Babesiosis

Babesiosis (piroplasmosis) is a potentially serious illness caused by intraerythrocytic protozoan parasites of the genus Babesia. Like ehrlichiosis, it is one of the most important tick-transmitted infectious diseases in dogs. Besides dogs, cats have also been affected, here especially in South Africa especially along the eastern and southern seaboard.  

During the last decades, an increasing number of clinical cases have been reported in the literature from around the world for dogs, especially in Central Europe where an increasing incidence is presumably due to the spread of the vector Dermacentor reticulatus. 

Canine and also feline babesiosis is reported from many areas in the world, but depending on the region, different Babesia species and strains have been identified. Local knowledge in this respect is important. Concomitantly, different tick vectors are known to transmit the respective pathogens. 

Pathogenicity of the different strains of Babesia may vary, but severe clinical or even fatal diseases occur frequently, if the dog remains untreated. 

Pathogens

Canine babesiosis is caused by intraerythrocytic protozoan parasites of the genus Babesia including the large species B. canis, B. vogeli, B. rossi and the small species B. gibsoni, which is extending its range in the USA and Europe. Traditionally differentiation of the species was performed on the basis of their size within parasitized erythrocytes: The larger organisms, classified as large Babesia (2 x 5 µm in the intraerythrocyte stages), occurring single or paired within the cells and the small babesians (1 x 3 µm; mostly less than 1/8 of the cell diameter), usually appearing singly as round or oval forms in parasitized cells. Originally the large Babesia pathogens were summarised into the Babesia canis complex including the three subspecies, which are nowadays considered to be separate species: B. canis, B. vogeli, B. rossi.

Microscopic image of intraerythrocytic stages of large Babesia species.
Intraerythrocytic stages of large Babesia species

Molecular studies have identified further small form babesians that infect dogs. One isolate discovered in the Iberian peninsula is closely related to the rodent piroplasm B. microti denominated B. microti-like piroplasm/Spanish isolate and sometimes referred to as Theileria annae, and another small piroplasm has been named B. conradae and is found in dogs in California. A fourth ‘large’ Babesia sp. has been described in a number of dogs in North Carolina (yet unnamed or referred to as Babesia sp. (Coco)). Additionally three Theileria species have been isolated in a small number of dogs’ blood in Europe (Theileria (Babesia) equi and Theileria annulata) and from dogs in South Africa (unnamed Theileria sp.).

Pathogenicity varies among the different species: B. rossi, the prevalent strain in South Africa, causes severe clinical disease; B. canis, the principle cause of babesiosis in Europe, is less pathogenic, although severe forms commonly occur. B. vogeli infection causes relatively mild disease worldwide. The relative importance of tick species in the transmission of canine babesiosis varies with geographical location. B. gibsoni is considered to be a highly pathogenic agent.

For feline babesiosis especially B. felis, B. leo, B. lengau and B. microti have been reported as pathogens of domestic cats particularly in South Africa.

Recent reports suggest that there are still unidentified Babesia species causing clinical signs in dogs and cats (Bosman et al., 2019; Baneth et al., 2020).

The canine Babesia species do not cause disease in humans. In the USA, B. microti is the most common cause of a mild human babesiosis; and the bovine pathogen B. divergens, transmitted by Ixodes ticks, causes severe clinical disease in humans in some parts of Europe.

Epidemiology

Canine babesiosis is mainly caused by Babesia canis, B. rossi, B. vogeli and increasingly by B. gibsoni. Among the disease-causing species B. canis is the prevalent species in Europe, B. rossi in South Africa and B. vogeli in Southern Europe, tropical and semitropical regions worldwide. B. gibsoni causes disease in Africa, Asia, USA, Southern Europe, the Middle East and Australia. The relatively new detected further small and large Babesia and Theileria species have a quite restricted geographical distribution: the unnamed large Babesia sp. (Babesia sp. (Coco)) in North Carolina, Theileria annae in Spain and Portugal, an unnamed Theileria sp. in South Africa and T. equi and T. annulata in Africa, Europe and Asia. The relative importance of tick species in the transmission of canine babesiosis varies with geographical location.

Feline babesiosis is especially reported from South Africa and here mainly along the eastern and southern seaboard and with a few foci on the eastern escarpment. The responsible species here are especially B. felis, B. leo, B. lengau and B. microti.

