GCRF-BBR: The Tick Cell Biobank: outposts in Asia, Africa and South America

Ticks are bloodfeeding arthropods which, as well as causing direct damage to their hosts, transmit many diseases of livestock, companion animals and humans. These diseases are caused by viruses, bacteria, protozoa and filarial worms. While ticks and tick-borne diseases (TBD) occur worldwide, the economic burden they impose falls disproportionately on least-developed and lower-middle-income countries (LMIC) in the tropics and sub-tropics. Losses are incurred through direct costs of tick and TBD control (acaricides, antibiotic and antiparasitic treatment, vaccines where these exist) and indirect costs of reduced productivity, mortality and time and manpower expended on applying control measures. Development of resistance by ticks to existing acaricides is an increasing problem worldwide, and major pharmaceutical companies are unwilling to invest in new chemical tick control approaches for the livestock sector in LMIC. To reduce the economic burden on smallholder farmers and livestock owners in LMIC, new acaricides and/or alternative tick control regimes, and affordable and effective vaccines and/or drug treatments for TBD, are urgently needed.

Research into prevention and cure of these diseases is greatly assisted by the use of cell culture systems to study both how tick cells function, and how and why they transmit disease-causing pathogens. Such culture systems, called cell lines, have been developed for many disease-carrying ticks, but they require special skills and much time and patience to establish and maintain. Tick cell lines are increasingly important research tools for study of tick-associated problems affecting LMIC; since they are relatively cheap and easy to grow, they enable many laboratories that lack infrastructure for feeding ticks on large animals to carry out many aspects of tick and TBD research. Seven years ago a central repository, the Tick Cell Biobank, was created in the UK for all the tick cell lines available now and in future. The Tick Cell Biobank distributes tick cell lines on request to research scientists and provides essential training in their maintenance. Currently it is difficult and expensive for LMIC researchers to obtain and maintain existing tick cell lines to support their tick and TBD research, as the cells must be imported from the UK and local training is unavailable. To address this issue and improve LMIC access to tick cell lines and associated expertise, we will establish regional outposts of the Tick Cell Biobank in Malaysia, Kenya and Brazil. The outposts will be sited at institutes with existing tick and/or TBD-related research programmes, in collaboration with experiences local scientists, and will offer a regionally-tailored portfolio of tick cell lines with training in their maintenance. We will also encourage establishment of novel cell lines from indigenous tick species by sharing expertise in the required techniques. We anticipate that the Tick Cell Biobank outposts will enable scientists in these and neighbouring countries to fully exploit the potential of TCL in their research. In the long term, this will build and expand local capacity for tick and TBD research, leading to more and better locally generated solutions for local and regional problems.

Ticks and tick-borne diseases are a huge economic drain on the resources of LMIC in the tropics and sub-tropics. There is a growing unmet need for development of novel control methods for ticks to replace existing acaricides due to the rapid spread of resistance, and for effective, affordable and widely available vaccines for tick-borne diseases. Tick cell lines are playing an increasingly important and valuable role in research into many aspects of tick and tick-borne pathogen biology and control. The Tick Cell Biobank is a UK-based biological resource that underpins UK and international tick and tick-borne disease research. The Tick Cell Biobank houses and supplies over 50 cell lines derived from 15 ixodid and two argasid tick species of veterinary and/or medical importance, and provides recipient scientists with training in tick cell maintenance and cell line establishment. However LMIC scientists face difficulties in accessing tick cell lines; as a result they are underrepresented amongst recipients and unable to fully exploit this valuable resource in their research. This GCRF proposal, which forms a component of the BBRF proposal "The Tick Cell Biobank - a UK and international biological resource", aims to address the problem of LMIC access to tick cell lines by establishing outposts of the Tick Cell Biobank in South-East Asia (Malaysia), Africa (Kenya) and South America (Brazil). These outposts will stock and supply a targeted selection of the most popular and regionally-relevant tick cell lines, and provide training in their maintenance, to scientists within each region, thereby raising the profile of, and improving access to, these unique and valuable research tools. In the long term, this will build and expand local capacity for tick and tick-borne disease research in both veterinary and medical fields, leading to more and better locally generated solutions for local and regional problems.

In addition to the academic beneficiaries listed in the previous section, the following groups should benefit from the proposed establishment of Tick Cell Biobank outposts in Malaysia, Kenya and Brazil in the short term:

- Scientific, legal and administrative staff of the three institutes housing the Tick Cell Biobank outposts will gain experience in managing an international culture collection, thereby enhancing their career development and employment prospects
- Links between the LMIC institutes involved in the project and University of Liverpool will be created and strengthened, facilitating future collaborations
- The profile of the UK Bioscience contribution to addressing and solving problems caused by ticks and tick-borne pathogens in LMIC, in both veterinary and human medicine, will be raised

In the longer term, use of tick cell lines by LMIC researchers will facilitate i) delivery of improved tick control methods using novel acaricides, plant-based products and anti-tick vaccines, and ii) improved detection, diagnosis, treatment and control of tick-borne pathogens based on pathogens propagated in tick cell lines. These will benefit the following groups:

- LMIC farmers and smallholders will have access to more effective and affordable tick control methods to reduce or eliminate tick burdens on their livestock, and more effective, accessible and affordable vaccines and/or treatments for the tick-borne diseases affecting their livestock
- This will in turn improve the access of poor farmers and smallholders, their families and consumers in the general population in LMIC to more and better quality sources of animal protein in their diets
- LMIC veterinarians will have access to improved products for diagnosis, treatment and control of ticks and tick-borne diseases affecting livestock and companion animals
- LMIC clinicians will similarly have access to increased knowledge of tick-borne diseases affecting humans and to improved products for diagnosis and treatment of tick-borne diseases affecting humans

The expertise in establishment of arthropod cell lines disseminated by the Tick Cell Biobank outposts will additionally benefit equivalent groups affected by arthropod vectors other than ticks (e.g. mites, sand flies, midges, lice, fleas) and the pathogens that these arthropods transmit, in ways similar to those outlined above.