CONTINUING EDUCATION FOR VETERINARIANS ® CE Article www.CompendiumVet.com American Canine Hepatozoonosis

Emily M. Medici, DVM Oklahoma State University

Johanna Heseltine, DVM, MS, DACVIM Canada West Veterinary Specialists and Critical Care Hospital

ABSTRACT: American canine hepatozoonosis (ACH) is a debilitating disease caused by Hepatozoon americanum and transmitted by ingestion of oocyst-containing Amblyomma maculatum ticks . A history of incomplete response to common antibiotics , together with physical findings of fever and muscle wasting and laboratory findings of leukocytosis and periosteal proliferation , should prompt testing for ACH. Muscle biopsy and whole-blood polymerase chain reaction are currently the most reliable methods of diagnosis. Treatment consists of a 2-week course of trimethoprim –sulfonamide, clindamycin, and pyrimethamine , followed by a 2-year course of decoquinate. Relapses are common, but prognosis is fair overall.

he cause of American canine hepato - GEOGRAPHIC DISTRIBUTION zoonosis (ACH) is Hepatozoon ameri - AND EPIDEMIOLOGY T canum, a protozoan transmitted by ACH has been reported in Texas, Louisiana, ingestion of Amblyomma maculatum ticks , or Alabama, Mississippi, Oklahoma, Georgia, Gulf Coast ticks , that contain the oocysts of the Tennessee , and Florida. 3,5,8–10 The geographic organism (Figure 1). Canine hepatozoonosis distribution of H. americanum is directly related was first recognized in North America in 1978 to the distribution of the Gulf Coast tick, in Texas .1 All infections in North America were which is the obligate definitive host and the originally thought to be caused by a more viru - source of infective oocysts of the protozoan. lent strain of Hepatozoon canis, the “Texas This tick , which was once confined to the Texas strain.” 2–5 In 1997, however, based on clinical, Gulf Coast , has now expanded its range as far serologic , and pathologic features ; gamont mor - north as southern Kansas and Kentucky. 11 The phology ; and inability to experimentally infect transport of ACH to nonendemic areas may Rhipicephalus sanguineus , the brown dog tick have occurred via widespread travel of humans and definitive host for H. canis , the cause of and pets. For example, Hurricane Katrina has ACH was designated as a new species, H. amer - broadened the distribution of ACH as dogs icanum (Table 1 ). 6 Molecular evidence separat - from the Gulf Coast region were moved ing H. canis from H. americanum has since throughout the country. a These animals may become available. 7 It is now well established aPersonal communication with T. Mark Neer, DVM, that ACH in North America is caused by H. MS, DACVIM, Oklahoma State University Center americanum. for Veterinary Health Sciences, September 20, 2006.

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Table 1. Comparison of Hepatozoon americanum with Hepatozoon canis 17