Transmission

Rhipicephalus sanguineus is the primary vector for Babesia vogeli in warmer regions worldwide, like in Southern Europe, Southern USA, Australia and Latin America. In Western and Central Europe, the main vectors for Babesia canis are Dermacentor ticks, esp. Dermacentor reticulatus. Transmission within the tick is both transstadial (infection at any stage for Rhipicephalus and the next stage being infectious) and transovarial (females of Rhipicephalus and Dermacentor may transfer infection to the next generation through eggs). As a consequence, nymphs and adults of Rhipicephalus can be infectious when larvae or nymphs have fed on an infected dog (transstadial), whereas adults of Dermacentor will only be infectious from the previous infected tick generation (transovarial), because larvae and nymphs of Dermacentor do not feed on dogs. In Southern Africa Babesia rossi is transmitted by Haemaphysalis elliptica (formerly Haemaphysalis leachi). The small piroplasm Babesia gibsoni is transmitted by Haemaphysalis longicornis in eastern Asia but the vector competence of Rhipicephalus sanguineus for Babesia gibsoni is a disputed matter. In the case of B. gibsoni outside Asia transmission is also caused by blood exchange in fighting dogs. In the case of the other described Babesia (also for felines) and Theileria species only for Theileria annae Ixodes hexagonus has been mentioned as putative vector, for the rest the vectors are unknown.

Babesiosis occurs sporadically and local outbreaks may occur in kennels with severe tick infestations. Prevalence in endemic areas is reported to range from 3.8% to 59%.

Transmission of all Babesia spp. is possible by needles or blood transfusion (iatrogenic).

Pathogenesis

The protozoans Babesia spp. are generally transmitted by ticks and reach the blood stream while the ticks are feeding. Once inside the host, the parasite attaches to an erythrocyte, is engulfed via endocytosis, matures, and then starts asexual reproduction, producing merozoites. Infected erythrocytes eventually rupture and released merozoites invade other erythrocytes. The main pathogenesis associated with babesiosis is haemolytic anaemia. Haemolytic anaemia is the result of direct erythrocyte injury caused by the parasites and also by immune-mediated mechanisms. In addition, most dogs with babesiosis have thrombocytopenia. Puppies are generally more susceptible to babesiosis and are at greatest risk of serious illness and death. Low blood oxygen (hypoxaemia) as a result of the anaemia contributes to morbidity and the most pathogenic strains cause kidney and liver injury, and systemic inflammatory disease. While the disease is recognised in dogs around the world, it is found only rarely in cats and often goes inapparent in wild felids.

Erythrocyte-bound autoantibodies are involved in the haemolytic form of the disease. There can be erythrocyte auto-agglutination and many dogs with babesiosis give a positive Coombs' test. In Babesia gibsoni infections haemoglobinaemia and haemoglobinuria occur secondary to oxidative damage in parasitized red blood cells. There is enhanced damage by anti-erythrocyte antibodies and erythrophagocytosis occurs predominantly in the spleen.

While the pathogenicity of B. gibsoni is uniformly high, pathogenicity varies among the large canine Babesia species: Babesia rossi causes severe clinical disease; Babesia canis is variously pathogenic, and Babesia vogeli infection causes relatively mild subclinical disease except in puppies. The severity of disease is also influenced by the age, breed and immune status of the dog, previous Babesia infections or coinfection.

Diagnosis

Canine babesiosis is suspected when there is a history of tick bites and when suggestive clinical signs are present and combined: fever, anaemia, haemoglobinuria, splenomegaly. Diagnosis of babesiosis is usually performed by detection of piroplasms in Giemsa-stained blood smears from capillary blood. Intraerythrocytic pear-shaped or circular organisms or large numbers of extraerythrocytic parasites are helpful diagnostic clues. Serologic tests (IFAT, ELISA, Dot-ELISA) and methods to detect parasite DNA in blood samples after amplification with polymerase chain reaction (PCR) are available at some laboratories. Hematologic changes are non-specific (anaemia, thrombocytopenia), although babesiosis should always be considered in cases of haemolytic anaemia and thrombocytopenia. Blood samples may auto-agglutinate in saline and may be Coombs' positive. The major differential diagnosis is immune-mediated haemolytic anaemia.

Serological testing by immunofluorescent antibody test (IFAT) or ELISA is not considered useful during acute infection or to differentiate between different Babesia species/subspecies, due to extensive cross reaction between different organisms. New, highly specific immunological tests are being developed, based on recombinant antigen technology. False negative results may occur if an acute disease onset precedes antibody development, and tests generally hardly distinguish between the different Babesia species due to antigenic cross-reactivity. However, serological testing may be very useful in sub-acute or chronic forms (parasites in low numbers or absent in blood).

