Roadmap for Vector Transmission Control (VTC)

What are we trying to achieve and why? What is the problem we are trying to solve?

To decrease vector challenge by treating the host with chemicals or biological agents (e.g., chemical poisons, chemical repellents, fungi).

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

Anti-vector treatments need to be developed that are non-toxic to the animal host, the environment and to humans.
Acaracide resistance in vectors is a huge problem worldwide and the acaracides also are an environmental contaminant. There are a number of challenges in this arena:

1. Determine how can the residual effect be increased to minimise treatment frequency and thus development of
   resistance?
2. Determine whether it is possible to delay acaracide resistanceby proper use.
3. Develop diagnostic tests to inform farmers regarding which acaracides that ticks in their area are susceptible to in order to prevent misuse and overuse of acaracides
4. Determine how frequency of use and dose of acaracides impact selection of acaracide resistant ticks
5. Understand the variety of modes of actions that acaracides could be developed to disrupt, thus having a greater variety to employ

Finding for alternatives to acaracides is a top priority – fungi could be a strong option for this

There are restrictions on use of insecticides for mosquito control – in urban areas in particular – determine how this affect vector challenge to livestock and poultry

Formulation is another important consideration when developing new tick control products since it can affect the efficacy, safety, and ease of use of the product. For example, topical formulations may be more effective at controlling ticks than oral formulations but may be more difficult to apply and the farmer has to weigh the cattle with pour￾on. New pour-on acaricides have very long half-life in the blood; cattle lick themselves so intake that way. Oxazoline is a synthetic made in last 5 years that is given as a tablet to dogs or cats but resistance is developing. In dairy cattle it is secreted in milk so have a 42-day withdrawal time. In beef cattle it is used differently (greater quantity) because don’t have milk. Registered in Brazil. Target Product Profile (TPP) important, e.g., pour on/spray preferred by farmers to injections.
Determining if systemic application (oral) is better than dipping/spraying and could this be employed without affecting the ability to market or consume food animal products? Advantage is that if use systematic treatment can eradicate ticks from pasture.
Laboratory conditions may not always reflect real-world conditions when it comes to acaricide resistance. It is important to conduct field studies to determine how well different products and strategies work in actual tick-infested environments but this is expensive.

What approaches could/should be taken to address the research question?

Delivery methods to ease application and contribute to proper use of acaricides:

• For application of anti-vector drugs use of boluses for long treatment (like anthelmintic application is done) may be an option.
• Consider delivery methods for delayed release for anti-vector antibodies or for drugs such as by microneedle patches.
• The use of oral acaricides, similar to anthelminthics, has been proposed as a way to reduce the risk of resistance developing. This approach could be particularly useful for controlling ticks in wildlife populations where topical treatments may be difficult to apply.

Delaying acaricide resistance:

• One approach suggested is the use of combination therapies, which involve using multiple acaricides with different modes of action at once
• Another approach is to rotate the use of different acaricides to prevent ticks from developing resistance to any one product
• Anecdotally, resistance is thought to occur in about 10 years but controlled studies need to be done to evaluate
  effectiveness of the proposed alternative strategies

Still need to continue to identify unique vector biochemical pathways to target

What else needs to be done before we can solve this need?

Improved understanding of insect physiology.
Mapping of where the various vector species are found.
Mapping of drug resistance in vectors.
Mapping of pathogens being carried by the vectors.

Existing knowledge including successes and failures

Oxazoline is a synthetic product that has shown promise in controlling ticks on livestock. It can be applied topically as a pour-on insecticide and has been shown to be effective against several species of ticks. However, further research is needed to determine long-term effectiveness of oxazoline and potential environmental impacts. Has a super long half-life.
University of Florida looking at potassium ion channels for novel drug target focusing on the AB422 protein for rapid engorgement.
Anthelminthic treatment knowledge: slow release
Preference for non-histamine blood so can attach to host
Cattle tick R. (boophilus) microplus in Brazil are resistant to 6 of the acaricides that includes all classes of acaricides. 75% of ticks in Brazil are resistant to 3 to 5 compounds. Doing sequencing to find SNPs associated with resistance.
The “larval packet test” is the gold standard for testing for acaricide resistance.