Canine babesiosis: introduction to a potential new disease threat

Since the introduction of the Pet Travel Scheme, babesiosis has been diagnosed with increasing frequency in dogs resident in the UK after travelling from enzootic areas of Europe (Shaw et al, 2003). However, a fatal case was confirmed in a dog residing in Kent with no history of foreign travel (Holm et al, 2006).

The APHA and Public Health England are investigating an outbreak of canine babesiosis in Harlow, Essex – and this has affected many animals that have never left the UK.

A tick removed from one of the dogs was sent to the APHA, confirming its identification of Dermacentor reticulatus – a species reported in several locations in Wales and southern England. The tick was infected with Babesia canis, distinct from other Babesia species that infect dogs (Phipps et al, 2016).

Babesiosis is a tick-borne disease of worldwide significance that affects humans and other mammals. Canine Babesia are morphologically classified into large and small forms. There are three antigenically different subspecies of B canis – the species typically affecting dogs in Europe, although other species exist.

Various species of ticks can transmit Babesia, with D reticulatus being the vector of B canis canis, the subspecies found in continental Europe. This tick is also referred to as the marsh tick and is distributed across Europe from the Atlantic Ocean to Kazakhstan.

Babesiosis can affect dogs of all ages, although disease mostly occurs in young dogs. The incubation period varies from 10 days to 21 days for B canis. The female ticks feed on the host for approximately one week and will have usually left the host before disease develops (Schoeman and Leisewitz, 2006).

Transmission of sporozoites from the salivary glands of a feeding tick into the subcutaneous tissues and bloodstream of the canine host is the route by which most dogs are infected with canine babesiosis. Once they are inside the host’s bloodstream, the parasites invade, feed, and multiply within erythrocytes during repeated phases of asexual reproduction, releasing merozoites that find and invade more red cells.

Transmission back to a vector may occur at any time parasitaemia exists; ticks are infected with piroplasms when they take a blood meal from a parasitaemic host. After ingestion by the tick, the piroplasms continue to develop by sexual reproduction and maturation, eventually migrating to the cells of the tick’s salivary glands in readiness for the next feeding, or to its ovaries for transovarial transmission to the next generation of ticks (Irwin, 2010).

Although vector-borne transmission is the natural means of infection, it has also been reported in some Babesia species via transplacental transmission to neonates, via blood transfusions and between fighting dogs (Schoeman and Leisewitz, 2006; Irwin, 2010).

Clinical signs

Severity of disease depends on the species of Babesia, the presence of concurrent infections and the age and immune status of the patient. Disease presentation varies widely from peracute to chronic and may be subclinical (Schoeman and Leisewitz, 2006). Most dogs develop haemolytic anaemia and/or thrombocytopaenia (Irwin, 2010).

Clinical signs include pallor, tachycardia, tachypnoea, depression, anorexia, weakness, splenomegaly and pyrexia. It is thought the clinical signs are the result of tissue hypoxia following anaemia and a concomitant systemic inflammatory response syndrome caused by cytokine release. The pathogenesis of the anaemia is not completely understood. Extra and intravascular haemolysis occurs, but other mechanisms, such as poor bone marrow response, are also thought to occur (Schoeman and Leisewitz, 2006; Irwin, 2010).

The anaemia does not correlate with the level of parasitaemia. Dogs tend to start to improve after parasiticidal treatment, although the haematocrit values generally drop further before starting to increase. In some cases there is an additional immune mediated breakdown of red blood cells.

Dogs showing positive saline agglutination reactions need to be carefully monitored for rapid decreases in haematocrit (Schoeman and Leisewitz, 2006).

Clinical findings in canine babesiosis include:

• loss of appetite and depression
• pale mucous membranes
• tachycardia
• tachypnoea
• pyrexia
• splenomegaly
• collapse
• icterus
• discoloured (red) urine (Schoeman and Leisewitz, 2006; Lobetti, 2010; Irwin, 2010)

The severe form of disease is characterised by marked haemolytic anaemia, severe acid-base abnormalities with frequent secondary multi-organ failure and complications, such as acute kidney injury, hepatopathy with marked icterus, hypoglycaemia, acute respiratory distress syndrome, cerebral pathology and additional immune-mediated red blood cell destruction (Schoeman and Leisewitz, 2006).

