Fleas, ticks, and vector-borne diseases (Proceedings)

Canine Ehrlichiosis/Anaplasmosis

Canine ehrlichiosis and anaplasmosis are multisystemic diseases that may be caused by different genera and species of gram-negative obligate intracellular bacteria. The taxonomy of this group of organisms has undergone significant changes due to new information derived from molecular biological characterizations. Most ehrlichial species of importance to companion animal veterinarians use ixodid ticks as vectors. Some are transmitted by a single tick species; others may utilize multiple tick vectors. Ehrlichia canis, the principle cause of canine ehrlichiosis, is transmitted in salivary secretions by the ubiquitous brown dog tick (R. sanguineus). Infections are acquired by larvae and nymphs and are transmitted by the next life cycle stage after the molt and successful attachment to a new canine host (transstadial transmission). Transmission from adult female ticks to her ova (transovarial transmission) does not occur. Clinical canine ehrlichiosis occurs as three phases. The acute phase of infection persists for 1- 3 weeks. The hallmark of the acute phase is the development of vascular inflammation and subsequent thrombocytopenia. Thrombocytopathia and hyperglobulinemia also are characteristics of the acute phase of disease. Dogs either eliminate the organism or enter the subclinical phase. During this phase, the parasite is restricted to somewhat dormant occupation of visceral (predominantly splenic) macrophages. The subclinical phase may last only for weeks, but can persist for years. During this phase many dogs remain antibody positive and some retain abnormal hemograms. Mechanisms of disease during the final or chronic phase of ehrlichiosis is poorly understood, but probably results from immune events induced by the parasite. Features of this phase include bleeding tendencies (thrombocytopenia), non-regenerative anemia, pronounced hyper-globulinemia and thrombocytopathy. Clinical finding in dogs represent a wide array of abnormalities and presenting signs. These include lethargy, anorexia, weight loss, epistaxis, melena, petechial and echymotic hemorrhage, retinal hemorrhage and hematuria. Additional findings might include enlarged lymph nodes, pale mucus membranes (anemia), and splenomegaly. Occasionally ocular disease (anterior uveitis, retinal changes) and CNS signs such as ataxia, proprioceptive defects, head tilt, nystagmus and seizures have been reported. Diseases caused by Anaplasma phagocytophilum (AKA Ehrlichia equi, Erhlichia phagocytophilus, HGE Agent), Ehrlichia chaffeensis and Ehrlichia ewingi are similar to E. canis except that polyarthritis appears more common with E. ewingi. Diagnosis of canine ehrlichiosis/ anaplasmosis is based on history, clinical signs, hemogram and chemistries, and the results of immunologic and/or molecular biologic testing. Keep in mind that dogs can be infected with multiple vector-borne agents, given the wide geographic ranges of ixodid ticks and their capability to feed on multiple hosts. The availability of commercially available serological tests (some capable of detecting multiple pathogens) can greatly assist veterinarians in diagnosing ehrlichiosis. However, cross-reaction between the different species occurs only within genotypic groups. This can be a positive aspect of diagnosis if response to treatment is successful for all members of the group (not always the case). It can be a hindrance if infection is caused by a species not detected by the particular test employed. Specimens must be referred to specialty laboratories for molecular based tests. Some reference laboratories may also perform serologic tests for Ehrlichia species other than those caused by E. canis. Dogs are also host to E. platys, E. ewingi, E. chaffeensis, Anaplasma phagocytophilum, and potentially with A. risticii. The treatment of choice for Ehrlichiosis/Anaplasmosis is doxycycline (10 mg/kg for 3-4 weeks). Other effective drugs include tetracycline, oxytetracycline, minocycline, and chloramphenicol. Only marginal success was achieved with imidocarb diproprionate. Ehrlichial infections in cats are uncommon (only 30-40 cases worldwide). Cats are host to E. canis, A. phagocytophilum, and A. risticiii. Humans can be infected with E. chaffeensis, E. canis, E. ewingi, and A. phagocytophilum.

Cannine Borreliossis (Lyme Disease)

