Ehrlichiosis, also known as Tropical Canine Pancytopenia
or Canine Rickettsiosis, is a tick-borne disease
caused by obligate intracellular bacteria of the genus Ehrlichia
of thefamilyrickettsiaceae. Dogs can become
naturally infected with several species of Ehrlichiaincluding
E. canis, E. equi, E. risticii, E. platys, and E.
ewingii. E. canis is the most common and causes the most
severe clinical disease. Dogs seropositive for E. canis
have been identified throughout most of the U.S.,
but most cases occur in areas with an increased concentration
of Rhipicephalussanguineus, the brown dog tick,
such as the Southwest and the Gulf coast. Canine ehrlichiosis
is principally of importance in Africa,
Asia, and India.
Ehrlichiacanis was discovered in Algeria
in 1935. The first case in the United
States was reported in 1963.
It was not until about 1968-1970, during the Vietnam war,
when the full pathologic potential of E. canis was
first recognized. A severe epizootic episode of Ehrlichiosis
occurred among U.S.
military dogs resulting in hundreds of cases of morbidity
Transmission: The arthropod vector of E. canis
is Rhipicephalussanguineus and transmission
is transstadial. Ticks acquire E. canis by feeding,
as either larvae or nymphs, on infected dogs and transmit
the infection as nymphs or adults. The organism can also
be transmitted by blood transfusions.
Pathogenesis: The life cycle of Ehrlichiacanis
is not completely understood. There are three intracellular
forms. Initial bodies are small spherical structures (1-2
microns) which are believed to develop into larger multiple
units known as morulae. The morula is thought to dissociate
into small granules called elementary bodies.
Once the organism has been transmitted, there are three
clinical phases of Ehrlichiosis: acute, subclinical, and chronic.
The acute phase begins after an incubation period of 8-20
days and lasts 2-4 weeks, during which time the organisms
multiply in reticuloendothelial cells, lymphocytes, and monocytes.
Infected mononuclear cells marginate in the small vessels
or migrate into endothelial tissues and vasculitis ensues.
Immunologic and inflammatory mechanisms are involved with
increased platelet consumption. Platelet-associated IgG and
antibodies that recognize platelet proteins in dogs with E.
canis infection may play a role in the thrombocytopenia.
In addition, platelet migration-inhibition factor (PMIF) has
been found to exist in dogs with Ehrlichiosis and its level
is related inversely to the platelet count. The acute phase
usually resolves spontaneously. The subclinical phase can
persist for years. Immunocompetent dogs may be able to eliminate
E. canis; however, the organism persists intracellularly
in most dogs, leading to the chronic phase. This phase may
be mild to severe. In the mild form, there is vague illness
and weight loss. Bone marrow hypoplasia leading to pancytopenia
occurs in the severe chronic form. The severity of the disease
depends on the dogs age (i.e., young dogs are more susceptible),
strain of the organism, the presence of concurrent disease,
and breed (e.g., German shepherds)are more likely to be infected.
Clinical signs: Clinical findings in dogs with Ehrlichiosis
vary with the phase of the infection. During the acute phase,
nonspecific signs such as fever, oculonasal discharge, anorexia,
weight loss, dyspnea, and lymphadenopathy may occur. Clinical
signs commonly seen during the chronic phase include depression,
weight loss, pale mucous membranes, abdominal pain, hemorrhage,
lymphadenopathy, spleno-megaly, dyspnea, increased lung sounds,
hepatomegaly, arrhythmias, pulse deficits, polyuria, polydypsia,
and stiff, swollen, painful joints. Ocular abnormalities
such as perivascular retinitis, hyphemia, retinal detachment,
anterior or posterior uveitis, and corneal edema may occur.
Abnormalities of the CNS, including meningeal pain, paresis,
cranial nerve deficits, and seizures have been reported.
Diagnosis:Ehrlichiosis is an important differential
diagnosis for pancytopenia. Hematological changes for infections
caused by E. canis generally include nonregenerative
anemia, thrombocytopenia, and leukopenia. Serum chemistry
abnormalities include hyperproteinemia with hyperglobulinemia,
and elevated alanineaminotransferase and alkaline phosphatase.
Other clinicopathologic findings include proteinuria, hematuria,
and prolonged bleeding time. CSF analysis in dogs with CNS
signs shows an increased protein level and predominant lymphocyticpleocytosis.
A definitive diagnosis of Ehrlichiosis can be made by demonstration
of morulae in leukocytes from blood smears or tissue aspirates
from spleen, lung, or lymph node.; however, finding morulae
on smears is often difficult and time-consuming. A diagnosis
of Ehrlichiosis is usually based on positive results of the
indirect FA test on serum. This test detects serum antibodies
as early as 7 days post-infection. Serum antibody levels
in untreated dogs peak at 80 days after infection. Most laboratories
measure an IgG titer. A titer of 20 or greater is generally
considered to be evidence of infection and/or exposure. An
ELISA test has also been developed to detect antibodies and
circulating antigen in dogs with E. canis. Cross-reactivity
occurs between several of the Ehrlichia species. For
academic interest, Western immunoblotting and PCR may be used
to characterize different organisms.
Pathologic findings:Ehrlichiosis is not characterized
by specific pathologic findings, but gross lesions may include
petechial and ecchymotic hemorrhages on the serosal surfaces
of the gastrointestinal and urogenital tracts and kidneys,
edematous or hemorrhagic enlargement of most lymph nodes,
and edema of the limbs. Dogs are generally emaciated at death
and may have signs of epistaxis. Splenomegaly and/or hepatomegaly
may be observed.
Histopathologic findings include widespread perivascular
accumulations of lymphoreticular and plasma cells, particularly
in the meninges, kidneys, liver and lymphopoietic tissues.
Multiple Kupffer cell hyperplasia and degeneration and acute
centrilobular necrosis of the liver may be seen. Lesions
of the CNS include hemorrhage and plasma cell accumulations
in the meninges and occasionally lymphocytic and plasma cell
infiltrations are present in the brain parenchyma. Other
microscopic findings may include crescent-shaped perifollicular
hemorrhages in the spleen, bone marrow hypoplasia, interstitial
pneumonia, and glomerulonephritis.
Ehrlichia organisms are difficult to detect histologically.
Ultrastructurally, morulae in blood monocytes are intracytoplasmic
inclusions made up of numerous organisms. The organisms are
round, ovoid, or elongated and are surrounded by a double
-By Jeanine Peters, Class of 2000
University of Georgia
-edited by Evan Janovitz, DVM, PhD