Issues

Ehrlichiosis (Anaplasma)

 

Ehrlichiosis (Anaplasma) is caused by Ehrlichia spp.—tick-borne rickettsial disease

Dogs

• Within the family Anaplasmataceae—three pathogenic genera: Ehrlichia, Anaplasma, and Neorickettsia.
• Ehrlichia spp.—divided into three groups: (1) E. canis: ehrlichiosis found intracytoplasmically in circulating leukocytes; (2) E. ewingii: canine granulocytic ehrlichiosis; like A. phagocytophilum, infects granulocytic cells in dogs, but differs in geographic distribution (mainly found in southeastern and south-central United States); (3) E. chaffeensis: like E. canis, tropism for mononuclear cells; mainly a human pathogen but causes disease in dogs; disease distribution based on vector (mainly Amblyomma americanum) range.
• Anaplasma spp.—two organisms of importance: (1) A. phagocytophilum: infects mainly horses but also the granulocytic cells of dogs; mainly found in northeastern and upper midwestern states and California based on distribution of vectors (hard ticks Ixodes spp.); (2) A  platys: tropism for platelets; shares serologic cross-reactivity with A. phagocytophilum.
• Although usually found in defined ranges, serologic evidence suggests E. canis and A. phagocytophilum occur in all 48 contiguous states.
• Neorickettsia spp.—two organisms of importance: (1) N. risticii: causes Potomac horse fever in horses but also infects dogs and cats; infections acquired by ingesting infected snails, free nematode life stages, or aquatic insects with encysted metacercaria; grazing or drinking from standing water explains why horses become infected more often than dogs; infected dogs have negative E. canis titers; (2) N. helminthoeca: causes salmon poisoning disease in dogs.

 

Cats

• Feline mononuclear ehrlichiosis (and E. risticii extremely rarely) can cause clinical disease.
• Serologic evidence for A. phagocytophilum infection but no disease.
• Serologic evidence—suggests a species that cross-reacts with E. canis can cause illness.

 

PATHOPHYSIOLOGY

• E. canis
• Rhipicephalus sanguineus—brown dog tick; transmits the disease to dogs in saliva; 1- to 3-week incubation period; three stages of the disease:
• Acute—spreads from bite site to the spleen, liver, and lymph nodes (causes organomegaly); then subclinical with mild thrombocytopenia; mainly endothelial cells affected; vasculitis; antiplatelet antibodies may exacerbate thrombocytopenia; variable leukopenia; mild anemia; severity depends on torganism.
• Subclinical—organism persists; antibody response increases (hyperglobulinemia); thrombocytopenia persists.
• Chronic—impaired bone marrow production (platelets, erythroid suppression); marrow hypercellular with plasma cells.

 

SYSTEMS AFFECTED

• Bleeding tendencies—thrombocytopenia and vasculitis.
• CNS, eyes (anterior uveitis), and lungs—rarely affected by vasculitis.
• Lymphadenopathy.
• Multisystemic.
• Splenomegaly.

 

INCIDENCE/PREVALENCE

• Occurs throughout the year; insidious.
• The average duration from onset to presentation—usually > 2 months.
• Prevalence depends on geographic locality.

 

SIGNALMENT

Species

• Dogs—can be infected with a number of species; E. canis, A. platys, A. phagocytophilum, E. ewingii, and E. chaffeensis produce main disease entities.
• Cats—E. risticii; serology suggests a species like E. canis, and A. phagocytophilum.

 

Breed Predilections

Chronic (E. canis)—seems more severe in Doberman pinschers and German shepherds.

 

• Mean Age and Range
• Average age—5.22 years
• Range 2 months–14 years

SIGNS

• General Comments
• Duration of clinical signs from initial acute illness to presentation—usually > 2 months.

 

Historical Findings

• Lethargy, depression, anorexia, and weight loss
• Fever
• Spontaneous bleeding—sneezing, epistaxis
• Respiratory distress
• Ataxia, head tilt
• Ocular pain (uveitis)

Physical Examination Findings

 

Acute

• Bleeding diathesis (petechiation of mucous membranes as a result of thrombocytopenia) associated with fever (with depression, anorexia, weight loss) and generalized lymphadenopathy should raise suspicions.
• Ticks—found in 40% of cases.
• Respiratory—dyspnea (even cyanosis); increased bronchovesicular sound.
• Diffuse CNS disease (meningitis).
• Ataxia with upper motor neuron dysfunction.
• Vestibular dysfunction.
• Generalized or local hyperesthesia.
• Most dogs recover without treatment and enter a subclinical state.