Clinical Signs

The duration of incubation is highly variable, in general 1-3 weeks, depending on the species of pathogen, but can occasionally be much shorter. The canine disease starts with fever, followed by reduced food intake, weight loss, anaemia, thrombocytopenia, splenomegaly, quite often icterus and the most suggestive coloration of urine that turns to brown in colour due to haemoglobinuria. Further signs including vomiting, syncope (fainting), oedema, ascites, bleeding in the skin and the mucosa and diverse other symptoms up to central nervous disorders (i.e. with Babesia rossi) can be observed. In case of Babesia canis and Babesia gibsoni a progressive haemolytic anaemia may occur, while B. rossi can even involve hypoxic, hypotensive shock with disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS).

Apart from the suggestive acute forms presented above, canine babesiosis quite often appears as chronic infection with moderate hyperthermia, weight loss, lethargy, pulmonary or renal disease. In enzootic areas where many dogs are reinfected, the disease may be discovered in dogs that only show reduction of activity and anorexia.

Animals that recover usually become chronic (months to possibly lifelong) carriers of Babesia sp., even after treatment. Although these animals appear healthy unless subjected to stress, they provide a reservoir of infection for susceptible animals and have suboptimal athletic performance. They pose a risk if used as blood donors.

In contrast to babesiosis in other domestic animals, feline babesiosis is not associated with pyrexia (Futter & Belonje, 1980). The disease in cats tends to be an afebrile, chronic, low‐grade disease. The most frequently reported signs are anorexia, listlessness, and anaemia, followed by icterus (Schoeman et al., 2001). Less common signs are weakness, constipation, and pica (Schoeman et al., 2001). Parasitaemias are variable and range between very low and extremely high. Laboratory findings commonly include regenerative anaemia, elevation of alanine transaminase (but not alkaline phosphatase) and total bilirubin concentrations, and a variety of electrolyte disturbances. Thrombocyte counts are variable and thrombocytopenia is an inconsistent finding. Secondary immune‐mediated haemolytic anaemia can be seen occasionally. Most affected cats seem to be young adults of less than three years of age (Schoeman et al., 2001).

The clinical presentation of canine babesiosis may be complicated by co-infection with other tick-borne pathogens. Most commonly, co-infection with Ehrlichia canis occurs, as both pathogens share Rhipicephalus sanguineus as a tick vector. Dogs co-infected with these two organisms may be more likely to have haemolytic anaemia complicated by haemorrhage secondary to the thrombocytopenia that occurs with canine monocytic ehrlichiosis (CME). Co-infections with other arthropod-borne agents have been documented, e.g. with bacteria of the genus Bartonella and Rickettsia.

As in dogs, also in cats concurrent infections (e.g., Mycoplasma haemofelis, feline leukaemia virus [FeLV], feline immunodeficiency virus [FIV]) may contribute to the clinical picture.

Treatment & Prevention

The treatment for canine babesiosis depends primarily upon the species of piroplasm causing the clinical disease. The drug of choice for the large piroplasms (Babesia canis) is imidocarb dipropionate, which is effective against B. canis but not Babesia gibsoni. Imidocarb also has some effect against Ehrlichia canis, thus, it may be useful for co-infections.

Diminazene aceturate has been used for many years to treat B. gibsoni infection but this has been superseded in recent years by the anti-malarial atovaquone in combination with azithromycin which has shown promise for the treatment of B. gibsoni.

Clinical cure and a good therapeutic response are much more likely achieved for infections by large-sized Babesia species than infections by the small-sized species, the latter of which tend to be more refractory to conventional treatments (Solano-Gallego & Baneth, 2011).

Other drugs reportedly effective against both B. canis and B. gibsoni include phenamidine isethionate, pentamidine isethionate and diminazine aceturate. Trypan blue (1% solution) is used in Southern Africa to treat complicated infection with Babesia rossi.

Supportive therapy in form of intravenous fluids and blood transfusions should be employed when necessary.

In many cases treatment does not completely eliminate the infection. Animals may become long-term chronic carriers of the organism and potential reservoirs of infection. Subclinically infected animals may have recurrence of disease with stress, immunosuppressive therapy or concurrent disease. In addition, dogs that have recovered from babesiosis should never be used as donors for blood transfusions because the recipients may develop the disease.

