CANINE

AND

FELINE EHRLICHIOSIS*

Nancy A. Vincent-Johnson, DVM, MS, DACVIM (Small Animal, Internal Medicine), DACVPM
Lieutenant Colonel, United States Army Veterinary Corps
Commander, National Capital District Veterinary Command
Fort Belvoir, VA

hrlichiosis was first recognized as a disease of dogs

in Algeria in 1935 but did not gain prominence
until the 1960s when a number of military working dogs stationed in Vietnam contracted a highly fatal
hemorrhagic disease. Termed tropical canine pancytopenia, the disease was caused by Ehrlichia canis, an
organism found to be transmitted by the brown dog
tick, Rhipicephalus sanguineus. Canine ehrlichiosis was
found to exist virtually anywhere this tick species was
found and has been reported in most tropical and subtropical regions of the world, including the United
States. Subsequently, other Anaplasma and Ehrlichia
spp were found to infect dogs, horses, and ruminants.
Ehrlichia spp are gram-negative, pleomorphic, obligate
intracellular cocci related to Rickettsia.
In the late 1980s, ehrlichiosis was identified as a
potentially fatal disease of humans. That spurred a
large interest in researching Ehrlichia organisms. In
recent years, genetic studies resulted in the discovery
of additional organisms and a taxonomic reclassification of some species. The genus Ehrlichia is now categorized within the family Anaplasmataceae, along
with three other genera: Anaplasma, Neorickettsia,
and Wolbachia. Some of the important veterinary
pathogens from this family are listed in Table 1; each
species listed has been reported to cause illness in
dogs. Ehrlichiosis has also been reported in a small
number of cats; the causative organisms resemble E.
canis, Neorickettsia risticii, and Anaplasma phagocytophilum. For ease of discussion, the term ehrlichiosis
as used in this article refers to the group of diseases
caused by any of the organisms in Table 1.

DIAGNOSTIC CRITERIA
Historical Information
Gender Predisposition: None.
Age Predisposition: None.
Breed Predisposition: All breeds are susceptible, but
German shepherds seem to elicit a poorer cell-mediated response and are predisposed to developing bone
marrow suppression that is more severe and less
responsive to treatment.
*The views expressed in this article are those of the author
and do not reflect the official policy or position of the
Department of the Army, the Department of Defense, or the
US Government.

Seasonality: Dogs infected with A. phagocytophilum

or Ehrlichia ewingii more often present in the spring
through early summer when the Ixodes scapularis and
Amblyomma americanumvector ticks are most
actively feeding. Dogs infected with E. canis present
any time of year because of the chronic nature of the
infection.
Owner Observations:
Acute phase: Typically lethargy, anorexia, weight
loss, and depression.
Chronic phase: Same as acute phase but with the
potential addition of signs of bleeding tendencies
(epistaxis, dermal petechiae, hyphema), central nervous system involvement (seizures, vestibular signs,
cervical pain), ocular disease (eye color change due
to corneal edema, hyphema, uveitis), or lameness.
Other Historical Considerations/Predispositions:
With E. canis, the disease is divided into three phases
(acute, subclinical, chronic). These phases are not
known to occur with the other Ehrlichia or Anaplasma
spp. The acute phase occurs 1 to 3 weeks after the animal is bitten by an infected tick. Signs are generally
mild and spontaneously resolve after 2 to 4 weeks. The
animal may then clear the infection or go into a subclinical phase that can last weeks to years, during
which time the animal is asymptomatic. Most animals
are presented during the chronic phase, with clinical
signs ranging from mild to very severe. Dogs and cats
can be co-infected with other tick-borne pathogens.
This may cause immunosuppression, making the animal more susceptible to severe disease.

Physical Examination Findings

Fever.
Depression, lethargy.
Weight loss.
Signs indicative of bleeding tendencies (epistaxis,
melena, petechial or ecchymotic hemorrhages,
hyphema, retinal hemorrhage, hematuria) occur in
25% to 60% of dogs.
Splenomegaly (25%).
Generalized lymphadenopathy (20%).
Central nervous system signs (hyperesthesia, stupor,
ataxia, paresis, seizures, head tilt, cerebellar dysfunction, vestibular signs, nystagmus, or other cranial nerve deficits).
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TA B L E 1
S o m e I m p o r t a n t Ve t e r i n a r y P a t h o g e n s o f t h e F a m i l y
Anaplasmataceae1
Pathogen