Canine Lyme borreliosis (CLB) is an infectious vector borne (potentially zoonotic) arthropathy that is enzootic in the northeastern US. Other smaller foci of infection occur in the upper midwest and the west. CLB is transmitted in the US by two species of ixodid tick. Ixodes scapularis is the primary vector in the northeastern, southern and midwestern US. Ixodes pacificus serves that same purpose in the west. The causative agent of CLB is Borrelia burgdorferi, one of more than 20 such small bacteria (spirochetes). Other species of Borrelia are responsible for the disease in other parts of the world. Differences in strains or species of the organisms can account for differences in the presentation and/or severity of resulting disease. Spirochetes gain entry into hosts (whether dog or human) in the saliva of the offending tick species. Severity of resulting disease is likely the result of the numbers of ticks that infest the host, as well as the number of organisms present and introduced by the ticks. As was mentioned for other agents, the disease syndrome is generally the result of the infected host's immune response. CLB is transmitted transtadially by nymphs and adults. Nymphs likely account for most human infections. The primary reservoir host in nature is the white-footed mouse. Clinical disease in dogs generally occurs 2-6 months after exposure to infected ticks. Signs include fever, shifting leg lameness, regional lymphadenopathy, and malaise. Polyarthritis is reported as the most common sign accompanying clinically significant canine infections. Glomerulopathy (azotemia, uremia, proteinuria, peripheral edema) has been observed occasionally, as has central nervous system disease. Diagnosis of CLB based on history, clinical signs, laboratory findings, results of serologic tests (IFA, ELISA), and rarely, detection of organisms by culture. An available point of care ELISA test that detects the so-called C6 protein is helpful in differentiating true infection titers from those that are vaccine induced. This test also detects antibodies to Ehrlichia canis and Ehrlichia chaffeensis, Anaplasma phagocytophilum, and antigens produced by the canine heartworm, Dirofilaria immitis. Idexx Corporation can quantify antibodies to C6 protein. This quantitative test can be helpful in identifying a treatment strategy in an asymptomatic dog, monitoring responses to treatment, and monitoring antibody responses in an asymptomatic dog over time. Tetracyclines and Clavamox are the treatments of choice for Lyme borreliosis.

Rocky Mountain Spotted Fever (RMSP)

RMSP is a disease of man, dogs and small mammals caused by Rickettsia rickettsii, an organism related to Ehrlichia sp. Dogs are infected following infestation by and subsequent feeding of ixodid ticks of the genus Dermacentor (D. variabilis, D. andersoni). Recent reports also suggest that Rhipicephalus sanguineus also can transmit RMSP. Ticks serve as both vectors and reservoirs for the disease, since the agent can persist and develop in successive generations of ticks without the necessity of infecting a vertebrate host. RMSP occurs throughout the United States but is seen with more frequency in the southeast in an area encompassing the Carolinas westward through Tennessee, Arkansas and Oklahoma. RMSF results from infection and replication of R. rickettsii in microvessels (arterioles and venules), causing disseminated vasculitis. Following an incubation period of 2 days to 2 weeks, the following clinical syndromes may result: lymphadenopathy, myalgia, cough, dyspnea, edema of face and extremities, congestion of vessels in the conjunctiva and sclera, abdominal pain, and petechiae/rash. Interestingly, rash, which is a principal presenting sign in humans, occurs only rarely in dogs. Diagnosis is based on history (including presence of ticks or exposure to ticks), clinical signs, laboratory data (thrombocytopenia), and serology. Tetracycline, (22 mg/kg, orally, 3 times daily for 14-21 days) is very effective against RMSP. Doxycycline and chloramphenicol have also been used.

Feline Cytauxzoonosis

Cytauxzoonosis is an often fatal tick-borne disease of rural outdoor cats caused by a dimorphic, biphasic protozoal parasite called Cytauxzoon felis. Cytauxzoonosis has been described in cats from many states in the southeastern US including Texas, Arkansas, Louisiana, Oklahoma, Missouri, Tennessee, Alabama, Georgia and Florida. Wild felids (e.g. bobcats) are probably natural hosts. Stages of the parasite occur in erythrocytes (piroplasms) and in leukocytes (schizonts). Both intraerythrocytic and leukocytic stages are structurally similar to parasites within the genus Theileria. Intraerythrocytic piroplasms are ingested by American Dog Ticks (Dermacentor variabilis) or perhaps other species. It is likely that a complex developmental cycle occurs in the tick which culminates in the production of infectious zoites. These zoites are injected when infected ticks feed on a susceptible feline host. Infection of mononuclear cells (macrophages) leads to the development of intracellular schizonts. These so-called "foamy" macrophages are found in a variety of organs including lung, spleen, liver and lymph nodes. It is this tissue phase of parasite development that is responsible for the clinical syndrome. Affected cats often develop a rapid course of disease which includes anorexia, dyspnea, lethargy, dehydration, depression, icterus, pallor, and high fever. Regenerative anemia and thrombocytopenia also have been observed. Hemoglobinuria and bilirubinuria are rare sequelae. The period of clinical illness is extremely rapid. Death usually occurs less than a week after development of initial clinical signs. The pathogenesis of the disease is not known but probably results from a combination of the obstructive effects of the proliferative tissue schizonts, and perhaps their production of toxic, vasoactive, and pyrogenic byproducts. The intraerythrocytic piroplasms may destroy erythrocytes or enhance their destruction and phagocytosis. Diagnosis of cytauxzoonosis is based on recognition of the clinical syndrome in outdoor cats with a history of exposure to ticks. Intraerythrocytic piroplasms are described as either "signet ring"-shaped bodies or bipolar "safety pin" forms that usually occur singly within infected erythrocytes. Necropsy usually reveals dehydration, pallor, icterus, and enlarged, edematous, and petechiated lymph nodes. The spleen and liver may be enlarged. The lungs are often congested and edematous. Hydropericardium is often observed. The lungs, liver, lymph nodes and spleen usually contain numerous schizont-infected ("foamy") macrophages. Feline cytauxzoonosis has been treated successfully with imidocarb diproprionate as per babesiosis in dogs, however, the second treatment should be administered within one week. The combination of atovaquone and azithromycin mentioned for treatment of babesiosis has also been used successfully to treat feline cytauxzoonosis. Tick control remains the best means of preventing the disease.

