Theileria parva, a tick transmitted protozoan parasite, causes a severe lymphoproliferative disease in cattle variously known as East Coast fever, January disease or corridor disease. The main vector of the parasite is a three-host tick Rhipicephalus appendiculatus. The disease is present in 10 countries in Eastern and Central Africa, however the vector is more widely distributed than the parasite and there is a potential danger of the disease spreading to other areas. Theileria parva is highly pathogenic to cattle and mortality in Bos taurus cattle and their crosses can approach 100%. The parasite is considered to be the major factor in inhibiting the introduction of highly productive taurine breeds of cattle in sub-Saharan Africa. Where such cattle are maintained successfully in Africa, it is through heavy cost to the farmer, involving the use of toxic and expensive chemicals to kill the vector. Estimated annual losses are around US$190 million. The most common form of the disease in cattle due to T. parva is East Coast fever (ECF). It is characterized by high mortality in exotic cattle and large numbers of schizonts and piroplasms. A mild form of the disease, known as January disease, occurs predominantly in Zimbabwe. This disease occurs seasonally, and the outbreaks, coinciding with the emergence from diapause of adult ticks in January, are usually characterized by high morbidity and low mortality with low numbers of parasites. The main vector of January disease is Rhipicephalus zambesiensis (Morzaria et al., 2000).
4. Microbial Pathogenesis
The sporozoite develops in the salivary glands of the vector and is introduced into the mammalian host during tick feeding. Sporozoites rapidly enter lymphocytes by a receptor-mediated process and differentiate into schizonts. After several cycles of multiplication, a proportion of schizonts undergo merogony to produce merozoites, which invade erythrocytes and develop into piroplasms, the infective stage for ticks. The disease is characterized by pyrexia, generalized lymphadenopathy, and leukopenia (Musoke et al., 1992).
5. Host Ranges and Animal Models
The African buffalo plays an important role in the epidemiology of the disease since it is a natural host that does not suffer from the disease but remains a constant source of infection for ticks. The disease that occurs in cattle after the introduction of T. parva from buffalo is referred to as corridor disease, and is characterized by high mortality and low parasitosis (Morzaria et al., 2000).
6. Host Protective Immunity
Cattle that recover from ECF develop solid, strain-specific immunity that lasts for several years. Experiments have shown that passive transfer of antibodies to the schizont and piroplasm stages from immune to naïve cattle is not protective. There is now strong evidence that protective immunity is mediated by the generation of MHC class I restricted cytotoxic T cells (CTLs) specific for schizont-infected lymphocytes (Morzaria et al., 2000).
II. Vaccine Related Pathogen Genes
1. p67
Gene Name :
p67
Sequence Strain (Species/Organism) : Theileria parva strain Mugaga
Molecule Role Annotation :
Immunization with recombinant forms of a sporozoite surface antigen (r-p67), derived from either bacterial or insect cells, induces high levels of sporozoite neutralizing antibodies in cattle.In vivo immunization studies have shown that approximately 30% of immunized cattle are nonreactors to a needle LD70 sporozoite challenge, 40% experience a mild disease reaction from which they recover, and the remaining 30% suffer severe disease and are clinically indistinguishable from controls. Transient parasitosis and mild clinical reactions are also observed in challenge of cattle immunized by infection and treatment and such responses constitute immunity to ECF. Hence, p67 is able to routinely induce immunity at a level of about 70% (Morzaria et al., 2000).
Vaccination Protocol:
The immunization regimen consisted of five inoculations in 2-ml vol containing 1 mg of recombinant p67 emulsified in 3% saponin (Merck) and administered subcutaneously at monthly intervals (Musoke et al., 1992).
Challenge Protocol:
Immunized groups were challenged 10 days after the final inoculation along with four nonimmunized control animals. In both experiments, the nonimmunized controls served to test the infectivity of the sporozoite stabilate (Musoke et al., 1992).
Efficacy:
Immunization with p67 induced protection in 70% of the immunized cattle (Musoke et al., 1992).
2. Theileria parva vaccine by Centre for Ticks and Tickborne Disease, Malawi
1. Boulter and Hall, 1999: Boulter N, Hall R. Immunity and vaccine development in the bovine theilerioses. Advances in parasitology. 1999; 44; 41-97. [PubMed: 10563395].
2. Graham et al., 2006: Graham SP, Pellé R, Honda Y, Mwangi DM, Tonukari NJ, Yamage M, Glew EJ, de Villiers EP, Shah T, Bishop R, Abuya E, Awino E, Gachanja J, Luyai AE, Mbwika F, Muthiani AM, Ndegwa DM, Njahira M, Nyanjui JK, Onono FO, Osaso J, Saya RM, Wildmann C, Fraser CM, Maudlin I, Gardner MJ, Morzaria SP, Loosmore S, Gilbert SC, Audonnet JC, van der Bruggen P, Nene V, Taracha EL. Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(9); 3286-3291. [PubMed: 16492763].
3. Morzaria et al., 2000: Morzaria S, Nene V, Bishop R, Musoke A. Vaccines against Theileria parva. Annals of the New York Academy of Sciences. 2000; 916; 464-473. [PubMed: 11193661].
4. Musoke et al., 1992: Musoke A, Morzaria S, Nkonge C, Jones E, Nene V. A recombinant sporozoite surface antigen of Theileria parva induces protection in cattle. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89(2); 514-518. [PubMed: 1731322].
