Theilerioses are a group of tickborne diseases caused by protozoan parasites of the Theileria genus. A large number of Theileria spp are found in domestic and wild ungulates in tropical and subtropical regions of the world. The most important species affecting cattle are T parva and T annulata, which cause acute disease resulting in high levels of mortality. T lestoquardi, T luwenshuni, and T uilenbergi are important causes of mortality in sheep, and T equi sometimes causes clinical disease in horses. A therapeutic drug, buparvaquone, is available to treat the diseases, but it is expensive, and control of the diseases usually involves either prevention of tick infestation or, in some areas, vaccination.
Both Theileria and Babesia are members of the suborder Piroplasmorina. Although Babesia are primarily parasites of RBCs, Theileria use, successively, WBCs and RBCs for completion of their life cycle in mammalian hosts. The infective sporozoite stage of the parasite is transmitted in the saliva of infected ticks as they feed. Sporozoites invade leukocytes and, within a few days, develop to schizonts. In the most pathogenic species of Theileria (eg, T parva and T annulata), parasite multiplication occurs predominantly within the host WBCs, whereas less pathogenic species multiply mainly in RBCs.
Development of the schizont stage of pathogenic Theileria causes the host WBC to divide; at each cell division, the parasite also divides. Thus, the parasitized cell population expands and, through migration, becomes disseminated throughout the lymphoid system. Later in the infection, some of the schizonts undergo merogony, releasing merozoites that infect RBCs, giving rise to piroplasms. Uptake of piroplasm-infected RBCs by vector ticks feeding on infected animals is the prelude to a complex cycle of development, culminating in transmission of infection by ticks feeding in their next instar (trans-stadial transmission). There is no transovarial transmission as occurs in Babesia.
Occurrence of disease is limited to the geographic distribution of the appropriate tick vectors. In some endemic areas, indigenous cattle have a degree of innate resistance. Mortality in such stock is relatively low, but introduced cattle are particularly vulnerable.
East Coast Fever
East Coast fever, caused by Theileria parva, is an acute disease of cattle. It is usually characterized by high fever, swelling of the lymph nodes, dyspnea, and high mortality. It is a serious problem in east and southern Africa.
Etiology and Transmission of East Coast Fever
T parva sporozoites are injected into cattle by infected vector ticks, Rhipicephalus appendiculatus, during feeding. Ticks acquire infection by feeding on infected cattle or African buffalo (Syncerus caffer), which carry the infection but do not show signs of disease. Both cattle- and buffalo-derived T parva are highly pathogenic when transmitted to cattle, but the latter do not develop to the piroplasm stage and therefore are usually not transmitted by ticks from infected cattle.
Pathogenesis and Clinical Findings of East Coast Fever
An occult phase of 5–10 days follows before infected lymphocytes can be detected by microscopic examination of smears of cells aspirated from affected lymph nodes. Subsequently, the number of parasitized cells increases rapidly throughout the lymphoid system, and from about day 14 onward, cells undergoing merogony are observed and piroplasm-infected erythrocytes are detected. This coincides with progressively severe lymphocytolysis, marked lymphoid depletion, and leukopenia.
Clinical signs vary according to the level of challenge, and they range from inapparent or mild to severe and fatal. Typically, fever occurs 7–10 days after parasites are introduced by feeding ticks, continues throughout the course of infection, and may be >107°F (42°C). Lymph node swelling becomes pronounced and generalized as the number of infected lymphoblasts increases. Anorexia develops, and the animal rapidly loses condition; lacrimation and nasal discharge may occur. Terminally, dyspnea is common. Just before death, a sharp decrease in body temperature is usual, and pulmonary exudate pours from the nostrils. Death usually occurs 18–24 days after infection.
The most striking postmortem lesions are generalized lymph node enlargement and massive pulmonary edema and hyperemia. Hemorrhages are common on the serosal and mucosal surfaces of many organs, sometimes together with obvious areas of necrosis in the lymph nodes and thymus. Anemia is not a major diagnostic sign (as it is in babesiosis).
Although the clinical and pathologic features and severity of disease caused by cattle- and buffalo-derived T parva are broadly similar, the latter (sometimes referred to as Corridor disease) differ by exhibiting lower levels of schizont-infected lymphoblasts and no piroplasms.
Animals that recover are immune to subsequent challenge with the same strains but may be susceptible to some heterologous strains. Most recovered or immunized animals remain carriers of the infection.
Tropical Theileriosis
T annulata is the causal agent of tropical theileriosis, which is widely distributed in north Africa, the Mediterranean coastal area, the Middle East, India, countries of the southern former USSR, and Asia. It is transmitted by several species of ticks of the genusHyalomma. T annulata can cause mortality of up to 90%, but strains vary in their pathogenicity.
The kinetics of infection and the main clinical features of the disease are similar to those produced by T parva, but unlike East Coast fever, anemia is often a feature of the disease. Characteristic signs include fever and swollen superficial lymph nodes, and if the disease progresses, cattle rapidly lose condition. Animals that recover from infection are immune to subsequent challenge.
