babesiosis

Preferred Scientific Name

• babesiosis

International Common Names

• English: babesiosis, babesia, in food animals- exotic; malignant jaundice; piroplasmosis; red water; texas fever; tick fever
• Spanish: fiebre del Texas; la tristeza
• French: piroplasmose bovine

Babesia
Babesia bigemina
Babesia bovis
Babesia caballi
Babesia canis
Babesia divergens
Babesia equi
Babesia gibsoni
Babesia motasi
Babesia ovis
Babesia trautmanni

The parasite Babesia is named after Babes, the scientist who first described it in sheep and cattle in 1888 (Levine, 1961). Organisms belonging to the genus Babesia are pear-shaped and parasitize red blood cells of mammals and invade the internal organs of ticks (Nyindo, 1992). In ticks, Babesia parasites may be transmitted trans-stadially (from larva to nymph to adult) and transovarially (Friedhoff and Soule, 1996). Although typically pyriform, they may be circular, oval or amoeboid with lateral chromatin in one or more nuclei (Morel, 1989).

Babesia belongs to the family Babesiidae (Poche, 1913). Organisms of the family Babesiidae are round to pyriform or amoeboid forms occurring in the erythrocytes. They multiply by binary fission or schizogony, in the red blood cells. The vectors are ixodid ticks (Soulsby, 1986). Babesia belongs to the order Piroplasmidia Wenyon,1926. Members of this order are blood parasites of vertebrates, and they are small, round or pleomorphic. Their apical complex is reduced and reproduction is by binary fission or schizogony. They are parasites of the haematopoetic system with ticks as their vectors (Soulsby, 1986). Babesia belong to the class Sporozoea Leuckart, 1879. Members of the class Sporozoea are parasitic and produce spores. They possess no organs of locomotion, such as cilia or flagella, except in the gamete stage. Reproduction is asexual by binary or multiple fission (schizogony) or sexual (gametogony). Gametogony leads to the formation of a zygote which in turn initiates the process of sporogony or spore formation (Soulsby, 1986).

Over 100 species of the genus Babesia have been described (Homer et al., 2000) and a large number occur in domesticated animals (Nyindo, 1992). Clinical cases are described as babesiosis whereas sub-clinical infections found in young animals and those recovered from clinical attack are termed babesiasis (Nyindo, 1992). On the basis of host and Babesia species involved, babesiosis may be termed bovine babesiosis, canine babesiosis, ovine babesiosis, equine babesiosis, porcine babesiosis (Morel, 1989; Nyindo, 1992). The Babesias affecting cattle are usually conveniently divided into two groups, large (Babesia bigemina and B. major) and small (Babesia divergens and B. bovis). The Babesias of dogs and wild canidae can also be described as large (B.canis) and small (B. gibsoni). Similarly, the Babesias of equines are either large (Babesia caballi) or small (Babesiaequi) and porcine Babesias also as large (Babesia trautmanni) or small (B. perroncitoi).

In sheep and goats, large (Babesia motasi) and small (Babesia ovis) Babesias may occur (Nyindo, 1992). Babesia felis occurs in cats whereas B.microti occurs in rodents. In the reindeer, Babesiajakimovi clinical infection is likely (Nyindo, 1992). In the past, speciation was mainly based on morphology of the parasite and the host affected. Today species are identified on the basis of molecular and antigenic data, host specificity and pathogenicity. Morphology is of relatively minor importance as it may be affected by the host species (Zintl et al., 2003).

Babesiosis is a composite term for diseases caused by parasites of the genus Babesia. The disease affects both domestic and wild mammals. Mammal species belonging to the same or related genera, are usually receptive to the same Babesia species. Thus Babesia bigemina and B. bovis can infect taurines, zebu, and African and Asian buffalo; B.motasi, B. ovis and B. crassa infect sheep, goats and all wild species or sub-species of the sub-family Ovinae; B caballi and B. equi infect horses, donkeys and zebra. Dogs, various wolves and jackals are receptive to B. canis and B. gibsoni (Morel, 1989). In endemic areas, the disease can causes serious economic losses to the livestock industry. Although infections with some of the less pathogenic bovine and ovine spp (such as, B. divergens, B. bigeminaB. motasi and B. crassa) are often associated with mild clinical signs and may be missed by the farmer or clinician (Atkas et al., 2005; Morel, 1989; Zintl et al., 2005), acute clinical babesiosis in cattle or sheep has a grave prognosis and may be fatal without treatment (30% for B.bigemina, 70-80% for B. bovis, 30-50% in B. ovis). Equine babesiosis has a mortality rate of 20-50% but can occur in acute, sub-acute or chronic forms (Friedhoff and Soulé, 1996). Similarly, clinical signs of canine babesiosis can range from subclinical to a hyperacute fulminating fatal disease similar to complicated malarial infections (Boozer and Macintire, 2003). Babesiosis in pigs is generally mild, although infections may be aggravated by concurrent infections or poor nutrition (Waal et al., 1992).