Associated Disease

Vector

Ehrlichia canis
Ehrlichia ewingii
Ehrlichia chaffeensis
Anaplasma phagocytophilum2
Anaplasma platys4
Neorickettsia helminthoeca

Canine monocytic ehrlichiosis

Canine granulocytic ehrlichiosis
Human monocytic ehrlichiosis
Human anaplasmosis,3 equine ehrlichiosis
Canine cyclic thrombocytopenia
Salmon poisoning of dogs

Neorickettsia risticii

Potomac horse fever

Rhipicephalus sanguineus
Amblyomma americanum
A. americanum
Ixodes spp
R. sanguineus?
Nanophyetus salmincola
(nematode)
Trematode cercariae found
in snails and aquatic insects

The presence of a morula in a monocyte or granulocyte is not necessarily specific for the organism listed; the terms monocytic and
granulocytic ehrlichiosis reflect historical designations.
2
Formerly Ehrlichia equi, Ehrlichia phagocytophilum.
3
Formerly human granulocytic ehrlichiosis.
4
Formerly Ehrlichia platys.

Lameness, joint pain or swelling (more commonly

seen with E. ewingii).
Polymyositis.
Other: Pale mucous membranes, ocular and nasal
discharge, dyspnea, limb or scrotal edema, uveitis,
and/or abdominal tenderness. Dogs may also show
clinical signs attributable to acute respiratory distress syndrome, glomerulonephritis, acute renal failure, or hyperviscosity syndrome.

Laboratory Findings
Thrombocytopenia (82%).
Mild to moderate anemia (82%; usually nonregenerative; may be Coombs positive).
Hyperproteinemia (33% to 75%), hyperglobulinemia (occasionally extreme).
Hypoalbuminemia.
Leukopenia, leukocytosis, or normal leukocyte count.
Lymphocytosis or lymphopenia, monocytosis.
Proteinuria.
Increases in alanine aminotransferase, alkaline phosphatase, amylase, blood urea nitrogen, creatinine.
Polyclonal or (rarely) monoclonal gammopathy on
protein electrophoresis.
Bone marrow aspirate:
Acute phase: Hyperplasia, especially of megakaryocytes.
Chronic phase: Hypoplasia of all three cell
lines, plasmacytosis.
Pancytopenia may be seen in chronic, severe cases
(less than 25%); occurs more often in German shepherds.
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Intracytoplasmic inclusion bodies (morulae) may

occasionally be seen during the acute phase in
monocytes (E. canis), granulocytes (E. ewingii, A.
phagocytophilum), or platelets (Anaplasma platys).
Coagulation panel (activated partial thromboplastin
time [aPTT], prothrombin time [PT], fibrin degradation products) is typically normal, but mucosal
bleeding time may be prolonged.
Concurrent infections are common (e.g., protozoan,
bacterial, urinary tract infection).

Other Diagnostic Findings

Radiographic or ultrasonographic examination may
reveal splenomegaly, hepatomegaly.
Ophthalmic examination may reveal anterior
uveitis, hyphema, conjunctivitis, conjunctival or
iridial petechiations, corneal opacity, photophobia,
papilledema, retinal hemorrhages, retinal detachment, or retinal vascular engorgement and tortuosity with circular to horseshoe-shaped perivascular
lesions.
Serology. $
Immunofluorescent antibody (IFA): Dogs
infected with E. canis typically have positive
IFA titers at the time of presentation; however,
clinical signs may occur before the development of antibodies. Titers do not necessarily
correlate with the severity or duration of infection. Many healthy dogs are seropositive
because of exposure and thus care must be
taken in interpreting antibody tests. Suspect
cases with negative or low titers should be
retested in 2 to 4 weeks to look for a rise in titer,
which would indicate recent exposure.