Canine Babesiosis

Babesiosis is a tick borne disease of dogs caused by several different species or subspecies of Babesia. Taxonomy of organisms in this group are currently under intense study. Babesia spp. that infect dogs in the Unites States are all thought to be transmitted by Rhipicephalus sanguineus. The possibility also exists that certain species are transmitted horizontally between infected dogs. Babesia spp. produce large (B. canis vogeli) or small (B. gibsoni, B. conradae ) intraerythrocytic piroplasms. Those of B. c. vogeli are usually 4-5 ?m, often occur paired within erythrocytes, and usually are bilobed. Those of B. gibsoni are 1-2 um, occur individually in erythrocytes, and are usually round to oval, or ring-shaped. Piroplasms of B. conradae are also smaller than B. c. vogeli. These intraerythrocytic stages are the only stages that occur in dogs. Ticks ingest piroplasms during feeding. A sexual cycle of development in the tick vector culminates in the production of infective zoites. Feeding on susceptible hosts by infected tick vectors leads to injection of infectious zoites and subsequent parasitemia. Successful transmission usually requires lengthy (at least 2-3 day) feeding by ticks. The piroplasms reproduce by binary fission within infected vertebrate erythrocytes. Other means of transmission may include transplacental transmission, transfusion, use of contaminated vaccination needles or instruments used during wound repair or surgery, and bite wounds resulting from dog fights. The latter appear to be causes for enzootics of B. gibsoni in certain breeds in the United States. Clinical signs of babesiosis vary depending on the species or subspecies of Babesia involved. However, common features of the disease include hemolytic anemia, thrombocytopenia, lethargy, fever, anorexia and hemoglobinuria. Many infected dogs are either subclinical carriers or become carriers after brief bouts of disease. Diagnosis of canine babesiosis is based on recognition of intraerythrocytic piroplasms, positive serologic tests, or response to treatment. Molecular-based diagnostic tests are available in laboratories conducting specialized research on these agents. Babesiosis can be treated with imidocarb diproprionate (6.6 mg/kg IM; repeat in 2 weeks). Imidocarb appears to be effective against B. c. vogeli. Atovaquone (13.5 mg/kg PO TID) and azithromycin (10 mg/kg PO Q 24 hr) in combination for 10 days are more effective against the smaller piroplasms. Supportive care may be necessary in severe or complicated cases.

American Hepatozoonosis

Hepatozoonosis is a canine disease caused by Hepatozoon americanum that is emerging in prevalence, particularly in the southeastern United States. It is a tick-transmitted hemosporazoon, distantly related to Babesia and the animal malaria-like organisms. The tick vector has been identified as Amblyomma maculatum. Other species also may serve as vectors in other areas of the US. Dogs suffering from hepatozoonosis present with a stiff gait, inactivity, weight loss, and myalgia. Other signs include bilateral ocular discharge and periosteal proliferations of the femur, pelvis and vertebrae. The latter sign appears to occur most commonly in young dogs. Other aids in diagnosis include profound leucocytosis (mature neutrophilia; 70,000-200,000 cells/?l), and elevated serum glucose and alkaline phosphatase. The disease is confirmed by demonstration of foci of pyogranulomatous inflammation in affected muscles. Also present are large cystic structures resembling onions, with a compact, often darkly staining center surrounded by concentric lamellar-like rings. These stages represent schizont-like structures present in the coccidia and coccidia-like organisms. Acute American hepatozoonosis is best treated with a combination of sulfadiazine/clindamycin/pyrimethamine. Long term (24 month) administration of decoquinate has been helpful in preventing relapses.

Canine and Feline Bartonellosis

Principle Bartonella species infecting dogs and cats include Bartonella vinsonii subsp berkhoffi and B. henselae. Canine bartonellosis (Bv) may present as endocarditis and/or granulomatous hepatitis. Some reports indicate that polyarthritis and lameness are also common findings. Anemia and thrombocytopenia have been reported in approximately 50% of the canine cases. The pathogenetic potential of B. henselae is questioned by some. Some reports implicate B. henselae as a cause of lymphadenopathy and stomatitis in cats. However, cats in these reports were co-infected with feline immunodeficiency virus. Serologic positivity is indicative of exposure or active infection. PCR tests confirm active infection. Improved culture techniques will likely increase our capability to recover B. henselae from infected cats. Bartonellosis has been treated with azithromycin (5-10 mg/kg PO q24 hours for 5 days). Humans with particular immunodeficiencies have been infected with Bartonella spp.

References Available On Request.