Ehrlichiosis and Related Infections - The Merck Veterinary Manual

Ehrlichiosis and Related Infections

Etiology

Epidemiology

In the past, a number of obligate intracellular organisms that infect eukaryotic cells were classified in the genus Ehrlichia on morphologic and ecologic grounds and were grouped according to the cell type they inhabit. With newer genetic analyses, these agents have been reclassified into the genera of Ehrlichia , Anaplasma , and Neorickettsia . Although no longer technically correct, usage of the term ehrlichiosis persists when describing infection caused by these agents.

Etiology:

Classical canine monocytic ehrlichiosis is caused by Ehrlichia canis , which infects the mononuclear cells of dogs; canine monocytic ehrlichiosis may also be caused by E chaffeensis , the etiologic agent of human monocytic ehrlichiosis. A monocytic ehrlichiosis has been identified in cats in Africa, France, and the USA; however, the exact species has not been determined. E ewingi is a granulocytic species that has been isolated from dogs and humans in the southern, western, and midwestern USA. Human granulocytic ehrlichiosis, caused by Anaplasma phagocytophilum is seen in the northern midwestern, northeastern, and western coastal regions of the USA and in Europe and Asia. The host range of infection and illness for various strains within this genogroup also includes horses and ruminants; dogs and cats may occasionally be infected. Anaplasma (Ehrlichia) platys is the cause of infectious cyclic thrombocytopenia of dogs. The following discussion of ehrlichiosis primarily describes infection in dogs caused by E canis .

Epidemiology:

E canis and A platys are enzootic in many parts of the USA and worldwide. These agents are transmitted by the brown dog tick, Rhipicephalus sanguineus . Rhipicephalus ticks become infected with E canis after feeding on infected dogs, and ticks transmit infection to other dogs during blood meals taken in successive life stages. Blood transfusions, or other means by which infected WBC can be transferred, may also transmit the pathogens. Other Ehrlichia and Anaplasma species have sylvan cycles in the environment involving various other tick species and wildlife reservoir hosts. In the USA, E chaffeensis and E ewingii are transmitted by Amblyomma americanum , the lone star tick. Anaplasma phagocytophilum is transmitted by Ixodes species of ticks; in the northeastern USA, infection is transmitted by I scapularis , the black-legged tick, whereas infection in western states is primarily associated with I pacificus , the Western black-legged tick. People, dogs, cats, and other domestic animals are incidental hosts of these pathogens.

Clinical Findings:

In E canis infections, signs arise from the involvement of the hemic and lymphoreticular systems and commonly progress from acute to chronic, depending on the strain of organism and immune status of the host. In acute cases, there is reticuloendothelial hyperplasia, fever, generalized lymphadenopathy, splenomegaly, and thrombocytopenia. Variable signs of anorexia, depression, loss of stamina, stiffness and reluctance to walk, edema of the limbs or scrotum, and coughing or dyspnea may occur. Most acute cases are seen in the warmer months, coincident with the greatest activity of the tick vector.

During the acute phase of E canis infection in dogs, the hemogram is usually normal but may reflect a mild normocytic, normochromic anemia; leukopenia; or mild leukocytosis. Thrombocytopenia is common, but petechiae may not be evident, and platelet decreases may be mild in some animals. Vasculitis and immune-mediated mechanisms induce a thrombocytopenia and hemorrhagic tendencies. Lymph node aspiration reveals hyperplasia. Death is rare during this phase; spontaneous recovery may occur, the dog may remain asymptomatic, or chronic disease may ensue.

Chronic ehrlichiosis caused by E canis may develop in any breed, but certain breeds, eg, German Shepherds, may be predisposed. Seasonality is not a specific hallmark of chronic infection, as appearance of chronic signs may be variably delayed following acute infection. In chronic cases, the bone marrow becomes hypoplastic, and lymphocytes and plasmacytes infiltrate various organs. Clinical findings vary based on the predominant organs affected, and may include marked splenomegaly, glomerulonephritis, renal failure, interstitial pneumonitis, anterior uveitis, and meningitis with associated cerebellar ataxia, depression, paresis, and hyperesthesia. Severe weight loss is a prominent finding.

The hemogram is usually markedly abnormal in chronic cases. Frequently, severe thrombocytopenia may cause epistaxis, hematuria, melena, and petechiae and ecchymoses of the skin. Variably severe pancytopenia (mature leukopenia, nonregenerative anemia, thrombocytopenia, or any combination thereof) may occur. Aspiration cytology reveals reactive lymph nodes and, usually, marked plasmacytosis. Frequently, polyclonal, or occasionally monoclonal, hypergammaglobulinemia occurs.

