Babesia canis and B. gibsoni are responsible for canine babesiosis throughout the world. Babesia canis consists of a group of three biologically different subspecies, namely B. c. canis, B. c. vogeli, and B. c. rossi. Babesia gibsoni is subdivided into 2 subspecies: the North American and Asian subspecies. Babesia c. canis is found in Europe, B. c. vogeli in northern Africa, North America and South Africa and B. c. rossi in southern Africa. The pear-shaped trophozoite of B. canis measures 4-5 μm long and is usually found in pairs within the erythrocyte, but up to eight or more may be present. In comparison, B. gibsoni is much smaller; is round to oval in shape; measures 3 μm long; and is found in Asia, Australia, North America and northern and eastern Africa.
The more commonly encountered complications of canine babesiosis are acute renal failure, cerebral babesiosis, coagulopathy, icterus and hepatopathy, immune-mediated haemolytic anaemia (IMHA), peracute babesiosis, ARDS, haemoconcentration, hypotension, myocardial pathology, pancreatitis, and shock. Rare complications include gastrointestinal disturbances, myalgia, ocular involvement, upper respiratory signs, necrosis of the extremities, fluid accumulation, and chronic disease. Different complications can overlap. The more recently reported complications: hypotension, myocardial changes, pancreatitis, hypoglycaemia, acid-base changes, and multiple organ dysfunction, will be discussed in this paper.
Hypotension
Dogs with severe and complicated babesiosis are frequently presented in a state of collapse and clinical shock. Shock in these animals can resemble the hyperdynamic phase of septic shock. Collapsed dogs with babesiosis may, however, not display the classic signs of shock syndrome, partially because of the haemodynamics of haemolytic anaemia. The pulse may be bounding or weak; temperature elevated or subnormal; and mucous membranes pale, icteric or congested (haemoconcentration). Babesial shock, like endotoxic shock, may pass through a hyperdynamic stage followed by a hypotensive stage. Hypotension occurs frequently in babesiosis and that the presence and severity of hypotension increases with increased disease severity. The presence of hypotension in a large proportion of dogs with complicated babesiosis is consistent with the hypothesis that inflammatory mechanisms play a major role in this disease, and can result in a sepsis-like state. It is likely that hypotension in babesiosis is a combination of vasodilation, reduced vascular volume due to increased vascular permeability and/or dehydration, and myocardial depression. Hypotension can play a role in the pathophysiology of the disease as it has been hypothesized to facilitate parasite sequestration.
Acute Pancreatitis
Gastrointestinal disturbances have generally been considered a rare complication of babesiosis; however, the aetiology of the reported gastrointestinal disturbances may have been acute pancreatitis. Digestive system abnormalities reported as a complication of canine babesiosis have included vomiting, diarrhoea, abdominal pain, gastritis, enteritis, and enterorrhagia. A recent study documented 23 dogs that developed pancreatitis as a complication of babesiosis, which was an incidence of 1.8% amongst hospitalised babesiosis cases. Median time of diagnosis based on serum amylase and lipase activities was 3 days post-admission. No sex predilection was identified, with primarily young, sexually intact dogs being affected. The severity of anaemia did not correlate with the severity or incidence of pancreatitis. The most common clinical signs of acute pancreatitis were anorexia, vomiting, melaena, and abdominal pain. Hypokalaemia was commonly identified, especially in icteric dogs. Early identification of these clinical signs in a dog with babesiosis should increase the clinician's index of suspicion for acute pancreatitis, with timeous diagnostic procedures and therapeutic intervention instituted.
Cardiac Changes
Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia, and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.
Hypoglycaemia
Hypoglycaemia is a common complication of virulent canine babesiosis. In a study were plasma glucose concentration was measured at presentation in 250 dogs with babesiosis, the prevalence of hypoglycaemia (< 3.3 mmol/l) was 9%. Twenty-two hypoglycaemic dogs required admission, making the prevalence of hypoglycaemia in admitted dogs 19.8%. Sixteen dogs had severe hypoglycaemia (<2.2 mmol/l), of which 5 had glucose < 1 mmol/l. Risk factors for hypoglycaemia were collapsed state, severe anaemia, icterus, under 6 months of age, and vomiting. Toy breeds and pregnant bitches were not at higher risk for hypoglycaemia than other dogs. Blood glucose concentration should ideally be measured in all dogs with babesiosis but is mandatory in collapsed dogs; puppies; and dogs with severe anaemia, vomiting, or icterus. In the past many dogs have probably been misdiagnosed with cerebral babesiosis, and thus hypoglycaemia should be suspected in any dog with coma or other neurological signs.
