Canis ISSN: 2398-2942

Hepatozoonosis

Contributor(s): Gad Baneth, Leah Cohn

Introduction

  • Two distinct species of the protozoa within the genus Hepatozoon result in well-described clinical syndromes in dogs; the syndromes are Old World canine hepatozoonosis and American canine hepatozoonosis.
  • Old World canine hepatozoonosis, caused by the protozoan Hepatozoon canis Hepatozoon canis , is usually a subclinical infection. However, high parasite burdens can result in a serious clinical illness.
  • American canine hepatozoonosis, caused by the protozoan Hepatozoon americanum Hepatozoon americanum , results in a chronic course of pain, weight loss, fever, and lethargy in infected dogs. Without appropriate treatment, infection is fatal.

Pathogenesis

Etiology

  • Old World hepatozoonosis:
    • Infectious disease caused by the protozoan parasite Hepatozoon canis.
    • Dogs acquire infection by ingestion of an infected tick. Although other tick species may also transmit infection, the major vector is the Brown dog tick, Rhipicephalus sanguineus Rhipicephalus sanguineus.
    • Canine infection with H. canis has been recognized for over 100 years. This species of Hepatozoon appears to be well adapted to the dog, often resulting in subclinical infection.
  • American hepatozoonosis:
    • Infectious disease caused by the protozoan parasite Hepatozoon americanum.
    • Dogs acquire infection by ingestion of an infected tick (Gulf Coast tick, Amblyomma maculatum Amblyomma maculatum).
    • American hepatozoonosis has been recognized only since 1978, with recognition of the species as H. americanumin 1997. This species of Hepatozoonis poorly adapted to the dog, resulting in severe morbidity and mortality.

Predisposing factors

General

  • Old World hepatozoonosis:
    • Often, infected dogs present with concurrent illness. It is likely that concurrent disease worsens the severity of parasitemia or contributes to the severity of clinical illness in these scenarios.
    • The bite of vector ticks may transmit infections besides H. canis (transmitted by ingestion of the tick), complicating the clinical presentation.
    • Immunosuppressive drug therapy, diseases which impact immunologic responsiveness, and youth are speculated to predispose infected dogs to severe parasitemia and clinical illness.
  • American hepatozoonosis: dogs that ingest the Gulf Coast tick will become infected.

Pathophysiology

  • For both H. canis and H. americanum the dog is an intermediate host while the tick vector is the definitive host.
  • Ticks become infected by ingesting gametes in the blood of an infected intermediate host (eg dog). Sexual reproduction occurs in the tick, producing oocysts.
  • Infection is not transmitted by the bite of the tick, but rather by ingestion of the tick.
  • Sporulated oocysts rupture from the ingested tick, releasing sporozoites into the intestinal lumen.
  • Sporozoites penetrate the intestinal wall and then invade phagocytic cells. These phagocytic cells transport the organism (via the circulatory system) to target tissues.
  • Organisms become resident in target tissues where they undergo multiple cycles of merogony.
  • Meronts eventually rupture, releasing merozoites.
  • Merozoites gain entry to peripheral blood cells, where they become infectious gamonts.
  • The cycle is repeated when a naïve tick feeds on the blood of an infected dog.
  • Old World hepatozoonosis H. canis.
    • Merogony and development of merozoites occurs in multiple tissues, but primarily in hemolymphatic tissues and visceral organs.
    • The classic morphologic feature of the tissue phase is a wheel spoke arrangement of merozoites in the meront surrounding a clear center space.
    • Gamonts are found primarily in peripheral blood neutrophils, but occasionally also in monocytes.
    • Large numbers of peripheral blood cells may contain gamonts.
  • American hepatozoonosis:
    • Merogony and development of merozoites occurs primarily in mononuclear cells located between skeletal and cardiac muscle striations.
    • The classic morphologic feature of the tissue phase is an onion skin cyst. The organisms cause the host to secrete mucopolysaccharides which encyst the infected mononuclear cells.
    • Eventually, merozoites are released from ruptured cysts. Cyst rupture results in profound pyogranulomatous inflammation and accompanying myositis.
    • Mononuclear cells brought to the site of inflammation become infected with organism.
    • Organisms within the infected mononuclear cells can either repeat the merogenous asexual reproductive cycle after re-encysting in muscle (perpetuating the myositis characteristic of the disease), or can form gamonts.
    • Gamonts circulate in mononuclear cells (the infectious form) in only very low numbers.
    • Chronic antigen-antibody complex formation can lead to secondary glomerulonephritis Glomerulonephritis. Chronic inflammation can lead to amyloidosis Amyloidosis. Either of these complications can result in nephrotic syndrome (ie proteinuria, edema/ascities, hypercholesterolemia, hypoalbuminemia) and its complications (eg renal failure, pro-thrombotic tendencies, systemic hypertension).
    • If organisms encyst in cardiac muscle, myocarditis and cardiac dysrhthmias can occur.