In general, the disease is less serious in the traditional management system in endemic areas where tick control is loose. This is thought to be due to a phenomenon known as enzootic stability. In such situations young animals are exposed to the parasites even before the disappearance of passive protection by colostral antibodies. Calves and foals are protected for up to a year by an additional mechanism, known as inverse age resistance, which is independent of the immune status of the mother (Christensson, 1987; Waal and Heerden, 1994). In these animals low levels of parasitaemia may persist for a long time without any apparent ill-effects. Thus, in areas with high infection pressure most animals acquire immunity without showing clinical signs. In modern management systems tick control can destroy the state of enzootic stability by making the vector scarce (after treatment) and thereby increasing the risk of clinical disease (Morel, 1989). Very high losses may also be sustained when groups of susceptible adult animals are moved into areas of endemic babesiosis (Adam et al., 1978).

The taxonomic position of B. equi among the Babesia spp. has been questioned for some time because it has a pre-erythrocytic stage in its life cycle (see below) similar to Theileria spp. Comparisons of the 18s rRNA gene sequence confirm its close relationship to Theileria (Homer et al., 2000; Friedhoff and Soulé, 1996). Similarly, B. microti, a rodent parasite and important pathogen of humans, is thought to be more closely related to Theileria than the other Babesia spp. (Homer et al., 2000).

blood and circulatory system diseases of large ruminants
blood and circulatory system diseases of pigs
blood and circulatory system diseases of small ruminants
digestive diseases of large ruminants
digestive diseases of pigs
digestive diseases of small ruminants
multisystemic diseases of large ruminants
multisystemic diseases of pigs
multisystemic diseases of small ruminants
urinary tract and renal diseases of large ruminants
urinary tract and renal diseases of pigs
urinary tract and renal diseases of small ruminants

The gross postmortem and microscopic lesions of bovine, ovine, equine and porcine babesiosis have been reviewed (Morel, 1989). In haemolytic babesiosis, icterus is seen upon opening the carcass, by the colour it gives to all the connective tissues, and internal and external mucosae. The bladder contains haemoglobinuric urine. Splenomegaly is invariably present, with a dark red, mushy pulp due to degeneration of the haematopoietic centres. Prominent Malpighian corpuscles, due to hyperplasia of the reticular tissue, are observed in the middle of this pulp. The liver is enlarged and congested, with discoloured patches on a brownish background. On section, the lobule is seen to have a yellow centre with a grey border. The bile is granular. In hypertrophic kidney the two zones, cortical and medullary, are not clearly distinguishable. In the case of pneumonia due to icterus, the lungs show hepatization and local congestion, with rust-red mucus, and sometimes small haemorrhages. Petechia may be present on the peritoneal and cardiac serosae. If icterus is slight, the muscles appear pale because of anaemia and fever.

In the case of babesiosis due to B. bovis with nervous signs, there are petechia and congestion spots in the cerebral cortex. Ecchymosis and petechia are observed on the epicardium, in the myocardium, on the kidney, and in the renal parenchyma. Microscopically, the hepatic parenchyma presents centrolobular necroses and hydropic vesicular degenerating patches. Many macrophages contain red blood cell with or without parasites. The kupffer cells contain hemosiderin deposit in the tubular epithelium and reticulum cells of the glomeruli. The main tubular epithelium degenerates in the nephrons. Other microscopic lesions of babesiosis due to B. bovis include microthrombi that dilate the cerebral cortical capillaries. They are composed of a mass of parasitized erythrocytes, with peripheral interstitial oedema. The same microthrombi from agglutinated parasitized erythrocytes are found in the interlobular capillaries of the kidneys, causing congestion and petechia.

In principle, the ovine and porcine babesiosis lesions are the same as those of bovine babesiosis. In pigs, congestion, petechia and oedema are more common and pronounced.

