Roadmap for Vector Transmission Control (VTC)

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

• Define mechanisms of vector control mediated by the host’s innate and acquired resistance mechanisms (host anatomical characteristics such as skin thickness, host skin microbiome, inflammatory responses, innate immune responses, MHC variability and acquired immunity) using animals that present with different levels of previous exposure to the vector, or histories of vaccination, or acaracide or other chemical or drug treatments.
• Certain drugs used to treat VBDs potentially have a negative impact upon generation of host immunity to the very VBDs that are being treated. (Sourcing such animals and defining mechanisms is needed in order to be able to select and breed vector-resistant animals or to genetically edit animals to enhance resistance.)

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

• Developing phenotypic and genetic resistance assessment protocols.
• Identifying populations of naïve animals showing differences in degrees of susceptibility vs resistant to vectors. For example, determine why certain breeds of cattle have lower tick loads than others (e.g., Bovidae in Indian subcontinent are more resistant, as are Bos indicus relative Bos taurus.) Does it represent co-evolution of cattle living in tick-infested areas?)
• Determining whether livestock can be bred to increase their natural resistance to vectors.
• Determining if host natural resistance is vector-species specific.
• Determining whether expression of innate resistance differs with environmental factors such as heat, humidity, nutrition, etc.
• Cataloguing the host’s behavioural factors (e.g., tail swishing; licking) that contribute to animal resistance to or repelling of ticks or other pathogen vectors.
• Determining the role of skin thickness and morphological structure (skin anatomy and physiology) in natural resistance.
• Determining the relationship between skin reactions and resistance to vectors.
• Determining which innate immune cells and other inflammatory components (neutrophils, macrophages, complement, acute phase reactants, etc.) are involved in natural resistance mechanisms.
• Studying genetic variation in both the host and parasite populations to identify genetic factors that influence susceptibility to infection, e.g., the pathogen’s resistance to complement-mediated killing or the host’s ability to mount complement-mediated protective responses.
• Identifying genetic polymorphisms including SNPs involved in conveying natural resistance that can be exploited to develop genetically edited hosts that can resist vector infestations without loss of productivity.
• Identifying biomarkers of resistance in hosts.
• Understanding the mechanisms behind histamine resistance. While it is known that ticks and mosquitoes are susceptible to histamine early in the feeding cycle but become resistant to histamine after some days.
• Others have suggested that repetitive feeding on rich blood makes them histamine resistant. The mechanisms behind this resistance are not well understood.

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

• Assuming populations of naturally resistant and susceptible animals can be identified and that these are stable phenotypes, naïve animals representing these two groups need to be bred to create herds of naïve animals.
• Using these animals, it may be possible to identify genetic markers including SNPs or other genetic polymorphisms that may be used as templates for gene editing studies.
• These herds of animals can also be used to evaluate behavioural, inherent physiological, and innate immune responses that differ between the two groups.
• Collectively, this knowledge will serve as criteria for selecting more resistant individuals from different breeds that are resilient to their environments for additional reasons (e.g., resistance to particular pathogens, heat-resistance, greater productivity with local grazing or feeding systems, etc.)

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

Establish herds of hosts with different levels of natural resistance for comparative studies.

Existing knowledge including successes and failures

• Babesia is a protozoan parasite that is transmitted by ticks and causes babesiosis in humans and animals. The host complement system plays an important role in controlling babesia infections by killing the parasites directly or marking them for destruction by other immune cells. Some strains of babesia have evolved mechanisms to evade the host complement system, allowing them to survive and replicate within the host. Understanding these mechanisms could provide new insights into how babesia and other TBD cause disease and lead to new approaches of control.
• Some breeds of cattle such as Nelore cattle in Brazil have a level of natural resistance to ticks. The crosses of Gir and Holstein to yield Girolandos and also crosses of Hereford and Gir to yield Braford were evaluated. The various breeds were evaluated by transcriptomics to see association with resistance using GWAS and found 4 pathways associated: MAPK, ROS, complement and wound repair.
• Latif AA, Punyua DK, Capstick PB, Newson RM. Tick infestations on Zebu cattle in western Kenya: host resistance to Rhipicephalus appendiculatus (Acari: Ixodidae). J Med Entomol. 1991 Jan;28(1):127-32.