Ehrlichiosis is a serious and potentially life-threatening disease that affects dogs worldwide. Caused by a group of Rickettsiales bacteria from the genus Ehrlichia, this tick-borne illness can lead to a variety of symptoms and, if left untreated, can result in severe complications. Understanding the nature of ehrlichiosis, its symptoms, and treatment options is important for dog owners to protect their pets from this dangerous disease.
Causes and Epidemiology
Ehrlichia canis causes canine monocytic ehrlichiosis (CME), an important disease of dogs exposed to ticks worldwide. The organism infects circulating monocytes and forms morulae (Latin for “mulberry”), a cluster of bacteria, within the monocyte cytoplasm. E. canis is transmitted by Rhipicephalus sanguineus ticks. Infection has been reported in dogs from Asia, Africa, Europe, and the Americas.
In the United States, disease is diagnosed most frequently in dogs living in the south-eastern and southwestern states, but because of chronic, subclinical infection, dogs can be incidentally transported to nonendemic regions before developing the condition. Ticks acquire infection by feeding as larvae or nymphs on infected dogs. Jackals, foxes, and potentially coyotes can serve as reservoir hosts. The organism is transmitted transstadially but not transovarially within the tick. No age, breed, or sex predilection for CME has been clearly documented. Cross-bred dogs may be less likely to develop disease.
Clinical Signs of Ehrlichiosis in dogs
The course of CME has been divided into acute and chronic phases, although these phases are not always clinically distinguishable. Transmission can occur within hours of tick attachment and acute signs of disease occur 8 to 20 days after infection. Common vague signs include lethargy, inappetence, fever, and weight loss. Replication of the organism in reticuloendothelial tissues is associated with generalized lymphadenopathy and splenomegaly. Ocular and nasal discharge, peripheral oedema, and less commonly, petechial and ecchymotic haemorrhages may occur.
Neurologic symptoms may involve muscle twitching, ataxia, seizures, vestibular dysfunction, heightened sensitivity to touch (hyperesthesia), and cranial nerve impairments. These signs are likely caused by meningeal inflammation or haemorrhage. Thrombocytopenia and sometimes mild leukopenia and anaemia occur 1 to 4 weeks after infection. Transient proteinuria has also been reported, which resolves within 6 weeks of infection. Dogs may recover from the acute phase after 2 to 4 weeks without treatment.
After the acute phase, some dogs remain sub-clinically infected for months to years. They may have mild persistent thrombocytopenia. Organisms may sequester within the spleen and evade host immune systems through antigenic variation. This stage can last anywhere from several months to years.
Chronic ehrlichiosis ranges in severity from mild to life-threatening, with signs that include lethargy, inappetence, bleeding tendencies, pallor, fever, weight loss, lymphadenopathy, splenomegaly, anterior uveitis, retinal haemorrhage, retinal detachment, polyuria/polydipsia, and oedema. Bleeding tendencies result from thrombocytopenia and platelet dysfunction. Cutaneous and mucosal petechial or ecchymotic haemorrhages, epistaxis, melena, haematochezia, haematuria, and prolonged bleeding from venepuncture sites have been reported. Polymyositis may develop, with muscle atrophy and tetra paresis. Secondary opportunistic infections such as viral papillomatosis, protozoal infections, and bacteriuria have also been described, although the precise underlying mechanism of immune suppression and how it relates to persistence of E. canis, has not yet been elucidated.
Pancytopenia on results of a complete blood count (CBC) typifies the severe chronic form of ehrlichiosis. It is caused by hypoplasia of all bone marrow cells. Thrombocytopenia and nonregenerative anaemia are common. Moderate to marked granular lymphocytosis (up to 17,000/mcL) and bone marrow plasmacytosis may occur. Some dogs have a monoclonal gammopathy, similar to that seen with some lymphocytic leukaemia or multiple myelomas. Dogs with well-differentiated lymphocytosis or an otherwise unexplained monoclonal gammopathy should be tested for E. canis infection.
Serum chemistry abnormalities in chronic ehrlichiosis include hypoalbuminemia, hyperglobulinemia, and elevated alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities. The hyperglobulinemia is usually due to a polyclonal gammopathy. A protein-losing nephropathy may develop as a result of an immunocomplex glomerulonephritis, which can be associated with azotaemia. Dogs with central nervous system (CNS) involvement may have increased cerebrospinal fluid (CSF) protein concentrations and cell counts.
Diagnosis of Canine Ehrlichiosis
Detection of morulae within monocytes using cytologic evaluation is diagnostic for monocytic ehrlichiosis but is insensitive. It is important to note that the morulae of E. canis and E. chaffeensis cannot be discriminated. In one study, morulae were found in 2 of 19 dogs with chronic monocytic ehrlichiosis. Diagnosis of ehrlichiosis is usually confirmed with serology, using indirect fluorescent antibody (IFA) or enzyme-linked immunosorbent assay (ELISA). Antibodies typically become detectable between 7 and 28 days following the initial infection. Therefore, dogs with acute ehrlichiosis may have negative test results if antibody production has not yet occurred. Retesting should be performed after 2 to 3 weeks to demonstrate seroconversion.
