CATTLE FEVER (BOVINE BABESIOSIS) IS A DISEASE THAT IS ESPECIALLY LETHAL IN ADULT CATTLE THAT HAVE NOT BEEN PREVIOUSLY EXPOSED TO IT. IT IS CAUSED BY SEVERAL DIFFERENT SPECIES OF PARASITES BUT SPREAD ONLY BY CATTLE FEVER TICKS, WHICH ARE INVASIVE IN THE US AND MEXICO. CATTLE FEVER WAS ONCE WIDESPREAD THROUGHOUT THE SOUTHERN US AND CAUSED ANNUAL LOSSES TO THE CATTLE INDUSTRY THAT WOULD AMOUNT TO MORE THAN $3 BILLION/YR TODAY. FORTUNATELY, INTENSIVE EFFORTS BY FEDERAL AND STATE AGENCIES LED TO THE ERADICATION OF CATTLE FEVER IN ALMOST ALL OF THE US BY 1960. THE SUCCESSFUL ERADICATION OF THE DISEASE WAS ACCOMPLISHED BY USING CHEMICALS TO ERADICATE CATTLE FEVER TICKS. HOWEVER, THE US NOW IMPORTS ABOUT 1 MILLION CATTLE EACH YEAR FROM MEXICO, WHERE CATTLE FEVER TICKS AND THE PARASITES REMAIN RAMPANT. TO MAKE MATTERS WORSE, TICK RESISTANCE TO CHEMICALS HAS GREATLY INCREASED IN MEXICO SINCE THE 1980S AND IS SPREADING INTO THE US. DESPITE RIGOROUS MEASURES BY THE USDA-APHIS TO PREVENT MEXICAN CATTLE FROM CARRYING TICKS INTO THE US, TICK INFESTATIONS HAVE INCREASED IN SOUTHERN TEXAS AND ARE SPREADING NORTH AND EAST. THIS COULD LEAD TO THE REINTRODUCTION OF CATTLE FEVER INTO THE SOUTHERN US, WHICH WOULD BE DEVASTATING TO THE US CATTLE INDUSTRY.BECAUSE CHEMICAL CONTROL IS BECOMING LESS EFFECTIVE ON RESISTANT TICKS, AN ALTERNATIVE STRATEGY FOR TICK CONTROL IS TO VACCINATE CATTLE AGAINST THE TICKS THEMSELVES. WHEN TICKS ATTACH AND BEGIN TO FEED, A VACCINATED COW WILL HAVE IMMUNE SYSTEM DEFENSES (ANTIBODIES) CIRCULATING IN ITS BLOOD THAT WILL ATTACK THE TICK AS IT FEEDS. THE BLOOD OF IMMUNIZED CATTLE CAUSES SIGNIFICANT MORTALITY IN TICKS AND GREATLY REDUCES THEIR REPRODUCTION. HOWEVER, CURRENT ANTI-TICK VACCINES ARE NOT ALWAYS EFFECTIVE AGAINST ALL CATTLE FEVER TICKS, PROBABLY BECAUSE A LARGE AMOUNT OF GENETIC VARIATION IS PRESENT IN TICK POPULATIONS. THE EFFECTIVENESS OF THESE VACCINES CAN BE IMPROVED BY CHARACTERIZING THE GENETIC VARIATION PRESENT IN TICK GENES USED AS VACCINE CANDIDATES, AND DEVELOPING MORE DIVERSE VACCINES THAT ARE BROADLY EFFECTIVE AGAINST ALL CATTLE FEVER TICK POPULATIONS. BECAUSE ANTI-TICK VACCINES AND CHEMICALS ARE THE TWO PRIMARY MANAGEMENT TOOLS USED TO PREVENT CATTLE FEVER TICKS AND THEIR DISEASES FROM ENTERING THE US, THIS PROJECT WILL PROVIDE CRITICALLY NEEDED INFORMATION TO OUR APHIS COLLABORATORS WHO DEPEND ON THESE MANAGEMENT TOOLS. WE WILL USE GENETIC ANALYSIS TO IMPROVE TICK CONTROL BY 1) CHARACTERIZING GENETIC MECHANISMS OF RESISTANCE TO CHEMICALS USED FOR TICK CONTROL, AND 2) IDENTIFYING GENETIC VARIATION IN TICK GENES THAT ARE HIGH PRIORITY CANDIDATES AS ANTI-TICK VACCINE TARGETS. IN DOING SO, THIS PROJECT WILL SECURE THE SUSTAINABILITY AND COMPETIVENESS OF THE US CATTLE INDUSTRY BY PREVENTING CATTLE FEVER FROM BECOMING REESTABLISHED IN THE US.