Towards integrated control of East Cost fever, a devastating disease of cattle

Infection of cattle with the tick-borne apicomplexan parasite Theileria parva results in the fatal lympho-proliferative disease known as East Coast fever (ECF). ECF is considered to be one of the most devastating diseases of livestock in sub-Saharan Africa affecting all sectors of livestock production. The three-host brown ear tick, Rhipicephalus appendiculatus is the primary vector of T. parva with all tick life stages adapted to feeding on cattle. Currently, there is no effective vaccine against ECF and control of R. appendiculatus and T. parva occurs primarily through the use of disease tolerant breeds, chemotherapy and acaricide application. Widespread application of acaricides for tick and tick borne-disease control is becoming less viable due to rapid development of acaricide resistance. Alternative measures for tick control based on integrated and sustainable methods are urgently needed.
Control of the one host tick Rhipicephalus microplus through anti-tick vaccination has been shown to be viable culminating in the commercial products GavacTM and TickGardTM. Both vaccines are based on the recombinant protein Bm86 expressed as concealed antigen in the R. microplus midgut. Vaccination elicits humoral immune response targeting Bm86 during tick feeding resulting in extensive gut damage. In this thesis, anti-tick vaccines were evaluated for their ability to control R. appendiculatus tick populations and to interfere with transmission of T. parva in their natural host-pathogen-vector system.
The R. appendiculatus homologue of Bm86, named Ra86, was examined for of its impact on nymphal and adult R. appendiculatus ticks after feeding on Ra86 vaccinated cattle. The molting success of nymphal ticks to the adult stage was significantly reduced in ticks feeding on Ra86 vaccinated animals in comparison control animals. Simulations based on our empirical data suggest that repeated Ra86 vaccinations would reduce tick populations over successive generations. This experiment showed for the first time that Ra86 based vaccination could play a part in integrated pest management and control strategies for R. appendiculatus. Reducing the nymphal population molting to adult instars has implications for
ECF clinical disease severity. T. parva transmission by adult ticks is commonly associated with more severe ECF disease symptoms when compared to nymph mediated transmission. Reduction of the number of adult ticks before they can transmit T. parva may lead to diminution of the negative impact of ECF on animal productivity. Additionally, Ra86 vaccination lowered T. parva infection levels in ticks that fed on vaccinated cattle indicating that targeting the tick gut could affect the uptake of T. parva from infected cattle and/or further development within the vector.
Vaccines that block parasite transmission either to- or from- the vertebrate host have been proposed for the control of numerous vector-borne diseases including ECF. Cattle were vaccinated with a multivalent recombinant antigen cocktail containing R. appendiculatus antigens TRP64, histamine binding protein (male and female variants) and subolesin. Included in this cocktail was the T. parva protein p67, located on the sporozoite surface. Transmission of T. parva sporozoites from infected ticks to the vaccinated cattle was compared to control cattle. Establishment of ECF was 20 % lower in the vaccinated animals indicating that this multivalent vaccine partially prevented disease establishment. Importantly, animals that showed no or only mild ECF symptoms after cocktail vaccination and infected tick exposure were solidly protected from lethal needle challenge with the homologous T. parva stock. This work demonstrated for the first time that transmission of T. parva can be reduced by vaccination resulting in lowering of ECF clinical cases while still advantageously enables establishment of immune protection.
Current experimental infection of animals with T. parva involves the needle administration of cryo-preserved isolated sporozoites. This highly artificial infection method differs from natural tick based T. parva infection in both the delivery route and the number of parasite injected over time. A reliable tick-based infection method for ECF resembling natural field situations is essential for future intervention studies. Here we show for the first time that the R. appendiculatus RAM-L tick line is a suitable tool that reproducibly delivers T. parva infectious sporozoite doses to cattle resembling endemically stable field situations. Our newly developed RAM-L tick based infection model can provide information on the potential protective capacity of experimental subunit T. parva vaccines requiring substantially smaller animal numbers than conventional field trials. Together, this work adds novel information on anti-tick and transmission blocking vaccine testing for control of R. appendiculatus and T. parva.