Diagnosis of Theileriosis in Cattle
Diagnosis is based on clinical signs and detection of parasites in lymph node aspirates.
Serology is only of value in detecting previous infection in recovered animals.
Confirmation of disease caused by T parva and T annulata relies on microscopic examination of Giemsa-stained smears of lymph node needle aspirates for the presence of schizonts in infected leukocytes. The intra-erythrocytic piroplasm stages are also readily detected in stained blood smears. Piroplasms assume various forms, but typically they are small and rod-shaped or oval. The schizonts and piroplasms of T parva and T annulata are morphologically similar.
Definitive diagnosis can also be confirmed using antigen-specific ELISAs or PCR on lymph node aspirates.
Treatment and Control of Theileriosis in Cattle
Buparvaquone, often accompanied by anti-inflammatory drugs and antidiuretics, if there is evidence of pulmonary edema
Only a single compound, buparvaquone, is available for treatment of the diseases caused by Theileria parasites. Treatment is effective when applied in the early stages of clinical disease but may require more than one dose. Treatment is less effective in the advanced stages, when there is extensive destruction of lymphoid and hematopoietic tissues. Development of resistance to buparvaquone has also been reported for T annulata.
Prevention of Theileriosis in Cattle
Spraying or dipping of animals with acaracides is the most frequently used method for prevention of theileriosis, but this needs to be applied at regular intervals to be effective. Pyrethroid compounds are often used where animals are challenged with both tickborne diseases and trypanosomes.
Vaccination of cattle against T parva using an infection-and-treatment procedure is gaining acceptance in some regions. The components for this procedure are a cryopreserved sporozoite stabilate of homogenized ticks infected with the appropriate strain(s) of T parva and a single dose of long-acting oxytetracycline given simultaneously. Although oxytetracycline has little therapeutic effect when given after development of disease, it inhibits development of the parasite when given at the outset of infection.
Live vaccines using in vitro-cultivated parasitized bovine cells containing the schizont stage of T annulata are used in some countries to vaccinate cattle against T annulata. The infected cells are held as cryopreserved stock and, after thawing, approximately one million cells are administered subcutaneously. The parasitized cells need to be subjected to prolonged passage in vitro to ensure they are attenuated.
Cattle should be immunized 3–4 weeks before being allowed on infected pasture.
Other Theilerioses of Cattle
The Theileria orientalis group, consisting of the closely related parasites T orientalis, T buffeli, and T sergenti, has a worldwide distribution. These parasites are transmitted by ticks of the genus Haemaphysalis. The piroplasms are larger than those of T parva and T annulata, and the parasites multiply principally by intraerythrocytic division. Although usually nonpathogenic, disease characterized by anemia and occasional mortality sometimes occurs, usually in dairy cattle. Outbreaks of more severe disease caused by one particular subtype of T orientalis have occurred in Australia and New Zealand in the past decade.
T mutans and T velifera are found in Africa, where they are transmitted by ticks of the genus Amblyomma. Multiplication occurs mainly by intraerythrocytic division. The piroplasms are morphologically indistinguishable from those of T orientalis, but the parasites can be differentiated by serologic tests such as indirect fluorescent antibody and by DNA typing. Some strains of T mutans are pathogenic as well. In addition, concurrent infection may add to the pathogenicity of T parva.
Ovine and Caprine Theilerioses
Theileria lestoquardi causes a disease in sheep and goats similar to that produced in cattle by T annulata, with which it is closely related. T lestoquardi is transmitted by ticks of the genus Hyalomma and has a similar geographical distribution to that of T annulata. Mortality can approach 100%. Schizonts can readily be demonstrated in Giemsa-stained smears of needle biopsies from swollen superficial lymph nodes.
Two species of Theileria, T luwenshuni and T uilenbergi, cause a severe disease in sheep in China. These species are morphologically indistinguishable and cause similar disease but can be distinguished by DNA typing methods. They are transmitted by ticks of the genus Haemaphysalis. Schizonts are detected in a range of tissues, but later and in smaller numbers than in other pathogenic Theileria spp. Piroplasms are consistently detected in RBCs. Morbidity and mortality rates of up to 65% (T luwenshuni) and 75% (T uilenbergi) have been seen in susceptible animals introduced into endemic areas. Affected animals show sustained fever and anemia.
Several other nonpathogenic Theileria spp (eg, T ovis) are also widely distributed. Piroplasms of these species are polymorphic.
Equine Theileriosis
Babesia equi was reclassified as T equi in 1998, based on DNA analysis and the finding that the parasite develops in leukocytes before infection of erythrocytes. Infection is often asymptomatic but can result in outbreaks of disease characterized by fever, anemia, and lethargy, leading to death of some animals. Although schizont-infected leukocytes are observed in lymphoid tissues, disease is largely attributable to destruction of erythrocytes. Thrombocytopenia and hemorrhage may also occur. (Also see Babesiosis in Animals.)