Although the lesions of equine babesiosis are not very different from bovine babesiosis, those of equines show some peculiarities. These include haemorrhage on the external and internal mucosae, hypertrophy and inflammation of the lymph nodes, and abundant exudates in the pericardium and peritoneum. The pathology of canine and feline babesiosis has been reviewed (Nyindo, 1992). The mucous membrane becomes pale but jaundice and haemoglobinuria are uncommon. The spleen increases in size, and ascites, oedema of subcutaneous tissue, keratitis and iritis may be observed. Dogs that die of chronic babesiosis are emaciated. The subcutaneous tissue, fascia, fat and mucous membranes are stained yellow. The spleen and liver are enlarged. Peritoneal, pleural and pericardial cavities are full of serous fluid. Lungs are oedematous and there is broncho-pneumonia. The heart may be distended but in most cases no striking lesions are seen. The food contents in the gastro-intestinal tract are coloured yellow. Kidney shows evidence of nephrosis and nephritis. The pathology of feline babesiosis is mainly that of icterus and anaemia (Urquhart et al., 1996).

There are two principal mechanisms by which babesial organisms cause cellular and tissue injury (Kakoma and Mehlhorn, 1994; Urquhart et al., 1996). The first, intravascular haemolysis, is a direct result of erythrocyte rupture caused by rapidly dividing and exiting parasites. The rate of haemolysis is directly proportional to the parasitaemia which may range between 0.01 - 0.2 % (typical for B. bovis) and 40% (e.g. B. bigemina, B. divergens). Depending on the Babesia species and the immune status and age of the host, the disease may be acute, chronic or inapparent. The acute syndrome is characterized by fever, anaemia, haemoglobinuria, jaundice and variable mortality. The chronic syndromes are poorly defined clinically and are associated with anaemia and variable weight loss, while the carrier state is asymptomatic (Losos, 1986). If untreated the acute form may be fatal within a few days, whereas the chronic form lasts several days or weeks (Urquhart et al., 1996). Following recovery from clinical disease, subclinical infections may last for several years. During recovery, the anaemia which was normocyctic at first, becomes macrocytic and leucocytosis due to a rise in the number of lymphocytes occurs. Relapses are associated with the resurgence of the parasitaemia. In field situations where there is repeated exposure to challenge, the incidence of detectable parasitaemia is higher than that found in single infections, fluctuates widely, and gradually decreases over a period of years. In enzootic areas, the incidence and level of patent parasitaemia decline as an animal ages since it is constantly exposed to re-infection by all the antigenic types found in a particular habitat (Losos, 1986). This simple haemolytic anaemia is characteristic of B. bigemina and B. divergens.

In other species such as B. bovis, B. canis and B. caballi, more severe disease signs are caused by the clumping of infected erythrocytes and adherence to capillaries. As a result, blood flow to vital organs is interrupted resulting in anoxia, organ damage and shock. Accumulated parasites cause allergic reactions at the site of concentration and trigger the release of kinins and other vasoactive substances, resulting in vasodilation, circulatory collapse and death. Involvement of the central nervous system is common and manifests itself in hyperexcitability, muscle trembling, teeth grinding, ataxia, paddling of limbs. Coma and death may ensue. This cellular adhesive phenomenon has been linked to ‘stellate protrusions’ formed on the surface of B. bovis-infected erythrocytes similar to the knobs typical of Plasmodium falciparum infections (Cooke et al., 2005). Another effect that has been described is an increase in erythrocyte fragility. This occurs in both B. bigemina and B. bovis infections and affects uninfected as well as infected erythrocytes.

The pathogenesis of B. bovis infection in cattle is summarized here(Nyindo, 1992). The early events consist of activation of Kallikrein system. Later there is a state of haemolytic anaemia and blockade of blood vessels of the central nervous system. Kallikrein is an enzyme which acts on plasma 2-globulins to produce bradykinin. Bradykinin increases vascular permeability, causes vasodilation and coagulation. Complement cascades are also activated. The results of these reactions are circulatory stasis and shock. The anaemia is macrocytic, hypochromic and the animal gets into a state of anoxia and shock. The osmotic fragility of the normal red blood cell increases and may facilitate parasite penetration, or lead to spontaneous lysis. Anaemia may also become more severe due to removal of erythrocytes by macrophages (Morel, 1989; Nyindo, 1992). Antigen and antibody complexes, with complement lodge in the kidneys and cause glomerulonephritis (Nyindo, 1992).

The haematological changes, which accompany the anaemia, include increased levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase, unconjugated billirubin, blood urea nitrogen (BUN) and, in the late stages of infection, a decrease of calcium. The whole blood clotting time, partial thromboplastin time and prothrombin time are prolonged, and the numbers of platelets are reduced. Leucocyte counts fall slightly at first but in the post-acute phase there is two- to three-fold increase over normal values due to lymphocytosis (Losos, 1986).

