Ehrlichia species are intracellular bacteria that are within the family of Anaplasmataceae of the order Rickettsiales. The family of Anaplasmataceae now includes the genera of Ehrlichia, Anaplasma, and Neoricketssia, after renaming of organisms (notably Ehrlichia equi and Ehrlicia platys as Anaplasma sp.) and reclassification in 2001 based on 16S RNA and groESL gene sequences in the bacteria (Allison and Little, 2013). The names of some species, however, remains unchanged. The genus now includes those organisms that infect leukocytes (e.g, Ehrlichia canis).
|Old name||New name||Species affected||Infected blood cell|
|Ehrlichia canis||Ehrlichia canis||Dogs, cats||Monocyte, lymphocyte (canine monocytic ehrlichiosis)|
|Ehrlichia ewingii||Erhlichia ewingii||Dogs||Neutrophils, eosinophils (polyarthritis)|
|Ehrlichia equi||Anaplasma phagocytophilum||Horses, dogs, cats, camelids, humans||Neutrophils, eosinophils (pathogenic)|
|Ehlrichia platys||Anaplasma platyus||Dogs||Platelets (cyclic thrombocytopenia)|
Disease in dogs
- Vector: Rhipicephalus sanguineus, Dermacenter variabilis.
- Cells: Monocytes, macrophages, lymphocytes. Morulae rarely seen in infected dogs and usually only in acute infection (Allison and Little 2013).
- Clinical signs: Fever, lethargy, anorexia, excess hemorrhage (attributed to platelet dysfunction as well as thrombocytopenia – thrombocytopenia is usually not severe enough to induce hemorrhage alone – platelet counts are usually moderately decreased, i.e. 50-150,000/uL). Some dogs have neurologic disease and may have increased numbers of granular lymphocytes in their cerebrospinal fluid (this finding is not specific for this organism).
- Bloodwork: Thrombocytopenia (characteristic, multiple mechanisms including platelet activation and immune-mediated destruction [Shropshire et al 2018]), non-regenerative anemia, and pancytopenia (from ineffective hematopoiesis in most dogs and bone marrow aplasia in chronic infections, particularly in German Shepherd dogs) have been reported. The organism may induce a lymphocytosis of granular lymphocytes, comprised of cytotoxic T cells (CD3+, CD8+), and can have a clonal T cell expansion on polymerase chain reaction for antigen receptor rearrangement testing (PARR), that mimics a chronic lymphocytic leukemia. All dogs with a lymphocytosis, particularly of granular lymphocytes, in blood should be tested for Ehrlichia canis, as should dogs with pancytopenia and ineffective hematopoiesis or bone marrow aplasia. In one study, leukogram changes were characterized weekly for 42 days after experimental infection with Ehrlichia canis in 13 Beagle dogs. Leukogram changes preceded the onset of clinical signs at day 21, with a significant decrease in all leukocytes by 14 days after infection. Not all infected dogs were neutropenic or lymphopenic. The nadir in neutrophil count occurred at day 21 and most infected dogs were neutropenic (<2,000/uL). Lymphocyte counts appeared to rebound at day 21. In contrast, either neutropenia and neutrophilia were seen in naturally infected cases (data retrospectively obtained from 20 dogs with acute ehrlichiosis). A left shift and toxic change in neutrophils were not common findings in these experimentally infected or naturally infected dogs, however the proportions of reactive lymphocytes (defined as intermediate to large cells with deep blue cytoplasm, immature chromatin or granules) peaked on day 7 after infection, indicating an antigenic response. Reactive lymphocytes were typically seen in naturally infected dogs. Low numbers of “activated” monocytes (having many clear vacuoles with or without mature chromatin) were described in 33% of experimentally infected dogs and some naturally infected dogs. However, identification of such cells is quite subjective and clinical pathologist-dependent. Clinical signs in experimentally infected dogs were not specific and included fever (all dogs), anorexia, depression, splenomegaly and lymphadenopathy. Some dogs were anemic and all were thrombocytopenic on day 21 (platelet counts ranged from 46,000-101,000/uL). A time course of changes were not described for platelets or erythrocytes (Gianopoulos et al 2016). In another study assessing hemostatic variables in 4 Beagles experimentally infected with E. canis by infusion of blood from an infected dog, a thrombocytopenia (average count, 75,000/uL) developed by week 1 with the nadir (average around 50,000/uL) by week 2. The count rebounded after doxycycline administration (increased to an average 125,000/uL within 1 week). Platelet-associated antibodies were detected at a week but peaked at 3 weeks after infection (after the nadir). The dogs were hypercoagulable with tissue factor-activated TEG and hypofibrinolytic (with addition of tPA), which may be a consequence of forming stronger clots that are more resistant to fibrinolysis. The hypercoagulability may be due to a combination of platelet activation and increased fibrinogen, which was increased within a week of infection (Shropshire et al 2018). The organism can also stimulate a restricted oligoclonal gammopathy that mimics a monoclonal gammopathy (due to multiple myeloma or other B cell neoplasia). The involved immunoglobulin is usually IgG.
- Diagnosis: Serologic testing, PCR.
- Vector: Amblyomma americanum.
- Cells: Neutrophils, eosinophils. Morulae frequently seen in infected dogs, with numbers of infected cells corresponding to severity of infection (Allison and Little, 2013). Morulae can also be seen in neutrophils within joint fluid, but may be only seen in <1% of cells in the fluid.
- Clinical signs: Fever, lethargy, anorexia, polyarthritis (the main differential diagnosis is Anaplasma phagocytophilum, which produces a similar disease). In one study of 41 dogs with natural infection, signs referable to arthritis (limb or joint pain) and fever were among the most commonly observed clinical signs, along with lymphadenopathy, and vomiting and diarrhea. Affected dogs had co-morbidities including heart murmurs (related to anemia in some dogs), renal disease, immune-mediated hemolytic anemia and cancer, to name a few. It is difficult to know whether the clinical signs were related to the bacterial infection or the comorbidities in the study. Rarely, infected dogs can lack obvious clinical signs. (Qurollo et al 2018).
- Bloodwork: Thrombocytopenia is the most characteristic finding in infected dogs, but anemia (mostly non-regenerative), neutrophilia and monocytosis were more common in the aforementioned study of 41 dogs and a few dogs had thrombocytosis (likely due to co-morbidities or drug treatment). Proteinuria was detected in 74% of tested dogs, most of which had an inactive urine sediment (Qurollo et al 2018).
- Diagnosis: Morulae in neutrophils in blood or synovial fluid. Serologic testing, but cross reactivity seen with other bacteria, including Anaplasma phagocytophilium and Ehrlichia chafeensis (latter usually not clinical in dogs). May get negative results with 4DX SNAP test in our experience, 4DX plus SNAP test usually positive. Polymerase chain reaction testing for bacterial DNA is usually positive.