Canine hepatozoonosis: two disease syndromes caused by separate Hepatozoon spp. Gad Baneth 1 , John S. Mathew 2 , Varda Shkap 3 , Douglass K. Macintire 4 , John R. Barta 5 and Sidney A. Ewing 6 1 School of Veterinary Medicine, Hebrew University, P.O. Box 12, Rehovot, 76100, Israel 2 Merck and Co., 203 River Road, Somerville, NJ 07950, USA 3 Department of Parasitology, Kimron Veterinary Institute, Beit Dagan, Israel 4 College of Veterinary Medicine, Auburn University, Auburn AL 36849-5523, USA 5 Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1 6 College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA Hepatozoonosis is caused by apicomplexan haemopara- sites of the genus Hepatozoon, which are closely related to Plasmodium spp. and piroplasms. Recent research revealed that two tick-borne Hepatozoon spp. infect dogs and cause distinct syndromes. Comparisons of these related species illustrates that whereas Hepato- zoon canis appears to be well adapted to its canine host, Hepatozoon americanum, an emerging pathogen producing severe and frequently fatal myositis, is highly virulent and might have recently crossed the species barrier from a wild host. Canine hepatozoonosis is a tick-borne infection caused by apicomplexan protozoa from the family Hepatozoidae. More than 300 species of Hepatozoon have been reported to infect animals [1] Hepatozoon spp. share a basic life cycle that includes sexual development and sporogony in a haematophagous invertebrate definitive host, and mer- ogony followed by gamontogony in a vertebrate intermedi- ate host. Unlike most tick-borne protozoal and bacterial pathogens that are transmitted via the tick salivary glands, Hepatozoon transmission takes place by ingestion of the definitive host, an invertebrate containing Hepato- zoon oocysts, by the intermediate host. Salivary transfer of this parasite has not been documented. It is presumed that dogs become infected with Hepatozoon through grooming ticks from their hair coat or feeding on prey infested with parasitized ticks. Hepatozoon gamonts from dog isolates originating in different geographical regions are morphologically similar, and therefore it was believed, until 1997, that canine hepatozoonosis was caused by a single species [2]. Recent research has shed light on the pathological and clinical syndromes associated with this infection [3–6], the genetic and antigenic characteristics of Hepatozoon isolates [7,8], the vector tick species that transmit canine hepatozoono- sis, and the parasite life cycle [9–11]. These studies have led to the recognition that two distinct Hepatozoon species infect dogs. Consequently, the parasite that infects dogs in the southern USA was named Hepatozoon americanum [4] and separated from the previously described Hepatozoon canis prevalent in southern Europe, Africa and Asia. Hepatozoon americanum infection is an emerging disease that is spreading north and east from coastal Texas, USA, where it was originally detected in 1978 [2]. It has since been reported also from Louisiana, Alabama, Oklahoma, Georgia, Tennessee and Florida. Hepatozoon canis Ingestion of a tick containing mature H. canis oocysts is followed by release of sporozoites in the gastrointestinal tract of the dog (Fig. 1). Sporozoites penetrate the intestinal wall and are transported haematogenously to haemolymphatic tissues including the spleen, bone marrow and lymph nodes, where meronts are formed. Merogony can also take place in other visceral organs, and is associated with hepatitis, pneumonia and glomerulonephritis [3]. Upon release from mature meronts, merozoites invade neutro- phils in which they develop to gamonts and then circulate in the peripheral blood. Hepatozoon canis infection (HCI) varies from being asymptomatic in apparently healthy dogs, to a severe and potentially fatal disease that causes extreme lethargy, cachexia and anaemia. A mild disease is the most common presentation of the infection and it is usually associated with a low level of H. canis parasitaemia (1 – 5% of neutro- phils are infected). A severe illness is found in dogs with a high parasitaemia, often approaching 100% of the periph- eral blood neutrophils [3]. High levels of parasitaemia are frequently accompanied by extreme neutrophilia reaching as high as 150 000 neutrophils per ml of blood. These dogs with leukocytosis and a high parasitaemia could have large numbers of circulating parasites with . 50 000 gamonts per ml of blood. This massive parasitaemia reflects the large number of tissue meronts, and takes its toll on the host by demanding nutrients and causing direct injury to affected tissues, leading to extreme weight Corresponding author: Gad Baneth (baneth@agri.huji.ac.il). Opinion TRENDS in Parasitology Vol.19 No.1 January 2003 27 http://trepar.trends.com 1471-4922/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S1471-4922(02)00016-8