Diagnostic Criterion H. americanum H. canis Geographic distribution Southern United States Africa, Asia, South America, Southern Europe Primary tick vector Amblyomma maculatum Rhipicephalus sanguineus Common clinical signs Severe disease: fever, lameness, mucopurulent Mild disease: fever, lethargy, ocular discharge, generalized hyperesthesia, weight loss ; may be asymptomatic lethargy Common laboratory findings Anemia, extreme leukocytosis (20,000 – Rare; anemia, extreme 200,000 WBCs /µL), elevated alkaline leukocytosis phosphatase, hypoglycemia, hypoalbuminemia Radiographic lesions Periosteal proliferation Nonspecific Major target organs Skeletal muscle, myocardium Spleen, bone marrow, lymph nodes Unique morphologic features “Onion skin ” cysts in muscle “Wheel spoke” meront in spleen Primary diagnostic procedure Muscle biopsy , PCR Blood smear Visualization of gamonts Rare; found in <0.1% of peripheral leukocytes Common; found in up to 100% of neutrophils Treatment Clindamycin, pyrimethamine, trimethoprim – Doxycycline, imidocarb sulfonamide, decoquinate diproprionate PCR = polymerase chain reaction; WBC = white blood cell have been infected with the disease before the hurricane variabilis have been unsuccessful . There is one report of and developed clinical signs after relocation. Therefore, transmission via R. sanguineus ,4 but others have been a thorough history is imperative in establishing the unable to duplicate this result .6,15,18 Two other possible potential for exposure to ACH. vectors (Haemaphysalis leporispalustris [Packard ], the H. americanum , or a similar organism, has been identi - rabbit tick, and Ixodes scapularis Say, the blacklegged fied in domestic dogs and feral coyotes, bobcats , and tick ) have been proposed because these three-host ticks ocelots in the southern United States. 1,12–14 The Gulf are found in areas endemic for ACH. Further research is Coast tick tends to feed on dogs primarily in its adult required to determine whether these ticks can transmit form, not as a larva or nymph, making it unlikely that the hepatozoon organism. 15 dogs are effective reservoirs or important hosts 15 ; dogs Transmission to intermediate hosts, including the are actually considered to be accidental hosts. 13 Because domestic dog and the coyote, is by ingestion of H. ameri - they are not effective reservoirs, infected dogs do not canum oocyst-containing Gulf Coast ticks, rather than pose an infection risk to other dogs in the area. Under through tick bites. 18 Transstadial transmission occurs natural conditions, the host range of larval and nymphal regardless of whether the tick acquires H. americanum as a Gulf Coast ticks includes birds and small mammals, larva or nymph, so dogs can acquire infection by ingesting making these species potential reservoir hosts. 11,16 The newly molted nymphs or adult ticks. 18,19 In utero or con - range of species susceptible to infection and serving as genital (vertical) transmission has been reported with H. natural reservoir hosts is not known. 17 canis but has not been documented for H. americanum. 20 There is no evidence that transmission occurs by con - TRANSMISSION sumption of a tissue stage of H. americanum , as has been The definitive host and vector for H. americanum is A. confirmed with Hepatozoon griseisciuri in squirrels .11 maculatum . Repeated attempts to achieve infection of R. There is a single report of a dog fed raw meat containing sanguineus, Amblyomma americanum, or Dermacentor cysts and pyogranulomas containing merozoites that was

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Figure 1. Amblyomma maculatum , the Gulf Coast tick. Figure 2. “Onion skin” cyst found in skeletal muscle of a dog infected with H. americanum. followed for 9 months and showed neither clinical signs nor hematologic or histologic evidence of infection. 6 ment of circulating gamonts can occur in as few as 32 days under experimental conditions 22,24 (Figure 3 ). LIFE CYCLE The occurrence of ACH is seasonal, peaking in the Following ingestion, sporocysts are quickly released from warmer months or early fall when dogs are most likely the fragile-walled oocysts .21 Exposure to bile enhances to be exposed to ticks. However, infected dogs may the liberation of sporozoites from the sporocysts in the exhibit clinical signs throughout the year as the cycles of dog’s intestines .22 Sporozoites penetrate the intestinal asexual reproduction and pyogranulomatous inflamma - mucosa and are distributed throughout the body to tion are repeated .17 undergo merogony , primarily between fibers of skeletal and cardiac muscle. 21 Sporozoites undergo merogony in PATHOGENESIS canine macrophages that secrete mucopolysaccharide in The first evidence of ACH appears as early as 3 weeks concentric layers surrounding the cell , creating an “onion postexposure, consists of a large zoite-containing macro- skin” cyst 23 (Figure 2 ). The latter is a structure unique to, phage situated between muscle fibers, and is clinically and diagnostic for , ACH. At completion of merogony, silent. 24 As the zoite develops, the host cell produces and the meront ruptures , releasing numerous merozoites and extrudes layers of mucopolysaccharides that surround the inducing a severe, localized pyogranulomatous reaction cell, protecting it from the canine immune system. The as well as systemic illness. 17 Free merozoites enter the inflammatory response to the infection is very limited vasculature and macrophages within the granuloma and while the organism is encysted, but when the cyst rup - either develop into parasitic gamonts or are redistributed tures, an acute inflammatory response occurs, followed in the tissue to undergo repeated asexual cycles. 23 by pyogranulomatous inflammation and clinical ill - When an A. maculatum tick feeds on an infected dog, ness .17,25 Waxing and waning elevations of body tempera - it ingests the gamonts in the peripheral leukocytes. A ture and neutrophilic leukocytosis have been observed 4 sexual stage of reproduction followed by asexual multi - to 5 weeks postexposure . Clinical evidence of disease, plication in the tick gut epithelium produces oocysts such as lethargy, bone pain, and ocular discharge, occurs that contain hundreds of sporocysts, each of which shortly thereafter. Gamonts have been observed in holds 10 to 26 sporozoites. 18 As the oocysts develop, peripheral blood leukocytes 4 weeks after exposure. 24 most dislodge from the gut epithelium and are freed Cysts have been found in muscle biopsy samples for up into the hemocoel (body cavity) of the tick. 18,19,22 A to 10 years after the initial infection. b gamont ingested by a tick requires 42 days to develop bPersonal communication with Roger J. Panciera, DVM, MS, into a mature , sporulated oocyst. Completion of the life PhD, DACVP, Oklahoma State University Center for Veteri - cycle in the dog from ingestion of an oocyst to develop - nary Health Sciences, October 17, 2008.