Dogs infected with A platys generally show minimal to no signs of infection despite the presence of the organism in platelets. The primary finding is cyclic thrombocytopenia, recurring at 10-day intervals. Generally, the cyclic nature diminishes, and the thrombocytopenia becomes mild and slowly resolves. Other ehrlichial infections not caused by E canis appear clinically similar to acute E canis infection, but the clinical course is usually more self-limiting. Shifting leg lameness and fever of unknown origin may be present. Thrombocytopenia and mild leukopenia or leukocytosis may occur during the acute course of infection, which is clinically more discrete. Chronic disease, as seen with E canis infection, is not typically seen in other ehrlichial infections.

Lesions:

During the acute or self-limiting phase of E canis infections, lesions generally are nonspecific, but splenomegaly is common. Histologically, there is lymphoreticular hyperplasia, and lymphocytic and plasmacytic perivascular cuffing. In chronic cases, these lesions may be accompanied by widespread hemorrhage and increased mononuclear cell infiltration in perivascular regions of many organs.

Diagnosis:

Because thrombocytopenia is a relatively consistent finding of infection with Ehrlichia and Anaplasma species, a platelet count is an important screening test. Clinical diagnosis may be confirmed by demonstrating the organisms within WBC, seen in intracytoplasmic inclusion bodies called morulae. This method of diagnosis lacks sensitivity, as low numbers of organisms make demonstration difficult. More commonly, a diagnosis is made by a combination of clinical signs, positive indirect serum fluorescent antibody titer, and response to treatment. The antibody response may be delayed up to 28 days; thus, serologic testing may not be a reliable diagnostic tool early in the course of the disease, and testing of paired sera and demonstration of increased antibody titers is recommended to confirm infection. Serologic cross-reactivity is strong between E canis , E chaffeensis , and E ewingi ; minimal cross-reactivity to Anaplasma phagocytophilum is also seen. These reactions should be considered in appropriate geographic areas. In some areas, ~50% of dogs infected with E canis also have a titer to A platys , which likely reflects co-infection; cross-reactivity between these agents is not observed.

PCR has been used to detect and identify specific Ehrlichia species in infected people and animals. Samples appropriate for PCR include blood, tissue aspirates, or biopsy specimens of reticuloendothelial organs such as lymph nodes, spleen, liver, or bone marrow. PCR can also be used to detect the effectiveness of treatment in clearing infection. PCR is not routinely available through commercial laboratories, although some veterinary schools and research institutions may offer it.

During the acute stage, differential diagnoses include other causes of fever and lymphadenomegaly (eg, Rocky Mountain spotted fever, brucellosis, blastomycosis, endocarditis), immune-mediated diseases (eg, systemic lupus erythematosus), and lymphosarcoma. During the chronic stage of E canis infection, differential diagnoses include estrogen toxicity, myelophthisis, immune-mediated pancytopenia, and other multisystemic diseases associated with specific organ dysfunction (eg, glomerulonephritis).

Treatment:

The drug of choice for all forms of infection caused by these organisms is doxycycline because of its superior intracellular penetration. The recommended dosage is 5-10 mg/kg, PO or IV, sid for 10-21 days. Tetracycline (22 mg/kg, PO, tid) can also be used for ≥2 wk in acute cases and 1-2 mo in chronic cases. Two doses of imidocarb dipropionate (5-7 mg/kg, IM), 2 wk apart, are variably effective against both ehrlichiosis and some strains of babesiosis. In acute cases receiving appropriate antibiotic therapy, body temperature is expected to return to normal within 24-48 hr after treatment. In chronic cases, the hematologic abnormalities may persist for 3-6 mo, although clinical response to treatment often occurs much sooner. Supportive therapy may be necessary to combat wasting and specific organ dysfunction; platelet or whole-blood transfusions may be required if hemorrhage is extensive. Concurrent broad-spectrum antibiotics may be needed if the dog has severe leukopenia. The E canis antibody titer should be measured again within 6 mo of illness to confirm a low or seronegative status indicative of successful therapy. Serum titers that persist at lower but positive levels should be rechecked in another 6 mo to ensure that they are not increasing.

Prevention:

Prevention is enhanced by controlling ticks and using seronegative screened blood donors. Prophylactic administration of tetracycline at a lower dose (6.6 mg/kg, PO, sid) is effective in preventing E canis infection in kennels where disease is endemic. Treatment must be extended for many months through at least one tick season if the endemic cycle is to be successfully eliminated.