Chronic

• In non-endemic areas.
• Spontaneous bleeding.
• Anemia.
• Generalized lymphadenopathy.
• Scrotal and limb edema.
• Splenomegaly.
• Hepatomegaly.
• Uveitis, usually bilateral (75%), can sometimes be the only presenting sign.
• Hyphema.
• Retinal hemorrhages and detachment with blindness.
• Corneal edema.
• Arthritis (rare).
• Seizures (rare).

 

RISK FACTORS

Concurrent infection with Babesia, Haemobartonella, A. platys, and Hepatozoon canis—worsens clinical syndrome.

 

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

• Rocky Mountain spotted fever (Rickettsia rickettsii)—usually seasonal between March and October; serologic testing for diagnosis; responds to same treatment as ehrlichiosis.
• Immune-mediated thrombocytopenia—not usually associated with fever or lymphadenopathy; serologic testing best distinguishes; may treat for both until results are known.
• Systemic lupus erythematosus—ANA test usually negative with ehrlichiosis; serologic testing for diagnosis.
• Multiple myeloma—serologic testing to differentiate and determine the cause of hyperglobulinemia.
• Chronic lymphocytic leukemia—differentiate by lymphocytosis and cytology of bone marrow.
• Brucellosis—serologic testing for diagnosis.

 

CBC/BIOCHEMISTRY/URINALYSIS

Acute

Thrombocytopenia—before the onset of clinical signs.

Anemia.

• Leukopenia—from lymphopenia and eosinopenia.
• Leukocytosis and monocytosis—as the disease becomes more chronic.
• Morulae—intracytoplasmic inclusions in leukocytes are rare; buffy coat smear increases the sensitivity of finding morulae.
• Nonspecific changes—mild increases in ALT, ALP, BUN, creatinine, and total bilirubin (rare).
• Hyperglobulinemia—progressively increases 1–3 weeks post-infection.
• Hypoalbuminemia—usually from renal loss.
• Proteinuria—with or without azotemia; about half of patients.

 

Chronic

• Pancytopenia—typical; monocytosis and lymphocytosis may be present.
• Hyperglobulinemia—the magnitude of globulin increase correlates with duration of infection; usually polyclonal gammopathy, but monoclonal (IgG) gammopathies occur.
• Hypoalbuminemia.
• High BUN and creatinine from primary renal disease.

 

OTHER LABORATORY TESTS

• Serologic Testing
• Most clinically useful and reliable method.
• IFA is highly sensitive; poor specificity with cross-reactivity between E. canis and A. phagocytophila, but not between E. canis and A. platys.
• More specific tests are being developed.
• Titers—reliable 3 weeks after infection; > 1:10 diagnostic.
• Coombs’-positive anemia—may be seen; may confuse the diagnosis.
• Test for other accompanying pathogens—Babesia, Mycoplasma haemofelis, A. platys, and Hepatozoon canis.
• Point-of-care screening serology testing for single or multiple agents is both practical, sensitive, and specific for IFA titers greater than 320. Positive tests should be confirmed with IFA and another testing (CBC) before treatment is initiated as false-positive results frequently occur. Immunoblotting can be used to distinguish cross-reactions (especially between E. canis and E. ewingii).
• PCR—more reliable than finding circulating morulae.
• PCR of blood for E. canis provides a species-specific diagnosis and is positive by day 7 post-infection, usually before the development of clinical disease (9–12 days post-infection) in experimental settings. It is less reliable in natural infections and should not be used as the only screening method of diagnosis. Real-time PCR techniques are proving to be more sensitive and may hold a place in initial diagnostic testing as more data on accuracy becomes available.

 

DIAGNOSTIC PROCEDURES

• Bone Marrow Aspirate
• Acute—hypercellularity of megakaryocytic and myeloid series.
• Chronic—often erythroid hypoplasia with increased M:E ratios and plasmacytosis.
• Increased numbers of mast cells seen on marrow smears.

 

PATHOLOGIC FINDINGS

• Acute—petechial hemorrhages on serosal and mucosal surfaces of most organs; generalized lymphadenopathy (brownish discoloration), splenomegaly, hepatomegaly, and red bone marrow (hypercellularity).
• Chronic—pale marrow (hypoplastic); subcutaneous edema; histologically, perivascular plasma cell infiltrate in numerous organs most characteristic; multifocal non-suppurative meningoencephalitis with lymphoplasmacytic cell infiltrate into the meninges common.