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tis, Lyme disease, Rocky Ingestion of tick by dog Mountain spotted fever, ehrli - chiosis, and immune-mediated Sporozoites penetrate the polyarthritis. dog gut Mucopurulent ocular dis - charge (Figure 4) is a common Mature oocysts in finding that may be secondary hemocoel to pyogranulomatous inflamma - tion of extraocular muscles or destruction of the lacrimal Merogony Secondary merogony glands. 17,25 Schirmer tear test Sporogony results reveal decreased tear pro - Tick vector Dog host duction in about 33% of dogs with discharge. 10 Less common ocular abnormalities include Release of Gametogenesis merozoites focal retinal scarring, retinal Gamontogony and fertilization from mature hyperpigmentation and hyper - meronts reflectivity, mild papilledema , Tick uptakes Penetration of and uveitis with active inflam - gamonts during leukocytes by matory fundic lesions. 17,25 blood meal merozoites Dogs may have a history of Figure 3. Life cycle of H. americanum. (Adapted with permission from Baneth G, Mathew JS, polydipsia and concurrent poly- ShkapV, et al. Canine hepatozoonosis: two disease syndromes caused by separate Hepatozoon spp. uria due to secondary glomeru - Trends Parasitol 2003;19[1]:27-31) lonephritis or renal amyloidosis in the chronic stage of the dis - ease. Transient bloody diarrhea, Continued reproduction of the organism and release abnormal lung sounds, cough, and lymphadenomegaly are of merozoites lead to waxing and waning clinical signs less common. Many dogs continue to eat despite severe and relapses after treatment. Chronic infections cause fever but exhibit progressive weight loss and muscle wast - persistent antigenic stimulation and secondary compli - ing due to increased caloric demands associated with the cations, including vasculitis, glomerulonephritis, and prolonged inflammatory state. 17,25 amyloid deposition in various organs. Prolonged infec - Although affected dogs may also exhibit variable tions commonly result in progressive weight loss and minor clinical signs, there should be a strong index of muscle wasting, with death occurring within 12 months suspicion for ACH when a dog in an endemic area pre- after ingestion. 17,25 sents with fever, hyperesthesia, poor response to antibi - otic therapy, and muscle wasting. These salient clinical CLINICAL FINDINGS signs , coupled with mature neutrophilic leukocytosis Common clinical signs of H. americanum infection and periosteal proliferation , can be considered initially include an antibiotic -resistant fever of 102.7 ° to 105.6° F diagnostic for ACH. Marked leukocytosis with few (39.3 ° to 40.9° C), cachexia, generalized muscle atrophy, signs of systemic illness should likewise raise the suspi - depression, hyperesthesia (especially in the paraspinal cion of ACH in dogs with potential exposure. area ), mucopurulent ocular discharge , and gait abnormal - ities. Gait problems include stiffness, generalized weak - LABORATORY FINDINGS ness, hindlimb paresis and ataxia , and inability or The most consistent laboratory abnormality in ACH is unwillingness to rise. Hyperesthesia attributed to pyo - an elevated leukocyte count of 20,000 to 200,000/ µL, granulomatous myositis and possibly periosteal reaction typically consisting of a mature neutrophilia with an may be generalized or localized to the cervical, back, or occasional mild to moderate left shift. 10 Mild normo - joint regions. 17,25 Diagnostic differentials for dogs cytic, normochromic, nonregenerative anemia is a fre - exhibiting these signs include meningitis, diskospondyli - quent finding , presumably due to chronic inflammation.

