Ticks and Tick-Borne Diseases

Ticks

Ticks are second to mosquitoes as global vectors of zoonoses, but are the most relevant vectors of disease-causing pathogens in domestic and wild animals.

Ticks and tick borne diseases place a major constraint on livestock production throughout most of the developing world, especially Sub-Saharan Africa.

Factors such as climate, host movement, animal husbandry practices, vector distribution and vector population changes, affect tick distribution and occurrence of tick-borne diseases.

Vaccination

The feasibility of vaccinating against at least one tick species, Rhipicephalus (Boophilus) microplus, has been demonstrated using the recombinant antigen Bm86 and commercially developed vaccines. This tick species has long been considered of minor importance in most of Africa, virtually absent throughout West Africa. However, in recent years it has been found that R. microplus has spread rapidly, infesting previously unaffected regions. Moreover, it has been found that R. microplus has displaced “endemic” species, R. decoloratus, throughout much of its range in eastern and southern Africa, including the Limpopo province in South Africa. Therefore, given the fecundity of this species, its adaptability to different climatic zones, efficiency as a disease vector and ability to develop pesticide resistance, the full impact of its introduction to the African continent is difficult to estimate and likely to be catastrophic in the long term. The latter necessitates the development and implimentation of effective control strategies to alleviate the increasing pressure this species places on livestock in Africa. Anti-tick vaccines offer the advantage of controlling both tick numbers and disrupting the tick vector-pathogen interface. Our group utilize cutting edge technologies (including transcriptome analysis, bioinformatics and immunoinformatics, in vivo and in situ gene silecing, molecular biology, recombiant protein expression, protein-protein interactions, and animal vaccination trials) to identify and validate protective antigens as vaccine candidates in order to lessen the socio-economical burdens associated with ticks and tick-borne pathogens. 

Secondly, the tick research program is supported by a program focusing on the genetic diversity and current acaricide resistance status of Rhipicephalus ticks from endemic South African regions. Analyses for five acaricide resistance genes and eight microsatellites have been optimized and are used in a large-scale screening of Rhipicephalus ticks. These studies will provide us with an understanding of the parasite-host-pathogen interactions and solutions to economical viable tick control measures.  

Thirdly, skills developed in the tick research program have now been extended to a broader vector control program, to include Culicoides (vector for Bluetongue virus and African Horse Sickness Virus) as well as and Anopheles species (vector for Plasmodium species). Currently, focus is on the identification of transcripts vital to vector feeding and fecundity, followed by in vivo evaluations on vector fitness during gene silencing. Finally, studies on evaluating promising anti-apicomplexan compounds are being evaluated in Babesia species, to determine their IC50 and mode of action using cutting edge functional genomics methods and comparative genomics between other apicomplexan parasites. This research is critical for future drug design and ensuring animal health.

Research objectives and current activities:

Currently, the following focus areas are addressed in order to identify and evaluate ant-tick vaccine candidates.

• Firstly, a reverse genetics approach using RNA-interference in both living ticks and in tick cell cultures. This approach allows the identification of transcripts with a lethal phenotype (i.e. possible new vaccine candidates), as well as determining the differential transcriptional response elicited in ticks after silencing a specific transcript (i.e. possible cocktail vaccine candidates).
• Secondly, we aim to unravel essential processes mediated by protein-protein interactions using the yeast two-hybrid screening system. Currently, we are focussing on the existing vaccines which will not only provide insight into their biological roles, but also identify more possible tick-control points.
• Thirdly, we also use functional genomics and immunoinformatics to identify highly immunogenic proteins that are expressed throughout the lifecycle of the two most prominent cattle tick species in South Africa (R. microplusand R. decoloratus).
• Fourthly, R. microplus and R. decoloratus from some 160 cattle farms throughout SA has been collected and are being analysed using mitochondrial- and nuclear genes as well as microsatellites to gain insight into their genetic diversity.
• Fifthly, acaricide resistance screening is conducted using PCR for the detection of resistance-induced SNPs, as well as protein docking of newly identified SNPs to evaluate their possible effects on the protein structure-function relationship.
• Finally, promising anti-babesia drugs are evaluated in vitro and their mode-of-action determined using transcriptome and proteome analysis.

References:

1. Towards a complete genome, transcriptome and interactome of the cattle tick R. microplus (2012-). Dr. Felix D. Guerrero (USDA-ARS Knipling-Bushland, US Livestock Insects Research Laboratory, Kerrville, Tx 78028, USA) & Dr. Matthew Bellgard (Director of Murdoch University's Center for Comparative Genomics, Murdoch University, Perth, Western Australia, Australia).
2. Evaluation of promising anti-malarial compounds against Babesia spp. Prof Eric Maréchal (Institut de Recherches en Technologies et Sciences pour le Vivant CEA-Grenoble, France).
3. Identification of subolesin interacting partners and homologous in South African mosquitoes and midges (2005-current) & Two-hybrid analysis of Anaplasma MSP-1 using tick cDNA libraries (2011-current). Prof. Jose de la Fuente (Instituto de Investigacion en Recursos Cinegeticos, IREC Ronda de Toledo s/n 13005 Ciudad Real, Spain and Department of Veterinary Pathobiology Center for Veterinary Health Sciences Oklahoma State University Stillwater, Oklahoma, USA)
4. Improvement of Bm86-and ATAQ-based anti-tick vaccines, as well as in vivo RNAi of vaccine candidates. Dr. A. Nijhof (Institut für Parasitologie und Tropenveterinärmedizin, Freie Universität Berlin, Germany).
5. Pfizer Pty (Ltd.) Genotyping and acaricide resistance screening of Rhipicephalus ticks throughout South Africa (Dr Chris van Dijk).
6. NHLS vector control unit: Validation of akirins as sterile insect-based control measure in South African mosquitoes (Prof Lizette Koekemoer)
7. Validation of akirins as sterile insect-based control measure in African midges (Dr Wilma Fick, Department of Genetics, UP).
8. University of Pretoria Biomedical Research Centre (2008-current): Validating vaccine candidates in cattle trials (Drs V Naidoo and T Pulker, Ms S Meyer)
9. Medical research council (2012-): Anti-sera production and small animal research (Mr K Venter)
10. University of Stellenbosch, Proteomics centre (Dr S Smit)
11. Malaria Research Program, Department of Biochemistry, University of Pretoria (2010-current): Evaluation of promising anti-malarial compounds against Babesia spp. (Ms I Rossouw, Prof L Birkholtz, Prof Eric Maréchal) and Expression of Plasmodium proteins in Pichia pastoris (2008) (Dr. L. Birkholtz, Ms. M. Dreyer)
12. Red Meat Research Development Trust of South Africa (RMRDT-SA). THRIP, International Foundation of Science (IFS, Sweden), Gauteng Department of Agriculture and Rural Development (GDARD), NRF Rated program, Pfizer (Pty.) Ltd., ITM (Belgium).
13. 16 BSc(Hons) of which 6 are cum laude
14. 6 MSc of which 3 are cum laude
15. 2 PhD
16. 2 Post-doctoral Fellows
17. 3 PhD
18. 6 MSc