Regarding feline babesiosis, antiprotozoal drugs and supportive care are the mainstays of therapy. Cats infected with Babesia felis should always be treated, as the infection is commonly fatal if left untreated (Hartmann et al., 2013). Most antibabesial drugs are not effective in cats and have shown variable or questionable results (Potgieter, 1981; Penzhorn et al., 2000). The drug of choice currently is primaquine phosphate, an antimalarial compound. It is capable of reducing parasitaemia, but it does not eliminate B. felis from the host. It furthermore frequently causes vomiting when administered orally and has a narrow therapeutic window in cats. Generally, the response to treatment in cats is good, but as in dogs recurrence of clinical signs and chronic persistent infections are possible (Futter et al., 1981) and repeated or extended treatment may be necessary (Penzhorn et al., 2004).

As babesiosis is a vector-borne disease, the prevention of the disease includes an effective and consistent prevention of tick bites in form of acaricidal products. Dogs living in non-endemic areas should ideally not be taken into endemic areas as these dogs usually develop a more severe disease. Owners wishing to travel with their pets to endemic areas should seek veterinary advice and take great care to prevent tick bites and potential disease transmission. Additionally, fighting with other dogs should be avoided especially in Babesia gibsoni endemic areas and any blood transfusions should be carefully screened to ensure absence of pathogens.

Vaccination against Babesia infection has been researched for long time and vaccines for dogs are registered in some European countries. Cross-immunity experiments have shown that the antigenic differences between the subspecies or even strains of the B. canis complex have important implications on the development of a vaccine as there is no complete cross-protection between the single pathogens. As a consequence the degree of protection may vary in vaccinated dogs.

References

Pathogens

Baneth G, Nachum-Biala Y, Birkenheuer AJ, et al.: Morphologic, molecular and pathogenic description of Babesia negevi sp. nov. a new Babesia species infecting dogs. Parasit Vectors. 2020, submitted 

Bosman AM, Penzhorn BL, Brayton KA, et al.: A novel Babesia sp. associated with clinical signs of babesiosis in domestic cats in South Africa. Parasit Vectors. 2019, 12, 138

 

Clinical Signs

Futter GJ, Belonje PC: Studies on feline babesiosis. 2. Clinical observations. J S Afr Vet Assoc. 1980, 51, 143-6 

Schoeman T, Lobetti RG, Jacobson LS, et al.: Feline babesiosis: signalment, clinical pathology and concurrent infections. J S Afr Vet Assoc. 2001, 72, 4-11

 

Treatment & Prevention

Futter GJ, Belonje PC: Studies on feline babesiosis. 2. Clinical observations. J S Afr Vet Assoc. 1980, 51, 143-6 

Hartmann K, Addie D, Belák S, et al.: Babesiosis in cats: ABCD guidelines on prevention and management. J Feline Med Surg. 2013, 15, 643-6 

Penzhorn BL, Schoeman T, Jacobson LS: Feline babesiosis in South Africa: a review. Ann N Y Acad Sci. 2004, 1026, 183-6 

Penzhorn BL, Lewis BD, Lopez-Rebollar LM et al.: Screening of five drugs for efficacy against Babesia felis in experimentally infected cats. J S Afr Vet Assoc. 2000, 71, 53-7

Potgieter FT: Chemotherapy of Babesia felis infection: efficacy of certain drugs. J S Afr Vet Assoc. 1981, 52, 289-93 

Further Reading

Bosman AM, Penzhorn BL, Brayton KA, et al.: A novel Babesia sp. associated with clinical signs of babesiosis in domestic cats in South Africa. Parasit Vectors. 2019, 12, 138

Bourdoiseau G: Canine babesiosis in France. Vet Parasitol. 2006, 138, 118-25 

Hartmann K, Addie D, Belák S, et al.: Babesiosis in cats: ABCD guidelines on prevention and management. J Feline Med Surg. 2013, 15, 643-6 

Irwin PJ: Canine babesiosis: From molecular taxonomy to control. Parasit Vectors 2009, 2 (Suppl. 1), S4

Irwin PJ: Canine babesiosis. Vet Clin North Am Small Anim Pract. 2010, 40, 1141-56 

Penzhorn BL, Schoeman T, Jacobson LS: Feline babesiosis in South Africa: a review. Ann N Y Acad Sci. 2004, 1026, 183-6 

Solano-Gallego L, Baneth G. Babesiosis in dogs and cats – expanding parasitological and clinical spectra. Vet Parasitol. 2011, 181, 48-60 

Solano-Gallego L, Sainz Á, Roura X, et al.: A review of canine babesiosis: the European perspective. Parasit Vectors. 2016, 9, 336

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