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Figure 4. Mucopurulent ocular discharge in a dog infected with H. americanum .

Platelet numbers are usually normal to slightly ele - Figure 5. Periosteal proliferation on the femur ( arrow ) vated, 17,25 but marked thrombocytosis has been reported seen in dogs with H. americanum infection. secondary to chronic inflammation. 9 However, if throm - bocytopenia is present, concurrent infection with ehrli - chiosis, babesiosis, Rocky Mountain spotted fever, or changes consistent with generalized polymyopathy, another tickborne disease should be considered. 17,25 lymph node aspirates consistent with reactive hyperpla - Common serum biochemistry abnormalities are eleva - sia, and bone marrow cytology findings that include tions in alkaline phosphatase levels, hypoglycemia , and granulocytic hyperplasia and erythroid hypoplasia with a hypoalbuminemia. 10 The alkaline phosphatase elevation high myeloid :erythroid ratio .17,25 is probably due to periosteal inflammation and reaction. Hypoglycemia, often ranging from 40 to 60 mg/dL, may RADIOGRAPHIC FINDINGS be the result of in vitro metabolism of glucose by white Dogs with ACH may have minimal bone abnormalities blood cells. Hypoalbuminemia is attributed to decreased or significant changes consisting of disseminated, sym - protein intake, chronic inflammation , or protein-losing metric, periosteal new bone formation that most fre - nephropathy secondary to glomerulonephritis or renal quently involves the diaphyses of the proximal long amyloidosis. Serum blood urea nitrogen (BUN) values bones of the limbs 17,26 (Figure 5 ). Flat and irregular may be decreased unless significant secondary renal dis - bones are less commonly affected .2,3,5,6,9,27 The process of ease is present, causing azotemia. Hypoglycemia, hypoal - periosteal proliferation is histologically detectable as buminemia , and a low BUN level mimic liver disease early as 5 weeks after exposure, and the lesions progress biochemically, but serum bile acid assays are usually nor - rapidly. The pathogenesis of these lesions is unknown, mal or only slightly elevated in dogs with ACH. Despite but the disseminated and symmetric distribution of pro - significant myositis, creatinine phosphokinase values are liferation is more likely attributable to stimulation by typically normal. Hyperglobulinemia is uncommon, humoral factors than to stimulation by local factors .26 chronic inflammation notwithstanding .17,25 The gross and microscopic bone lesions of ACH are Urinalysis may reveal proteinuria , with an elevated very similar to those seen with hypertrophic osteopathy. urine protein:creatinine ratio in dogs with secondary In both conditions, the periosteal reaction occurs with - glomerular disease. Other diagnostic tests and subse - out cortical destruction, and the lesions primarily affect quent findings include electromyography revealing the diaphyses of long bones. With ACH , the onset and