 ELISA: An in-house combination test for E.

canis, Borrelia burgdorferi, and heartworm is
available in the United States (SNAP 3Dx,
IDEXX Laboratories, Inc., Westbrook, ME). The
test is highly sensitive (95%) and specific
(99%). A positive ELISA result corresponds with
an IFA titer of 1:100 or higher for E. canis but
not related pathogens.
Cross-reactivity exists between species but is
highest among species of the same genus.
Therefore, infection with various ehrlichial
species may yield a positive result on an IFA for
E. canis. Western immunoblotting or polymerase chain reaction (PCR) can be used to distinguish between them. Despite cross-reactivity,
only about 50% of dogs with E. ewingii test positive on E. canis tests. This percentage would be
expected to be much lower in dogs infected
with A. phagocytophilum, A. platys, and N. risticii; thus titers to those species should be
requested when indicated.
Infected cats may have low or negative titers.
PCR assays. $
PCR is used to confirm infection by amplifying
and subsequently detecting DNA of the infectious organism in the sample. Generic primers
are used to screen for organisms in related
genus groups; specific primers are used to identify a particular species. It is important to use a
laboratory with excellent quality control as
both false-positive and false-negative results
can occur when quality control is lacking.
Whole blood in EDTA is typically used for submission. Although it is a fairly sensitive test,
false-negative results can occur when there is a
lack of organisms in the blood because of
sequestration in tissue reticuloendothelial cells.
PCR should always be used in conjunction with
serology.
PCR has identified an E. canislike organism
present in three cats that were serologically
negative.
Blood culture is not recommended outside a
research setting: It is expensive and not widely
available, and positive results may take up to 8
weeks to develop.

Summary of Diagnostic Criteria

Clinical signs vary from vague (anorexia, weight
loss, lethargy) to more specific. A high index of suspicion is warranted in patients with bleeding tendencies (epistaxis, petechiae, ecchymosis) or
extreme hyperglobulinemia.
Thrombocytopenia: The majority of affected dogs

CHECKPOINTS

Although screening of healthy dogs for E.

canis antibody is controversial among the
experts, it has become a reality with the
introduction of the SNAP 3Dx in-house
combination test. Many apparently healthy
dogs test positive for E. canis. The big
question is what to do with these dogs.
The ACVIM Consensus Statement
recommendation is to discuss the pros and
cons of treatment with the owner to come
up with the best management plan for the
dog in question.
Two alternative recommendations are:
Perform a complete blood count (CBC) to
evaluate the dog for evidence of anemia
and/or thrombocytopenia. If either is
present, treat the dog with a course of
doxycycline. If the CBC is normal, the
dog can be either treated empirically
with doxycycline or simply monitored
for overt clinical signs over the next few
months.
OR
Perform PCR testing. If Ehrlichia spp DNA
is detected, treatment is indicated.

will have thrombocytopenia; however, do not rule

out ehrlichiosis when platelet counts are normal.
Serology: A positive result with concurrent clinical
signs strongly supports but does not confirm the
diagnosis because many healthy animals in an
endemic area will be positive. Serology may be
negative early in the course of infection or if the
infecting species is not the exact species tested for.
PCR: A positive result confirms an infection. PCR
may be falsely negative if the organism is
sequestered in tissue outside of blood.
Morulae: Although morulae are not frequently seen,
their presence in monocytes, granulocytes, or
platelets on a blood smear confirms the diagnosis.

Differential Diagnosis
Because ehrlichiosis can mimic so many different diseases, it is important to test for Ehrlichia and related
species when the following diseases are suspected:
Immune-mediated thrombocytopeniaAnimals
with thrombocytopenia should be thoroughly
screened for other causes before presuming it is
idiopathic. Testing should be done to check for
ehrlichiosis and other infectious causes. No specific
test exists for diagnosing immune-mediated thrombocytopenia. In fact, dogs with ehrlichiosis can
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develop antiplatelet antibodies, which would yield

a positive result if using an antiplatelet antibody test
to confirm immune-mediated thrombocytopenia.
PancytopeniaTesting should be done to check
for ehrlichiosis. If negative, a bone marrow aspirate
should be performed to look for other causes.
Rodenticide toxicityThe bleeding disorder that
occurs in animals with anticoagulant rodenticide
toxicity is due to inhibition of vitamin K1, the result
being a reduction in activity of the coagulation factors II, VII, IX, and X. A coagulation profile would
show prolonged activated clotting time, PT, and/or
aPTT. The bleeding tendencies that occur with
ehrlichiosis are caused by platelet dysfunction and
a decrease in platelet numbers. A coagulation profile is usually normal in animals with ehrlichiosis.
Multiple myelomaEhrlichiosis can cause a monoclonal gammopathy, Bence Jones proteinuria, and
plasmacytosis of bone marrow that mimics multiple
myeloma. Dogs with these signs should be tested
for ehrlichiosis. Dogs with multiple myeloma frequently have radiographic evidence of osteolytic
bone lesions that would be absent in dogs with
ehrlichiosis.
Lymphocytic leukemiaDogs with ehrlichiosis
may exhibit granular lymphocytosis. The increased
lymphocyte numbers in conjunction with increased
granularity of the cytoplasm may be difficult to differentiate from chronic lymphocytic leukemia, particularly if there is monoclonal gammopathy and
Bence Jones proteinuria. Dogs with these findings
should be tested for ehrlichiosis before presuming a
diagnosis of leukemia.
PolyarthritisAnimals with clinical signs of joint
pain or swelling should be tested for ehrlichiosis
(particularly E. ewingii and A. phagocytophilum).
Morulae may be seen within cells from joint fluid;
their presence is diagnostic for infection.
Polymyositis.
Meningitis.
GlomerulonephritisEhrlichiosis can induce proteinuria and/or glomerulonephritis.

