Canine babesiosis

Canine babesiosis

 

Robert Lo, Ph.D, D.V.M

 

Canine babesiosis occurs worldwide and results from infections with a variety of Babesia spp., tick-borne hemoprotozoa. The disease was first described in cattle with hemolytic anemia in 1888 by a Rommanian bacteriologist, Victor Babes (Babes, 1888). Babesiosis is one of the most important tick-borne infectious diseases of domestic and wild mammals and still poses significant diagnostic and therapeutic challenges for veterinary practitioners around the world. More than 100 Babesia spp. were reported in vertebrate hosts (El-Bahnasawy et al., 2002). With the expansion of tick habitats, the spread of parasites into new geographical areas has been an increasing problem worldwide.

 

The Babesia genus belongs to the order Piroplasmida in the phylum Apicomplexa and can be seen as non-pigment forming pear or signet-ring shaped organisms in mammalian erythrocytes. Asexual reproduction occurs in canine erythrocytes while the sexual conjugation and the sporogony stages of their life-cycles occurs in a variety of hard ticks, which can transmit the organism transovarially. Based on their morphology, Babesia are classified into the small Babesia group (trophozoites of 1.0-2.5 µm; including B. gibsoni, B. microti, and B. rodhaini), and the large Babesia group (2.5-5.0 µm; including B. bovis, B. caballi, and B. canis).

 

Etiology and epidemiology

Dogs are mainly infected by two species of Babesia: B. canis and B. gibsoni though they can also be infected by several other species of Babesia. Babesia canis has a piriform (teardrop) shape and frequently more than one merozoite is found in a single erythrocyte (Fig. 1). Babesia gibsoni is more pleomorphic (usually oval or signet-ring shapes) (Fig. 2).

 

 

Fig. 1. Two pear-shaped Babesia canis organisms in an erythrocyte. (Duh et al., 2004)

 

 

Fig. 2. Babesia gibsoni in erythrocytes in a blood smear stained with modified Wright technique. (Trotta et al., 2009)

 

Babesia canis was further categorized into three subspecies (B. canis canis, B. canis rossi, B. canis vogeli) on the basis of cross-immunity, serological testing, vector specificity and molecular phylogeny (Uilenberg et al., 1989). These three subspecies of babesia are significantly different in their clinical presentation, geographical distribution and vector specificity. With the advent of molecular phylogenetic analysis, in particular that of the 18S rRNA gene, these subspecies are now considered to be separate species (Carret et al., 1999; Lack et al., 2012; Zahler et al., 1998). Recently an unnamed fourth “large” Babesia sp. (coco) has been found in dogs in North Carolina in the US (Birkenheuer et al., 2004) and has caused babesiosis in immunocompromised dogs (Sikorski et al., 2010). The small Babesia are more genetically closer to Theileria spp. than to Babesia spp. based on study of the 185 rRNA gene locus.

 

Babesia canis, transmitted by Dermacentor reicultatus, is the most common pathogen of canine babesiosis in temperate regions of Europe and has been reported sporadically around the world (Solano-Gallego wt al., 2011). Most of clinical cases are reported in spring and autumn, which is associated with the seasonal activity of tick vector (Solano-Gallego et al., 2011; Matijatko et al., 2012).

 

Babesia vogeli, transmitted by Rhipicephalus sanguincus, is a less pathogenic species and is found not only in tropical and subtropical regions but also in colder areas (Cassini et al., 2009).

 

Babesia rossi, transmitted by Haemaphysalis elliptica (syn. Haemaphysalis leachi) (Penzhorn, 2011), is the most virulent species among large Barbesia species and is endemic in southern Africa but has been reported in other regions of eastern and southern Africa (Oyamada et al., 2005).

 

Babesia gibsoni, a virulent parasite in dogs of all ages, is endemic in Asia and occurs sporadically in the rest of the world. Ticks of the complex R. sanguineus may serve as potential vectors for B. gibsoni, at least in Europe, while in Asia, its main distribution range is attributed to transmission by the tick Haemaphysalis longicornis (Hatta et al., 2013; Iwakami et al., 2014). In addition, B. gibsoni can be transmitted by blood exchange when dogs fight (Irwin, 2009).

 

Transmission

Babesia spp. are mainly transmitted through tick bites and can infect a wide variety of domestic and wild animals as well as humans (Schnittger et al., 2012). Hard ticks are the main vectors for Babesia spp.; within the tick, Babesia spp. undergo the sexual stage in the tick gut is followed by sporogony in its tissues. The parasite then reaches the tick salivary glands. A blood meal will ultimately transmit the sporozoites from the tick’s salivary gland to their new vertebrate host (Chauvin et al., 2009), where the protozoan undergoes asexual replication (merogony) within the red blood cells. Babesia spp. are transmitted both transstadially and transovarially (Chauvin et al., 2009).