As Babesia infections in ticks persist through molts (trans-stadial maintenance) and is transmitted transovarially (Lewis and Young, 1980), the parasite may be maintained in the tick population for several generations even in the absence of infected mammalian hosts (Donnely and Peirce, 1975). Much progress has been made in the elucidation of the life cycles of the different species of Babesia in ticks. The developmental stages are recognized in the tick gut, haemolymph, ovary and salivary glands (Nyindo, 1992).

Riek (1966) provided a detailed account of the different morphological forms of Babesia bigemina developing in the tick Booplulus microplus. Mehlhorn et al. (1980) outlined the development of B. canis in Dermacentor reticulatus. Moltman et al., (1982) described the fine structure of B. ovis in Rhipicephalus bursa. Electron microscopic studies of the developmental forms of B. divergens in the tick gut, haemolymph, ovary and salivary glands have provided detailed information on the life cycle of the parasites in the vector (Mackenstedt et al., 1990).

The developmental forms of B. bovis in the gut, haemolymph, epidermis, muscle, Malphigian tubules, ovary and eggs of the tick R. bursa have been recognized and names such as merozoites, vermicules or spherical bodies have been assigned to them. However, Moltmann et al (1982) argue that since there is evidence for a sexual stage in Babesia the name kinete should be ascribed to all motile forms previously described under the different names.

Light and electron microscopic studies on the developmental stages of B. canis in the gut of D. reticulatus have been made. Examination of the gut contents of ticks after repletion showed that most of the pear-shaped parasites were lysed (Levine, 1988). Only the ovoid forms persisted and appeared to undergo further development. In the erythrocytes of Beagle dogs, parasites contained many vacuoles, double walled organelles and a homogenous nucleus. Some of the ovoid forms developed spiky protrusions, which contained 1 to 5 microtubules (‘ray bodies’). Within 48 hours following repletion red blood cells were digested and the ovoid forms and those with spikes were released. Each form was bounded by a typical membrane. The liberated forms invaded the gut wall of the tick. Two forms have been recognized in the gut cells: those with only one nucleus and those with more than one nucleus.

According to Nyindo (1992), studies involving B. microti and Ixodes dammini demonstrated the presence of parasites each with an arrowhead structure. Microtubules and cytostomes were also seen. The parasites occurred in the gut lumen and in close contact with gut cells or basal lamina. After syngamy parasites entered cells of the gut and transformed into club- or cigar-shaped kinetes. Kinetes of B. ovis, B. bigemina, B. caballi and B. divergens enter the tick haemolymph from where they are disseminated throughout various tissues including the musculature, epidermis, Malpighian tubes and ovaries. Here the kinetes undergo secondary cycles of schizogony to produce more kinetes. Developing eggs may be invaded followed by a secondary cycle of schizogony in gut cells of the transovarially infected embryo.

In contrast, B. microti and B. merionis do not produce progeny kinetes. In these latter species the parasites invade the salivary glands soon after leaving the gut. Developmental stages in the tick salivary glands have been described in a number of species (Schein et al., 1979; Moltman et al., 1982; Mackenstedt et al., 1990).

Usually 24 h following the tick attachment, cigar-shaped kinetes can be recognized in the haemolymph. By 48 h the kinetes are found in the cytoplasm of non-secretory glands where they develop into sporozoites. Sporozoites increase in number by binary fission or by schizogony. After binary fission or schizogony no further development of the sporozoites occurs and at this stage the parasites are not infective to mammalian hosts. Parasite differentiation and acquisition of infectivity is induced while the tick is feeding on the animal or by incubating ticks at 37°C (Nyindo, 1992). Sporozoites are released in the tick saliva and are infective to the respective mammalian hosts when the tick is feeding.

