For many years, only one species of Hepatozoon organism (H. canis) was thought to infect dogs. H. canis commonly infects dogs in the Middle East and Asia, but they may not become clinically ill as the organism appears to be only mildly pathogenic. Infected dogs have H. canis gametocytes visible as oblong inclusion bodies in their neutrophils.

In 1999, however, a different species of Hepatozoon was identified at Auburn University in Alabama (H. americanum).

The organism is primarily seen in the southeastern USA, mostly along the gulf coast. H. americanum infection has been diagnosed in Alabama, Louisiana, Florida, Texas, Mississippi, Oklahoma and Tennessee. The definitive host is the Gulf Coast tick, Amblyomma maculatum. Transmission occurs by ingestion of the tick rather than a tick bite. Rhipicephalus sanguineous, may also serve as a definitive host for H. americanum, like it does for H. canis, but this has not been confirmed. Coyotes serve as reservoirs of infection for dogs, and tend to be carriers of the organism.

The organism undergoes both sexual and asexual reproduction. The host tick, A. maculatum, sucks blood from an infected mammal and ingests leukocytes containing H. americanum gametocytes. These gametocytes are released from the leukocytes, mate, and form oocysts. Each tick can contain hundreds of oocysts, which have numerous sporocysts, and which, in turn, contain numerous sporozoites. The ingested oocysts release their sporozoites in the gastrointestinal (GI) tract of the dog.

As sporozoites pass through the GI tract, they may cause transient diarrhea, and are ingested by neutrophils and macrophages. These white blood cells lodge in tissues, especially skeletal muscle, but also in other tissues such as spleen, bone marrow, liver and lung. Asexual reproduction occurs in the host cell which enlarges and ruptures causing a pyogranulomatous inflammatory reaction with fever and leokocytosis. Mature neutrophilia occurs about 3-4 weeks post-infection. Additional leukocytes are invaded and multiple life cycles of organisms occur.

Clinical signs are chronic waxing and waning illness with intermittent, high fever. There is stiffness, cervical pain, weight loss, and cachexia. Affected dogs may not be able to stand, but sit in a rigid posture. Ocular discharge may be present due to marked myositis of facial and extraocular muscles. Their appetite tends to remain normal, and they may be classified as having fever of unknown origin.