 

Pathogenesis and clinical signs

After sporozoites enter the red blood cells, Babesia multiply via repeated binary fission, resulting in up to 16 merozoites. The parasites induce FLP (fibrinogen like proteases) that cause the red blood cells to become sticky, resulting in capillary sludging. Parasitized cells are sequestered in the spleen, and extravascular and intavascular hemolysis occurs. The incubation period following tick transmission is 10-21 days.

 

The clinical picture is similar for all Babesia infections, whether they involve large or small Babesia. Pathogenicity is more severe in young dogs, immunosuppressed dogs, heavily parasitized dogs, and when there is exposure to a virulent strain or concurrent infection (Hunfeld et al., 2008; Matijatko et al., 2012; Schetters et al., 1997; Solano-Gallego L et al., 2008). Infected dogs may exhibit either peracute, acute, or subclinical signs of disease (Freeman et al., 1994; Jacobson, 2006; Wlosniewski et al., 1997).

 

Peracute signs include acute onset of hypotensive shock, vasculitis, extensive tissue damage, hypoxia, and death. Signs of acute disease include fever, lethargy, hemolytic anemia, thrombocytopenia, splenomegaly, lymphadenopathy, icterus, and hemoglobinuria. Less common signs include ascites, peripheral edema, ulcerations, stomatitis, gastroenteritis, CNS signs, acute renal failure, and rhabdomyolysis. Acute infections of virulent strains of B. canis have been associated with induction of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) secondary to massive immune stimulation and cytokine release. Signs of MODS can include coagulopathies (DIC), adult respiratory distress syndrome (ARDS), cerebral dysfunction, and acute renal failure.

 

Some dogs remain asymptomatic carriers of parasites, presenting high antibody titers for a period as long as one year. This carrier state is known as premunition. The asymptomatic infected animals facilitate the transmission of parasites to tick vectors. Dogs may develop clinical babesiosis several times during their lifetimes because of loss of immunity or as a result of infection with different genetic (and antigenic) strains.

 

Diagnosis

During acute infection, microscopy is reasonably method at detecting intraerythrocytic parasites in Giemsa or Wright’s stained blood smears and re-mains the simplest and most accessible diagnostic test. The detection of B. gibsoni on blood smears may be complicated because many of the erythrocytes in anemic dogs are vacuolated and pitted (Conrad et al., 1991). The blood smear examination presents a low sensitivity (Di Cicco et al., 2012) and it is preferable for the sample to be taken from peripheral capillaries such as those in the ear tip or nail bed, rather than using venous blood.

 

The indirect fluorescent antibody test (IFAT) is the test most commonly used to detect specific antibody in canine babesiosis (Vercammen et al., 1995). Serology can be used to detect dogs with occult parasitemia. Serology does not strongly discriminate among species and subspecies, because antibodies are often cross-reactive between different species and even other protozoans.

 

Molecular diagnostic assays (PCR or real-time quantitative PCR) have been widely used for the diagnosis of babesiosis (Birkenheuer et al., 2003; Costa-Júnior et al., 2012). These molecular diagnostic methods have greatly increased the sensitivity and specificity of Babesia detection.

 

Treatment

The reference treatment against B canis, B. rossi, and B. vogeli are imidocarb dipropionate. The recommended dosage is 5.0–6.6 mg/kg IM or SC, twice at an interval of two to three weeks. This drug is also effective against Ehrlichia canis and Hepatozoon canis, and is the drug of choice in multiple parasite infections. Parasitemia and clinical signs of disease are usually eliminated within 24-48 hours after administration (Vial and Gorenflot, 2006), but many dogs will develop a subclinical carrier state. However, this drug is not effective against B. gibsoni. Diminazene aceturate is also a drug commonly used worldwide. It is given IM at a dosage of 3.5 mg/kg once only.

 

Combination therapy with atovaquone (13.3 mg/kg PO every 8 h) and azithromycin (10 mg/kg PO every 24 h) was the first described treatment to eliminate or suppress parasite numbers of B. gibsoni below detectable levels in the majority of dogs with no adverse reactions (Birkenheuer et al., 2001). Using triple antibiotic combinations: doxycycline (5 mg/kg, orally, twice daily), clindamycin (25 mg/kg, orally, twice daily), metronidazole (15 mg/kg, orally, twice daily) is another optional treatment for B. gibsoni (Suzuki et al., 2001).

 

Prevention

The best prevention is achieved by avoiding exposure to the vector. This should be considered when deciding to take a dog from non-endemic into (highly) endemic areas. Regular examination of dogs to remove ticks soon after they attach is important as it takes a minimum of 48 hours before Babesia transmission occurs.

 

Only two vaccines against B. canis infection in dogs are available in Europe, both based on concentration of culture supernatants (Schetters et al., 2006). Vaccination effectively prevents against infection by the homologous strain for 5-8 months. Unfortunately, this vaccine affords no protection against other strains.

 

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