Upon inoculation into a new host, Babesia usually invade erythrocytes directly. The only exception to this rule is B. equi, which invades lymphocytes during a pre-erythrocytic stage (Friedhoff and Soulé, 1996). The process by which Babesia invade red blood cells is poorly understood but appears to involve sialic acid residues on the host cells surface (Gaffar et al., 2003; Okamura et al., 2005; Zintl et al., 2002). After attachment to the host cell and orientation of the apical end towards the erythrocyte surface, secretory products released by the rhoptries cause the erythrocyte membrane to invaginate. At first a parasitophorous vacuole encloses the sporozoite. As the vacuole membrane disintegrates, the parasite is eventually limited by one single plasma membrane, which is directly in contact with the erythrocyte cytoplasm (Gorenflot et al., 1991; Igarashi et al., 1988). Development in the erythrocyte begins with the trophozoite. It is circular, elliptical, small in size, and with a nucleus. It grows in size and the nucleus doubles to form the trophoblast. Budding of the trophoblast gives two or four oval or pyriform organisms, linked by the cellular debris of the trophozoite. The whole represents the schizont. The separate elements are the merozoites, each with one nucleus in the case of a tetrad, or with two nuclei for a pair. Each merozoite continues the infective cycle after destruction of the erythrocyte. The vast majority of merozoites continue to multiply asexually while a small proportion turn into non-dividing spherical gamonts, which remain inside erythrocytes until they are taken up by ticks during feeding (Mackenstedt et al., 1990).

Of the more than 70 species of Babesia that infect domestic animals, bovine babesiosis is undoubtedly the most economically important. It is estimated that up to 500 million cattle are infected with Babesia parasites each year, representing a huge economic burden on the beef and dairy industry worldwide (Cooke et al., 2005). Depending on the pathogens involved and the susceptibility of local cattle, economic losses due to tick-borne babesiosis may represent up to 20% of the value of the livestock (Morel, 1989). This assertion, which is general, is dated 1989. In Brazil, annual losses due to Boophilus microplus vector of babesiosis and anaplasmosis, stood at US$ 1 billion as at 1992 (Evans, 1992). Babesiosis was estimated to cost the Australian beef industry $A30 million per year in 1994 (Harper et al., 1994) and possibly 10 million cattle are at risk. A study carried out in Cuba between 1985 and 1995, estimated that the losses arising from morbidity, mortalities and reduced milk production caused by tick-borne diseases and the cost of ascaricide treatment amounted to almost US $7 million per year (Fuente et al., 1998). A now rather dated estimate for the British Isles put the annual incidence of B. divergens on the island of Ireland at 15,000 cases per year (Gray and Murphy, 1985).

Human infections with Babesia divergens, B. microti, B. bovis, or B. canis have been reported (Gorenflot et al., 1998). In Yugoslavia B. bovis was incriminated (Skrabalo and Deanovic, 1957), in Ireland B. divergens, and in northeastern USA B. microti of rodents was the causal agent (Healy et al., 1976). In Europe the territorial range of the disease coincides with that of bovine babesiosis caused by B. divergens, for which cattle are reservoir hosts and the vector is Ixodes ricinus. B. microti is transmitted by I. dammini, which also transmits Borrelia burgdorferi, the agent of Lyme disease. Simultaneous B. microti and B. burgdorferi infections can occur in man (Nyindo, 1992).

Human babesiosis cases in Europe are very uncommon but require rapid aggressive treatment. In the past most have occurred in splenectomised patients and were caused by B. divergens. Parasitaemias may range between 1 and 80% causing severe intravascular haemolysis with haemoglobinuria. The subsequent nonspecific clinical presentation can be easily confused with malaria; jaundice due to severe hemolysis is accompanied by persistent nonperiodic high fever (40 to 41°C), shaking chills, intense sweats, headaches, and myalgia as well as lumbar and abdominal pain.

Vomiting and diarrhea may be present. Total hemoglobin levels may fall to 70 to 80 g/liter, In the most severe cases, patients develop shock-like symptoms, with renal failure induced by intravascular hemolysis and pulmonary edema (Gorenflot et al., 1998). Unless treated rapidly, the infection is usually fatal.

In contrast, hundreds of cases of human infection with Babesia (chiefly B. microti, but also several other as yet unidentified strains or species) have been reported in the USA.Depending on the immune status of the host, clinical manifestations of human B. microti infections range widely. Although they may be asymptomatic in an otherwise healthy individual, infections may be severe and even fatal in immunocompromized patients (Gorenflot et al., 1998). It has been suggested that inapparent or latent infections may be quite common. For example, Orsono (1975) found that approximately 38% of individuals in a rural endemic area of animal babesiosis in Mexico showed serological evidence of infection.

Since transmission of human babesiosis is through tick bites, fear of pathogen survival in meat, meat inspection and food hygiene are not a concern.