Multiple Organ Involvement
In a study in dogs with babesiosis 52% demonstrated organ damage in one organ and 48% had multiple organ damage. In the cases with single organ involvement, the liver was most commonly involved (34%), followed by kidneys (24%), lungs (17%), CNS (17%), and muscle (7%). In double organ damage the organs involved were liver (61%), lungs (46%), muscle (46%), kidneys (38%), and CNS (8%). The organ combinations were liver/lungs (31%), liver/kidneys (23%), liver/muscle (15%), muscle/kidney (15%), muscle/ lungs (8%) and muscle/ CNS (8%). In cases of triple organ damage, the liver was involved in 92%, muscle in 83%, kidneys in 58%, lungs in 50% and CNS in 17%. The organ combinations were liver/muscle/kidney in 33%, liver/muscle/lungs in 25%, liver/kidneys/lungs in 17%, liver/muscle/CNS in 17%, and muscle/kidneys/lungs in 8%. Outcome was not affected by whether one or multiple organs showed evidence of damage. However, the specific organ involved significantly affected outcome: CNS involvement and renal dysfunction had a 57-fold and 5-fold increased risk of death, respectively. Liver or muscle damage did not affect the outcome.
Acid-Base Disturbances
The most commonly reported acid-base disturbance in dogs with babesiosis and severe anaemia is metabolic acidosis. However, more recent studies suggest that a mixed acid-base disturbance is present in many cases, which would reflect a more complex pathophysiology than previously assumed. Dogs with severe canine babesiosis showed a combination of abnormalities, including hyperchloraemic (low SID) metabolic acidosis; high anion gap (probably due to hyperlactataemia) metabolic acidosis; hypoalbuminaemic alkalosis; hyperphosphataemic acidosis, dilutional acidosis, and respiratory alkalosis. Respiratory alkalosis was as common as metabolic acidosis and arterial blood pH was a poor indicator of the complexity of the pathology.
Therapy
The three drugs that are recognized and recommended for the treatment of B. canis are diminazene aceturate, imidocarb, and trypan blue. Other drugs that have been used include amicarbalide, euflavine, quinuronium sulphate and chloroquine; however, because of poor efficacy and severe adverse effects, they are no longer recommended and are used infrequently.
The antimalarial drug atovaquone combined with azithromycin has been shown to be effective in treating B. gibsoni.
Curdlan sulphate, an anti-HIV drug, has been shown to have a significant inhibitory effect on B. bigemina parasites both in vitro and in a mouse model.
Blood transfusions are based on the magnitude of anaemia. In cases of babesiosis, however, factors such as acuteness of onset, clinical signs, degree of erythrocyte regeneration, and presence of concurrent cardiac or respiratory disease must be considered. Dogs with babesiosis are considered candidates for transfusion when the haematocrit is 15% or lower. Blood is almost invariably administered at a haematocrit below 10%. Blood transfusions are also given when a clinical need such as dyspnoea or tachypnoea is apparent. The degree of parasitaemia is not an important factor because it often bears little relation to the degree of anaemia.
Packed erythrocytes are the component of choice for treating haemolytic anaemia. Administering the plasma component of whole blood is usually unnecessary and can place the patient at risk of volume overload. If rehydration is required, crystalloid replacement solutions are preferable. Fresh whole blood has a favourable effect on oxygen status and acid-base balance and replaces sub-functional haemoglobin with functional haemoglobin.
A vaccine against a specific, less virulent canine babesiosis strain is available in France; however, cross-immunity between the different Babesia strains apparently does not occur with this vaccine. A recent study has shown that protective immunity to a virulent strain can occur if the infection is not sterilized; therefore, vaccines from different strains of the parasite are feasible. Pre-immunity has been recognized as important in controlling clinical signs of the virulent form of babesiosis in endemic areas. Complete eradication of parasites from infected animals therefore may not be advantageous in these areas, and the use of drugs to sterilize the infection may be undesirable. The role of pre-immunity in areas with less virulent strains is unknown.
References
References are available upon request.