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extremely high number of organisms in actively infected dogs. Evaluation of multiple biopsy samples can increase the likelihood of diagnosis. 17,25 A real-time polymerase chain reaction (PCR ) test for ACH has been developed .c This test targets the 18S rRNA gene of H. americanum and is capable of detect - ing ACH when there are as few as 7 organisms/mL of blood. It also distinguishes H. americanum from other , similar protozoa such as H. canis , Babesia gibsoni , and Babesia canis. The test is conducted on blood samples treated with EDTA , and the samples can be shipped by regular mail. 30 An ELISA to identify serum antibodies to ACH has been developed at Oklahoma State Univer - sity but is not commercially available .31

PATHOLOGIC FINDINGS Figure 6. H. americanum gamont in a leukocyte ( arrow ) seen on peripheral blood smear. At necropsy, cachexia and muscle atrophy are consistent gross findings in dogs chronically infected with ACH, along with thickened, roughened bone surfaces. Pyo - progression are faster and usually occur in the proximal granulomas may appear as 1 - to 2 -mm, white to tan foci bones of the limbs. With hypertrophic osteopathy , the scattered throughout muscle and other tissues. Pyogran - proliferation tends to begin in the metacarpals and ulomas, cysts , and meronts can be visualized microscop - metatarsals and is typically associated with a primary ically in skeletal and cardiac muscle and may be found pulmonary lesion. The pathogenesis of the bone lesions in adipose tissue, lymph nodes, intestinal smooth mus - in both conditions is incompletely understood. 26 cle, and spleen, skin, kidney, salivary gland, liver, pan - Scintigraphy has been used to study the onset and dis - creas , and lung tissue .29 An immunohistochemical tribution of the early skeletal lesions of ACH. Lesions staining procedure using polyclonal antibodies to sporo - are bilaterally symmetrical, have high intensity , and zoites of H. americanum has been developed to identify occur primarily proximal to the carpus or tarsus on the muscle cysts. 32 Various organs exhibit vascular changes axial skeleton. These lesions were detected as early as that include fibrinoid degeneration of vessel walls, min - day 67 postinfection, suggesting that bone scintigraphy eralization and proliferation of vascular intima, and pyo - may be a useful method for identifying ACH bone granulomatous vasculitis. Renal lesions are common , lesions. 28 including focal pyogranulomatous inflammation with mild glomerulonephritis, lymphoplasmacytic interstitial DIAGNOSTIC CONFIRMATION nephritis, mesangioproliferative glomerulonephritis, Fewer than 0.1% of peripheral blood leukocytes are and , occasionally , amyloidosis. The spleen, lymph nodes, infected, making gamont-containing leukocytes few and small intestine , and liver may also contain amyloid difficult to find. Gamonts appear within the cytoplasm of deposits. Pulmonary congestion, splenic coagulative leukocytes as pale blue to clear oblong capsules measuring necrosis, lymphadenomegaly , and congestion of the gas - approximately 8.8 × 3.9 µm, with a faintly stained tric mucosa are less common .29 nucleus 17,25 (Figure 6 ). Because peripheral blood smears rarely demonstrate the organism, buffy coat smears may be TREATMENT conducted to increase the chance of detecting gamonts. 29 Remission of clinical signs can be achieved quickly in Muscle biopsy is the most reliable method of con - most cases by initiating treatment with trimetho - firming the diagnosis of ACH .29 Tissue samples (2 ×2 prim –sulfonamide , clindamycin , and pyrimethamine cm) are taken from the biceps femoris or semitendi - (TCP combination) for 14 days (Table 2). Although the 10 nosus muscle . Muscle lesions consist of cysts, pyogran - cThis test is available from the Auburn University Molecular ulomas with merozoite-containing macrophages, and Diagnostics Laboratory. For more information, please visit myositis. 29 False -negative findings are rare due to the http://www.vetmed.auburn.edu/index.pl/molecular_diagnostics .

