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Background

Small ruminant theileriosis

Theileria parasites infect a large number of wild and domestic animals and are transmitted trans-stadially by various members of tick vectors of the family Ixodidae. Generally, the life-cycle of Theileria involves both the transmitting invertebrate tick vector, in which sexual reproduction and sporogony takes place, and the vertebrate host, in which asexual reproduction by schizogony and merogony occurs [1,2,3]. A number of Theileria species capable of infecting small ruminants have so far been described. Many of them are non-pathogenic such as Theileria ovis, T. separata , and T. recondita. There are three other species which are highly pathogenic for small ruminants:

Sheep

• T. lestoquardi is pathogenic to sheep and goats, is transmitted by Hyalomma anatolicum anatolicum and causes a disease called malignant theileriosis. It is expected to occur where the vector tick species is found, mainly in northern Africa, southern Europe and the Middle East [4]. Similar to the bovine pathogens T. annulata and T. parva, T. lestoquardi transforms its host leucocytes.

• T. uilenbergi and T. luwenshuni have recently been described as new pathogenic Theileria species of sheep and goats in northern China [5]. It has been shown that both nymphs and adults of Haemaphysalis qinghaiensis could efficiently transmit both of these Theileria parasites to sheep and goats. Unlike the case with T. lestoquardi, where goats are kno wn to be more resistant than sheep, there is no evidence that sheep and goats differ in their susceptibility to the infection [5,6] and neither of these parasites is able to transform its host leucocytes.

Diagnosis

In the laboratory, demonstration of the parasites is based on microscopical examinations of Giemsa-stained smears of blood or lymph node aspirates [7]. In general, serological tests such as immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) are more suitable as surveillance tools. A number of PCR-based tools to detect parasite DNA such as PCR and Reverse line blotting (RLB) have been established. Recently, loop-mediated isothermal amplification of DNA (LAMP) has been shown to be a promising tool in the diagnosis of theileriosis [8,9].

Theileria lestoquardi

Vaccination

In the case of T. lestoquardi, attenuated live vaccines based on inoculation of schizont-infected leucocytes have been utilised for the control of malignant theileriosis only in Iran and Iraq. It is envisioned that improvement and distribution of a live attenuated vaccine will contribute to the control of this important small ruminant disease.

Immune response

Infection with the related bovine parasites, Theileria annulata and T. parva, is associated with the establishment of a solid immunity. It is well known that both antibody-dependent and antibody-independent mechanisms are involved. Antibodies are able to neutralise the infectivity of the sporozoites but on the other hand do not prevent initiation of an infection. However, T-cells play a crucial role in induction and maintenance of this immunity. Based on the cytokine profile and lytic effect of the T-cells, it seems that both CD4+/- and CD8+/-T cells are involved in the mediation of such immunity. Cytotoxic- and helper-T-cells recognise parasite-antigens, which are presented by the infected cells via MHC I and MHC II, respectively. To date, CD8+ T cells (cytotoxic T lymphocytes, CTL) are known to be the major anti-Theileria effectors and are activated in both T. annulata and T. parva infections. They offer immunity by directly lysing schizont-infected cells and their generation is closely related to the control of the infection. The innate immune response is also believed to play a role in protecting against T. annulata infection, involving the activation of cytokine-producing macrophages. However, little is known about the mechanisms of the immune response to T. lestoquardi or to T. uilenbergi infection. Experience gained from defining the response to bovine Theileria will be useful for addressing this knowledge gap in small ruminants. Moreover, understanding the immune response of small ruminants to Theileria may help in understand their immune responses to other pathogens [10,11,12,13,14,15,16,17,18,19,20].

References

1. Barnett SF. Theileriasis. In: Infectious Blood Diseases of Man and Animals. 1968 D. Weinmann and M. Ristic (Eds), pp. 269-328. Academic Press, New York.

2. Mehlhorn H, Schein E. The piroplasms: Life cycle and sexual stages. Advances in Parasitology 1984 23, 37-103.

3. Mehlhorn H, Schein E. The Piroplasms: "A Long Story in Short" or "Robert Koch has seen it". European Journal of Protistology 1993 29, 279-293.

