Babesiosis

Johanna L. Watson • Jerry L. Zaugg

Babesiosis is a tick-borne intraerythrocytic disease of domestic and wild mammals and humans caused by protozoan para­sites of the genera Babesia and Theileria.

■ TABLE 37.1

Babesia Species (Babesiosis)

^aSuspected vector.From Kuttler, KL: Foreign animal diseases, Richmond, VA, 1984, United States Animal Health Association, p 77.

differentiation is required for specific identification of the various disease-producing species, all can be categorized as being either “large” or “small” in size.

Babesiosis in the Bovine

Etiology

Known variably as bovine babesiosis, piroplasmosis, Texas fever, redwater, tick fever, and tristeza, the disease may be caused by at least six Babesia spp. (see Table 37.1). Animals other than cattle known to be susceptible to agents of bovine babesiosis include white-tailed deer, American bison, water buffalo, reindeer, and African buffalo. Infections in these species are nominal, and except under unusual conditions, such hosts are probably not significant reservoirs.

Of greatest concern in the western hemisphere are Babesia bigemina and Babesia bovis. B. bigemina is a large Babesia char­acteristically appearing within mature erythrocytes as nonpig­mented, paired, pear-shaped bodies joined at an acute angle. Irregularly shaped, round, or amoeboid forms are also seen. B. bovis is a small, pleomorphic Babesia often identified as a single round body or as paired pear-shaped bodies joined at an obtuse angle within mature erythrocytes. Of the two species, B. bovis is usually considered the most virulent.

Natural transmission of both species occurs primarily by the feeding of various stages of the one-host ticks of the genus Boophilus. Ticks are most commonly infected transovarially (vertically). The female tick becomes infected by the ingestion of parasites during engorgement. After it drops off the host, the babesial organisms reproduce within the tick's tissues. Some of the reproducing organisms are incorporated within develop­ing tick embryos, and the disease agents are transmitted to new vertebrate hosts by the feeding of ensuing tick larvae, nymphs, or adults.

Clinical Signs

Clinical signs manifest 2 to 3 weeks after tick infestation. The incubation period following blood inoculation may be fewer than 5 days to more than 3 weeks, depending on the volume of inoculum. Clinical signs of fever (40° to 42° C [104° to 107.6° F]), depression, icterus, anorexia, tachycardia, tachypnea, anemia, hemoglobinemia, hemoglobinuria, abor­tion, and death are seen. Anemia is caused by intravascular destruction of erythrocytes by escaping merozoites following intraerythrocytic reproduction of the babesias by binary fission. In addition, the osmotic fragility of the whole erythrocyte population increases terminally, such that massive lysis occurs even though the parasitemia may be less than 1%.¹ In addition, an immune-mediated condition may result and the spleen will remove both damaged and healthy erythrocytes from circulation. Thus the degree of anemia may exceed that expected with a low parasitemia. Anemia may occur rapidly, with 75% or more of erythrocytes destroyed in just a few days. The exit of B. bigemina and B. bovis parasites from infected erythrocytes releases two or more parasite-associated proteolytic enzymes into the plasma. These enzymes and other parasite metabolic products are believed to interact with blood components and are responsible for such clinical signs as metabolic acidosis and anoxia. Tachycardia may be dramatic and heart sounds pronounced.

Cerebral babesiosis, characterized by hyperexcitability, convulsions, opisthotonos, coma, and death, may be observed in cattle infected with either B. bigemina or B. bovis, but especially with the latter. Central nervous system (CNS) signs are due to brain anoxia resulting from severe anemia and/or erythrocyte blockage of cerebral capillaries.

Death is caused by a shocklike syndrome associated with the accumulation of toxins, release of vasoactive substances, and anemic anoxia. Most cases with cerebral involvement are fatal, but mortality is extremely variable and depends on the Babesia strain, host susceptibility, and management and envi­ronmental stress factors. Many cattle that survive the acute phase recover but become chronic carriers. Other survivors often experience episodes of recrudescence, eventually suc­cumbing to the disease, or they may die from secondary infections contracted during their debilitated state.