COMPENDIUM www.CompendiumVet.com November 2008 • Vol. 30, No. 11 American Canine Hepatozoonosis CE ® E7 CONTINUING EDUCATION FOR VETERINARIANS clinical response to treatment can be striking, relapse Table 2. CurrentTreatment Protocol for often occurs in 2 to 6 months when this treatment is American Canine Hepatozoonosis used alone .29 Decoquinate, a coccidiostat, has been found to reduce relapses. It is ineffective in resolving active dis - Medication Dosages ease but can arrest the development of merozoites as Trimethoprim – 15 mg/kg PO q12h for 14 days they are released from mature meronts. Dogs with ACH sulfonamide that experience relapse should be treated with the TCP Clindamycin 10 mg/kg PO q8h for 14 days combination for 14 days , after which decoquinate should Pyrimethamine 0.25 mg/kg PO q24h for 14 days be reinstituted . The optimum duration of decoquinate Decoquinate 10– 20 mg/kg PO q12h for 2 years treatment is debatable, and current recommendations include conducting whole-blood PCR testing every 3 to 6 months and discontinuing the drug once the test result have found the 2-year survival rate for dogs that received is negative .d Decoquinate is available as a feed additive in the TCP combination therapy plus daily decoquinate to be 50-lb bags at a concentration of 27.2 g/lb of premixed greater than 84%, compared with 12.5% for dogs that powder. The powder can be mixed into moist food at a received TCP combination therapy alone. 33 dose of 0.5 to 1 tsp /10 kg of body weight. 33 Treatment of ACH can be discouraging because no PREVENTION therapy can eliminate the tissue stages of the organism. Tick control is the mainstay of prevention for ACH and Relapses are frequent, and the disease’s natural relaps - should consist of effective preventive and acaricidal ing –remitting cycle can make treatment success difficult treatments and regular examination to remove ticks. to evaluate. Relapses result from continued release of Environmental control of ticks is also necessary, so yards merozoites into muscle and other tissues as meronts and outdoor kennels should be sprayed routinely. It is undergo replication and development. Current treatments also prudent to refrain from feeding dogs raw meat or cannot penetrate host cells to arrest the development of organs of wildlife from endemic areas. Although this encysted meronts. Relapses increase the likelihood of route of infection has not been documented for ACH, it long-term complications such as glomerulonephropathy, can occur with other species of Hepatozoon .17,25 amyloidosis, vasculitis , and chronic cachexia .17,25 Palliative treatment with NSAIDs may provide CONCLUSION immediate relief of fever and muscle pain and can be With dogs being redistributed throughout the United initiated concomitantly with TCP therapy. 17,25 Imido - States as a result of recent hurricanes, it is incumbent on carb diproprionate has been suggested as a treatment for clinicians to maintain a high index of suspicion for ACH , but it does not clear the encysted stage. 33 Toltra- ACH, regardless of where they practice. Likewise, if H. zuril, a coccidiostat, has induced excellent initial clinical americanum appears to be spreading through the area responses in dogs with ACH but cannot completely during the summer months, clinicians should warn eliminate the parasites , and remission was transient in clients and educate them about preventive measures. most dogs. 9 Toltrazuril is currently not available in the United States . REFERENCES 1. Davis DS, Robinson RM, Craig TM. Naturally occurring hepatozoonosis in PROGNOSIS a coyote. J Wildl Dis 1978;14:244-246. In the past , the prognosis for dogs with ACH was consid - 2. Craig TM, Smallwood JE, Knauer KW, et al. Hepatozoon canis infection in dogs: clinical, radiographic, and hematologic findings. JAVMA 1978;173:967- ered guarded to poor. Many dogs died or were euthanized 972. due to the severity of their clinical signs. The use of TCP 3. Barton CL, Russo EA, Craig TM, et al. Canine hepatozoonosis: a retrospec - combination therapy followed by daily decoquinate admin - tive study of 15 naturally occurring cases. JAAHA 1985;21:125-134. istration has markedly improved this picture. Relapses are 4. Nordgren RM, Craig TM. Experimental transmission of the Texas strain of now less severe and less frequent , with a lower occurrence Hepatozoon canis . Vet Parasitol 1984;16:207-214. of glomerulonephritis and amyloidosis. 17,25 Researchers 5. Panciera RJ, Gatto NT, Crystal MA, et al. Canine hepatozoonosis in Okla - homa. JAAHA 1997;33:221-225. d Personal communication with Douglass K. Macintire, DVM, 6. Vincent-Johnson NA, Macintire DK, Lindsay DS, et al. A new hepatozoon MS, DACVIM, DACVECC, College of Veterinary Medicine species from dogs: description of the causative agent of canine hepatozoono - at Auburn University, March 23, 2007. sis in North America. J Parasitol 1997;83:1165-1172.

