrlichiosis?
a. lethargy, fever, and weight loss
b. epistaxis and fever
c. lameness and lethargy
d. secondary infections
5. Which Ehrlichia species most commonly causes lameness?
c. E. equi
a. E. canis
b. E. chaffeensis
d. E. ewingii

Compendium April 2002

6. A positive E. canis titer in an asymptomatic dog in an

endemic area indicates that the dog has
a. been exposed and has produced antibodies.
b. entered the subclinical phase of infection.
c. been infected in the past but has cleared the organisms.
d. any of the above
7. Infection with _________ is the most likely explanation for observed granulocytic morulae and a negative
E. canis titer.
c. E. equi
a. E. ewingii
b. E. platys
d. E. chaffeensis
8. Six months after treating an infected dog with doxycycline, a positive E. canis IFA titer can reveal

Ehrlichiosis 289

a. persistence of the titer despite elimination of the

organisms.
b. persistence of the organism.
c. re-infection with organisms.
d. any of the above
9. Administration of ______________ for _______ days
is the recommended treatment protocol for chronic
ehrlichiosis.
a. doxycycline; 21
c. doxycycline; 7 to 10
b. tetracycline; 7 to 10
d. enrofloxacin; 21
10. ___________ has not been reported to infect humans.
c. E. equi
a. E. chaffeensis
b. E. ewingii
d. E. platys