A positive serum antibody titre for E. canis may occur with previous exposure and does not equate with diagnosis. Serology results must be interpreted in the context of the clinical signs and results of testing for other conditions. Dogs with chronic E. canis infection typically have extremely high IFA titres, sometimes >1 : 600,000. Antibodies may persist despite treatment, suggesting persistence of the organism. These test results do not correlate with severity of hyperglobulinemia or disease. Serologic cross-reactivity to other Ehrlichia species occurs, including E. ewingii and particularly E. chaffeensis. Cross-reactivity to Anaplasma phagocytophilum antigens can occur but is minor.
A variety of ELISA assays detect antibodies to E. canis. A point-of-care lateral flow ELISA device detects canine heartworm antigen, antibodies to E. canis or E. ewingii, antibodies to Borrelia burgdorferi, and antibodies to A. phagocytophilum in canine serum, plasma, or whole blood (SNAP 4Dx Plus, IDEXX Laboratories, Westbrook, ME.). This test includes recombinant surface proteins of E. canis and E. ewingii. The antigens of E. canis and E. ewingii are combined together in a single spot, so a positive result reflects either seroreactivity to E. canis, E. ewingii, or both pathogens. The sensitivity of this assay for detection of antibodies to E. canis when compared with IFA was 131/134 (97.8%) and specificity was 217/235 (92.3%). Other point of-care ELISA assays detect E. canis antibodies. In addition, a diagnostic laboratory-based ELISA assay detects antibodies to E. canis, B. burgdorferi, A. phagocytophilum and D. immitis (Accuplex 4, Antech Laboratories). It is recommended that dogs incidentally identified to have E. canis seroreactivity when screened using ELISA assays that simultaneously detect heartworm antigen should undergo a thorough physical examination and have a complete blood count, chemistry panel, and urinalysis to evaluate for thrombocytopenia, hyperglobulinemia, and proteinuria. Treatment of seroreactive clinically healthy dogs is controversial, since it does not change their outcome and has the potential to lead to antimicrobial resistance or adverse effects of drug therapy.
PCR is widely available for routine diagnosis of E. canis infection as part of “vector-borne pathogen” panels offered by veterinary diagnostic laboratories. Assay results must be interpreted in the context of the history, clinical signs, and serologic assay results. E. canis DNA can be detected using PCR on blood, lymph node aspirates, splenic aspirates, or bone marrow. However, sensitivity of PCR from bone marrow for diagnosis of chronic ehrlichiosis can be as low as 25%. Thus, PCR alone is not suitable for screening potential blood donors for infection but may be useful for confirming infection in the first week of illness, when serologic assays are often negative.
Treatment of Ehrlichiosis in Dogs
The recommended treatment for CME is doxycycline (10 mg/kg PO q 24 h) for 28 days. Shorter periods of treatment (e.g., 16 days) may be effective for dogs with acute CME. Most dogs show clinical improvement within 24 to 48 hours, but those with severe chronic disease may not respond to therapy or their “cytopenias” may gradually resolve over several months. Platelet counts generally improve and normalize within 2 weeks of initiating therapy. Following therapy, titres may decline and become negative over 6 to 9 months, while some retain high titres for years. Treatment for such dogs should be based on resolution of platelet counts and decreases in hyperglobulinemia. Hyperglobulinemia may take months to resolve after treatment is discontinued. Platelet counts should be reassessed 1 and 3 months after discontinuation of therapy because of the potential for relapse or reinfection. Other causes of illness should be considered in dogs that fail to respond to treatment.
Alternative drugs, used with variable success, include chloramphenicol, imidocarb dipropionate, and enrofloxacin. Members of the E. canis genogroup appear to have intrinsic gyrase-mediated resistance to fluoroquinolones. While enrofloxacin therapy may lead to clinical improvement, its use is not recommended. The efficacy of imidocarb dipropionate has been controversial.
For dogs that are dehydrated or anaemic, intravenous fluids or blood products may also be required. Use of darbepoetin or granulocyte colony-stimulating factor could be considered for dogs with severe chronic ehrlichiosis. If thrombocytopenia fails to respond to doxycycline administration, adding a short course (up to a week) of immunosuppressive doses of glucocorticoids may be beneficial.
Prevention and Public Health Significance
Prevention of canine monocytic ehrlichiosis relies on tick control combined with careful searching for and prompt removal of attached ticks. DNA of an E. canis-like organism has been detected in people with clinical signs of monocytic ehrlichiosis. Appropriate precautions are indicated when handling engorged ticks, blood, or tissue specimens from infected dogs.
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