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7. Baneth G, Barta JR, Shkap V, et al. Genetic and antigenic evidence supports 30. Kaltenboeck B . Canine hepatozoonosis . Accessed March 2007 at the separation of Hepatozoon canis and Hepatozoon americanum at the species vetmed.auburn.edu/index.pl/canine_hepatozoonosis. level. J Clin Microbiol 2000;38:1298-1301. 31. Mathew JS, Saliki JT, Ewing SA, et al. An indirect enzyme-linked 8. Gosset KA, Gaunt SD, Aja DS. Hepatozoonosis and ehrlichiosis in a dog. immunosorbent assay for diagnosis of American canine hepatozoonosis. J Vet JAAHA 1985;21:265-267. Diagn Invest 2001;13:17-21. 9. Macintire DK, Vincent-Johnson NA, Dillon AR, et al. Hepatozoonosis in 32. Panciera RJ, Mathew JS, Cummings CA, et al. Comparison of tissue stages of dogs: 22 cases (1989-1994). JAVMA 1997;210:916-922. Hepatozoon americanum in the dog using immunohistochemical and routine histologic methods. Vet Pathol 2001;38:422-426. 10. Macintire DK, Vincent-Johnson NA. Canine hepatozoonosis. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII Small Animal Practice . Philadel - 33. Macintire DK, Vincent-Johnson NA, Kane CW, et al. Treatment of dogs phia: WB Saunders; 2000:310-313. infected with Hepatozoon americanum : 53 cases (1989-1998). JAVMA 2001;218:77-81. 11. Ewing SA, Panciera RJ, Mathew JS, et al. American canine hepatozoonosis, an emerging disease in the new world. Ann NY Acad Sci 2000;216:81-92. 12. Mercer SH, Jones LP, Rappole JH, et al. Hepatozoon sp in wild carnivores in Texas. J Wildl Dis 1988;24:574-576. 13. Kocan AA, Breshears M, Cummings C, et al. Naturally occurring hepato - CE TEST zoonosis in coyotes from Oklahoma. J Wildl Dis 1999;35:86-89. The Auburn University College o f Veterinary Medicine CE 14. Lane JR, Kocan AA. Hepatozoon sp infection in bobcats. JAVMA approves this article for 3 contact hours of continuing 1983;183:1323-1324. education credit. Subscribers may take individual CE 15. Ewing SA, Mathew JS, Panciera RJ. Transmission of Hepatozoon americanum (Apicomplexa:Adeleorina) by ixodids (Acari:Ixodidae). J Med Entomol tests or sign up for our annual CE program . Those who 2002;39:631-634. wish to apply this credit to fulfill state relicensure requirements 16. Ewing SA, Panciera RJ, Mathew JS. Persistence of Hepatozoon americanum should consult their respective state authorities regarding the (Apicomplexa:Adeleorina) in a naturally infected dog. J Parasitol applicability of this program . 2003;89:611-613. 17. Macintire DK, Vincent-Johnson NA, Craig TM. Hepatozoon americanum infection. In: Greene CE , ed. Infectious Diseases of the Dog and Cat . 3rd ed . St. 1. Dogs become infected with Hepatozoon ameri - Louis: Elsevier; 2006:708-711. canum through 18. Mathew JS, Ewing SA, Panciera RJ, et al. Experimental transmission of a. consumption of raw meat . Hepatozoon americanum Vincent-Johnson et al., 1997 to dogs by the Gulf Coast tick, Amblyomma maculatum Koch. Vet Parasitol 1998;80:1-14. b. the bite of Amblyomma maculatum, the Gulf Coast 19. Ewing SA, DuBois JG, Mathew JS, et al. Larval Gulf Coast ticks ( Ambly - tick . omma maculatum ) [Acari:Ixodidae] as host for Hepatozoon americanum [Api - c. the bite of Rhipicephalus sanguineus, the brown dog complexa:Adeleorina]. Vet Parasitol 2002;103:43-51. tick . 