Cattle of all breeds are susceptible to babesiosis, but Bos indicus breeds exhibit a definite degree of resistance to both B. bigemina and B. bovis and the tick vectors.² Calves possess a natural immunity to babesiosis. Such immunity was believed to be reinforced by colostral antibodies for calves born to previously infected dams.³ However, erythrocytes of young bovines may contain factor(s) independent of antibody that provide an innate resistance to severe babesiosis.⁴ Thus calves infected up to the age of 9 months experience a minimum reaction to the disease, becoming asymptomatic carriers. Carriers remain resistant to clinical disease for at least 4 years.⁵ The carrier state can be overcome, however, by such stresses as calving, malnutrition, or concurrent disease.⁶

Clinical Pathology

Clinical signs observed in cattle located in enzootic areas where Boophilus ticks occur may provide sufficient data for a presump­tive diagnosis. Other conditions that may exhibit some of the same signs as babesiosis are anaplasmosis, trypanosomiasis, theileriosis, leptospirosis, chronic copper toxicity, and bacillary hemoglobinuria. The cerebral signs may be confused with rabies and other encephalitides. A positive diagnosis requires identification of Babesia on Giemsa-stained thin blood smears, positive serologic tests (IFA, ELISA, CF), or molecular diag­nostics (PCR).⁷ In acute infection, Babesia spp.

Specific anti-Babesia antibodies are detectable in cattle sera in fewer than 7 days following infection.¹⁰ Such antibodies also exist for at least 252 days after the disappearance of detectable parasites.¹¹ The CF and IFA tests are the most widely used.^10,12 The CF test follows the same basic procedure used in anaplasmosis CF testing,¹¹ but with a Babesia antigen.¹² The test is effective, but about 100 days after infection, CF antibodies drop below a reliable diagnostic level.¹⁰ The IFA test uses the whole intraerythrocytic parasite as antigen rather than an extract and commercially prepared rabbit antibovine γ-globulin conjugated to fluorescein.¹⁰ Other serologic tests include latex particle agglutination,¹³ rapid card agglutination,¹⁴ and enzyme­labeling immunoassay (EIA).¹⁵ It should be noted that the immunologic assays are indirect methods and do not detect the causal organisms in samples obtained from a suspected infected animal. Recombinant DNA techniques using selected clones containing inserts of Babesia genomic DNA sequences are now available to be used as specific, highly sensitive DNA or RNA probes to detect the presence of the hemoparasite DNA in an infected animal or tick vector.¹⁶

Necropsy Findings

Postmortem findings in cattle that die peracutely are charac­teristic of an acute hemolytic crisis. Such findings include a generalized pallor or icterus throughout the carcass; an enlarged icteric liver; gallbladder distended with thick, dark green bile; and a markedly enlarged dark, soft spleen. Hydropericardium and subepicardial/subendocardial petechiation may be seen. The blood is thin and watery. The urinary bladder is frequently distended with dark red urine. There may be subserosal ecchymotic hemorrhages in abomasal and intestinal mucosa, and the lymph nodes are edematous. The carcass of an animal that dies after a prolonged illness is generally emaciated and icteric.

Treatment and Prognosis

After the onset of hemoglobinuria or cerebral signs, the prognosis is poor. Acute cases with PCV values above 12% usually respond well to treatment. The prognosis decreases for cases with PCV values below 10%. Successful treatment depends on early diagnosis and prompt therapy. In addition to specific treatment, supportive therapy such as blood transfu­sions (4 L of whole blood per 250 kg of body weight), fluids, hematinics, and prophylactic antibiotics are important. However, wild excitable cattle may best be left alone. With severe hemolytic anemias, any exertion associated with restraint and treatment may precipitate an anoxic crisis.

The small Babesia spp. are more resistant to chemotherapy and may require increased dosages or additional treatments. Chemotherapy with imidocarb can be both therapeutic and prophylactic, but there are concerns with milk and meat residue. In enzootic areas its use prevents clinical infection for as long as 2 months but at the same time allows mild subclinical infections to occur, resulting in premunition immunity.^17,18

Prevention and Control

Eradication of Boophilus tick vectors has provided effective control in the United States. Most procedures aimed at reducing tick infestations (i.e., acaricide applications [on host or over environment], controlled range burning, cultivation, prolonged pasture rest, and use of repellents) are beneficial. Care should be taken to prevent accidental transfer of blood from one animal to another in routine surgery (e.g., dehorning, castration, ear marking, hormone implanting) and vaccination procedures.