In the past, treatment of babesiosis was mainly by use of azo-dyes of benzidine group, quinuronium derivatives, acridine derivatives, diamidine derivatives (Hall, 1977; Morel, 1989; Nyindo, 1992) and tetracyclines (Sackey et al., 1989; Pipano et al., 1988). The trypan blue and trypan red (azo-dyes) were the first drugs introduced for the treatment of babesiosis, but were withdrawn when more effective drugs were discovered (Nyindo, 1992). The quinuronium derivatives widely used in the past for the treatment of babesiosis include acaprin, babesan, piroplamin, pirevan and piroparv; whereas the acridine derivatives commonly used are acriflavine, gonacrine and flavin. The diamidine derivatives used include stilbamidine, propamidine, phenamidine, berenil and diamprone. A number of effective babesicides have been identified. However, because of residue and safety concerns their use is restricted in most countries. Diminazene aceturate is active against Babesia spp. in cattle, sheep, horses and dogs (Peregrine, 1994). It is marketed under trade names such as Berenil, Veriben or Ganaseg and is widely used in the tropics as both a babesicide and a trypanocide. Diminazene does not eliminate B. bovis or B. divergens, but it can eliminate B. bigemina. Quinuronium sulfate is very fast and effective but also the most toxic babesicide, affecting the parasympathetic nervous system. It was extensively used as a babesiacide until the 1940s when it was withdrawn because of its narrow therapeutic index (see Table). However, in the Middle East, it is still commonly used for ovine babesiosis. It is given at a single dose of 1 mg/kg bodyweight intramuscularly (BW i.m.) (Hall, 1977). It is also useful in treating pigs. The only drug licensed for use in the USA, Australia and most of Europe is imidocarb diproprionate. It is the drug of choice for infection with B. bigemina, B. bovis, B.divergens B. canis and B. gibsoni. Furthermore, unlike the other compounds that are marketed as babesiacides, imidocarb has significant prophylactic activity against Babesia spp., especially B. bigemina, which generally lasts 4-6 weeks (Peregrine, 1994). It is marketed as Imizol or Carbesia (Wellcome). Because of its persistence in tissues it has a withholding period in cattle and restrictions apply to its use in dairy cattle. Tetracyclines, both short-acting and long-acting preparations, have been useful as a prophylactic treatment against babesiosis at the dose rate of 5-20 mg/kg BW i.m. (Peregrine, 1994). Animals that are exposed to Babesia during the period of prophylaxis develop protective immunity (Urquhart et al., 1996).

In the past, the persistence of small numbers of parasites in the bloodstream was deemed necessary for the maintenance of resistance to reinfection. Today the concept of premunition is no longer accepted. While a certain period of antigenic exposure is necessary before treatment to facilitate the establishment of immunity, cattle treated with imidocarb diproprionate end up with a solid sterile immunity (Lewis et al., 1981). Long- term persistence of low-level parasitaemia is now considered a disadvantage. Remaining parasites may give rise to recrudescence under adverse conditions, treated cattle may act as a source of infection (Purnell et al., 1981), and parasites surviving at low levels of babesicide may acquire resistance.

Drug therapy of babesiosis

Drugs	Concentration	Route	B. bigemina	B. bovis B. divergens	B. caballi	B. equi
Diminazene aceturate	7%	i.mi.v.	2-4 mg/kg *** for treatment;7-10 mg/kg for sterilization;	5-6 mg/kg** for treatment;	2-4 mg/kg *** for treatment;7-10 for sterilization	5-6 mg/kg** for treatment;5 mg/ kg for premunition
Imidocarb dipropionate	12%	i.ms.c.	0.5-1 mg/kg ***for treatment;2 mg/kg for prophylaxis andsterility	1-2 mg/kg **for treatment;2-4 mg/kg for prophylaxis 2-5 mg/kg for sterilization	2 mg/kg*** for prophylaxis 2-4 mg/kg/dx2 at 72 h	5 mg/kg **for treatment;4 mg/kg/dx2 at 72h for sterilization
Quinuronium sulphate	5%	s.c.	0.5-0.75 mg/kg*	1 mg/kg*	0.3 mg/kg 2 at 6-hourly interval	-

* average activity
** good activity
*** excellent activity

In spite of these concerns, drug resistance has yet to constitute a constraint to the efficacy of the compounds that are currently used for babesiosis (Peregrine, 1994). The withdrawal of drugs previously used for babesiosis has not been due to drug resistance, but because of a decline in demand and residue concerns. The choice of drug for treatment of babesiosis thus depends on the Babesia species involved and tick/disease status of the area. Information on medicinal plants and herbal preparations effective in the treatment of babesiosis is starting to emerge (Kasahara et al., 2005; Subeki et al., 2005).