 

TREATMENT

APPROPRIATE HEALTH CARE

• Inpatient—initial medical stabilization for anemia and/or hemorrhagic tendency resulting from thrombocytopenia.
• Outpatient—stable patients; monitor blood and response to medication frequently.

 

NURSING CARE

• A balanced electrolyte solution is indicated for dehydration.
• Blood transfusion is indicated for anemia.
• Platelet-rich plasma or a blood transfusion is indicated for hemorrhage resulting from thrombocytopenia.

 

CLIENT EDUCATION

• Acute—prognosis excellent with appropriate therapy.
• Chronic—response may take 1 month; prognosis poor if the bone marrow is severely hypoplastic.
• Progression from acute to chronic can be easily prevented by early, effective treatment; but many dogs remain seropositive and may relapse (even years later).
• German shepherds and Doberman pinschers—more chronic and severe form of disease.

 

MEDICATIONS

DRUG(S) OF CHOICE

• Doxycycline (treatment of choice)—5 mg/kg PO q12h for 4 weeks; give IV for 5 days if the dog is vomiting.
• Glucocorticoids—prednisolone or prednisone; 1–2 mg/kg PO q12h for 5 days; maybe indicated when thrombocytopenia is life-threatening (thought to be a result of immune-mediated mechanisms); because immune-mediated thrombocytopenia is a principal differential diagnosis, maybe indicated until results of serologic tests are available.
• Androgenic steroids—to stimulate bone marrow production in chronically affected dogs with hypoplastic marrows; oxymetholone (2 mg/kg q24h PO until response) or nandrolone decanoate (1.5 mg/kg IM weekly).

 

CONTRAINDICATIONS

• Tetracycline (and derivatives)—do not use in dogs < 6 months old (permanent yellowing of teeth occurs); do not use with renal insufficiency (try doxycycline because it can be excreted via the gastrointestinal tract).
• Enrofloxacin not effective against Ehrichia spp. but is against Anaplasma spp.

 

PRECAUTIONS

Glucocorticoids—prolonged use at immunosuppressive levels may interfere with the clearance and elimination of E. canis after use of tetracycline.

 

ALTERNATIVE DRUG(S)

• Oxytetracycline and tetracycline—22 mg/kg PO q8h for 21 days; effective and less expensive; minocycline (10 mg/kg PO q12h for 4 weeks) is effective if doxycycline is difficult to obtain
• Chloramphenicol—20 mg/kg PO q8h for 14 days; for puppies < 6 months of age; avoids yellow discoloration of erupting teeth caused by tetracyclines; warn client of public health risks; avoid in dogs with thrombocytopenia, pancytopenia, or anemia.

 

FOLLOW-UP

PATIENT MONITORING

• Platelet count—every 3 days after initiating antirickettsial agent until normal; improvement is rapid in acute cases.
• Serologic testing—repeat in 9 months; most dogs will become seronegative; positive titer suggests reinfection or ineffective treatment (reinstitute treatment regimen).

 

PREVENTION/AVOIDANCE

• Control tick infestation—dips or sprays containing dichlorvos, chlorfenvinphos, dioxathion, propoxur, or carbaryl; flea and tick collars may reduce reinfestation but reliability unproven; avoid tick-infested areas.
• Removing ticks by hand—use gloves (see “Zoonotic Potential”); ensure mouthparts are removed to avoid a foreign body reaction.

 

EXPECTED COURSE AND PROGNOSIS

• Acute—excellent prognosis with appropriate and early treatment.
• Chronic—may take 4 weeks for a clinical response; prognosis poor with hypoplastic marrow.

 

MISCELLANEOUS

ASSOCIATED CONDITIONS

• Babesia
• Haemobartonella
• platys

 

ZOONOTIC POTENTIAL

• Serologic evidence indicates that E. canis (or possibly a related species) occurs in people; probably not directly infected from dogs; tick exposure thought to be necessary; R. sanguineus probably not the vector in humans.

 

SYNONYMS

• Canine hemorrhagic fever
• Canine rickettsiosis
• Canine typhus
• Lahore canine fever
• Nairobi bleeding disease
• Tracker dog disease
• Tropical canine pancytopenia

 

ABBREVIATIONS

ALP = alkaline phosphatase

ALT = alanine transaminase

ANA = antinuclear antibody

CNS = central nervous system

IFA = indirect fluorescent antibody

PCR = polymerase chain reaction

 

Visit your veterinarian as early recognition, diagnosis, and treatment are essential.

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