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. November 2008 • Vol. 30, No. 11 E1 COMPENDIUM Copyright © 2008 Veterinary Learning Systems. This document is to be used for internal purposes only. Reprinting or posting on an external website without written permission from VLS is a violation of copyright laws. CE American Canine Hepatozoonosis E2 ® CONTINUING EDUCATION FOR VETERINARIANS 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 COMPENDIUM www.CompendiumVet.com November 2008 • Vol. 30, No. 11 American Canine Hepatozoonosis CE ® E3 CONTINUING EDUCATION FOR VETERINARIANS 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.