This report presents evidence that dogs recover from acute canine monocytic ehrlichiosis (CME) after 16 days of doxycycline treatment (10 mg/kg of body weight every 24 h). Blood PCR was as valuable as splenic aspirate PCR for early diagnosis of acute CME. Splenic aspirate PCR was, however, superior to blood PCR for the evaluation of ehrlichial elimination.Canine monocytic ehrlichiosis (CME) is a tick-borne disease with a global distribution (9). Diagnosis of CME is confirmed by demonstration of morulae in blood smears, serology, culturing of the rickettsiae, and PCR using Ehrlichia canis-specific primers. Tetracyclines are commonly used in the treatment of CME, with doxycycline in particular being the most acceptable and widely used (2, 3).Blood samples are presently used for PCR evaluation of ehrlichial infection and response to therapy (15). A previous study has demonstrated ehrlichial DNA in splenic aspirates of two subclinically experimentally infected dogs whose blood and bone marrow aspirates were found to be negative for E. canis DNA, suggesting the importance of splenic aspirates in the diagnosis of ehrlichial carriers (6). This finding questioned the validity of previous blood-based PCR studies for evaluating treatment regimens for CME, and the length of doxycycline treatment required for E. canis infection remained uncertain.The aims of this study were (a) to investigate whether splenic aspirates are superior to blood samples as a sample source for E. canis PCR; (b) to determine whether dogs with acute CME remain persistently infected despite concurrent treatment; and (c) to determine the duration of doxycycline treatment required to eliminate E. canis DNA, as measured by PCR in cases of acute CME.Five beagle dogs, 4 to 6 years old and negative serologically and by PCR for E. canis, were used in this study. The dogs were artificially infected by intravenous injection of 5 ml of E. canisinfected blood. This blood was drawn from an acutely ill, naturally infected dog. Infection of the donor dog with E. canis was confirmed by serology using the indirect immunofluorescence antibody (IFA) test (11), by blood culture of DH82 cells (4), and by p30-based nested PCR for E. canis (14).
In order to determine whether dogs in the subclinical phase of canine monocytic ehrlichiosis (CME) are carriers of Ehrlichia canis and to determine the significance of persistent indirect immunofluorescent anti-E. canis antibody titers during this phase, PCR was performed with blood, bone marrow, and splenic aspirates collected 34 months postinoculation from six clinically healthy beagle dogs experimentally infected with E. canis. At least one of the three samples (spleen, bone marrow, and blood) from four of the six dogs was PCR positive. The spleens of all four of these dogs were PCR positive, and the bone marrow and blood of two of the four dogs were PCR positive. Indirect immunofluorescent-antibody titers increased progressively during the first 5 months postinfection, remained high for an additional period of more than 11 months, and declined thereafter, suggesting that the dogs were recovering from the disease. Five of the dogs remained seropositive 34 months postinfection. The data obtained in this study demonstrate for the first time that clinically healthy dogs in the subclinical phase of CME are carriers of the rickettsia. It was shown that dogs can harbor E. canisfor years without developing the chronic clinical disease and that dogs can eliminate the parasite and recover from CME without medical treatment. Our findings suggest that the spleen is the organ most likely to harbor E. canis parasites during the subclinical phase and the last organ to accommodate the parasite before elimination. It was concluded that PCR of DNA extracted from splenic aspirates is a reliable method for determining the carrier state of CME.
One hundred cases of monocytic ehrlichiosis diagnosed in Israeli dogs were confirmed by the presence of anti-Ehrlichia canis indirect immunofluorescent antibody titres greater than 1:40. The disease occurred in all age groups and there was no sex predilection. German shepherd dogs were significantly over-represented whereas crossbreed dogs were significantly under-represented (P > 0.0005). The most common clinical signs were depression, lethargy, lymphadenomegaly, fever, anorexia, panting, pale mucous membranes and bleeding, of which epistaxis was most common. Thrombocytopenia, anaemia (mainly normocytic normochromic) and lymphopenia were the predominant haematological findings. Forty-nine of the 100 cases were followed up for a year. Thirty-two dogs survived and 17 died. A Cox proportional hazards regression model was used to examine the effect of host, environmental, and haematological prognostic factors on survival. It was concluded that severe anaemia, severe leucopenia, pancytopenia, a tendency to bleed (especially epistaxis) and being a German shepherd dog were important indicators of poor survival in cases of monocytic ehrlichiosis in dogs.
Canine monocytic ehrlichiosis (CME) is a potentially fatal tick-borne disease caused by the rickettsia Ehrlichia canis (16). The etiologic agent was first recognized in Algeria in 1935 (8). Since then, it has been reported worldwide, causing extensive morbidity and mortality among domestic dogs and other canids (11, 28, 51). The principal vector of CME is Rhipicephalus sanguineus (11). Recently, it has been shown experimentally that Dermacentor variabilis is also capable of transmitting E. canis (24). The pathogenesis of CME consists of an incubation period of 8 to 20 days, followed sequentially by acute, subclinical, and in some cases chronic phases. The disease may be manifested by a wide variety of clinical signs of which depression, lethargy, weight loss, anorexia, pyrexia, lymphadenomegaly, splenomegaly, and bleeding tendencies are the most common. Principal hematologic abnormalities include thrombocytopenia, mild anemia and mild leukopenia during the acute stage, mild thrombocytopenia in the subclinical stage, and pancytopenia in the severe chronic stage. The main biochemical abnormalities include hypoalbuminemia, hyperglobulinemia, and hypergammaglobulinemia (16). CME has been researched extensively in the last decade, and special efforts have been made to elucidate the pathogenesis of the disease. Better understanding of major mechanisms involved in the pathogenesis of the disease may assist clinicians in understanding the disease process and providing appropriate treatment, affording a better prognosis to their patients. In the light of the recent emergence of similar ehrlichial pathogens that infect human patients, the understanding of pathogenic processes in CME may contribute to the understanding of human monocytic ehrlichiosis and human granulocytic ehrlichiosis. This article reviews recent investigations in the pathogenesis of CME with special reference to platelet disorders and serum protein alterations, the principal hematological and biochemical abnormalities in CME, respectively. Host immune response in both acute and persistent E. canis infection is discussed and is proposed to be involved in the pathogenesis of disease manifestations.
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