Timecourse

  • Old World hepatozoonosis:
    • Parasitemia has been detected as soon as 28 days post infection or as late as 12 weeks post infection.
    • Following forced ingestion of infected ticks, serum IgM titers were detected a mean of 26 days post-infection while IgG titers were detected a mean of 29 days post infection.
    • Although serum titers in some experimentally infected dogs may wane or even disappear, parasitemia may persist indefinitely.
    • Illness may develop rapidly, or never at all. Concurrent disease or immune suppression may contribute to worsened parasitemia and clinical illness.
    • Parastemia usually resolves within several weeks of appropriate chemotherapy.
  • American hepatozoonosis:
    • H. americanum can become encysted within the muscles as early as 2 weeks after infection.
    • H. americanum gamonts are formed as early as 32 days after infection.
    • Radiographic bone lesions can be detected as early as 6 weeks after infection.
    • Although infection can be associated with a waxing and waning course, self cure is not recognized.
    • Left untreated, most infected dogs die or are euthanized within a year of infection.
    • Remission of clinical signs occurs rapidly in response to treatment.
    • The disease is currently considered incurable, and encysted forms can be found in muscle years after infection is diagnosed and treatment begun.

Epidemiology

  • Old World hepatozoonosis:
    • Dogs become infected after eating infected ticks, usually the brown dog tick (R. sanguineus).
    • Vertical transmission of H. canis infection has been documented.
    • Prevalence of infection varies geographically. Parasitemia has been documented in as many as 22% of dogs in Nigeria and in 1% of dogs from Israel. Reported seroprevalence in Israeli dogs is far higher at 33%.
  • American hepatozoonosis:
    • Dogs become infected after eating infected nymphal or adult Gulf Coast ticks.
    • Gulf Coast ticks are three-host ticks. The favored host range for these ticks during each stage of the life cycle is unknown.
    • Although larval and nymphal Gulf Coast ticks (A. maculatum) are easily infected by feeding on infected dogs, dogs are not preferred hosts for the ticks. Therefore, dogs are not likely to be a major reservoir host in nature.
    • Vertical transmission is possible for the related organism H. canis. This, combined with detectionH. americanuminfection in very young pups suggests that vertical transmission may be possible.
    • Prevalence of H. americanum infection in the Gulf Coast is unknown but is likely low.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Attipa C, Maguire D, Solano-Gallego L et al (2018) Hepatazoon canis in three imported dogs: a new tickborne disease reaching the United Kingdom. Vet Rec 183, 716 PubMed.
  • Cummings C A, Panciera R J, Kocan K M et al (2005) Characterization of stages of Hepatozoon americanum and of parasitized canine host cells. Vet Path 42 (6), 788-796 PubMed.
  • Baneth G, Mathew J S, Shkap V et al (2003) Canine hepatozoonosis: two disease syndromes caused by separate Hepatozoon spp. Trends Parasit Parasitol 19 (1), 27-31 PubMed.
  • Ewing S A, Panciera R J (2003) American canine hepatozoonosis. Clin Microbiol Rev 16 (4), 688-697 PubMed.
  • Vincent-Johnson N A (2003) American canine hepatozoonosis. Vet Clin N Am Small Anim Prac 33 (4), 905-920 PubMed.
  • Macintire D K, Vincent-Johnson N A, Kane C W et al (2001) Treatment of dogs infected with Hepatozoon americunum: 53 cases (1989-1998). J Am Vet Med Assoc 218 (1), 77-82 PubMed.
  • Baneth G, Barta J R, Shkap V et al (2000) Genetic and antigenic evidence supports the separation of Hepatozoon canis and Hepatozoon americanum at the species level. J Clin Microbiol 38 (3), 1298-1301 PubMed.
  • Baneth G, Weigler B (1997) Retrospective case-control study of hepatozoonosis in dogs in Israel. J Vet Intern Med 11 (6), 365-370 PubMed.


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