Theileriases are a group of tickborne diseases caused by Theileria spp. A large number of Theileria spp are found in domestic and wild animals in tick-infested areas of the Old World. The most important species affecting cattle are T parva and T annulata, which cause widespread death in tropical and subtropical areas of the Old World. T lestoquardi, T lowenshuni, and T uilenbergi are important causes of mortality in sheep.
Both Theileria and Babesia are members of the suborder Piroplasmorina. While Babesia are primarily parasites of RBC, Theileria use, successively, WBC and RBC 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 WBC, whereas less pathogenic species multiply mainly in RBC. 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 RBC, giving rise to piroplasms. Uptake of piroplasm-infected RBC 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, an acute disease of cattle, is characterized usually by high fever, swelling of the lymph nodes, dyspnea, and high mortality. Caused by Theileria parva, it is a serious problem in east and central Africa.
Etiology and Transmission
T parva sporozoites are injected into cattle by infected vector ticks, Rhipicephalus appendiculatus, during feeding. Based on clinical and epidemiologic parameters, 3 subtypes of T parva are recognized, but these are probably not true subspecies. T parva parva and T parva bovis are both maintained by transmission between cattle. T parva parva is highly pathogenic and can cause high levels of mortality, whereas T parva bovis is less pathogenic. T parva lawrencei is maintained in buffalo and is highly pathogenic when transmitted to cattle, but it does not develop to the piroplasm stage and cannot be transmitted from infected cattle.
Pathogenesis, Clinical Findings, and Diagnosis
An occult phase of 5–10 days follows before infected lymphocytes can be detected in Giemsa-stained smears of cells aspirated from the local draining lymph node. Subsequently, the number of parasitized cells increases rapidly throughout the lymphoid system, and from about day 14 onward, cells undergoing merogony are observed. This is associated with widespread lymphocytolysis, marked lymphoid depletion, and leukopenia. Piroplasms in RBC infected by the resultant merozoites assume various forms, but typically they are small and rod-shaped or oval.
Clinical signs vary according to the level of challenge and 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. Lymphoblasts in Giemsa-stained lymph node biopsy smears contain multinuclear schizonts. Anorexia develops and the animal rapidly loses condition; lacrimation and nasal discharge may occur. Terminally, dyspnea is common. Just before death, a sharp fall 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 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) because there is minimal division of the parasites in RBC, and thus no massive destruction of them.
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.
Treatment and Control
Treatment with parvaquone and its derivative buparvaquone is highly effective when applied in the early stages of clinical disease but is less effective in the advanced stages in which there is extensive destruction of lymphoid and hematopoietic tissues. Immunization of cattle against T parva using an infection-and-treatment procedure is practical and is gaining acceptance in some regions. The components for this procedure are a cryopreserved sporozoite stabilate of the appropriate strain(s) of Theileria derived from infected ticks and a single dose of long-acting oxytetracycline given simultaneously; although oxytetracycline has little therapeutic effect when administered after development of disease, it inhibits development of the parasite when given at the outset of infection. Cattle should be immunized 3–4 wk before being allowed on infected pasture. Parasitized bovine cells containing the schizont stage of T parva and T annulata can be cultivated in vitro as continuously growing cell lines. In the case of T annulata, cattle can be infected with a few thousand cultured cells. Attenuated strains produced by serial passage of such cultures form the basis of live vaccines used in several countries, including Israel, Iran, India, and the former USSR.
Incidence of East Coast fever can be reduced by rigid tick control, but this is not feasible in many areas because of cost and the high frequency of acaricidal treatment required.
T annulata, the causal agent of tropical theileriosis, is widely distributed in north Africa, the Mediterranean coastal area, the Middle East, India, the former USSR, and Asia. It is transmitted by several species of ticks of the genus Hyalomma. T annulata can cause mortality of up to 90%, but strains vary in their pathogenicity. The kinetics of infection and the main clinical findings are similar to those produced by T parva, but unlike in East Coast fever, anemia is often a feature of the disease. Characteristic signs include fever and swollen superficial lymph nodes. If the disease progresses, cattle rapidly lose condition. The schizonts and piroplasms are morphologically similar to those of T parva. Animals that recover from infection are immune to subsequent challenge. Treatment and control are as described for East Coast fever (see East Coast Fever).
Other Theileriases of Cattle
The T 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 they multiply principally by intraerythrocytic division. Mortality, particularly in indigenous cattle, is rare, but infection can result in progressive chronic anemia.
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 and T taurotragi (an African parasite of eland and cattle), 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 Theileriases
T lestoquardi (formerly T hirci) 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 geographic distribution to that of T annulata. Mortality can approach 100%. Schizonts can readily be demonstrated in Giemsa-stained biopsy smears from swollen superficial lymph nodes.
Recently, two species of Theileria, T lewenshuni and T uilenbergi, have been identified as the causal agents of 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 RBC. Morbidity and mortality rates of up to 65% (T lewenshuni) and 75% (T uilenbergi), have been observed 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.
Babesia equi was reclassified as T equi in 1998, based on DNA analysis and other biologic data (see Babesiosis).
Last full review/revision July 2011 by W. Ivan Morrison