4. Uilenberg G. Theilerial species of domestic livestock. In: Advances in the control of theileriosis. 1981. Irvin, A.D., Cunningham, M.P. and Young, A.S. (Eds). Martinus Nijhoff Publishers, The Hague, pp 4-37.

5. Yin H, Schnittger L, Luo J, Seitzer U, Ahmed JS. Ovine theileriosis in China: a new look at an old story. Parasitol Res. 2007 Sep;101 Suppl 2:S191-5.

6. Hooshmand-Rad P, Hawa NJ. Malignant theileriosis of sheep and goats. Tropical Animal Health and Production 1973a 5, 97-102.

7. Uilenberg G. Diagnostic microscopique des maladies transmises par les tiques au Maghreb. Arch Inst Pasteur Tunis 2004 81(1-4): 35-40.

8. Salih DA, Liu Z, Bakheit MA, Ali AM, El Hussein AM, Unger H, Viljoen G, Seitzer U, Ahmed JS. Development and evaluation of a loop-mediated isothermal amplification method for diagnosis of tropical theileriosis. Transbound Emerg Dis. 2008 55(5-6):238-43.

9. Liu Z, Hou J, Bakheit MA, Salih DA, Luo J, Yin H, Ahmed JS, Seitzer U. Development of loop-mediated isothermal amplification (LAMP) assay for rapid diagnosis of ovine theileriosis in China. Parasitol Res. 2008 103(6):1407-12.

10. Ververken C, Geysen D, Loots K, Janssens ME, Guisez Y, Goddeeris BM. Orientation of bovine CTL responses towards PIM, an antibody-inducing surface molecule of Theileria parva, by DNA subunit immunization. Vet Immunol Immunopathol. 2008 124(3-4):253-63.

11. Goddeeris BM, Morrison WI , Teale AJ, Bensaid A, Baldwin CL. Bovine cytotoxic T-cell clones specific for cells infected with the protozoan parasite Theileria parva: parasite strain specificity and class I major histocompatibility complex restriction. Proc Natl Acad Sci U S A. 1986 83(14):5238-42.

12. McKeever DJ, Taracha EL, Innes EL, MacHugh ND, Awino E, Goddeeris BM, Morrison WI. Adoptive transfer of immunity to Theileria parva in the CD8+ fraction of responding efferent lymph. Proc Natl Acad Sci U S A. 1994 91(5):1959-63.

13. Ahmed JS, Hartwig H, Schein E. Generation of Theileria annulata-specific cytotoxic T lymphocytes coincides with the control of tropical theileriosis. Parasitol. Res. 1999 85: 870-872.

14. Conze G, Campbell JDM, Nichani AK, Glass EJ, Spooner RL, Ahmed JS. Evidence for strain specificity in cytotoxic T-lymphocyte-mediated, major histocompatibility complex class 2-dependent killing of Theileria annulata-infected cells. Parasitol Res 1998 84: 593-595.

15. MacHugh ND, Burrells AC, Morrison WI. Demonstration of strain-specific CD8 T cell responses to Theileria annulata. Parasite Immunol. 2008 May 21.

16. McKeever DJ, Taracha EL, Morrison WI, Musoke AJ, Morzaria SP. Protective immune mechanisms against Theileria parva: evolution of vaccine development strategies. Parasitology Today 1999 15(7): 263-267.

17. Preston PM, Brown CG, Spooner RL. Cell-mediated cytotoxicity in Theileria annulata infection of cattle with evidence for BoLA restriction. Clin Exp Immunol 1983 53: 88-100.

18. Innes EA, Millar P, Brown CG, Spooner RL. The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneic Theileria annulata-infected lymphoblastoid cell lines. Parasite Immunol 1989 11: 57-68.

19. Ahmed JS, Rothert M, Steuber S, Schein E. In vitro proliferative and cytotoxic responses of PBL from Theileria annulata-immune cattle. J Vet Med (B) 1989 36: 584-592.

20. Ahmed JS, Glass EJ, Salih DA, Seitzer U. Innate immunity to tropical theileriosis. Inate Immun. 2008 14(1):5-12.