Initial Treatment
Dogs suspected of having ehrlichiosis should be
started on specific treatment immediately rather
than waiting for positive test results. Dramatic
improvement usually occurs within 24 to 48 hours
of initiating therapy. Dogs with chronic manifestations, including pancytopenia, glomerulonephritis,
and hyperviscosity syndrome, respond more slowly
and may have irreversible changes.
A P R I L

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THE

NEWS

FRONT

The etiologic agent of human monocytic

ehrlichiosis is E. chaffeensis, whereas
that of human anaplasmosis (previously
human granulocytic ehrlichiosis) is A.
phagocytophilum. Severe illness and death
have been associated with ehrlichiosis in
humans. Animals may act as sentinels for
human infection.

Doxycycline (dogs and cats): 10 mg/kg PO q24h for

28 days. In cats, the capsule or liquid form of doxycycline is preferable to the pill form, which has a
higher risk of causing esophagitis and strictures. The
capsules can be coated in butter, and at least 6 ml
of water should be given after a capsule is administered to help get it into the stomach. $
One report suggests that E. chaffeensis in dogs may
be more resistant than E. canis to doxycycline therapy. However, it is likely that the dogs cited in the
report were reinfected via continued exposure to
ticks. Humans infected with E. chaffeensis do not
exhibit resistance to doxycycline.

Alternative/Optional
Treatments/Therapy
Imidocarb dipropionate (5 mg/kg IM or SC followed
by a second injection 2 weeks later) is an alternative
treatment, but some variability in its efficacy is
reported. It can be used in animals whose owners
are unable to administer daily oral doxycycline or
for those animals that cannot tolerate doxycycline.
The most common adverse effects of imidocarb
injection are pain at the injection site and mild
cholinergic signs (salivation, nasal drip, vomiting).
Pretreatment with atropine at 0.022 mg/kg IM or SC
20 minutes before the imidocarb injection can prevent cholinergic effects.
Enrofloxacin and other quinolones are not effective
in treating ehrlichiosis.

Supportive Treatment

TREATMENT
RECOMMENDATIONS

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ON

Depending on the severity and type of clinical

signs, supportive treatment consisting of nutritional
supplementation, anabolic steroids, fluid therapy,
and/or blood transfusions may be necessary in
some animals.
Short-term immunosuppressive glucocorticoid therapy may be needed to treat severe, life-threatening
thrombocytopenia. Glucocorticoids are often administered initially while awaiting test results because of
the difficulty distinguishing between ehrlichiosis and
immune-mediated thrombocytopenia.

Patient Monitoring
Platelet counts begin to improve within 24 to 48
hours of initiating therapy and are usually normal
within 14 days. To monitor efficacy, platelet counts
should be rechecked 48 to 72 hours after initiating
therapy and again at 7 and 14 days. Platelet counts
should be checked 4 to 8 weeks after therapy to
ensure that a relapse of thrombocytopenia has not
occurred.
Most dogs undergo a decline in antibody titer following treatment and become antibody negative
over a course of 6 to 9 months. Some treated dogs
maintain high titers for years yet appear clinically
healthy. It is not known whether this is because of
continued infection, reinfection, or simply persistence of antibodies. Therefore, titers are not the best
method to assess treatment efficacy. The antibodies
are not protective against reinfection.
PCR may prove to be useful in distinguishing clinically cured animals that retain high posttreatment
IFA titers from unsuccessfully treated animals with
persistent infection. If PCR is used, testing should
take place 2 weeks after discontinuing antibiotic
treatment. If PCR is positive, the animal should be
re-treated for an additional 4 weeks and retested
after discontinuing the antibiotic for 2 weeks. If the
results are positive after these two treatment cycles,
the alternative drug, imidocarb dipropionate,
should be given. If PCR results are negative, the test
should be repeated in 2 months. If still negative,
treatment was likely successful.
The organism may be sequestered in the spleen,
even in animals that are clinically cured and test
negative on PCR or blood culture. One study
showed that of four dogs subclinically infected with
E. canis, one remained PCR positive following a 42day course of doxycycline at 10 mg/kg PO q24h.

