Babesiosis (piroplasmosis) in the dog - Bibliovet The Encyclopaedia of Veterinary Medicine

Details: Category: Schede; Published: 19 October 2011; Hits: 13

Disciplina: Parassitologia
Specie: Cane

Canine babesiosis or piroplasmosis is a disease caused by a variety of intra-erythrocytic parasitic protozoa belonging to the Apicomplexa phylum, Piroplasmida order and the Babesia and Theileria genera. The micro-organisms belonging to these two genera are usually defined piroplasms because of their flame-shape during intracellular life and because their transmission occurs through blood meals of some species of hard ticks (Ixodidae). The Babesia spp. are historically divided into Babesia canis (now considered a true complex of various different species: B. canis canis, B. canis vogeli, B. canis rossi), or large Babesia spp., and the small Babesia spp., of which the most well-known is B. gibsoni. The geographical distribution of the large babesia has been increasing both in Europe and in USA and these parasites can, therefore, be considered emerging pathogens.

The large babesia (B. canis sensu latu complex) and the small babesia (generally B. gibsoni) are historically differentiated on the basis of their size within the infected red blood cells. The protozoa of the B. canis complex are larger (2 x 5 microns in the intra-erythrocyte stage) and are visible singly or in pairs within the red blood cells. The parasites belonging to the B. gibsoni species are smaller (1 x 3 microns; usually less than an eighth of the diameter of the red blood cell) and generally appear as single, round or oval bodies within the infected red cells. During the hyperacute phases of the disease, the parasite replicates very quickly and it is easy to see multiple babesia in single red blood cells.

The B. canis complex comprises three main species, with different phylogenetic, molecular, and serological characteristics, different vector specificities and different pathogenic potentials. B. canis rossi is the most prevalent species in South Africa and causes a severe clinical picture. B. canis canis is the main aetiological agent in Europe and is less pathogenic although it can give rise to severe signs. B. canis vogeli is widespread in the south of Europe and in tropical and subtropical zones throughout the world; it is the cause of mild forms of piroplasmosis. A fourth species of large babesia was recently isolated in North Carolina from dogs with clinical and haematological findings compatible with piroplasmosis. So far, B. canis canis and B. canis vogeli are the only large babesia that have been found to cause infections in Italy (Fig. 1).

As far as concerns the small babesia, B. gibsoni is strongly pathogenic and is present in Africa, Asia, USA, south-east Europe and Australia and has been found in Italy. Recent molecular studies have identified new species of small babesia, besides B. gibsoni, in the dog; one of these, isolated in the Iberian peninsula, seems to be very similar to B. microti, a species occurring in rodents which can occasionally infect humans, and is called Theileria annae (Fig. 2). Another microbabesia, called B. conradae, was recently isolated from infected dogs in California.

The geographical distribution of babesiosis is patchy, a characteristic typical of tick-borne diseases. The prevalence of the infection in enzootic areas can range from 3.8% to 59%. The Babesia spp. that cause canine piroplasmosis do not cause human disease. In the USA, B. microti is the most common aetiological agent of human babesiosis, while B. divergens, transmitted by ticks of the Ixodes genus, causes a form of piroplasmosis in cattle and in humans in some parts of Europe (Fig. 3).

Hard ticks (Ixodidae) of different species and genera (Rhipicephalus, Ixodes, Haemaphysalis, Dermacentor), and consequently with different biological and ecological characteristics, are responsible for the transmission of babesiosis; the importance of these arthropod vectors varies depending on the geographical area. In Europe the main tick species involved in the transmission of babesia are Rhipicephalus sanguineus, Dermacentor reticolatus and D. marginatus and, probably, Ixodes hexagonus (Figs. 4a, 4b1, 4b2 and 4c).

Rhipicephalus sanguineus is the main vector of babesia in temperate regions of the whole world and in particular in the south of Europe, in the south of the USA, in Latin America and in Australia. In eastern and central Europe the main tick vector of piroplasms is dermacentor, in particular D. reticolatus. The transmission of piroplasms between ticks can occur both through the trans-stadial route (rhipicephalus), in which the infection is transferred from one biological stage to the next, and through the transovarial route (rhipicephalus and dermacentor), in which the protozoa are transmitted from one generation to the successive one through the eggs. Consequently, adult and nymphal rhipicephalus can become infected after the preceding biological stages (nymphs and larvae, respectively) have ingested blood from infected dogs; in contrast, the transmission for dermacentor occurs predominantly by the transovarial route in that it is unlikely that the larvae and nymphs of this species feed on dogs (see figure below).

As shown in the figure, the transmission of piroplasms in the tick can occur through both the transovarial route, in which the protozoa are transmitted from one generation to the next through the eggs, and the trans-stadial route, in which the infection is transferred from one biological stage to the next. In the former case, starting from one subject (an adult female) which has fed on the blood from a parasitaemic dog, thousands of potentially infectious ticks can be generated. Transmission is also possible through blood transfusions (iatrogenic infection); furthermore, in the case of B. gibsoni it has been demonstrated that the parasite has been transmitted in the blood between fighting dogs.