Complications associated with the disease include:

• hypoglycaemia
• hepatopathy and marked icterus
• pancreatitis
• immune-mediated haemolytic anaemia
• hypovolaemia
• multiple-organ dysfunction
• respiratory distress syndrome
• cerebral signs
• acute kidney injury
• severe mixed acid-base abnormalities
• disseminated intravascular coagulation (Schoeman and Leisewitz, 2006; Lobetti, 2010; Irwin, 2010)

Diagnosis

Diagnosis of acute B canis infection is based on the clinical presentation and demonstration of intracellular parasites on Diff-Quick-stained thin capillary blood smears. Large Babesia are typically seen as paired pyriform to round bodies, although some red blood cells can contain up to eight bodies. Parasitaemia has been shown to be higher in capillaries compared with central blood at presentation. Blood samples taken at the ear margin may, therefore, be more representative (Schoeman and Leisewitz, 2006).

In more chronic cases, parasitaemia may be below the microscopic detection limit (Schoeman and Leisewitz, 2006; Irwin, 2010). In these cases, diagnosis may be achieved through positive indirect fluorescent antibody titres or PCR (although false negatives can occur), together with history and physical examination findings. Examination of thick smears, or along the periphery of the blood smear, may assist in the detection of parasites (Schoeman and Leisewitz, 2006).

Active infection may be demonstrated by confirming increasing antibody titres over two to three weeks. Diagnosis should not be purely made on seropositivity, as clinically normal dogs from endemic areas may be seropositive. In dogs that have never left the UK, seropositivity would provide good evidence of current infection (Schoeman and Leisewitz, 2006).

Other blood smear findings typically reflect the underlying regenerative haemolytic anaemia, such as anisocytosis, polychromasia and reticulocytosis. The regenerative response takes three to five days so, in acute disease, a non-regenerative (pre-regenerative) anaemia may be apparent. Thrombocytopenia is a hallmark of disease and is often marked (Schoeman and Leisewitz, 2006). Spherocytosis may be seen in dogs with secondary immune-mediated haemolytic anaemia and a left shift neutrophilia may be seen due to a marked systemic inflammatory response (Schoeman and Leisewitz, 2006).

Elevation of liver enzymes may occur in cases with hepatopathies. Serum potassium is frequently low, especially in icteric cases. Serum bilirubin concentrations are elevated in relation to the degree of anaemia and accompanying hepatopathy. Azotaemia may be present in dehydrated patients and those with acute kidney injury. Urinalysis may demonstrate bilirubinuria, haemoglobinuria, proteinuria, renal tubular epithelial cells and granular cysts. Acid-base imbalances are common, especially metabolic acidosis and respiratory alkalosis (Schoeman and Leisewitz, 2006).

Laboratory findings in canine babesiosis include:

• low haematocrit, haemoglobin and red cell count
• normoblastemia
• reticulocytosis
• spherocytosis
• leukopenia (in the early stages)
• left-shift neutrophilia lymphocytosis
• marked thrombocytopenia
• in-saline positive red blood cell agglutination
• elevated liver enzymes
• elevated serum bilirubin
• hypoglycaemia
• raised serum amylase and lipase
• raised urea (often with normal creatinine)
• hypokalaemia
• mild hypoalbuminaemia and hyperglobulinaemia
• acid-base abnormalities, most commonly mixed metabolic acidosis and respiratory alkalosis (Schoeman and Leisewitz, 2006; Lobetti, 2010).

Treatment and prognosis

The primary goals of treatment are to eliminate the parasite and reverse life-threatening anaemia. Imidocarb dipropionate can be administered as a single dose of 7.5mg/kg or at 7mg/kg given twice, 14 days apart IM (Schoeman and Leisewitz, 2006). Alternative dosing schedules and medications have also been reported.

However, a 100% safe and efficacious treatment is not available. Treated dogs should be regarded as potentially affected for life, as it is difficult to completely cure the disease (Irwin, 2010) despite resolution of clinical signs.

Patients with mild or moderate anaemia may only require parasitic medications. Markedly anaemic animals, or those with any of the previously mentioned complications, will require additional supportive treatments (Schoeman and Leisewitz, 2006).

Approximately 85% to 90% of canine patients worldwide survive the illness. Dogs developing complications can, however, have a poor prognosis despite interventions (Schoeman and Leisewitz, 2006).

Prevention

Educating owners on examining their pets daily for the presence of ticks should be strongly recommended, as the tick must feed on the host for at least three days to transmit B canis (Schoeman and Leisewitz, 2006).

Identification of tick-infested areas and their avoidance should be promoted. This can help to reduce the exposure of dogs to the ticks; however, other wild mammals will still face exposure and could potentially move infected ticks over widespread distances.

A variety of tickicidal and tick repellent products are commercially available for veterinary use.

Dog owners can also send any found ticks to Public Health England’s Tick Surveillance Scheme for identification (Phipps et al, 2016).

Significant research will be required to ascertain the underlying cause surrounding this outbreak and whether it is related to the removal in 2012 of the requirement of tick treatment prior to entry into the UK of pets travelling from Europe.

• Please note the drug mentioned in this article is used under the cascade.