RESOURCE LIST
ELISAIn-house combination test for E. canis,
Borrelia burgdorferi, and heartworm: SNAP 3Dx,
IDEXX Laboratories, Inc., Westbrook, ME. $
PCR and serology are available through the North
Carolina State University College of Veterinary
Medicine Tick Borne Disease Laboratory. Phone:
919-513-6357; Web: www.cvm.ncsu.edu/docs/
tickbornediseaselab.html. $

of initiating specific therapy. The diagnosis should

be reconsidered if there is a lack of significant
improvement in clinical signs and hematologic
abnormalities after 1 to 2 weeks of initiating treatment. Failure to improve may be indicative of coinfection with another organism or concurrent
noninfectious disease.
In cases of severe bone marrow suppression, regeneration may require several months if it occurs at
all.
Gammopathies generally resolve within 3 to 9
months but may take up to 15 months to normalize
in some cases.

Treatment Contraindications
Although immunosuppressive doses of glucocorticoids
are sometimes indicated to treat severe thrombocytopenia or other complications of ehrlichiosis, they
should not be given without concurrently initiating
specific treatment with doxycycline or imidocarb
dipropionate. When used, corticosteroids should be
tapered rapidly while sequentially monitoring platelet
counts. Doxycycline should be administered for a full
4 weeks following corticosteroid administration.

PROGNOSIS
Favorable Criteria

Home Management
Because of the marked improvement following initiation of doxycycline, no special home management
is normally needed other than routine observation.
Prior infection does not infer immunity following
doxycycline treatment; thus tick control is important to prevent reinfection. In addition to environmental control, the use of amitraz-impregnated
collars, fipronil, or permethrin products is recommended for dogs.
In highly endemic areas during tick season, dogs
can be maintained on 3 mg/kg doxycycline PO
q24h to prevent infection.

Clinical improvement shortly after initiating therapy.

Normalization of serum protein levels and hematologic parameters, resolution of proteinuria.

Unfavorable Criteria
Lack of significant clinical and hematologic improvement within 48 hours.
Severe pancytopenia and bone marrow suppression
(may be irreversible).
Irreversible renal damage and proteinuria.

RECOMMENDED READING
Breitschwerdt EB: Ehrlichiosis: A new zoonosis? Compend Contin
Educ Pract Vet 24(suppl 1A):1014, 2002.

Milestones/Recovery
Time Frames
Marked clinical improvement within 24 to 48 hours

Cohn LA: Ehrlichiosis and related infections. Vet Clin North Am

Small Anim Clin 33(4):863884, 2003.

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Greig B: Granulocytic ehrlichioses, in Bonagura JD (ed): Kirks

Current Veterinary Therapy XIII Small Animal Practice.
Philadelphia, WB Saunders, 2000, pp 298300.
Harrus S, Waner T, Aizenberg I, Bark H: Therapeutic effect of
doxycycline in experimental subclinical canine monocytic
ehrlichiosis: Evaluation of a 6-week course. J Clin Microbiol
36(7):21402142, 1998.
Kidd L, Breitschwerdt EB: Transmission times and prevention of
tick-borne diseases in dogs. Compend Contin Educ Pract Vet
25(10):742751, 2003.

McQuiston JH, McCall CL, Nicholson WL: Ehrlichiosis and

related infections. JAVMA 223(12):17501756, 2003.
Neer TM: Ehrlichia canis: A clinical approach to diagnosis and
treatment. Compend Contin Educ Pract Vet 24(suppl
1A):1518, 2002.
Neer TM, Breitschwerdt EB, Greene RT, Lappin MR: Consensus
statement on ehrlichial disease of small animals from the
infectious disease study group of the ACVIM. J Vet Intern Med
16(3):309315, 2002.