PATHOGENESIS

Babesia are generally transmitted by hard ticks (Ixodidae) and reach the blood stream in the form of sporozoites, while the arthropods eat the blood of their host. Once within the host, the parasite adheres to erythrocytes, and is internalised into the cell by endocytosis, matures and starts the asexual phase of its reproduction giving rise to numerous parasites called merozoites. Finally, the red blood cell ruptures and releases the merozoites into the circulation, ready to invade new erythrocytes and replicate. The main pathogenic effect of infection with piroplasms is haemolytic anaemia, which is often progressive. The haemolysis present in the case of babesiosis derives from direct damage caused by the intracellular replication of the parasite (intravascular haemolysis), from oxidative damage to red blood cells (in the case of the small babesia) and by immune-mediated mechanisms such as erythrophagocytosis and opsonisation of the red blood cells by anti-erythrocyte antibodies. The spleen is the main site of the destruction of damaged red cells and elimination of the opsonised ones through the action of the reticulo-endothelial system (extravascular haemolysis); consequently, the volume of the spleen appears to increase in this parasitosis. Infected dogs can develop auto-agglutination of red blood cells and a positive Coombs’ test. Many dogs also have thrombocytopenia.

Babesia can also cause peripheral vasodilatation, drawing fluid from the extracellular compartment and thereby worsening the anaemia (haemodilution).

The low level of blood oxygenation as a result of depletion of red blood cells contributes to the pathogenesis of babesiosis.

The more pathogenic strains of babesia (e.g. B. canis rossi) can cause multiple organ failure (liver and kidneys), shock, and disseminated intravascular coagulation associated with a systemic inflammatory response syndrome (SIRS). Puppies are usually more susceptible to infection and have a higher risk of developing severe symptoms.

Dogs that are clinically cured may remain carriers of babesia for months and potentially life-long, even after appropriate pharmacological treatment. These animals, although appearing healthy (unless subjected to severe stress), constitute a reservoir of the parasites from which the infection can be transmitted, via ticks, to other susceptible dogs.

The clinical picture of babesiosis can be complicated by concomitant infections with other pathogens transmitted in the saliva of the ticks. The most common co-infection is with Ehrlichia canis, which, like B. canis vogeli, has a haematophagous vector, R. sanguineus. Dogs co-infected with both micro-organisms can develop haemolytic anaemia complicated by haemorrhages secondary to the marked thrombocytopenia occurring in canine monocytic ehrlichiosis. Co-infections with bacterial genera, Bartonella and Rickettsia, have also been documented.

SIGNS

While B. gibsoni (microbabesia) is always strongly pathogenic, there are considerable differences in pathogenicity between the various strains of the B. canis sensu latu complex (large babesia).

B. canis rossi always causes a severe disease, B. canis canis has variable pathogenicity and B canis vogeli gives rise to moderate and often subclinical forms of babesiosis, clinically evident only in puppies. Obviously the severity of the clinical picture is influenced by factors such as age, immune status, genetic predisposition and any co-infections or re-infections.

The duration of incubation varies very greatly depending on the strain and species of babesia involved (generally ranging from 1 to 3 weeks). However, hyperacute forms, in which the incubation period is much shorter, can occur occasionally. The early signs of the disease are fever and loss of appetite, followed by anaemia, thrombocytopenia, splenomegaly, often jaundice, and, above all, haemoglobinuria (the characteristic hyperpigmented urine) with muscle pain and sometimes punch tenderness over the kidneys (positive Giordano’s sign) because of the nephrotoxic effect of haemoglobin on renal tubules (Figs. 5, 6a and 6b; Videos 1 and 2).

Less common signs include vomiting, syncope, easy fatigue, oedema, ascites, bleeding of the skin and mucous membranes, and even neurological disorders (especially in the case of B. canis rossi). Besides the acute form, canine babesiosis also often presents as chronic infection with moderate hyperthermia, weight loss, lethargy and signs of kidney and lung disease. In areas in which the disease is enzootic, the only signs of babesiosis in dogs may be loss of appetite and asthenia.

DIAGNOSIS

A diagnosis of canine babesiosis must be suspected in a dog with a past history of tick bites associated with some characteristic signs such as fever, anaemia, haemoglobinuria and splenomegaly, present individually or in combination. Optical microscopy remains the simplest and most widely available method for diagnosing a babesia infection.

During the acute stages of the disease, microscopic examination is sufficiently sensitive to detect intra-erythrocytic parasites in a peripheral blood smear stained with Giemsa or modified Wright’s stain (rapid Romanowsky method).

The differentiation between small and large babesia is also made relatively easily with a microscope. Furthermore, microscopic study is the only diagnostic means available in many developing countries in which babesiosis is enzootic.

Taking the blood sample from a capillary bed (ear tip, nail bed) and examination of cells from the buffy coat of a haematocrit tube improve the possibility of finding babesia parasites (at least the large species).