The most common form of immunization consists of inoculating live organisms (virulent or attenuated) into sus­ceptible calves to induce a state of premunition. Inoculation of older animals is followed by nonsterilizing chemotherapy as needed to modify clinical effects.¹⁹ Although a premunition approach is useful in endemic areas, it is less desirable in areas with low infection rates because the premunized carriers provide a large reservoir of infection. Subunit vaccines were proven effective in protecting against severe clinical disease.^20,21

Babesiosis in the Horse

ETIOLOGY. Babesiosis/theileriosis of the horse (piroplas- mosis) is a febrile tick-borne disease of equids caused by Babesia caballi and Theileria equi¹¹ (see Table 37.1). B. caballi is a large Babesia resembling B. bigemina, which affects cattle. A unique characteristic of T. equi is that the intraerythrocytic parasites divide into four cells to form a Maltese cross.²³

Equine piroplasmosis is widely distributed throughout the tropics and subtropics and to a lesser extent in temperate regions. The distribution roughly corresponds to that of the tick vectors. Both species are naturally transmitted by ticks of the genera Dermacentor, Hyalomma, and Rhipicephalus. B. caballi is passed transovarially (vertically) from one tick generation to the next. Transmission of T. equi apparently only occurs transstadially (horizontally); that is, one tick stage (larvae or nymphs) becomes infected, and the disease agent is passed to the next vertebrate host in the next tick stage (nymph or adult). Because of the widespread prevalence of potential tick vectors in the United States (Dermacentor albipictus, Dermacentor iteus, Dermacentor variablis), equine piroplasmosis could become a problem in the United States at any time.

CLINICAL SIGNS. Apparently, all equids are susceptible to both parasite species. The zebra in Africa is naturally infected with T. equi but not B. caballi. Once infected, survivors remain chronic carriers. At least T. equi can be transmitted transpla- centally. Clinical features following an incubation period of 5 to 28 days are fever (39° to 42° C [102° to 107.6° F]), hemolytic anemia, jaundice, hemoglobinuria, and death. Generalized signs of depression, anorexia, incoordination, lacrimation, mucous nasal discharge, swelling of the eyelids, and frequent lying down are seen. T. equi is considered the most pathogenic of the two species and is responsible for a greater incidence of hemoglobinuria and death. B. caballi causes a more persistent fever and anemia. Differential diagnoses include equine monocytic ehrlichiosis, EIA, liver failure with hemolytic anemia, and other hemolytic anemias of the horse.

CLINICAL PATHOLOGY. A fever associated with anemia, jaundice, and hemoglobinuria, with the detection of parasite- infected erythrocytes in Geimsa-stained blood smears, is diagnostic. A significant increase in relative and absolute numbers of monocytes and absence of eosinophils may be observed in horses infected with T. equi. Hemoglobinuria is rare in animals infected with B. caballi, but urine is often dark yellow in color. The official testing method is the cELISA test. There is also a PCR test for both equine diseases. As with the bovine infections, both B. caballi and T. equi infections can be specifically detected with nucleic acid probes.¹⁷

NECROPSY. Postmortem features are similar to those seen in bovine babesiosis, but jaundice is even more prominent throughout the carcass. There is excessive fluid in the body cavities, especially the pericardial sac. Pulmonary edema is evident. The liver is swollen, and hepatic vessels contain large yellowish clots. The spleen is enlarged, with rounded edges.

TREATMENT AND PROGNOSIS. The drug of choice for eliminating the carrier state of infected animals is imidocarb. Imidocarb at the level of 2.2 mg/kg given two times in 24 hours is effective against B. caballi. A 4-mg/kg IM dose given every 72 hours for four doses is effective against T. equi of eastern hemisphere origin.²⁴ However, donkeys receiving similar treatment died from drug toxicosis.²⁴ The higher doses of imidocarb often produce transient colic in horses. To date, attempts to consistently eliminate the carrier state of T. equi of Eastern European origin have been unsuccessful.²⁵

PREVENTION AND CONTROL. Control of tick infestations does much to reduce disease incidence, as does care to prevent blood transfer during such routine surgical procedures as castration. No vaccines effectively prevent equine babesiosis. Although premunition as used in bovine babesiosis is of limited value in some enzootic areas, it is not widely practiced. This is because early treatment without sterilization is effective, and the resulting chronic carriers resist further disease challenge. If a horse is diagnosed with T. equi in the United States, the veterinarian can enroll the horse in the USDA controlled treatment program to ensure appropriate quarantine, treatment, and subsequent release of cleared animals.