20. Murata T, Makoto I, Susumu T, et al. Vertical transmission of Hepatozoon d. ingestion of Amblyomma maculatum, the Gulf Coast canis in dogs. J Vet Med Sci 1993;55:867-868. tick . 21. Ewing SA, Panciera RJ. American canine hepatozoonosis. Clin Microbiol Rev 2003;16:688-697. 2. Exposure to bile enhances the liberation of 22. Mathew JS, Ewing SA, Panciera RJ, et al. Sporogonic development of Hepa - tozoon americanum (Apicomplexa) in its definitive host, Amblyomma macula - ______in the dog’s intestines . tum (Acarina). J Parasitol 1999;85:1023-1031. a. oocysts 23. Cummings CA, Panciera RJ, Kocan KM, et al. Characterization of stages of b. sporocysts Hepatozoon americanum and of parasitized canine host cells. Vet Pathol c. sporozoites 2005;42:788-796. d. gamonts 24. Panciera RJ, Ewing SA, Mathew JS, et al. Canine hepatozoonosis: compari - son of lesions and parasites in skeletal muscle of dogs experimentally or natu - rally infected with Hepatozoon americanum . Vet Parasitol 1999;82:261-272. 3. The most common clinical sign(s) of ACH 25. Vincent-Johnson NA. American canine hepatozoonosis. Vet Clin North Am include Small Anim Pract 2003;33:905-920. a. fever . 26. Panciera RJ, Mathew JS, Ewing SA, et al. Skeletal lesions on canine hepato - b. mucopurulent ocular discharge . zoonosis caused by Hepatozoon americanum . Vet Pathol 2000;37:225-230. c. muscle wasting . 27. Panciera RJ, Ewing SA, Mathew JS, et al. Observations on tissue stages of d. all of the above Hepatozoon americanum in 19 naturally infected dogs. Vet Parasitol 1998;78:265-276. 28. Drost WT, Cummings CA, Mathew JS, et al. Determination of time of onset 4. The most consistent laboratory finding in dogs and location of early skeletal lesions in young dogs experimentally infected with ACH is with Hepatozoon americanum using bone scintigraphy. Vet Radiol Ultrasound a. ALP elevation . 2003;44:86-91. b. leukocytosis . 29. Vincent-Johnson NA, Macintire DK, Baneth G. Canine hepatozoonosis: pathophysiology, diagnosis and treatment. Compend Contin Educ Pract Vet c. thrombocytosis . 1997;19:51-65. d. hypoglycemia .

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5. Periosteal proliferation associated with ACH 8. H. americanum parasitizes which type of canine most closely resembles which disease process? host cell ? a. hypertrophic osteopathy a. macrophage b. hypertrophic osteodystrophy b. neutrophil c. osteomyelitis c. eosinophil d. neoplasia d. basophil

6. The major target tissue of H. americanum is 9. The current recommended treatment protocol a. the spleen. for ACH is b. skeletal muscle. a. imidocarb diproprionate . c. smooth muscle. b. toltrazuril . d. the lymph nodes. c. decoquinate . d. trimethoprim –sulfonamide, clindamycin, pyrimetha- 7. What is the most accurate method for confirm - mine, and decoquinate . ing the diagnosis of ACH? a. identification of gamonts in leukocytes in peripheral 10. When used to treat ACH, decoquinate is blood smears a. capable of killing mature meronts . b. muscle biopsy b. usually administered on an empty stomach . c. PCR c. ineffective against active infections . d. ELISA d. given twice daily for 6 months .

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