The changes in haematological parameters induced by piroplasmosis are non-specific. Laboratory studies can show anaemia, thrombocytopenia, hypoalbuminaemia, hyperbilirubinaemia and bilirubinuria. The anaemia, initially normocytic and normochromic and non-regenerative, tends to evolve into a macrocytic, hypochromic anaemia with features of marked regeneration and reticulocytosis (Figs. 7 and 8).

Babesia should always be included in the differential diagnoses of subjects with haemolytic anaemia and thrombocytopenia.

Serological tests (immunofluoresence antibody test; enzyme-linked immunosorbent assay – ELISA; dot-ELISA) and biomolecular ones (polymerase chain reaction) can be used to detect babesia. A search for antibodies to piroplasms is considered of little use during the acute stages of the infection and does not enable differentiation between the various Babesia spp. because of the extensive cross-reactivity of the piroplasm antigens. False negative serological tests can occur when acute parasitosis precedes the development of the antibody response. Serological tests can be useful in the diagnosis of subacute and chronic forms, particularly in the case that the parasites are no longer visible in the blood by microscopy.

TREATMENT

Pharmacological treatment of babesiosis is effective in terms of clinical resolution of the disease and in limiting its mortality, but does not always guarantee elimination of all the protozoa in the body (parasitological cure). Two injections of imidocarb diproprionate at a dose of 5-6.6 mg/kg subcutaneously or intramuscularly, 2 or 3 weeks apart, are considered effective in the control of the infection. Imidocarb is also active against B. canis at a dose of 2.13 mg/kg but it is better to use the higher dose regimen because of the possibility of a co-infection with ehrlichia.

Alternatively, a single intramuscular dose of dimenazene aceturate 5 mg/kg can be given. Support therapy (intravenous fluid therapy; blood transfusion or plasma substitute) should be used as necessary. In the case of complicated forms with the development of shock, the use of phenamidine isethionate (10-20 mg/kg subcutaneously after 24 hours) is advised.

It is good practice to warn owners that dogs with clinically resolved piroplasmosis can remain subclinically infected, acquiring a state of latency, and the symptoms can recur in the case of weakened immune defences or, more rarely, in a cyclical mode in the spring period. These dogs should, consequently, never be used as blood donors.

PROPHYLAXIS

There is currently no commercially available vaccine capable of protecting dogs from babesiosis. The vaccines on the market, based on soluble plasma antigens (SPA) of babesia, can limit the clinical signs of the infection by blocking the start of many processes involved in the pathogenesis of babesiosis and can contribute to reducing the parasitaemia. The serological protection induced by the soluble antigens of a given strain of babesia has been found to be effective only against the same strain. Further studies showed that a combination of soluble antigens of B. canis canis and B. canis rossi induces broad spectrum immunity.

Ectoparasite chemoprophylaxis is fundamental in preventing tick bites and thus preventing transmission of piroplasms. The drugs used must guarantee both good acaricide activity and an effective antifeeding action against the ticks, must be easy for the owners to use and must be of low toxicity to the dog. The most widely used formulations are “spot on” forms and antiparasite collars. It is important to remember that in most cases of tick-transmitted diseases, the transmission of the pathogens occurs 24-48 hours after the blood meal (during the stage of regurgitation of haematic fluids).

FELINE BABESIOSIS

Feline babesiosis is a relatively uncommon disease caused by four species of small babesia able to induce clinical manifestations: B. felis, B. cati, B. leo, and B. microti-like spp.

Babesia felis is extremely small (0.9 × 0.7 microns) and is the most pathogenic species. The piroplasms in the cat are usually spherical and are found inside the red blood cells singly or in pairs (more rarely in double pairs in the form of a “Maltese cross”).

The disease is more common in animals under 3 years old (and Siamese and Oriental breeds are particularly susceptible). In elderly subjects it is usually related to immunosuppression (feline immunodeficiency virus or feline leukaemia virus infection; post-traumatic conditions).

Transmission is presumed to be via tick bites (Ixodes, Dermacentor, Rhipicephalus, Amblyomma, Haemophysalis) also in cats. Within the red blood cell, the membrane of the piroplasm degenerates giving rise to direct contact with the cytoplasm and an often variable parasite morphology.

The signs are variable, also in view of the limited number of cases reported. Changes in appetite, apathy, weight loss, vomiting and diarrhoea are the most common signs, while fever and jaundice are less common. Anaemia fluctuates and is present in about 50% of infected subjects. Thrombocytopenia is rare.

The diagnosis is based on the finding of the parasites in a blood smear (preferably peripheral blood). This diagnostic method is, however, less sensitive in the cat than in the dog. In doubtful cases, polymerase chain reaction analysis is preferable, since this is more sensitive and specific.

There is no standardised treatment and therapy is based mainly on the results of trials conducted in experimentally infected cats and anecdotal reports. Primaquine phosphate is considered the drug of choice for cats. The suggested dose is 0.5-1 mg/kg in a single administration (orally, intramuscularly or intravenously) for 3 consecutive days. The therapeutic index of this drug is, however, very narrow and doses greater than 1 mg/kg can be fatal. Disease-targeted treatment must always be associated with symptomatic treatment.